Intraoperative Doppler sonogram in pediatric liver transplants: a pictorial review of intraoperative and early postoperative complications

Abstract

A spectrum of vascular complications can be seen in pediatric liver transplant patients, including occlusion and hemodynamically significant narrowing of the vessels that provide inflow to or outflow from the graft. Intraoperative Doppler ultrasound (US) has the potential benefit of identifying vascular complications in pediatric liver transplant patients prior to abdominal closure. Importantly, intraoperative Doppler US can be used as a problem-solving tool in situations such as position-dependent kinking of the portal or hepatic veins, or in suspected vasospasm of the hepatic artery. Furthermore, this technique can be used for real-time reassessment after surgical correction of vascular complications. This pictorial review of intraoperative Doppler US in pediatric liver transplant patients illustrates normal findings and common vascular complications, including examples after surgical correction, in the perioperative period.

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Late breast cancer treatment-related symptoms and functioning: associations with physical activity adoption and maintenance during a lifestyle intervention for rural survivors

Abstract

Purpose

Physical activity may be difficult for survivors with poorer functioning following primary treatment. The study examined whether late symptoms of breast cancer treatment impact PA adoption (0–6 months) and maintenance (6–18 months) during a weight management intervention, and whether late symptoms influence PA when accounting for overall functioning.

Methods

Secondary analyses were conducted using a sample of survivors participating in a weight management intervention and who provided valid weight and accelerometer data at baseline and 6 months (N = 176). The Breast Cancer Prevention Trial Symptom Checklist (BCPT) assessed late treatment-related symptoms. SF-12 Physical Component Scale (PCS) and Mental Component Scale (MCS) scores assessed functioning.

Results

Change in bouted moderate to vigorous physical activity (MVPA) min/week from baseline to 6 months was not associated with BCPT scales (all p values > 0.05). When adding SF-12 scores to the model, change in bouted MVPA min/week was significantly associated with the PCS (p = 0.045). Change in MVPA min/week from 6 to 18 months was significantly associated with cognitive symptoms (p = 0.004), but not musculoskeletal or vasomotor symptoms (p values > 0.05). When adding 6-month SF-12 scores to the model, MVPA min/week was significantly associated with PCS (p = 0.001) and MCS (p = 0.028); however, BCPT cognitive problems score became non-significant (p > 0.05).

Conclusions

Poorer physical functioning was associated with lower PA adoption, and poorer mental and physical functioning was associated with lower maintenance of PA, while late symptoms generally were not. Interventionists should consider level of functioning when identifying individual PA goals during weight management interventions.

http://ift.tt/2BXTV29

Myeloid neoplasms with t(12;22)(p13;q12)/MN1-EVT6: a systematic review of 12 cases

Abstract

t(12;22)(p13;q12) is a rare but recurrent chromosomal abnormality involving the ETS transcription factor ETV6 and meningioma 1 (MN1) genes. In this study, we analyzed the clinical, cytogenetic, and molecular features of five new patients with the t(12;22)/MN1-EVT6 who presented with acute myeloid leukemia or chronic myelomonocytic leukemia. We subsequently reviewed the literature and identified seven additional cases reported with t(12;22)/MN1-EVT6. Our data suggest that neoplasms carrying the t(12;22)/MN1-ETV6, although rare, can commonly present as myeloid neoplasms at the initial diagnosis, including acute myeloid leukemia (n = 8), myelodysplastic syndrome (n = 2), and myelodysplastic/myeloproliferative neoplasms (n = 2). There were five men and seven women with a median age of 43 years (range, 15–63 years) at initial diagnosis. Cytogenetics revealed t(12;22) as the sole abnormality in five patients, with the remaining seven patients harboring additional chromosomal aberrations. Of the five patients who received known therapy regimens, all of them had poor response to the idarubicin/mitoxantrone + cytarabine regimen. Of the seven patients with follow-up information, six patients died with a median overall survival time of only 5 months (range, 1–12 months) after the emergence of t(12;22). In summary, patients with t(12;22) are frequently associated with myeloid neoplasms, poor response to chemotherapy, and inferior outcome.

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Red and processed meat consumption and breast cancer: UK Biobank cohort study and meta-analysis

Publication date: February 2018
Source:European Journal of Cancer, Volume 90
Author(s): Jana J. Anderson, Narisa D.M. Darwis, Daniel F. Mackay, Carlos A. Celis-Morales, Donald M. Lyall, Naveed Sattar, Jason M.R. Gill, Jill P. Pell
AimRed and processed meat may be risk factors for breast cancer due to their iron content, administration of oestrogens to cattle or mutagens created during cooking. We studied the associations in UK Biobank and then included the results in a meta-analysis of published cohort studies.MethodsUK Biobank, a general population cohort study, recruited participants aged 40–69 years. Incident breast cancer was ascertained via linkage to routine hospital admission, cancer registry and death certificate data. Univariate and multivariable Cox proportional hazard models were used to explore the associations between red and processed meat consumption and breast cancer. Previously published cohort studies were identified from a systematic review using PubMed and Ovid and a meta-analysis conducted using a random effects model.ResultsOver a median of 7 years follow-up, 4819 of the 262,195 women developed breast cancer. The risk was increased in the highest tertile (>9 g/day) of processed meat consumption (adjusted hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.08–1.35, p = 0.001). Collation with 10 previous cohort studies provided data on 40,257 incident breast cancers in 1.65 million women. On meta-analysis, processed meat consumption was associated with overall (relative risk [RR] 1.06, 95% CI 1.01–1.11) and post-menopausal (RR 1.09, 95% CI 1.03–1.15), but not pre-menopausal (RR 0.99, 95% CI 0.88–1.10), breast cancer. In UK Biobank and the meta-analysis, red meat consumption was not associated with breast cancer (adjusted HR 0.99 95% CI 0.88–1.12 and RR 1.03, 95% CI 0.99–1.08, respectively).ConclusionsConsumption of processed meat, but not red meat, may increase the risk of breast cancer.



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Optimal adjuvant endocrine treatment of ER+/HER2+ breast cancer patients by age at diagnosis: A population-based cohort study

Publication date: February 2018
Source:European Journal of Cancer, Volume 90
Author(s): G.M.H.E. Dackus, K. Jóźwiak, G.S. Sonke, E. van der Wall, P.J. van Diest, M. Hauptmann, S. Siesling, S.C. Linn
BackgroundPrior randomised controlled trials on adjuvant hormonal therapy included HER2any patients; however, a differential effect of aromatase inhibitors (AIs) versus tamoxifen (TAM) may have been missed in ER+/HER2+ patients that comprise 7–15% of all breast cancer patients.In addition, a woman's hormonal microenvironment may influence sensitivity to TAM and AIs in the adjuvant setting, which changes during menopausal transition, a process that takes years. We studied the efficacy of AIs versus TAM in ER+/HER2+ breast cancer patients grouped by age at diagnosis as a proxy for menopausal status using treatment and outcome data from the nationwide population-based Netherlands Cancer Registry (NCR).Patients and methodsAll women diagnosed between 2005 and 2007 with endocrine-treated, TanyNanyM0, ER+/HER2+ breast cancer were identified through the NCR (n = 1155). Patients were divided by age at diagnosis: premenopausal (≤45 years; n = 326), perimenopausal (45<years≤55; n = 304) and postmenopausal (>55 years; n = 525). A time-dependent variable, indicating whether AI or TAM was received for >50% of endocrine treatment duration, was applied to subdivide groups by predominant treatment received. Recurrence-free survival (RFS) and overall survival (OS) were assessed using Kaplan–Meier survival estimation and Cox regression. Hazard ratios (HRs) were adjusted for chemotherapy, trastuzumab, age at diagnosis, N-status, grade, pT-stage and ovarian ablation.ResultsDuring follow-up, 237 recurrences and 182 deaths occurred. Perimenopausal women derived significant RFS and OS benefit from AI compared with TAM, HR 0.47 (95% CI 0.25–0.91; P = 0.03) and HR 0.37 (95% CI 0.18–0.79; P = 0.01), respectively, whereas premenopausal women derived no benefit from AI compared with TAM. Treatment effects differed significantly between these age groups (interaction P = 0.03 and P = 0.02, respectively). Among postmenopausal women a small but non-significant AI benefit was observed.ConclusionAI treatment, preferably without any TAM treatment, was associated with the best RFS and OS outcome in ER+/HER2+ perimenopausal breast cancer patients.



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3-Methoxytyramine: An independent prognostic biomarker that associates with high-risk disease and poor clinical outcome in neuroblastoma patients

Publication date: February 2018
Source:European Journal of Cancer, Volume 90
Author(s): I.R.N. Verly, A.B.P. van Kuilenburg, N.G.G.M. Abeling, S.M.I. Goorden, M. Fiocco, F.M. Vaz, M.M. van Noesel, C.M. Zwaan, G.J.L. Kaspers, J.H.M. Merks, H.N. Caron, G.A.M. Tytgat
IntroductionPrognosis of neuroblastoma patients is very diverse, indicating the need for more accurate prognostic parameters. The excretion of catecholamine metabolites by most neuroblastomas is used for diagnostic purposes, but their correlation with prognosis has hardly been investigated. Therefore, we performed an in-depth analysis of a panel of elevated urinary catecholamine metabolites at diagnosis and their correlation with prognosis.Patients and methodsRetrospective study of eight urinary catecholamine metabolites in a test (n = 96) and validation (n = 205) cohort of patients with neuroblastoma (all stages) at diagnosis.ResultsMultivariate analyses, including risk factors such as stage and MYCN amplification, revealed that 3-methoxytyramine (3MT) was an independent risk factor for event-free survival (EFS) and overall survival (OS). Furthermore, only 3MT appeared to be an independent risk factor for both EFS and OS in high-risk patients, which was independent of modern high-risk therapy and immunotherapy. Among high-risk patients, those with elevated 3MT and older than 18 months had an extremely poor prognosis compared to patients with non-elevated 3MT and younger than 18 months (5-year EFS of 14.3% ± 4% and 66.7% ± 18%, respectively, p = 0.001; 5-year OS of 21.8% ± 5% and 87.5% ± 12%, respectively, p < 0.001).ConclusionsElevated 3MT at diagnosis was associated with high-risk disease and poor prognosis. For high-risk patients, elevated 3MT at diagnosis was the only significant risk factor for EFS and OS. 3MT was also able to identify subgroups of high-risk patients with favourable and extremely poor prognosis.



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Long-term follow-up of retinoblastoma survivors: Experience from India

Rachna Seth, Amitabh Singh, Vijay Guru, Bhavna Chawla, Sushmita Pathy, Savita Sapra

South Asian Journal of Cancer 2017 6(4):176-179

Background: Retinoblastoma (Rb) is the most common primary intraocular tumor of infancy and childhood. Survivors' ocular and visual problems and increased risk for subsequent malignancy are well documented, but data on long-term health status of Rb survivors are limited, this being particularly true for India. Methodology: Children who had completed treatment for Rb at least 2 years ago before and were under follow-up at the after cancer treatment clinic were evaluated. Results: In our series of 213 patients, the median age was 29 months, there was a male preponderance, and majority had unilateral disease. Enucleation was done in almost three-fourth and 3% underwent bilateral enucleation. Majority of the patients received chemotherapy, and few received radiation. Growth was affected in about one-third and majority were those who had received radiation. Diminished vision was noticed in about one-sixth. Orbital hypoplasia and contracted socket were seen in 14.1% cases. 2.7% were hearing impaired. About one-sixth had a global intelligence delay. Second neoplasms were seen in 0.01%. No other abnormalities were seen. Conclusions: Common late effects in our Rb survivors include diminished vision in the salvage eye, intellectual disability, and contracted socket; there is a need for timely institution of prosthesis to avoid late effects such as hypoplasia, contracted sockets, and better cosmesis and enhanced self-esteem. Second neoplasm is a concern. Lifelong follow-up and counseling of a healthy lifestyle are needed for Rb survivors.

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Role of percutaneous computed tomography-guided radiofrequency ablation in treatment of osteoid osteoma

Ajay R Upadhyay, Nikunj Chandrakant Desai, Digish U Vaghela

South Asian Journal of Cancer 2017 6(4):139-140

Aim: The aim of the study was to evaluate efficacy of percutaneous computed tomography (CT)-guided radiofrequency ablation (RFA) of nidus in osteoid osteoma (OO). Materials and Methods: RFA was performed on fifty patients with clinically and radiologically diagnosed OO. RFA was done in the department of radio-diagnosis in our institute (a tertiary care providing institute in Ahmedabad, Western India). Ablation was performed by putting at an electrode tip (3–5 mm) into nidus under CT guidance with targeted temperature of 90°C for 3 min. Results: All procedures were technically successful. No immediate major or minor complications were observed. Complete clinical success was achieved in 46 patients. Only four patients required second intervention. Conclusion: Our experience indicates a 98% success rate. No major complications were noted.

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Male breast cancer: A retrospective review of clinical profile from a tertiary cancer care center of India

Dharma Ram, Suhas K Rajappa, Veda P Selvakumar, Himanshu Shukla, Ashish Goel, Rajeev Kumar, Kapil Kumar

South Asian Journal of Cancer 2017 6(4):141-143

Aim: Present study was done with an aim to analyse the clinicopathological and survival characteristics of male breast cancer patients. Methods: We did a retrospective review of our database and analysed total 27 patients who presented to breast oncology unit of Rajiv Gandhi cancer centre and research institute from January 2010 to April 2016. Results: Most common stage at presentation in our study was in stage II. The median follow up was 32.75 months. The actuarial 5-year survival was 92.30% and DFS was 76.30%. Only hormone receptor status was found as a significant prognostic variable among the prognostic factors studied for disease free survival. Conclusions: Carcinoma breast in male is a relatively rare disease and management principles are translated from our understanding of breast cancer in women. A relatively early stage at presentation is a contrasting finding of our series which may be responsible for a significantly better actuarial 5 year survival rates.

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Myoepithelial carcinoma of the breast: Case report of a rare entity and its response to chemotherapy

Sanyo P Dsouza, Ajit Kulkarni, Nandini Sharma, SD Banavali

South Asian Journal of Cancer 2017 6(4):185-194



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Osimertinib in Indian patients with T790M-positive advanced nonsmall cell lung cancer

Vanita Noronha, Swaratika Majumdar, Amit Joshi, Vijay Patil, Vaishakhi Trivedi, Anuradha Chougule, Kumar Prabhash

South Asian Journal of Cancer 2017 6(4):143-146



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Cutaneous Hodgkin's lymphoma

Asawari Anant Ambekar, Chitralekha S Soman

South Asian Journal of Cancer 2017 6(4):170-175



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Tolerance and adverse event profile with sorafenib in Indian patients with advanced hepatocellular carcinoma

Vikas Ostwal, Tarachand Gupta, Supriya Chopra, Sherly Lewis, Mahesh Goel, Shraddha Patkar, Nitin Shetty, Anant Ramaswamy

South Asian Journal of Cancer 2017 6(4):144-146

Background: The current standard of treatment for advanced hepatocellular cancer Hepatocellular carcinoma (HCC) is Sorafenib. Data regarding its tolerance and adverse event profile in Indian patients is scarce. Materials and Methods: The primary aim of this analysis was to assess the adverse events (Grade 3 and Grade 4 as per CTCAE v4.0) and requirements for dose reduction with sorafenib in advanced HCC. Details of consecutive patients started on 800 mg/day dosing were obtained from a prospectively maintained database (over a period of 6 months) and analyzed. Results: Thirty-nine patients were available for inclusion in the study. Median age was 58 years (range: 20–75). All patients were classified as Barcelona clinic liver cancer C. Common side effects seen were liver dysfunction (38.5%), hand-foot-syndrome-rash (HFSR) (Grade 2 and 3-25.6%), fatigue (Grade 2 and Grade 3–10.3%), and diarrhea (7.7%). Dose reduction was required in 43.6% of patients. Drug interruptions/cessation was required in 38.5% of patients within the first four months of treatment. Nearly 41% of patients required cessation of sorafenib due to intolerable side-effects while 28.2% stopped sorafenib due to progressive disease. At a median follow-up of 4.9 months, median event-free survival (EFS) was 4.20 months (95% confidence interval: 3.343–5.068). Conclusion: A higher incidence of liver dysfunction and HFSR is seen in Indian patients as compared to published data. A significant proportion of patients required cessation of sorafenib due to adverse events in our series. However, EFS remains on par with that seen in larger studies with sorafenib in advanced HCC.

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Adolescents and young adults: A study of distribution of cancer at ages 15–39 years in a tertiary care hospital from North India: Epidemiological considerations

Neha Kakkar, Ajay Gupta, Neeraj Kumar Sharma, Prachi Agarwal, Jaspreet Kaur

South Asian Journal of Cancer 2017 6(4):180-182

Purpose: This study aimed to analyze cancer pattern among adolescents and young adults (AYA) in a tertiary care center in North India. Materials and Methods: A retrospective study from January 2011 to December 2014 was undertaken on AYA cancer patients (aged 15–39 years). Results: Totally 1077 cases of AYA cancers were identified for analyzing the frequency and pattern of cancer distribution. The most common cancer was head and neck (32%) followed by breast (14.2%). The distribution pattern was observed to be varying in different age groups with lymphoma, leukemia, bone tumors, and sarcomas in adolescents while carcinomas being more frequent in young adults. Conclusion: Cancer distribution patterns are distinct among AYA in terms of epidemiology and biology.

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Metastatic anorectal melanomas – An exploratory retrospective analysis on the benefits of systemic therapy versus best supportive care in a resource-limited setting from India

Arvind Sahu, Anant Ramaswamy, Nitin Singhal, Vipul Doshi, Jimmy Mirani, Ashwin Desouza, Shripad Banavali, Avanish Saklani, Vikas Ostwal

South Asian Journal of Cancer 2017 6(4):147-150

Aim: Data regarding the optimal management of metastatic anorectal melanoma (mARM) is scarce. The primary aim was to evaluate the potential benefits of systemic therapy in mARM. Materials and Methods: This is a retrospective analysis of all mARM who presented between July 2013 and June 2015 at the Department of GI Medical Oncology, Tata Memorial Hospital. Results: Of a total of 37 patients, twelve patients were planned for best supportive care (BSC) only while the remaining 25 patients received systemic therapy. The median overall survival (OS) for the whole cohort was 27 weeks. The OS was significantly better in patients who received first-line therapy as compared to those who were offered BSC (median OS: 14 vs. 33 weeks; P = 0.04). Patients with PS of 1 did significantly better than PS of 2 more (OS 70 vs. 17 weeks; P = 0.015). Conclusion: mARM should be offered chemotherapy, especially in good performance patients. Paclitaxel/Platinum or Capecitabine/Temozolomide regimens can be considered as the preferred regime in the resource-limited setting where immunotherapy may not be a feasible option.

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Profile of patients undergoing palliative radiotherapy: A single-institute study from a tertiary care oncology center

Virender Suhag, BS Sunita, Pankaj Vats, Nilotpal Chakravarty, Mayuri Jain, Rekha S Vashisht

South Asian Journal of Cancer 2017 6(4):190-193

Background: Palliative radiotherapy (PRT) plays a significant role in the palliation of symptoms in patients with cancer and constitutes nearly 50% of the workload in different settings. Aims: The aim is to study patient-, disease-, and treatment-related characteristics in locoregionally advanced and metastatic malignancies meriting palliative management. Setting and Design: This was a retrospective observational study in a tertiary care government institute with academic and research potential. Methodology: The electronic medical records, medical documents, and radiotherapy (RT) treatment charts were retrieved and studied. Observations: A total of 460 patients were included in the study over 2 years, forming 30% of the total number of patients treated during the study period. Three hundred and ninety-six patients received PRT to the metastatic sites, while 64 patients received extremely hypofractionated PRT to the primary for symptomatic relief. Totally 442 patients showed good symptomatic response to PRT. One hundred and thirty-eight patients underwent re-irradiation. Lung was the most common primary site seen in 155 cases. The most common indication for PRT was palliation of pain from painful metastases as seen in 240 cases, and the next common indication was palliative whole-brain RT for brain metastases as seen in 159 cases. Conclusion: PRT forms an integral and important aspect of palliative care to the vast number of patients harboring metastatic disease that warrants some form of treatment for symptomatic relief. Short course of PRT in outdoor setting is a preferred mode of treatment to improve the quality of life of these distressed patients.

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Musculoskeletal chronic graft versus host disease – A rare complication of allogeneic hematopoietic stem cell transplantation: A case report and review of its literature

Vasu Babu Goli, Reetu Jain, Ganapathi Bhat, Anjana Sainani, SH Advani

South Asian Journal of Cancer 2017 6(4):150-168



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Regional reporting of the incidence of Anaplastic Lymphoma Kinase mutation in 379 non-small-cell lung cancer patients from Kolkata: Using immunohistochemistry as the diagnostic modality in a significant subset

Koushik Chatterjee, Raja Bhowmik, Bhargab Chattopadhyay

South Asian Journal of Cancer 2017 6(4):169-170

Context: Regional epidemiology of anaplastic lymphoma kinase (ALK) mutation in non-small-cell lung cancer (NSCLC) is an unmet need in India, and so is the knowledge of its incidence based on immunohistochemistry (IHC). Aims: Reporting the incidence of ALK mutation in NSCLC from Kolkata, incorporating IHC as the diagnostic modality in a considerable subset of patients. Subjects and Methods: It is a retrospective observational study done on NSCLC patients with adenocarcinoma histology, unselected by epidermal growth factor receptor, whose samples were tested for ALK mutation status between March 1, 2013, and March 15, 2017. The study involved all cancer facilities in Kolkata, except Tata Medical Centre. Up to June 2015, the tests were done by fluorescence in situ hybridization (FISH) and from July 2015 to the end, tests were done using IHC, as per the standard testing guidelines existing during the respective time periods. Results were documented in a de-identified manner to analyze the incidence of ALK mutations. Results: A total of 379 patients was tested for ALK mutations. March 2013 to June 2015, 200 (52.77%) patients were tested by FISH, 17 (8.5%) samples were unreportable and 4 patients [(2.19%) 4/183] tested positive for ALK mutations. From July 2015 to March 2017, 179 (47.22%) patients were tested by IHC, 9 (5.02%) samples were unreportable, and 10 patients [(5.88%) 10/170] tested positive for ALK mutations. Overall, 26 (6.8%) samples were unreportable and 14 [(3.9%) 14/353] patients tested positive for ALK mutations. Conclusions: The overall incidence of ALK mutation positive NSCLC in Kolkata is 3.9%. The incidence by IHC is 5.88% and by FISH is 2.19%, in the subset of patients tested by these two modalities respectively.

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Prognostic significance of bone only metastasis compared to visceral metastasis in patients with carcinoma cervix treated with platinum-based chemotherapy

Suresh Babu Mallekavu, Aditi Harsh Thanky, Govind Babu Kanakasetty, Lakshmaiah Kuntegowdanahalli, Lokanatha Dasappa, Linu A Jacob

South Asian Journal of Cancer 2017 6(4):151-153

Context: Carcinoma cervix is a leading cause of cancer in Indian females where 15%–60% of the cases eventually metastasize. Bone only metastasis is rare, and data on its response and survival with systemic therapy as compared to other visceral metastasis are limited. Settings and Design: The study design was a retrospective analysis. Materials and Methods: We retrospectively analyzed our data between May 2013 and April 2015 to identify the cases of bone only metastasis and visceral metastasis and tried to analyze their outcomes with paclitaxel- and carboplatin-based chemotherapy and bisphosphonates (for bone metastasis only). Results: Totally, 12 cases with bone only metastasis (Group 1) and 43 cases with visceral metastasis (Group 2) were identified. Most common sites of bone metastasis were vertebrae (66.67%) and pelvis (25%) while that of visceral metastasis was liver (44.18%) and lung (34.88%). Only 33.33% and 34.88% of cases in Group 1 and Group 2, respectively, could complete all six cycles of chemotherapy. Overall, response rates were 41.67% and 30.32% in Group 1 and Group 2, respectively. Median progression-free survival and overall survival (OS) were 10 months and 14 months, respectively, in Group 1 as compared to 4 months and 9 months, respectively, in Group 2. The difference in survival was statistically significant. Statistical Analysis Used: It was carried out by SPSS software version 20. Conclusion: Bone only metastasis is a rare and distinct entity with favorable outcomes as compared to visceral metastasis. However, disease remains aggressive and poor OS emphasizing the need of further research.

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Clinicopathological and molecular epidemiological study of lung cancer patients seen at a tertiary care hospital in Northern India

Randeep Singh, Nitesh Rohtagi

South Asian Journal of Cancer 2017 6(4):171-175

Aims: The primary objective of this study was to estimate the clinicopathological and molecular profile of lung cancer patients along with the evaluation of their clinical characteristics at a tertiary care hospital in Northern India. Subjects and Methods: A total of 421 patients with lung cancer histology who were treated at Max Super Speciality Hospitals were included in the study. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki and permission was obtained from the Ethics Committee before the start of the study. Clinical characteristics and molecular profiling data were collected from the patient's medical records. Results: There were 330 (78.4%) men and 91 (21.6%) women with a median age of 62 years (range: 30–93 years). Of the 421 patients, 388 (92.2%) patients had the nonsmall cell lung cancer (NSCLC) histology whereas 33 (7.8%) patients were of SCLC histology. Histology and gender had a significant association with NSCLC and SCLC (P < 0.05). Epidermal growth factor receptor (EGFR) and echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene testing was done in 120 and 93 patients, respectively. Of the 120 patients, 24 (20%) cases were positive for EGFR mutations whereas EML4-ALK fusion gene was present in 8 (8.6%) out of 93 patients. Conclusions: Our study confirms the importance of molecular testing in the NSCLC patient subgroup with an aim to identify the exact molecular targets that can benefit from the newer generation of targeted therapies.

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Retraction: Recurrent Glioblastoma: Where we stand

South Asian Journal of Cancer 2017 6(4):153-153



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Good response to erlotinib in a patient after progression on osimertinib: A rare case of spatiotemporal T790M heterogeneity in a patient with epidermal growth factor receptor-mutant nonsmall cell lung cancer

Venkata Pradeep Babu Koyyala, Ullas Batra, Parveen Jain, Mansi Sharma, Pankaj Goyal, Kshitiz Domadia, Sneha Botra

South Asian Journal of Cancer 2017 6(4):179-185



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Oncology gold standard® practical consensus recommendations for the use of monoclonal antibodies in the management of squamous cell carcinoma of head and neck

Govind Babu, Ankur Bahl, GS Bhattacharya, KT Bhowmik, PS Dattatraya, Nikhil Ghadyalpatil, SM Karandikar, Padmaj Kulkarni, Nithya Sridharan, Purvish Parikh, Kumar Prabhash, T Raja, S Rajasundaram, S Subramanian, Kaustav Talapatra, Ashok Vaid

South Asian Journal of Cancer 2017 6(4):154-160

We present the 2017 Oncology Gold Standard Practical Consensus Recommendation for use of monoclonal antibodies in the management of advanced squamous cell carcinoma of head neck region.

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Epidemiology of cancer in young in central India: An analysis of rural cancer hospital data

Novak Gupta, Prakash Chitalkar, Renu Mishra, Ankur Punia

South Asian Journal of Cancer 2017 6(4):183-185

Background: Cancers in teenage and young adults (TYAs), though an increasing cause of mortality in our country, have been scarcely studied. The lack of studies of TYAs can significantly affect the outcomes of the youth in the prime of their lives. Aims: The aim of this study was to study the type of cancers in the TYA at a rural cancer center in central India. Design and Methods: A prospective study in the department of medical oncology, from the period of January 2013 till March 2016, was done. Data regarding socioepidemiological factors were collected for new cancer patients between the age group of 15–30 years in semi-structured questionnaire and from the hospital records. Cancers were classified according to the Birch classification. The cases were analyzed according to the epidemiological profile, classification of cancer, and age-wise distribution using descriptive analysis. Results: In this study, out of 5221 cancer patients, TYAs accounted for 327 (6.26%) with 189 males and 138 females (M: F– 1.37:1). The maximum cases were seen in 25–30 years' age group. Carcinoma was the most common malignancy (54.74%) with an increase from 19.56% in the 15–19 years' age group to 64.82% in the 25–30-year-old patients. Conclusion: The present study gives a glimpse of the TYA cancers in the central India. More than half of the young cancer patients suffer from carcinomas with about half of these being head and neck cancers.

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Short message service prompted mouth self-examination in oral cancer patients as an alternative to frequent hospital-based surveillance

Sagar Vaishampayan, Akshat Malik, Prashant Pawar, Kavi Arya, Pankaj Chaturvedi

South Asian Journal of Cancer 2017 6(4):161-164

Introduction: Oral squamous cell carcinoma (OSCC) are amongst commonest cancer in the Indian sub-continent. After treatment, these patients require frequent followup to look for recurrences/second primary. Mouth Self Examination (MSE) has a great potential in all levels of prevention of oral cancer. However, the compliance to self-examination has been reported as poor. Mobile phone is a cheap and effective way to reach out to people. Short Message Service (SMS) is extremely popular can be a very effective motivational and interactive tool in health care setting. Methodology: We aimed to identify in adequately treated OSCC patients, the influence of health provider initiated SMS on the compliance to the MSE and to establish the efficacy of MSE by comparing patients' MSE interpretation via replies to the SMS with that of the experts' opinion on clinical examination status during follow up. Conclusion: We conclude that MSE can be very useful in adequately treated OSCC patients for evaluating disease status. All treated OSCC patients must be adequately educated for MSE as an integral part of treatment & follow-up protocol by the health provider facility. Health provider generated SMS reminders do improve motivation and compliance towards MSE but don't seem to reduce dropouts in follow up for large and diverse population like that in India.

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EMERALD: Emergency visit audit of patients treated under medical oncology in a tertiary cancer center: Logical steps to decrease the burden

Amit Joshi, Vijay M Patil, Vanita Noronha, Anant Ramaswamy, Sudeep Gupta, Atanu Bhattacharjee, Avinash Bonda, MV Chandrakanth, Vikas Ostwal, Navin Khattry, Shripad Banavali, Kumar Prabhash

South Asian Journal of Cancer 2017 6(4):186-189

Background: We are a tertiary care cancer center and have approximately 1000–1500 emergency visits by cancer patients undergoing treatment under the adult medical oncology unit each month. However, due to the lack of a systematic audit, we are unable to plan steps toward the improvement in quality of emergency services, and hence the audit was planned. Methods: All emergency visits under the adult medical oncology department in the month of July 2015 were audited. The cause of visit, the demographic details, cancer details, and chemotherapy status were obtained from the electronic medical records. The emergency visits were classified as avoidable or unavoidable. Descriptive statistics were performed. Reasons for avoidable emergency visits were sought. Results: Out of 1199 visits, 1168 visits were classifiable. Six hundred and ninety-six visits were classified as unavoidable (59.6%, 95% CI: 56.7–62.4), 386 visits were classified as probably avoidable visit (33.0%, 95% CI: 30.4–35.8) whereas the remaining 86 (7.4%, 95% CI: 6.0–9.01) were classified as absolutely avoidable. Two hundred and ninety-seven visits happened on weekends (25.6%) and 138 visits converted into an inpatient admission (11.9%). The factors associated with avoidable visits were curative intention of treatment (odds ratio - 2.49), discontinued chemotherapy status (risk ratio [RR] - 8.28), and private category file status (RR – 1.89). Conclusion: A proportion of visits to emergency services can be curtailed. Approximately one-fourth of patients are seen on weekends, and only about one-tenth of patients get admitted.

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LIF drives neural remodeling in pancreatic cancer and offers a new candidate biomarker

Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive stroma and pathogenic modifications to the peripheral nervous system that elevate metastatic capacity. In this study, we show that the IL-6-related stem cell promoting factor LIF supports PDAC-associated neural remodeling (PANR). LIF was overexpressed in tumor tissue compared to healthy pancreas, but its receptors LIFR and gp130 were expressed only in intratumoral nerves. Cancer cells and stromal cells in PDAC tissues both expressed LIF, but only stromal cells could secrete it. Biological investigations showed that LIF promoted the differentiation of glial nerve sheath Schwann cells and induced their migration by activating JAK/STAT3/AKT signaling. LIF also induced neuronal plasticity in dorsal root ganglia neurons by increasing the number of neurites and the soma area. Notably, injection of LIF-blocking antibody into PDAC-bearing mice reduced intratumoral nerve density, supporting a critical role for LIF function in PANR. In serum from human PDAC patients and mouse models of PDAC, we found that LIF titers positively correlated with intratumoral nerve density. Taken together, our findings suggest LIF as a candidate serum biomarker and diagnostic tool and a possible therapeutic target for limiting the impact of PANR in PDAC pathophysiology and metastatic progression.

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LIF drives neural remodeling in pancreatic cancer and offers a new candidate biomarker

Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive stroma and pathogenic modifications to the peripheral nervous system that elevate metastatic capacity. In this study, we show that the IL-6-related stem cell promoting factor LIF supports PDAC-associated neural remodeling (PANR). LIF was overexpressed in tumor tissue compared to healthy pancreas, but its receptors LIFR and gp130 were expressed only in intratumoral nerves. Cancer cells and stromal cells in PDAC tissues both expressed LIF, but only stromal cells could secrete it. Biological investigations showed that LIF promoted the differentiation of glial nerve sheath Schwann cells and induced their migration by activating JAK/STAT3/AKT signaling. LIF also induced neuronal plasticity in dorsal root ganglia neurons by increasing the number of neurites and the soma area. Notably, injection of LIF-blocking antibody into PDAC-bearing mice reduced intratumoral nerve density, supporting a critical role for LIF function in PANR. In serum from human PDAC patients and mouse models of PDAC, we found that LIF titers positively correlated with intratumoral nerve density. Taken together, our findings suggest LIF as a candidate serum biomarker and diagnostic tool and a possible therapeutic target for limiting the impact of PANR in PDAC pathophysiology and metastatic progression.

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Tumor side as model of integrative molecular classification of colorectal cancer

It has long since been recognized that colorectal cancer is molecularly heterogeneous and its clinical behavior differs if primary tumor was located in the right or left side of the colon. Recent studies have shown that part of this heterogeneity is captured by the anatomical location of the tumor.

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Alteration of the tumor stroma using a consensus DNA vaccine targeting Fibroblast Activation Protein (FAP) synergizes with anti-tumor vaccine therapy in mice

Purpose: Fibroblast activation protein (FAP) is over-expressed in cancer-associated fibroblasts and is an interesting target for cancer immune therapy, with prior studies indicating a potential to impact the tumor stroma. Our aim was to extend this earlier work through development of a novel FAP immunogen with improved capacity to break tolerance for use in combination with tumor antigen vaccines. Experimental Design: We used a synthetic consensus (SynCon) sequence approach to provide MHC class II help to support breaking of tolerance. We evaluated immune responses and anti-tumor activity of this novel FAP vaccine in pre-clinical studies, and correlated these findings to patient data. Results: This SynCon FAP DNA vaccine was capable of breaking tolerance and inducing both CD8+ and CD4+ immune responses. In genetically diverse, outbred mice, the SynCon FAP DNA vaccine was superior at breaking tolerance compared to a native mouse FAP immunogen. In several tumor models, the SynCon FAP DNA vaccine synergized with other tumor-antigen specific DNA vaccines to enhance anti-tumor immunity. Evaluation of the tumor microenvironment showed increased CD8+ T cell infiltration and a decreased macrophage infiltration driven by FAP immunization. We extended this to patient data from the Cancer Genome Atlas, where we find high FAP expression correlates with high macrophage and low CD8+ T cell infiltration. Conclusions: These results suggest that immune therapy targeting tumor antigens in combination with a micro-consensus FAP vaccine provides a two fisted punch inducing responses that target both the tumor microenvironment and tumor cells directly.

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Biomarker Based Therapy in Pancreatic Ductal Adenocarcinoma: An Emerging Reality?

Over the last decade many of the major solid organ cancers have seen improvements in survival due to development of novel therapeutics and corresponding biomarkers that predict treatment efficacy or resistance. In contrast, in pancreatic ductal adenocarcinoma (PDAC) favorable outcomes remain challenging, in part related to the lack of validated biomarkers for patient and treatment selection and thus optimal clinical decision-making. Nonetheless, increasingly therapeutic development for PDAC is accompanied by bioassays to evaluate response and study mechanism of actions with a corresponding increase in the number of trials in mid to late-stage with integrated biomarkers. Additionally, blood based biomarkers that provide a measure of disease activity and allow for minimally invasive tumor analyses are emerging, including circulating tumor DNA, exosomes and circulating tumor cells. In this article, we will review potential biomarkers for currently approved therapies as well as emerging biomarkers for therapeutics under development.

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Tumor side as model of integrative molecular classification of colorectal cancer

It has long since been recognized that colorectal cancer is molecularly heterogeneous and its clinical behavior differs if primary tumor was located in the right or left side of the colon. Recent studies have shown that part of this heterogeneity is captured by the anatomical location of the tumor.

http://ift.tt/2zdNT88

Alteration of the tumor stroma using a consensus DNA vaccine targeting Fibroblast Activation Protein (FAP) synergizes with anti-tumor vaccine therapy in mice

Purpose: Fibroblast activation protein (FAP) is over-expressed in cancer-associated fibroblasts and is an interesting target for cancer immune therapy, with prior studies indicating a potential to impact the tumor stroma. Our aim was to extend this earlier work through development of a novel FAP immunogen with improved capacity to break tolerance for use in combination with tumor antigen vaccines. Experimental Design: We used a synthetic consensus (SynCon) sequence approach to provide MHC class II help to support breaking of tolerance. We evaluated immune responses and anti-tumor activity of this novel FAP vaccine in pre-clinical studies, and correlated these findings to patient data. Results: This SynCon FAP DNA vaccine was capable of breaking tolerance and inducing both CD8+ and CD4+ immune responses. In genetically diverse, outbred mice, the SynCon FAP DNA vaccine was superior at breaking tolerance compared to a native mouse FAP immunogen. In several tumor models, the SynCon FAP DNA vaccine synergized with other tumor-antigen specific DNA vaccines to enhance anti-tumor immunity. Evaluation of the tumor microenvironment showed increased CD8+ T cell infiltration and a decreased macrophage infiltration driven by FAP immunization. We extended this to patient data from the Cancer Genome Atlas, where we find high FAP expression correlates with high macrophage and low CD8+ T cell infiltration. Conclusions: These results suggest that immune therapy targeting tumor antigens in combination with a micro-consensus FAP vaccine provides a two fisted punch inducing responses that target both the tumor microenvironment and tumor cells directly.

http://ift.tt/2BwzRoh

Biomarker Based Therapy in Pancreatic Ductal Adenocarcinoma: An Emerging Reality?

Over the last decade many of the major solid organ cancers have seen improvements in survival due to development of novel therapeutics and corresponding biomarkers that predict treatment efficacy or resistance. In contrast, in pancreatic ductal adenocarcinoma (PDAC) favorable outcomes remain challenging, in part related to the lack of validated biomarkers for patient and treatment selection and thus optimal clinical decision-making. Nonetheless, increasingly therapeutic development for PDAC is accompanied by bioassays to evaluate response and study mechanism of actions with a corresponding increase in the number of trials in mid to late-stage with integrated biomarkers. Additionally, blood based biomarkers that provide a measure of disease activity and allow for minimally invasive tumor analyses are emerging, including circulating tumor DNA, exosomes and circulating tumor cells. In this article, we will review potential biomarkers for currently approved therapies as well as emerging biomarkers for therapeutics under development.

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R-2HG Targets FTO to Increase m6A Levels and Suppress Tumor Growth [Research Watch]

R-2HG, thought to be an oncometabolite in IDH-mutant tumors, has antitumor activity in leukemia and glioma.

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mTORC2-Driven Lipid Synthesis Promotes Liver Tumorigenesis [Research Watch]

mTORC2-induced lipid metabolism promotes hepatosteatosis progression to hepatocellular carcinoma.

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Targeting JAG1 Sensitizes Bone Metastases to Chemotherapy [Research Watch]

Chemotherapy induces JAG1 expression in osteoblasts, promoting chemoresistance in bone metastases.

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PEGPH20 May Improve Standard-of-Care Therapy in Pancreatic Cancer [Research Watch]

The HA-degrading drug PEGPH20 plus standard therapy extends survival in metastatic pancreatic cancer.

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Endotracheal Tube Connector: Holding Breaths!

No abstract available

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Mu-Opioid Receptors in Ganglia, But Not in Muscle, Mediate Peripheral Analgesia in Rat Muscle Pain

BACKGROUND: Previous studies have demonstrated the participation of peripheral μ-opioid receptors (MOR) in the antinociceptive effect of systemically administered morphine and loperamide in an orofacial muscle pain model, induced by hypertonic saline, but not in a spinally innervated one, in rats. In this study, we determine whether this peripheral antinociceptive effect is due to the activation of MOR localized in the muscle, ganglia, or both. METHODS: To determine the local antinociceptive effect of morphine and loperamide, 2 models of acute muscle pain (trigeminal and spinal) were used. Also, to study the MOR expression, protein quantification was performed in the trigeminal and spinal ganglia, and in the muscles. RESULTS: The behavioral results show that the intramuscular injection of morphine and loperamide did not exert an antinociceptive effect in either muscle (morphine: P = .63, loperamide: P = .9). On the other hand, MOR expression was found in the ganglia but not in the muscles. This expression was on average 44% higher (95% CI, 33.3–53.9) in the trigeminal ganglia than in the spinal one. CONCLUSIONS: The peripheral antinociceptive effect of systemically administered opioids may be due to the activation of MOR in ganglia. The greater expression of MOR in trigeminal ganglia could explain the higher antinociceptive effect of opioids in orofacial muscle pain than in spinal muscle pain. Therefore, peripheral opioids could represent a promising approach for the treatment of orofacial pain. Accepted for publication October 23, 2017. Funding: This study was supported by the Ministry of Science and Innovation of Spain (SAF2012-40075-C02-01) and General Directorate for Scientific Research of Community of Madrid (S-2011/BMD-2308). The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Eva María Sánchez-Robles, PhD, Facultad Ciencias de la Salud, Área de Farmacología y Nutrición, Universidad Rey Juan Carlos, Avda Atenas, s/n. 28922 Alcorcón, Madrid, Spain. Address e-mail to eva.sanchez@urjc.es. © 2017 International Anesthesia Research Society

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The Effect of High-Frequency, Structured Expert Feedback on the Learning Curves of Basic Interventional Ultrasound Skills Applied to Regional Anesthesia

BACKGROUND: Proficiency in needle-to-ultrasound beam alignment and accurate approach to structures are pivotal for ultrasound-guided regional anesthesia. This study evaluated the effects of high-frequency, structured expert feedback on simulation training of such abilities. METHODS: Forty-two subjects randomly allocated as controls or intervention participated in two 25-trial experiments. Experiment 1 consisted of inserting a needle into a bovine muscular phantom parallel to the ultrasound beam while maintaining full imaging of the needle. In experiment 2, the needle aimed to contact a target inside the phantom. Intervention subjects received structured feedback between trials. Controls received a global critique after completing the trials. The slopes of the learning curves derived from the sequences of successes and failures were compared. Change-point analyses identified the start and the end of learning in trial sequences. The number of trials associated with learning, the number of technical errors, and the duration of training sessions were compared between intervention and controls. RESULTS: In experiment 1, learning curves departed from 73% (controls) and 76% (intervention) success rates; slopes (standard error) were 0.79% (0.02%) and 0.71% (0.04), respectively, with mean absolute difference of 0.18% (95% confidence interval [CI], 0.17%–0.19%; P = 0). Intervention subjects' learning curves were shorter and steeper than those of controls. In experiment 2, the learning curves departed from 43% (controls) and 80% (intervention) success rates; slopes (standard error) were 1.06% (0.02%) and 0.42% (0.03%), respectively, with a mean difference of 0.65% (95% CI, 0.64%–0.66%; P = 0). Feedback was associated with a greater number of trials associated with learning in both experiment 1 (mean difference, 1.55 trials; 95% CI, 0.15–3 trials; P = 0) and experiment 2 (mean difference, 4.25 trials; 95% CI, 1.47–7.03 trials; P = 0) and a lower number of technical errors per trial in experiments 1 (mean difference, 0.19; 95% CI, 0.07–0.30; P = .02) and 2 (mean difference, 0.58; 95% CI, 0.45–0.70; P = 0), but longer training sessions in both experiments 1 (mean difference, 9.2 minutes; 95% CI, 4.15–14.24 minutes; P = .01) and 2 (mean difference, 7.4 minutes; 95% CI, 1.17–13.59 minutes; P = .02). CONCLUSIONS: High-frequency, structured expert feedback compared favorably to self-directed learning, being associated with shorter learning curves, smaller number of technical errors, and longer duration of in-training improvement, but increased duration of the training sessions. Accepted for publication November 10, 2017. Funding: None. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Getúlio Rodrigues de Oliveira Filho, MD, PhD, Department of Surgery, Federal University of Santa Catarina, Rua Luiz Delfino 111/902, Florianópolis, Santa Catarina 88015, Brazil. Address e-mail to getulio.filho@ufsc.br. © 2017 International Anesthesia Research Society

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Why a Proactive Perioperative Medicine Policy Is Crucial for a Sustainable Population Health Strategy

No abstract available

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Intravenous Iron for Treatment of Anemia in the 3 Perisurgical Phases: A Review and Analysis of the Current Literature

Anemia is a common comorbidity throughout the entire hospital stay. Treatment options include intravenous (IV) iron, oral iron, erythropoietin, and red blood cell (RBC) transfusions. IV iron has gained in popularity with the implementation of patient blood management programs. A variety of studies have been performed to investigate the use of IV iron in preoperative, perioperative, and postoperative settings. An objective review on these studies has yet to be performed. The current narrative review provides an overview of trials investigating IV iron use in the preoperative, perioperative, and postoperative settings. We performed a literature research of English articles published between 1964 and March 2017 in Pubmed including Medline and The Cochrane Library. Only studies with a control group were included. The final review includes 20 randomized controlled trials (RCTs), 7 observational trials, and 5 retrospective studies. Measured outcomes included hemoglobin (Hb) levels, reticulocyte counts, and/or RBC concentrates. Meta-analyses of RCTs using IV iron administration before surgery led to an increase in Hb levels, a reduction of RBC use, and an improvement in patient outcome. Only a few studies investigated the use of IV iron in the perioperative setting. These studies recommended the use of perioperative IV iron in cases of severe anemia in orthopedic surgery but not in all types of surgery. Published RCTs in the postoperative setting have shown positive effects of IV iron on Hb levels, length of hospital stay, and transfusion requirements. Some studies demonstrated an increase of Hb of 0.5–1 g/dL over 4 weeks postoperatively, but the clinical relevance and effect of this increase on an improvement of patient's long-term outcomes are uncertain. To summarize, the evidence to use IV iron is strongest in the preoperative setting, while it remains an individual treatment decision to administer IV iron perioperatively or postoperatively. Accepted for publication September 15, 2017. Funding: A.U.S. is supported by a DFG grant (STE-1895-4/1). The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Andrea U. Steinbicker, MD, MPH, Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Albert-Schweitzer Campus 1, Bldg A1, 48149 Muenster, Germany. Address e-mail to andrea.steinbicker@ukmuenster.de. © 2017 International Anesthesia Research Society

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Prospective Observational Study of Intraoperative Anesthetic Events in District Hospitals in Namibia

BACKGROUND: Access to safe surgery and anesthesia care is grossly inadequate in low- and middle-income countries, with a shortage of anesthesia providers contributing to this crisis. In Namibia, medical officers typically receive no >3 months of informal training in anesthesia. This study sought to determine the prevalence, currently unknown, of intraoperative adverse anesthetic events in this setting. Further, we assessed surgical volume, complications, and mortality outcomes at the district hospital level. METHODS: This was a prospective observational study over 7 months involving 4 district hospitals from geographically separate and diverse areas of Namibia. A standardized protocol was used to record adverse anesthetic events during surgery, surgical volume, and complications including mortality. RESULTS: A total of 737 surgical procedures were performed during the study period. There was a 10% prevalence of adverse anesthetic events intraoperatively. Of these, 70% were related to hypotension and 17% due to hypoxia and/or difficult/failed intubation. Ninety-eight percent of patients were classed as low risk (American Society of Anesthesiologists I or II). Seventy-two percent of the surgical workload was in obstetrics and gynecology, with over half being for urgent obstetrics. Perioperative mortality rate was 1.4/1000, with an overall surgical complication rate of 1.6% and a surgical infection rate of 0.8%. CONCLUSIONS: We found a 10% prevalence of adverse anesthetic events intraoperatively when anesthesia was administered by medical officers with no >3 months of informal training in this low-resource environment. The patients were considered low risk by the medical officers responsible for the anesthesia, yet these events had the potential to lead to patient harm. Accepted for publication October 23, 2017. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Andrew J. Ottaway, BMBS, MPH, FANZCA, Hobart Anaesthetic Group, 303 Macquarie St, Hobart, Tasmania 7000, Australia. Address e-mail to aottaway@internode.on.net. © 2017 International Anesthesia Research Society

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Continuous Noninvasive Arterial Pressure Monitoring Using the Vascular Unloading Technique (CNAP System) in Obese Patients During Laparoscopic Bariatric Operations

BACKGROUND: Increasing rates of obesity create new challenges for hemodynamic monitoring in the perioperative phase. Continuous monitoring of arterial pressure (AP) is important in severely obese patients who are at particular risk for cardiovascular complications. Innovative technologies for continuous noninvasive AP monitoring are now available. In this study, we aimed to compare continuous noninvasive AP measurements using the vascular unloading technique (CNAP system; CNSystems, Graz, Austria) compared with invasive AP measurements (radial arterial catheter) in severely obese patients during laparoscopic bariatric surgery. METHODS: In 29 severely obese patients (mean body mass index 48.1 kg/m2), we simultaneously recorded noninvasive and invasive AP measurements over a period of 45 minutes and averaged the measurements using 10-second episodes. We compared noninvasive (test method) and invasive (reference method) AP measurements using Bland-Altman analysis and 4-quadrant plot/concordance analysis (2-minute interval). RESULTS: We observed a mean of the differences (±SD, 95% limits of agreement) between the AP values obtained by the CNAP system and the invasively assessed AP values of 7.9 mm Hg (±9.6 mm Hg, −11.2 to 27.0 mm Hg) for mean AP, 4.8 mm Hg (±15.8 mm Hg, −26.5 to 36.0 mm Hg) for systolic AP, and 9.5 mm Hg (±10.3 mm Hg, −10.9 to 29.9 mm Hg) for diastolic AP, respectively. The concordance rate was 97.5% for mean AP, 95.0% for systolic AP, and 96.7% for diastolic AP, respectively. CONCLUSIONS: In the setting of laparoscopic bariatric surgery, continuous noninvasive AP monitoring with the CNAP system showed good trending capabilities compared with continuous invasive AP measurements obtained with a radial arterial catheter. However, absolute CNAP- and arterial catheter–derived AP values were not interchangeable. Accepted for publication September 27, 2017. Funding: CNSystems Medizintechnik AG (Graz, Austria) provided the technical equipment for the study. CNSystems Medizintechnik AG was not involved in the collection of the data, drafting of the manuscript, or decision to submit the manuscript for publication. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Dorothea E. Rogge, MD, Department of Anesthesiology, Centre of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. Address e-mail to d.rogge@uke.de. © 2017 International Anesthesia Research Society

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Misaligned Feeding May Aggravate Pain by Disruption of Sleep–Awake Rhythm

BACKGROUND: Increasing evidence suggests that patients with eating disorders are more likely to develop chronic pain. A misaligned diet has been reported to disrupt the sleep–awake rhythms. Combined with our previous investigation on circadian pain, we aimed to investigate the role of misaligned diet in the pain sensitivity and the underlying mechanisms. METHODS: Two-month-old C57BL/6J male mice were administered chronic constriction injury (CCI) surgery to establish neuropathic pain models. CCI mice were randomized to scheduled food access throughout the whole day (CCI-free), during the daytime (CCI-misaligned), and at night (CCI-aligned), respectively. The paw withdrawal mechanical threshold, indicating pain behavior, was measured by Von Frey. The gross motor activity pattern indicating the sleep–awake rhythm was monitored by Mini-Mitter. Melatonin (Mel) was administered to ameliorate the sleep–awake rhythm (CCI-free + Mel and CCI-misaligned + Mel). The expressions of circadian pain–related proteins were detected by quantitative polymerase chain reaction and western blot. The primary outcome is the pain threshold and the secondary outcome is the sleep–awake rhythm. RESULTS: Misaligned diet during the peri-CCI surgery period significantly decreased the paw withdrawal mechanical threshold compared with the CCI-free mice (day 14: 0.40 ± 0.09 vs 0.64 ± 0.15; P = .03;) and altered the sleep–awake rhythm. Mel pretreatment alleviated the increased pain (day 14, CCI-misaligned + Mel versus CCI-misaligned: day 14: 0.60 ± 0.13 vs 0.35 ± 0.12; P = .022) and the disrupted sleep–awake rhythm caused by misaligned feeding. The mRNA levels of N-methyl-D-aspartate receptor subtype 2B (NR2B), Ca2+/calmodulin-dependent protein kinase II (CaMKII), and cyclic adenosine monophosphate-response element binding protein (CREB) in the spinal dorsal horn increased in CCI-misaligned mice compared with the CCI-free mice. The phosphor-NR2B, phosphor-CaMKII, and phosphor-CREB also increased in CCI-misaligned mice compared with the CCI-free mice. However, the expressions of NR2B, CaMKII, and CREB were decreased in CCI-misaligned + Mel mice compared to CCI-misaligned mice at both transcriptional and translational levels. CONCLUSIONS: Misaligned diet might aggravate pain sensitivity through the disruption of the sleep–awake cycle, which could be recovered by Mel. NR2B-CaMKII-CREB may participate in the disruption of sleep–awake rhythm–mediated pain aggravation. Accepted for publication November 2, 2017. Funding: This study was supported by National Natural Science Foundation of China (81371207, 81171047, 81070892, and 81171048), Natural Science Foundation of Jiangsu Province (BK2010105), and the Grant from the Department of Health of Jiangsu Province of China (XK201140, RC2011006). The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). The first authors Xu and Zhao contributed equally to this study. The authors Ma and Gu contributed equally to this study. Reprints will not be available from the authors. Address correspondence to Xiaoping Gu, PhD, MD, and Zhengliang Ma, PhD, MD, Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University, 321 Zhong Shan Rd, Nanjing, Jiangsu 210008, People's Republic of China. Address e-mail to xiaopinggu@nju.edu.cn and mazhengliang1964@nju.edu.cn. © 2017 International Anesthesia Research Society

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Extracorporeal Membrane Oxygenation Appropriateness: An Interdisciplinary Consensus-Based Approach

We describe a quality improvement initiative aimed at achieving interdisciplinary consensus about the appropriate delivery of extracorporeal membrane oxygenation (ECMO). Interdisciplinary rounds were implemented for all patients on ECMO and addressed whether care was consistent with a patient's minimally acceptable outcome, maximally acceptable burden, and relative likelihood of achieving either. The rounding process was associated with decreased days on venoarterial ECMO, from a median of 6 days in 2014 (first quartile [Q1]–third quartile [Q3], 3–10) to 5 days in 2015 (Q1–Q3, 2.5–8) and in 2016 (Q1–Q3, 1–8). Our statistical methods do not allow us to conclude that this change was due to our intervention, and it is possible that the observed decreases would have occurred whether or not the rounding process was implemented. Accepted for publication October 26, 2017. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Michael Nurok, MBChB, PhD, Division of Cardiac Surgery, Department of Surgery and Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, 127 San Vicente Blvd, Suite 3100, Los Angeles, CA 90048. Address e-mail to michael.nurok@cshs.org. © 2017 International Anesthesia Research Society

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Redefining the Ki-67 Index Stratification for Low-Grade Pancreatic Neuroendocrine Tumors: Improving Its Prognostic Value for Recurrence of Disease

Abstract

Background

The Ki-67 index is an established prognostic marker for recurrence after resection of pancreatic neuroendocrine tumors (PanNETs) that groups tumors into three categories: low grade (< 3%), intermediate grade (3–20%), and high grade (> 20%). Given that the majority of resected PanNETs have a Ki-67 less than 3%, this study aimed to stratify this group further to predict disease recurrence more accurately.

Methods

The Ki-67 index was pathologically re-reviewed and scored by a pathologist blinded to all other clinicopathologic variables using tissue microarray blocks made in triplicate. All patients who underwent curative-intent resection of non-metastatic PanNETs at a single institution from 2000 to 2013 were included in the study. The primary outcome was recurrence-free survival (RFS).

Results

Of 113 patients with well-differentiated PanNETs resected, 83 had tissue available for pathologic re-review. The Ki-67 index was lower than 3% for 72 tumors (87%) and between 3 and 20% for 11 tumors (13%). Considering only Ki-67 less than 3%, the tumors were further stratified by Ki-67 into three groups: group A (< 1%, n = 43), group B (1–1.99%, n = 23), and group C (2–2.99%, n = 6). Compared with group A, groups B and C more frequently had advanced T stage (T3: 44% and 67% vs 12%; p = 0.003) and lymphovascular invasion (50% and 83% vs 23%; p = 0.007). Groups B and C had similar 1- and 3-year RFS, both less than group A. After combining groups B and C, a Ki-67 of 1–2.99% was associated with decreased RFS compared with group A (< 1%). This persisted in the multivariable analysis (hazard ratio [HR] 8.6; 95% confidence interval [CI] 1.0–70.7; p = 0.045), with control used for tumor size, margin-positivity, lymph node involvement, and advanced T stage.

Conclusions

PanNETs with a Ki-67 of 1–2.99% exhibit distinct biologic behavior and earlier disease recurrence than those with a Ki-67 lower than 1%. This new stratification scheme, if externally validated, should be incorporated into future grading systems to guide both surveillance protocols and treatment strategies.

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Timing of Surgical Resection for Curative Colorectal Cancer with Liver Metastasis

Abstract

Purpose and Design

Optimal surgical strategy for resectable synchronous colorectal cancer with liver metastasis (SCRLM) remains a therapeutic dilemma. Multiple retrospective studies including several meta-analyses have been published since 2001 to help facilitate the decision making process and identify the optimal surgical approach. Controversy limits the generalization of available data to draw conclusions. A review of available literature on appropriate surgical timing may alleviate confusion among physicians and promote a more evidence based approach.

Results and Conclusion

Current evidence supports the feasibility, safety, and equivalent oncological outcomes of simultaneous curative resection of stage IV colorectal cancer with liver metastasis in appropriately selected patients.

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Factors Associated with 60-Day Readmission Following Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy

Abstract

Introduction

Readmission rates following surgery are subject to scrutiny in efforts to control health care costs. This study was designed to define the 60-day readmission rate following cytoreduction and HIPEC at a high-volume center and to identify factors associated with readmission.

Methods

Patients who underwent complete cytoreduction and HIPEC at a single institution from August 2007 through June 2014 were identified from a prospectively maintained database. Multiple preoperative and operative factors were analyzed for their ability to predict 60-day readmission following surgery.

Results

A total of 250 patients were identified. Forty patients (17%) experienced readmission within 60 days of surgery. The most common reasons for readmission were ileus/dehydration (12, 31%), deep space infection (8, 21%), and DVT/PE (6, 15%). Initial postoperative length of stay was longer for patients readmitted within 60 days (median 12 vs. 9 days, p = 0.013). Of categorical variables analyzed, including gender, histology, HIPEC agent, intraoperative transfusion, and individual procedures performed during cytoreduction, adjuvant systemic therapy, and postoperative morbidity, only Charlson comorbidity index CCI (odds ratio (OR) = 3.80 [1.68–8.60]) and stoma creation (OR = 6.04 [1.56–12.14]) were associated with 60-day readmission.

Conclusions

Few measurable variables are associated with readmission following cytoreduction and HIPEC. Patients with high CCI and those with stomas created at the time of CRS/HIPEC may be at increased risk of readmission within 60 days. Earlier or more frequent follow-up for high-risk patients should be considered as a strategy to reduce readmissions.

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Cervicothoracoscopic Approach in Esophagectomy

Abstract

Backgrounds

Esophageal cancer frequently metastasizes to lymph nodes along the recurrent laryngeal nerve (RLN).1 Therefore, it is essential to dissect RLN nodes for curative esophagectomy. Complete RLN node dissection without injury to the organs at the cervicothoracic junction requires experienced techniques. This report describes the cervicothoracoscopic approach, whereby the complete dissection can be safely performed.

Methods

With this approach, both cervical and laparoscopic procedures are performed in the open-leg supine position before the thoracoscopic procedure is performed in the prone position. For RLN node dissection, the paratracheal lymphatic chain is detached from RLNs at the cervicothoracic junction in the cervical operation field, and the detached tissue is retrieved together with the mediastinal RLN lymph nodes via thoracoscopy. This approach was applied to all squamous cell carcinoma patients and to patients with Siewert type 1 tumors of stage 2 or more, except for patients with clinically suspected T4 tumors.

Results

Of 91 patients, 27 (29.7%) experienced RLN palsy and 15 (16.5%) experienced postoperative pneumonia. Hoarseness due to RLN palsy was improved in almost all the patients within 6 postoperative months, and persistent paralysis was seldom observed. Within 30 days, neither a reoperation nor a hospital mortality occurred.

Conclusions

The cervicothoracoscopic approach enables complete en bloc dissection of the lymphatic chain that lies along RLN in the cervicothoracic junction. Also, with this approach, RLNs can be identified easily because RLNs are already exposed at the upper mediastinum by the cervical procedure. Therefore, this approach may contribute to improving the surgical curability and preventing RLN injury.

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The Annals of Surgical Oncology : An Oncology Journal for Surgeons

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Radioactive Seed Localization Versus Wire Localization for Nonpalpable Breast Lesions: A Two-Year Initial Experience at a Large Community Hospital

Abstract

Background

Radioactive seed localization (RSL) is a safe and effective alternative to wire localization (WL) for nonpalpable breast lesions. While several large academic institutions currently utilize RSL, few community hospitals have adopted this technique.

Objective

The aim of this study was to examine the experience of RSL versus WL at a large community hospital.

Methods

A retrospective chart review of patients who underwent RSL or WL for breast-conserving surgery from 1 November 2013 to 31 November 2015.

Results

The total number of lesions examined was 382. RSL was utilized in 205 (54%) lesions, with 187 undergoing single RSL, while WL was used in 155 (40%) lesions, with 109 undergoing single WL; both techniques were used in 22 (6%) lesions. Pathology was benign in 142 (48%) lesions, with 93 RSLs and 49 WLs. For malignant lesions, mean specimen size was 36.3 g for single RSL and 35.9 g for single WL (p = 0.904). Re-excision for margin clearance was required for 16 (17%) malignant lesions in the RSL group and 10 (17%) in the WL group (p = 0.954). For malignant lesions, mean operating room time was 86 min for single RSL versus 70 min for single WL (p = 0.014).

Conclusions

The use of RSL is a viable option in the community setting, with several benefits over WL. While operative times were slightly longer with RSL, there was no difference in specimen size or re-excision rate for malignant lesions.

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Four-Dimensional Computed Tomography: Clinical Impact for Patients with Primary Hyperparathyroidism

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When Should Negative Endobronchial Ultrasonography Findings be Confirmed by a More Invasive Procedure?

Abstract

The treatment of non-small cell lung cancer is largely dependent on accurate staging in order to determine appropriate therapy. Despite advances in imaging, such as computed tomography and positron emission tomography, invasive mediastinal staging is frequently needed to rule out mediastinal involvement prior to curative-intent stereotactic ablative radiotherapy or surgical resection. Surgical mediastinal staging with mediastinoscopy, or anterior mediastinotomy, were traditionally considered the gold standard for invasive mediastinal staging. Endobronchial and endoscopic ultrasound have emerged as modern techniques that are being used as first-line options instead of surgical staging. As experience is gained with these newer techniques, the need for confirmatory surgical staging continues to diminish. This article addresses the situations in which negative results should be confirmed by a more invasive procedure.

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Minimally Invasive and Open Approaches to Mediastinal Nodal Assessment

Abstract

There is no consensus on mediastinal lymph node dissection versus sampling for early-stage lung cancer. There are also mixed data on the ability to remove an adequate number of lymph nodes by a minimally invasive approach. In this review, we discuss the difference between dissection and sampling, what circumstances dictate the use of one or the other during an anatomic pulmonary resection for lung cancer, and when it is appropriate to use minimally invasive versus open approaches in the assessment of mediastinal nodes.

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Systematic Review of Cytoreductive Surgery and Bevacizumab-Containing Chemotherapy in Advanced Ovarian Cancer: Focus on Safety

Abstract

Background

Initial experiences reported increased surgical morbidities in patients receiving cytoreductive surgery for colorectal cancer after bevacizumab-containing chemotherapy; however, more recent literature suggests a favorable toxicity profile in patients with advanced ovarian cancer (AOC). With the aim of providing a more objective point of view on this controversial issue, we present here a systematic literature review.

Methods

Systematic revision of the available literature was conducted using the PubMed, MEDLINE, and EMBASE electronic databases. All studies reporting safety data regarding cytoreductive surgery performed before or after bevacizumab-containing chemotherapy have been analyzed for the purposes of this study. The study has been prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results

Forty-eight studies were retrieved from the electronic databases, with 23 (47.9%) being excluded due to an unsatisfactory study design. Among the remaining 25 manuscripts, 16 did not report data regarding surgical morbidities after cytoreductive surgery, therefore only 9 studies were included in the final analysis. Overall, 198 AOC patients received bevacizumab-containing neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) in the context of five studies, among whom 21 women experienced grade 3/4 postoperative complications (10.6%), which appears to be in line with data reported in patients receiving IDS after carboplatin-paclitaxel NACT. Results from phase I–II clinical trials, and dataset analysis from GOG-0218, did not observe an increased incidence of complications in AOC patients receiving bevacizumab-containing adjuvant chemotherapy after cytoreductive surgery.

Conclusions

The incorporation of bevacizumab into first-line chemotherapy was not associated with increased morbidities before and after cytoreductive surgery in women with AOC.

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Adjuvant Chemoradiotherapy is Associated with Improved Survival for Patients with Resected Gallbladder Carcinoma: A Systematic Review and Meta-analysis

Abstract

Background

The impact of adjuvant radiotherapy (ART) on survival from gallbladder carcinoma (GBC) remains underexplored, with conflicting results reported. A systematic review and meta-analysis was performed to clarify the impact of ART in GBC.

Methods

A systematic literature search of several databases was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, from inception to August 2016. Studies that reported survival outcomes for patients with or without ART after curative surgery were included.

Results

All the inclusion criteria was met by 14 retrospective studies including 9364 analyzable patients, but most of the studies had a moderate risk of bias. Generally, the ART group had more patients with unfavorable characteristics than the group that had surgery alone. Nevertheless, the pooled results showed that ART significantly reduced the risk of death (hazard ratio [HR], 0.54; 95% confidence interval [CI] 0.44–0.67; p < 0.001) and recurrence (HR 0.61; 95% CI 0.38–0.98; p = 0.04) of GBC compared with surgery alone. Exploratory analyses demonstrated a survival benefit from ART for a subgroup of patients with lymph node-positive diseases (HR 0.61; p < 0.001) and R1 resections (HR 0.55; p < 0.001), but not for patients with lymph node-negative disease (HR 1.06; p = 0.78). No evidence of publication bias was found (p = 0.663).

Conclusions

This study is the first meta-analysis to evaluate the role of ART and to provide supporting evidence that ART may offer survival benefits, especially for high-risk patients. However, further confirmation with a randomized prospective study is needed to clarify the subgroup of GBC patients who would benefit most from ART.

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Locally Advanced Colorectal Cancer: True Peritoneal Tumor Penetration is Associated with Peritoneal Metastases

Abstract

Background

Findings show T4 colorectal cancer (CRC) to be a risk factor for the development of peritoneal metastases (PM). Heterogeneity regarding peritoneal involvement of T4 tumors might explain the wide range of reported PM incidences (8–50%). Hyperplastic and mesothelial inflammatory reactions complicate evaluation of the exact primary tumor involvement of the peritoneal layer. This retrospective cohort study aimed to assess the association between either inflammatory peritoneal reaction or peritoneal involvement of the primary tumor and the risk of PM.

Methods

Since 2010, pathologists at UZ Leuven have systematically categorized peritoneal involvement in peritoneal reaction with tumor less than 1 mm from the peritoneal surface or true peritoneal penetration. All patients undergoing resection of CRC between January 2010 and July 2013 who fulfilled either of these pathologic criteria were included in this study.

Results

The study enrolled 159 CRC patients. Peritoneal reaction with tumor less than 1 mm from the peritoneal surface was present in 43 patients and true peritoneal penetration in 116 patients. Overall, 29 patients (18%) had synchronous PM, and 30 patients (23%) had metachronous PM. In the multivariable analysis, true peritoneal penetration, in contrast to peritoneal reaction with tumor less than 1 mm from the peritoneum, was associated with greater risk of PM (odds ratio [OR], 2.518; range, 1.038–6.111; p = 0.041) and lymph node involvement (N1: OR, 1.572; range, 0.651–3.797 vs N2: OR, 4.046; range, 1.549–10.569; p = 0.014).

Conclusion

Histologically confirmed true peritoneal penetration by CRC, rather than inflammatory peritoneal reaction constitutes a high risk for PM. With evolving treatment strategies that aim to treat PM in an earlier phase, identification of high-risk patients becomes highly important clinically.

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Timing of Surgical Resection for Curative Colorectal Cancer with Liver Metastasis

Abstract

Purpose and Design

Optimal surgical strategy for resectable synchronous colorectal cancer with liver metastasis (SCRLM) remains a therapeutic dilemma. Multiple retrospective studies including several meta-analyses have been published since 2001 to help facilitate the decision making process and identify the optimal surgical approach. Controversy limits the generalization of available data to draw conclusions. A review of available literature on appropriate surgical timing may alleviate confusion among physicians and promote a more evidence based approach.

Results and Conclusion

Current evidence supports the feasibility, safety, and equivalent oncological outcomes of simultaneous curative resection of stage IV colorectal cancer with liver metastasis in appropriately selected patients.

http://ift.tt/2Bup0LB

Factors Associated with 60-Day Readmission Following Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy

Abstract

Introduction

Readmission rates following surgery are subject to scrutiny in efforts to control health care costs. This study was designed to define the 60-day readmission rate following cytoreduction and HIPEC at a high-volume center and to identify factors associated with readmission.

Methods

Patients who underwent complete cytoreduction and HIPEC at a single institution from August 2007 through June 2014 were identified from a prospectively maintained database. Multiple preoperative and operative factors were analyzed for their ability to predict 60-day readmission following surgery.

Results

A total of 250 patients were identified. Forty patients (17%) experienced readmission within 60 days of surgery. The most common reasons for readmission were ileus/dehydration (12, 31%), deep space infection (8, 21%), and DVT/PE (6, 15%). Initial postoperative length of stay was longer for patients readmitted within 60 days (median 12 vs. 9 days, p = 0.013). Of categorical variables analyzed, including gender, histology, HIPEC agent, intraoperative transfusion, and individual procedures performed during cytoreduction, adjuvant systemic therapy, and postoperative morbidity, only Charlson comorbidity index CCI (odds ratio (OR) = 3.80 [1.68–8.60]) and stoma creation (OR = 6.04 [1.56–12.14]) were associated with 60-day readmission.

Conclusions

Few measurable variables are associated with readmission following cytoreduction and HIPEC. Patients with high CCI and those with stomas created at the time of CRS/HIPEC may be at increased risk of readmission within 60 days. Earlier or more frequent follow-up for high-risk patients should be considered as a strategy to reduce readmissions.

http://ift.tt/2zbTkVe

Cervicothoracoscopic Approach in Esophagectomy

Abstract

Backgrounds

Esophageal cancer frequently metastasizes to lymph nodes along the recurrent laryngeal nerve (RLN).1 Therefore, it is essential to dissect RLN nodes for curative esophagectomy. Complete RLN node dissection without injury to the organs at the cervicothoracic junction requires experienced techniques. This report describes the cervicothoracoscopic approach, whereby the complete dissection can be safely performed.

Methods

With this approach, both cervical and laparoscopic procedures are performed in the open-leg supine position before the thoracoscopic procedure is performed in the prone position. For RLN node dissection, the paratracheal lymphatic chain is detached from RLNs at the cervicothoracic junction in the cervical operation field, and the detached tissue is retrieved together with the mediastinal RLN lymph nodes via thoracoscopy. This approach was applied to all squamous cell carcinoma patients and to patients with Siewert type 1 tumors of stage 2 or more, except for patients with clinically suspected T4 tumors.

Results

Of 91 patients, 27 (29.7%) experienced RLN palsy and 15 (16.5%) experienced postoperative pneumonia. Hoarseness due to RLN palsy was improved in almost all the patients within 6 postoperative months, and persistent paralysis was seldom observed. Within 30 days, neither a reoperation nor a hospital mortality occurred.

Conclusions

The cervicothoracoscopic approach enables complete en bloc dissection of the lymphatic chain that lies along RLN in the cervicothoracic junction. Also, with this approach, RLNs can be identified easily because RLNs are already exposed at the upper mediastinum by the cervical procedure. Therefore, this approach may contribute to improving the surgical curability and preventing RLN injury.

http://ift.tt/2BxyaXt

The Annals of Surgical Oncology : An Oncology Journal for Surgeons

http://ift.tt/2zbSFTK

Radioactive Seed Localization Versus Wire Localization for Nonpalpable Breast Lesions: A Two-Year Initial Experience at a Large Community Hospital

Abstract

Background

Radioactive seed localization (RSL) is a safe and effective alternative to wire localization (WL) for nonpalpable breast lesions. While several large academic institutions currently utilize RSL, few community hospitals have adopted this technique.

Objective

The aim of this study was to examine the experience of RSL versus WL at a large community hospital.

Methods

A retrospective chart review of patients who underwent RSL or WL for breast-conserving surgery from 1 November 2013 to 31 November 2015.

Results

The total number of lesions examined was 382. RSL was utilized in 205 (54%) lesions, with 187 undergoing single RSL, while WL was used in 155 (40%) lesions, with 109 undergoing single WL; both techniques were used in 22 (6%) lesions. Pathology was benign in 142 (48%) lesions, with 93 RSLs and 49 WLs. For malignant lesions, mean specimen size was 36.3 g for single RSL and 35.9 g for single WL (p = 0.904). Re-excision for margin clearance was required for 16 (17%) malignant lesions in the RSL group and 10 (17%) in the WL group (p = 0.954). For malignant lesions, mean operating room time was 86 min for single RSL versus 70 min for single WL (p = 0.014).

Conclusions

The use of RSL is a viable option in the community setting, with several benefits over WL. While operative times were slightly longer with RSL, there was no difference in specimen size or re-excision rate for malignant lesions.

http://ift.tt/2BwtP6U

Four-Dimensional Computed Tomography: Clinical Impact for Patients with Primary Hyperparathyroidism

http://ift.tt/2zbU1xw

When Should Negative Endobronchial Ultrasonography Findings be Confirmed by a More Invasive Procedure?

Abstract

The treatment of non-small cell lung cancer is largely dependent on accurate staging in order to determine appropriate therapy. Despite advances in imaging, such as computed tomography and positron emission tomography, invasive mediastinal staging is frequently needed to rule out mediastinal involvement prior to curative-intent stereotactic ablative radiotherapy or surgical resection. Surgical mediastinal staging with mediastinoscopy, or anterior mediastinotomy, were traditionally considered the gold standard for invasive mediastinal staging. Endobronchial and endoscopic ultrasound have emerged as modern techniques that are being used as first-line options instead of surgical staging. As experience is gained with these newer techniques, the need for confirmatory surgical staging continues to diminish. This article addresses the situations in which negative results should be confirmed by a more invasive procedure.

http://ift.tt/2BuKFTN

Minimally Invasive and Open Approaches to Mediastinal Nodal Assessment

Abstract

There is no consensus on mediastinal lymph node dissection versus sampling for early-stage lung cancer. There are also mixed data on the ability to remove an adequate number of lymph nodes by a minimally invasive approach. In this review, we discuss the difference between dissection and sampling, what circumstances dictate the use of one or the other during an anatomic pulmonary resection for lung cancer, and when it is appropriate to use minimally invasive versus open approaches in the assessment of mediastinal nodes.

http://ift.tt/2zc6WQ8

Redefining the Ki-67 Index Stratification for Low-Grade Pancreatic Neuroendocrine Tumors: Improving Its Prognostic Value for Recurrence of Disease

Abstract

Background

The Ki-67 index is an established prognostic marker for recurrence after resection of pancreatic neuroendocrine tumors (PanNETs) that groups tumors into three categories: low grade (< 3%), intermediate grade (3–20%), and high grade (> 20%). Given that the majority of resected PanNETs have a Ki-67 less than 3%, this study aimed to stratify this group further to predict disease recurrence more accurately.

Methods

The Ki-67 index was pathologically re-reviewed and scored by a pathologist blinded to all other clinicopathologic variables using tissue microarray blocks made in triplicate. All patients who underwent curative-intent resection of non-metastatic PanNETs at a single institution from 2000 to 2013 were included in the study. The primary outcome was recurrence-free survival (RFS).

Results

Of 113 patients with well-differentiated PanNETs resected, 83 had tissue available for pathologic re-review. The Ki-67 index was lower than 3% for 72 tumors (87%) and between 3 and 20% for 11 tumors (13%). Considering only Ki-67 less than 3%, the tumors were further stratified by Ki-67 into three groups: group A (< 1%, n = 43), group B (1–1.99%, n = 23), and group C (2–2.99%, n = 6). Compared with group A, groups B and C more frequently had advanced T stage (T3: 44% and 67% vs 12%; p = 0.003) and lymphovascular invasion (50% and 83% vs 23%; p = 0.007). Groups B and C had similar 1- and 3-year RFS, both less than group A. After combining groups B and C, a Ki-67 of 1–2.99% was associated with decreased RFS compared with group A (< 1%). This persisted in the multivariable analysis (hazard ratio [HR] 8.6; 95% confidence interval [CI] 1.0–70.7; p = 0.045), with control used for tumor size, margin-positivity, lymph node involvement, and advanced T stage.

Conclusions

PanNETs with a Ki-67 of 1–2.99% exhibit distinct biologic behavior and earlier disease recurrence than those with a Ki-67 lower than 1%. This new stratification scheme, if externally validated, should be incorporated into future grading systems to guide both surveillance protocols and treatment strategies.

http://ift.tt/2BuoWeP

Systematic Review of Cytoreductive Surgery and Bevacizumab-Containing Chemotherapy in Advanced Ovarian Cancer: Focus on Safety

Abstract

Background

Initial experiences reported increased surgical morbidities in patients receiving cytoreductive surgery for colorectal cancer after bevacizumab-containing chemotherapy; however, more recent literature suggests a favorable toxicity profile in patients with advanced ovarian cancer (AOC). With the aim of providing a more objective point of view on this controversial issue, we present here a systematic literature review.

Methods

Systematic revision of the available literature was conducted using the PubMed, MEDLINE, and EMBASE electronic databases. All studies reporting safety data regarding cytoreductive surgery performed before or after bevacizumab-containing chemotherapy have been analyzed for the purposes of this study. The study has been prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results

Forty-eight studies were retrieved from the electronic databases, with 23 (47.9%) being excluded due to an unsatisfactory study design. Among the remaining 25 manuscripts, 16 did not report data regarding surgical morbidities after cytoreductive surgery, therefore only 9 studies were included in the final analysis. Overall, 198 AOC patients received bevacizumab-containing neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) in the context of five studies, among whom 21 women experienced grade 3/4 postoperative complications (10.6%), which appears to be in line with data reported in patients receiving IDS after carboplatin-paclitaxel NACT. Results from phase I–II clinical trials, and dataset analysis from GOG-0218, did not observe an increased incidence of complications in AOC patients receiving bevacizumab-containing adjuvant chemotherapy after cytoreductive surgery.

Conclusions

The incorporation of bevacizumab into first-line chemotherapy was not associated with increased morbidities before and after cytoreductive surgery in women with AOC.

http://ift.tt/2zcBW2z

Adjuvant Chemoradiotherapy is Associated with Improved Survival for Patients with Resected Gallbladder Carcinoma: A Systematic Review and Meta-analysis

Abstract

Background

The impact of adjuvant radiotherapy (ART) on survival from gallbladder carcinoma (GBC) remains underexplored, with conflicting results reported. A systematic review and meta-analysis was performed to clarify the impact of ART in GBC.

Methods

A systematic literature search of several databases was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, from inception to August 2016. Studies that reported survival outcomes for patients with or without ART after curative surgery were included.

Results

All the inclusion criteria was met by 14 retrospective studies including 9364 analyzable patients, but most of the studies had a moderate risk of bias. Generally, the ART group had more patients with unfavorable characteristics than the group that had surgery alone. Nevertheless, the pooled results showed that ART significantly reduced the risk of death (hazard ratio [HR], 0.54; 95% confidence interval [CI] 0.44–0.67; p < 0.001) and recurrence (HR 0.61; 95% CI 0.38–0.98; p = 0.04) of GBC compared with surgery alone. Exploratory analyses demonstrated a survival benefit from ART for a subgroup of patients with lymph node-positive diseases (HR 0.61; p < 0.001) and R1 resections (HR 0.55; p < 0.001), but not for patients with lymph node-negative disease (HR 1.06; p = 0.78). No evidence of publication bias was found (p = 0.663).

Conclusions

This study is the first meta-analysis to evaluate the role of ART and to provide supporting evidence that ART may offer survival benefits, especially for high-risk patients. However, further confirmation with a randomized prospective study is needed to clarify the subgroup of GBC patients who would benefit most from ART.

http://ift.tt/2BuTLjv

Locally Advanced Colorectal Cancer: True Peritoneal Tumor Penetration is Associated with Peritoneal Metastases

Abstract

Background

Findings show T4 colorectal cancer (CRC) to be a risk factor for the development of peritoneal metastases (PM). Heterogeneity regarding peritoneal involvement of T4 tumors might explain the wide range of reported PM incidences (8–50%). Hyperplastic and mesothelial inflammatory reactions complicate evaluation of the exact primary tumor involvement of the peritoneal layer. This retrospective cohort study aimed to assess the association between either inflammatory peritoneal reaction or peritoneal involvement of the primary tumor and the risk of PM.

Methods

Since 2010, pathologists at UZ Leuven have systematically categorized peritoneal involvement in peritoneal reaction with tumor less than 1 mm from the peritoneal surface or true peritoneal penetration. All patients undergoing resection of CRC between January 2010 and July 2013 who fulfilled either of these pathologic criteria were included in this study.

Results

The study enrolled 159 CRC patients. Peritoneal reaction with tumor less than 1 mm from the peritoneal surface was present in 43 patients and true peritoneal penetration in 116 patients. Overall, 29 patients (18%) had synchronous PM, and 30 patients (23%) had metachronous PM. In the multivariable analysis, true peritoneal penetration, in contrast to peritoneal reaction with tumor less than 1 mm from the peritoneum, was associated with greater risk of PM (odds ratio [OR], 2.518; range, 1.038–6.111; p = 0.041) and lymph node involvement (N1: OR, 1.572; range, 0.651–3.797 vs N2: OR, 4.046; range, 1.549–10.569; p = 0.014).

Conclusion

Histologically confirmed true peritoneal penetration by CRC, rather than inflammatory peritoneal reaction constitutes a high risk for PM. With evolving treatment strategies that aim to treat PM in an earlier phase, identification of high-risk patients becomes highly important clinically.

http://ift.tt/2zboc8n

Genomic Profiling Tests Cleared by FDA Can Help Guide Cancer Treatment, Clinical Trial Enrollment

The FDA has recently approved two tests to identify genetic alterations in tumors. One of the tests can be used to identify patients who may be candidates to receive specific targeted therapies.

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Genomic Profiling Tests Cleared by FDA Can Help Guide Cancer Treatment, Clinical Trial Enrollment

The FDA has recently approved two tests to identify genetic alterations in tumors. One of the tests can be used to identify patients who may be candidates to receive specific targeted therapies.

http://ift.tt/2BM9IhY

Interaction of the epigenetic integrator UHRF1 with the MYST domain of TIP60 inside the cell

The nuclear epigenetic integrator UHRF1 is known to play a key role with DNMT1 in maintaining the DNA methylation patterns during cell division. Among UHRF1 partners, TIP60 takes part in epigenetic regulations...

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Outcomes and Predictive Factors of Isolated Limb Infusion for Patients with In-transit Melanoma in China

Abstract

Purpose

This study was designed to evaluate the efficacy of isolated limb infusion (ILI) treatment in Chinese patients with in-transit melanoma and to identify factors predictive of the outcome.

Methods

A total of 150 patients with in-transit melanoma who received a single ILI between 2007 and 2016 were identified from a prospectively collected database.

Results

All patients had AJCC Stages IIIb, IIIc, and IV disease. Acral lentiginous melanoma (ALM) accounted for 79% of patients, and 59% had a high burden of disease (BOD). The complete response (CR) and partial response (PR) rates were 6 and 35%, respectively. Forty-five percent of patients experienced grade III–IV limb toxicities, but no grade V toxicity was observed. Patients with a low BOD, high limb temperature, high peak creatine phosphokinase (CK) level, and grade III–IV limb toxicity achieved higher response rates. Stage IV disease and high BOD were associated with worse infield progression-free survival (PFS) and overall survival (OS), whereas patients with CR or PR to ILI had better infield PFS and OS. Multivariate analyses showed that disease stage, BOD, and a CR were independent predictors of infield PFS, whereas disease stage and a response to ILI were independent predictors of OS.

Conclusions

ILI is well-tolerated but the response rate in Chinese patients was lower than that reported in US and Australian studies. The prevalence of the ALM histological type, advanced disease stages, and a high BOD may be the main reasons for this. A response to ILI, BOD, and disease stage are prognostic factors for survival.

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Reply to "Questions About In-Breast Tumor Recurrence in Patients Treated with Breast-Conserving Therapy"

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Outcomes and Predictive Factors of Isolated Limb Infusion for Patients with In-transit Melanoma in China

Abstract

Purpose

This study was designed to evaluate the efficacy of isolated limb infusion (ILI) treatment in Chinese patients with in-transit melanoma and to identify factors predictive of the outcome.

Methods

A total of 150 patients with in-transit melanoma who received a single ILI between 2007 and 2016 were identified from a prospectively collected database.

Results

All patients had AJCC Stages IIIb, IIIc, and IV disease. Acral lentiginous melanoma (ALM) accounted for 79% of patients, and 59% had a high burden of disease (BOD). The complete response (CR) and partial response (PR) rates were 6 and 35%, respectively. Forty-five percent of patients experienced grade III–IV limb toxicities, but no grade V toxicity was observed. Patients with a low BOD, high limb temperature, high peak creatine phosphokinase (CK) level, and grade III–IV limb toxicity achieved higher response rates. Stage IV disease and high BOD were associated with worse infield progression-free survival (PFS) and overall survival (OS), whereas patients with CR or PR to ILI had better infield PFS and OS. Multivariate analyses showed that disease stage, BOD, and a CR were independent predictors of infield PFS, whereas disease stage and a response to ILI were independent predictors of OS.

Conclusions

ILI is well-tolerated but the response rate in Chinese patients was lower than that reported in US and Australian studies. The prevalence of the ALM histological type, advanced disease stages, and a high BOD may be the main reasons for this. A response to ILI, BOD, and disease stage are prognostic factors for survival.

http://ift.tt/2DqGaae