Cancer by Sfakianakis Alexandros: 01/08/18

Δευτέρα 8 Ιανουαρίου 2018

MiR-29 silencing modulates the expression of target genes related to proliferation, apoptosis and methylation in Burkitt lymphoma cells

Abstract

Purpose

Burkitt lymphoma (BL) is a B-cell lymphoma frequently diagnosed in children. It is characterized by MYC translocations, which lead to the constitutive expression of the MYC oncogene. MYC contributes to miR-29 repression through an E-box MYC binding site on the miR-29b-1/miR-29a promoter region. We evaluated the role of miR-29a/b/c and their predicted targets in BL pathogenesis.

Methods

Mature sequences of miR-29a/b/c were transfected to the BL cell lines BL41 and Raji, and evaluated for DNMT3B, MCL1, BIM, CDK6, AKT and TCL1 protein expression as well as for MCL-1 and CDK6 mRNA expression. BL cells were treated with 5-aza-2′-deoxycytidine (decitabine) and evaluated for miR29 expressions and methylation status. DNMT3B inhibition was performed by DNMT3B siRNA.

Results

Ectopic expression of miR-29s in BL cells decreased CDK6, DNMT3B, TCL1 and MCL-1 protein levels, but CDK6 and MCL-1 mRNA expression was unaffected by miR-29. Decitabine enhanced miR-29 expression levels and decreased CDK6 protein expression. Additionally, inhibition of DNMT3B by siRNA increased miR-29a/b expression. Notably, the miR-29a/b1 and miR-29b2/c promoter genes showed methylated CpG sequences that were demethylated after decitabine treatments. Furthermore, MYC-negative tumours had higher levels of miR-29 expression compared with MYC-translocated cases, suggesting that MYC regulates miR-29 in BL tumours.

Conclusions

Our results suggest a significant role for miR-29s in BL pathogenesis in altering the expression of targets involved in critical cancer pathways, such as cell cycle control, apoptosis inhibition and DNA methylation. Moreover, methylation-mediated miR-29 epigenetic silencing may occur during BL development.

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MiR-29 silencing modulates the expression of target genes related to proliferation, apoptosis and methylation in Burkitt lymphoma cells

Abstract

Purpose

Methods

Results

Conclusions

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Prospective blinded surveillance screening of Swedish women with increased hereditary risk of breast cancer

Abstract

Purpose

To evaluate the sensitivity and specificity of different screening modalities in women with a family history of breast cancer.

Methods

Our blinded, prospective, comparative cohort analysis included three types of screening, mammography, ultrasound, and clinical breast examination once per year for 6 years. Eligible patients for this study were healthy women with ≥ 17% lifetime risk of breast cancer or with a mutation in BRCA1 or BRCA2.

Results

A total of 632 women were screened between 2002 and 2012 (each for 6 years). During the study, 30 women were diagnosed with breast cancer, with 10 of these diagnoses occurring between screening visits, and six of the 10 diagnosed women were gene carriers. The clinical presentation for the women diagnosed with breast cancer was followed until 2017. No consistent patterns for the diagnostic capacity of the different screening modalities were found, although mammography showed low sensitivity, whereas ultrasound showed better sensitivity in three of the six rounds. The specificity was high in mammography and improved in ultrasound over time. Most importantly, clinical breast examination provided no additional information toward the diagnosis of breast cancer.

Conclusion

Neither mammography nor ultrasound performed yearly were sensitive enough as standalone modalities, although high specificity was confirmed. Our findings indicate that high risk (> 29% life time risk) individuals and gene carriers can be screened biannually, using the same protocol as used in mutation carriers. Our results also suggest that low-risk groups (< 20%) may continue to be referred to population mammography screening program, while clinical breast examination may be omitted in all risk groups, and could be optional in gene carriers.

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BET’ing on Dual JAK/BET Inhibition as a Therapeutic Strategy for Myeloproliferative Neoplasms

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): Qingfei Jiang, Catriona Jamieson
In this issue of Cancer Cell, Kleppe et al. describe a combination strategy designed to inhibit BET bromodomain and JAK/STAT signaling as a method for effectively inhibiting NF-κB and cytokine production in myeloproliferative neoplasms (MPNs). The results provide a strong rationale for clinical evaluation of dual BET/JAK inhibition in MPNs.

Teaser

In this issue of Cancer Cell, Kleppe et al. describe a combination strategy designed to inhibit BET bromodomain and JAK/STAT signaling as a method for effectively inhibiting NF-κB and cytokine production in myeloproliferative neoplasms (MPNs). The results provide a strong rationale for clinical evaluation of dual BET/JAK inhibition in MPNs.

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What’s in a Name? Cell Fate Reprogramming in Sarcomagenesis

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): Kevin B. Jones
Differentiation features in cancer cells are typically attributed to the cell of origin. In this issue of Cancer Cell, Drummond et al. demonstrate a transdifferentiation program apparent in rhabdomyosarcomas (cancers with skeletal muscle differentiation features) arising through cell fate reprogramming from a single oncogene activation in endothelial cell precursors.

Teaser

Differentiation features in cancer cells are typically attributed to the cell of origin. In this issue of Cancer Cell, Drummond et al. demonstrate a transdifferentiation program apparent in rhabdomyosarcomas (cancers with skeletal muscle differentiation features) arising through cell fate reprogramming from a single oncogene activation in endothelial cell precursors.

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Characterizing the Killer Colorectal Carcinomas

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): Stanley R. Hamilton
In this issue of Cancer Cell, Yaeger et al. report mutations, copy number variations, and selected rearrangements from a large series of metastatic colorectal carcinomas and primaries that produced metastases. The results provide important insights into differences in anatomical site of origin, age at onset, etiologic factors, and therapeutic responses.

Teaser

In this issue of Cancer Cell, Yaeger et al. report mutations, copy number variations, and selected rearrangements from a large series of metastatic colorectal carcinomas and primaries that produced metastases. The results provide important insights into differences in anatomical site of origin, age at onset, etiologic factors, and therapeutic responses.

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Molecular Predictors of Gastric Neoplastic Progression

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): Paul Lochhead, Emad M. El-Omar
In this issue of Cancer Cell, Huang et al. describe comprehensive genetic and epigenetic profiling of gastric intestinal metaplasia lesions from a longitudinal cohort in which outcome data allowed for identification of potential markers of gastric neoplastic progression.

Teaser

In this issue of Cancer Cell, Huang et al. describe comprehensive genetic and epigenetic profiling of gastric intestinal metaplasia lesions from a longitudinal cohort in which outcome data allowed for identification of potential markers of gastric neoplastic progression.

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A TFIID-SAGA Perturbation that Targets MYB and Suppresses Acute Myeloid Leukemia

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): Yali Xu, Joseph P. Milazzo, Tim D.D. Somerville, Yusuke Tarumoto, Yu-Han Huang, Elizabeth L. Ostrander, John E. Wilkinson, Grant A. Challen, Christopher R. Vakoc
Targeting of general coactivators is an emerging strategy to interfere with oncogenic transcription factors (TFs). However, coactivator perturbations often lead to pleiotropic effects by influencing numerous TFs. Here we identify TAF12, a subunit of TFIID and SAGA coactivator complexes, as a selective requirement for acute myeloid leukemia (AML) progression. We trace this dependency to a direct interaction between the TAF12/TAF4 histone-fold heterodimer and the transactivation domain of MYB, a TF with established roles in leukemogenesis. Ectopic expression of the TAF4 histone-fold fragment can efficiently squelch TAF12 in cells, suppress MYB, and regress AML in mice. Our study reveals a strategy for potent MYB inhibition in AML and highlights how an oncogenic TF can be selectively neutralized by targeting a general coactivator complex.

Graphical abstract

Teaser

Xu et al. show that TAF12 is a coactivator of MYB and protects MYB from degradation. TAF12, in a heterodimer with TAF4, interacts with the transactivation domain of MYB. Perturbation of this interaction by squelching TAF12 impairs MYB activity and leads to regression of acute myeloid leukemia in mouse models.

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TFIID and MYB Share a Therapeutic Handshake in AML

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): Charles C. Bell, Mark A. Dawson
Selectively disrupting oncogenic transcription factors in cancer remains an elusive ambition of targeted therapeutics. In this issue of Cancer Cell, Xu et al. provide an elegant proof-of-concept study demonstrating that interaction between MYB and the general transcriptional coactivator TFIID can be specifically disrupted to mediate a therapeutic effect in AML.

Teaser

Selectively disrupting oncogenic transcription factors in cancer remains an elusive ambition of targeted therapeutics. In this issue of Cancer Cell, Xu et al. provide an elegant proof-of-concept study demonstrating that interaction between MYB and the general transcriptional coactivator TFIID can be specifically disrupted to mediate a therapeutic effect in AML.

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TIM-3 Regulates CD103+ Dendritic Cell Function and Response to Chemotherapy in Breast Cancer

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): Álvaro de Mingo Pulido, Alycia Gardner, Shandi Hiebler, Hatem Soliman, Hope S. Rugo, Matthew F. Krummel, Lisa M. Coussens, Brian Ruffell
Intratumoral CD103⁺ dendritic cells (DCs) are necessary for anti-tumor immunity. Here we evaluated the expression of immune regulators by CD103⁺ DCs in a murine model of breast cancer and identified expression of TIM-3 as a target for therapy. Anti-TIM-3 antibody improved response to paclitaxel chemotherapy in models of triple-negative and luminal B disease, with no evidence of toxicity. Combined efficacy was CD8⁺ T cell dependent and associated with increased granzyme B expression; however, TIM-3 expression was predominantly localized to myeloid cells in both human and murine tumors. Gene expression analysis identified upregulation of Cxcl9 within intratumoral DCs during combination therapy, and therapeutic efficacy was ablated by CXCR3 blockade, Batf3 deficiency, or Irf8 deficiency.

Graphical abstract

Teaser

de Mingo Pulido et al. show that intratumoral CD103⁺ dendritic cells (DCs) highly express TIM-3. Anti-TIM-3 antibody promotes CXCL9 expression by these DCs, which enhances the function of CD8⁺ T cells, thereby improving paclitaxel's therapeutic activity in breast cancer models.

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Oncogenic KRAS Regulates Amino Acid Homeostasis and Asparagine Biosynthesis via ATF4 and Alters Sensitivity to L-Asparaginase

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): Dana M. Gwinn, Alex G. Lee, Marcela Briones-Martin-del-Campo, Crystal S. Conn, David R. Simpson, Anna I. Scott, Anthony Le, Tina M. Cowan, Davide Ruggero, E. Alejandro Sweet-Cordero
KRAS is a regulator of the nutrient stress response in non-small-cell lung cancer (NSCLC). Induction of the ATF4 pathway during nutrient depletion requires AKT and NRF2 downstream of KRAS. The tumor suppressor KEAP1 strongly influences the outcome of activation of this pathway during nutrient stress; loss of KEAP1 in KRAS mutant cells leads to apoptosis. Through ATF4 regulation, KRAS alters amino acid uptake and asparagine biosynthesis. The ATF4 target asparagine synthetase (ASNS) contributes to apoptotic suppression, protein biosynthesis, and mTORC1 activation. Inhibition of AKT suppressed ASNS expression and, combined with depletion of extracellular asparagine, decreased tumor growth. Therefore, KRAS is important for the cellular response to nutrient stress, and ASNS represents a promising therapeutic target in KRAS mutant NSCLC.

Teaser

Gwinn et al. show that oncogenic KRAS regulates amino acid homeostasis and cellular response to nutrient stress via ATF4. They identify ASNS as a key target of the KRAS-ATF4 axis in KRAS-driven non-small-cell lung cancer, revealing a therapeutic vulnerability in asparagine biosynthesis.

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Hedgehog Pathway Drives Fusion-Negative Rhabdomyosarcoma Initiated From Non-myogenic Endothelial Progenitors

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): Catherine J. Drummond, Jason A. Hanna, Matthew R. Garcia, Daniel J. Devine, Alana J. Heyrana, David Finkelstein, Jerold E. Rehg, Mark E. Hatley
Rhabdomyosarcoma (RMS) is a pediatric soft tissue sarcoma that histologically resembles embryonic skeletal muscle. RMS occurs throughout the body and an exclusively myogenic origin does not account for RMS occurring in sites devoid of skeletal muscle. We previously described an RMS model activating a conditional constitutively active Smoothened mutant (SmoM2) with aP2-Cre. Using genetic fate mapping, we show SmoM2 expression in Cre-expressing endothelial progenitors results in myogenic transdifferentiation and RMS. We show that endothelium and skeletal muscle within the head and neck arise from Kdr-expressing progenitors, and that hedgehog pathway activation results in aberrant expression of myogenic specification factors as a potential mechanism driving RMS genesis. These findings suggest that RMS can originate from aberrant development of non-myogenic cells.

Graphical abstract

Teaser

Using genetic fate mapping, Drummond et al. show that hedgehog pathway activation in endothelial progenitors results in aberrant expression of myogenic specification factors, myogenic transdifferentiation, and rhabdomyosarcoma (RMS). The finding may explain how RMS develops in sites devoid of skeletal muscle.

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Clinical Sequencing Defines the Genomic Landscape of Metastatic Colorectal Cancer

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): Rona Yaeger, Walid K. Chatila, Marla D. Lipsyc, Jaclyn F. Hechtman, Andrea Cercek, Francisco Sanchez-Vega, Gowtham Jayakumaran, Sumit Middha, Ahmet Zehir, Mark T.A. Donoghue, Daoqi You, Agnes Viale, Nancy Kemeny, Neil H. Segal, Zsofia K. Stadler, Anna M. Varghese, Ritika Kundra, Jianjiong Gao, Aijazuddin Syed, David M. Hyman, Efsevia Vakiani, Neal Rosen, Barry S. Taylor, Marc Ladanyi, Michael F. Berger, David B. Solit, Jinru Shia, Leonard Saltz, Nikolaus Schultz
Metastatic colorectal cancers (mCRCs) are clinically heterogeneous, but the genomic basis of this variability remains poorly understood. We performed prospective targeted sequencing of 1,134 CRCs. We identified splice alterations in intronic regions of APC and large in-frame deletions in CTNNB1, increasing oncogenic WNT pathway alterations to 96% of CRCs. Right-sided primary site in microsatellite stable mCRC was associated with shorter survival, older age at diagnosis, increased mutations, and enrichment of oncogenic alterations in KRAS, BRAF, PIK3CA, AKT1, RNF43, and SMAD4 compared with left-sided primaries. Left-sided tumors frequently had no identifiable genetic alteration in mitogenic signaling, but exhibited higher mitogenic ligand expression. Our results suggest different pathways to tumorigenesis in right- and left-sided microsatellite stable CRC that may underlie clinical differences.

Graphical abstract

Teaser

Yaeger et al. perform prospective sequencing of metastatic colorectal cancers (mCRCs). Right-sided primary microsatellite stable mCRCs are associated with increased oncogenic mutations whereas most left-sided tumors lack identifiable genetic mitogenic signaling alterations but highly express mitogenic ligands.

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Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): A. Gordon Robertson, Juliann Shih, Christina Yau, Ewan A. Gibb, Junna Oba, Karen L. Mungall, Julian M. Hess, Vladislav Uzunangelov, Vonn Walter, Ludmila Danilova, Tara M. Lichtenberg, Melanie Kucherlapati, Patrick K. Kimes, Ming Tang, Alexander Penson, Ozgun Babur, Rehan Akbani, Christopher A. Bristow, Katherine A. Hoadley, Lisa Iype, Matthew T. Chang, Andrew D. Cherniack, Christopher Benz, Gordon B. Mills, Roel G.W. Verhaak, Klaus G. Griewank, Ina Felau, Jean C. Zenklusen, Jeffrey E. Gershenwald, Lynn Schoenfield, Alexander J. Lazar, Mohamed H. Abdel-Rahman, Sergio Roman-Roman, Marc-Henri Stern, Colleen M. Cebulla, Michelle D. Williams, Martine J. Jager, Sarah E. Coupland, Bita Esmaeli, Cyriac Kandoth, Scott E. Woodman

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Arid1a Has Context-Dependent Oncogenic and Tumor Suppressor Functions in Liver Cancer

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): Xuxu Sun, Sam C. Wang, Yonglong Wei, Xin Luo, Yuemeng Jia, Lin Li, Purva Gopal, Min Zhu, Ibrahim Nassour, Jen-Chieh Chuang, Thomas Maples, Cemre Celen, Liem H. Nguyen, Linwei Wu, Shunjun Fu, Weiping Li, Lijian Hui, Feng Tian, Yuan Ji, Shuyuan Zhang, Mahsa Sorouri, Tae Hyun Hwang, Lynda Letzig, Laura James, Zixi Wang, Adam C. Yopp, Amit G. Singal, Hao Zhu

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Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment

Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): Qianghu Wang, Baoli Hu, Xin Hu, Hoon Kim, Massimo Squatrito, Lisa Scarpace, Ana C. deCarvalho, Sali Lyu, Pengping Li, Yan Li, Floris Barthel, Hee Jin Cho, Yu-Hsi Lin, Nikunj Satani, Emmanuel Martinez-Ledesma, Siyuan Zheng, Edward Chang, Charles-Etienne Gabriel Sauvé, Adriana Olar, Zheng D. Lan, Gaetano Finocchiaro, Joanna J. Phillips, Mitchel S. Berger, Konrad R. Gabrusiewicz, Guocan Wang, Eskil Eskilsson, Jian Hu, Tom Mikkelsen, Ronald A. DePinho, Florian Muller, Amy B. Heimberger, Erik P. Sulman, Do-Hyun Nam, Roel G.W. Verhaak

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Clinical Sequencing Defines the Genomic Landscape of Metastatic Colorectal Cancer

Graphical abstract

Teaser

Arid1a Has Context-Dependent Oncogenic and Tumor Suppressor Functions in Liver Cancer

Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment

11q23 deletion syndrome (Jacobsen syndrome) with severe bleeding: a case report

11q23 deletion syndrome, also known as Jacobsen syndrome, is characterized by growth retardation, psychomotor retardation, facial dysmorphism, multiple congenital abnormalities, and thrombocytopenia. In 11q23 ...

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Validation of clinical prognostic scores for patients treated with curative-intent for recurrent colorectal liver metastases

Background

Scoring systems were developed to stratify patients with colorectal liver metastases considered for liver resection into different risk groups. Such scores have never been evaluated in recurrent liver metastases. The aim of this study was to evaluate whether these scores are applicable to patients with recurrent colorectal liver metastases and treated with curative intent.

Methods

We retrospectively analyzed data from 375 consecutive patients who underwent liver surgery for colorectal liver metastases between June 2010 and August 2015. Seventy-three patients developed liver-limited recurrence treated with curative intent. The predictive value of 6 scores (Fong, Sofocleous, Nagashima, Nordlinger, Konopke, and the Basingstoke index) was assessed in this set of patients.

Results

Median follow-up was 36.2 months. Overall survival and progression-free survival were 33.6 and 5.6 months, respectively. When scores were applied for OS, none showed a significant stratification between patients, although Nagashima's score showed a significant difference in overall survival between patients from the low-risk group and those from the intermediate- and high-risk groups (40.8 vs 30.5 months, P = 0.039). For PFS, only Fong's score showed a statistically significant stratification (6.6 vs 4.7 months, P = 0.027).

Conclusion

Scoring systems are of limited-value in stratifying patients operated on for recurrent colorectal liver metastases.

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Mid- to long-term clinical outcome of giant cell tumor of bone treated with calcium phosphate cement following thorough curettage and phenolization

Background and Objectives

Giant cell tumors of bone (GCTB) are intermediate and locally aggressive bone tumor. Calcium phosphate cement (CPC) is a bone void filler used in orthopaedic surgery. This study investigated the clinical outcome of GCTB treated with thorough curettage, phenolization, and CPC.

Methods

We investigated 26 patients with at least 36 months of follow-up. The mean age and follow-up were 37 years (range: 19-63) and 87 months (range: 38-169), respectively. Radiological outcomes including consolidation of CPC to the surrounding bone, cortical bone defect remodeling, and clinical outcomes were investigated.

Results

The consolidation of CPC to the surrounding bone was excellent in 22 cases (84.6%), good in three (11.5%), and acceptable in one (3.8%). Local recurrence occurred in three cases (11.5%). Pulmonary metastasis occurred in one case (3.8%). Cortical bone defect remodeling appeared in 22 cases (84.6%). The mean Musculoskeletal Tumour Society score was 28.7 (95.7%). Osteoarthritis, chronic synovitis, and fracture were observed in one case each (3.8%), which were managed conservatively.

Conclusions

Phenolization did not prevent the consolidation of CPC to the bone. CPC provided biological interface and long lasting stability without internal fixation, with comparable complication rates to other published series.

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Trends of genetic screening in patients with pheochromocytoma and paraganglioma: 15-year experience in a high-volume tertiary referral center

Background and Objectives

Genetic testing for pheochromocytoma and paraganglioma allows for early detection of hereditary syndromes and enables close follow-up of high-risk patient. We investigated the trends in genetic testing among patients at a high-volume referral center and evaluated the prevalence of pheochromocytomas and paragangliomas.

Methods

We reviewed the charts of 129 patients who underwent adrenalectomy for pheochromocytoma and paraganglioma between January 2000 and July 2015. To evaluate for trends in genetic testing, patients were divided by year of diagnosis: 2000-2005 (group 1, n = 35), 2006-2010 (group 2, n = 44), and 2011-2015 (group 3, n = 50).

Results

Among 129 patients the mean age was 47 years and 56% were women. Groups 2 and 3 were more frequently referred for genetic consultation than group 1, 73%, and 94% versus 26% (P < 0.001). A total of 67% followed up on the referral. The prevalence of genetic mutation was 50% (21/42 tested). The percentage with a genetic syndrome was 23%, 28%, and 22% respectively for groups 1, 2, and 3.

Conclusions

Referral for genetic counseling significantly increased in the past 15 years. However, only two-thirds of patients followed up with genetic counselors and, therefore, clinicians can do more to improve the adherence rate for genetic counseling.

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Evaluation of extended antibiotic prophylaxis in patients undergoing indicated non-cosmetic panniculectomy at the time of gynecologic surgery

Background

Panniculectomy at time of gynecologic surgery is used to improve visualization and prevent major complications in morbidly obese patients. We examine the role of extended antibiotic prophylaxis in prevention of surgical site infections (SSI), specifically based on patient risk factors (hypertension, diabetes, smoking).

Methods

A prospective cohort study of all women who underwent panniculectomy at the time of gynecologic surgery from September 2014 to March 2016 at a university-affiliated hospital. The EAP cohort received standard antibiotics (cefazolin, 2 g) and continued oral antibiotic (doxycycline) for 10 days afterwards. Patients in this cohort were compared to historical controls from the same institution from 1990 to 2014. Specific attention was paid to the reduction of SSIs in patients with hypertension, diabetes, and a history of smoking.

Results

The mean age was 56.0 ± 12.6 years, and mean body mass index 44.5 ± 9.3 kg/m² (range 31-63.4 kg/m²). The EAP cohort experienced fewer surgical-site infections overall, however these results were not significantly decreased from the historical controls, (13/56 [23.2%] vs 94/300 [31.3%]; P = 0.469).

Conclusion

Though initially promising, extended antibiotic prophylaxis did not reduce surgical site infections in the obese women after indicated non-cosmetic panniculectomy at the time of gynecologic surgery.

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Anesthesia for Same Day Discharge After Craniotomy: Review of a Single Center Experience

Same day discharge or outpatient surgery for intracranial procedures has become possible with the advent of image-guided minimally invasive approaches to surgery and availability of short-acting anesthetic agents. In addition, patient satisfaction and the benefits of avoiding hospital stay have resulted in the evolution of neurosurgical day surgery. We reviewed our experience and the available literature to determine the perioperative factors involved which have promoted and will improve this concept in the future. Craniotomy and biopsy for supratentorial brain tumors and surgical clipping of intact cerebral aneurysms have been successfully performed as day surgeries. Patient perceptions and satisfaction surveys have helped in better understanding and delivery of care and successful outcomes. There are major differences in health care across the globe along with socioeconomic, medicolegal, and ethical disparities, which must be considered before widespread application of this approach. Nevertheless, collaborative effort by surgeons, anesthesiologists, and nurses can help in same day discharge of patients after cranial neurosurgery. Veena Sheshadri, MD, Department of Neuroanesthesia and Neurocritical Care, Gleneagles Global Hospitals, Bengaluru, Karnataka, India. All the authors contributed substantially to the conception and design of the manuscript and to the interpretation of data. S.V., V.L., and M.P.: contributed to the literature search, acquisition, and analysis of data. The authors have no funding or conflicts of interest to disclose. Address correspondence to: Lashmi Venkatraghavan, MD, FRCA, FRCPC, Department of Anesthesia, Toronto Western Hospital, University Health Network, University of Toronto, 399 Bathurst St, Toronto, ON, M5T 2S8, Canada (e-mail: lashmi.venkatraghavan@uhn.on.ca). Received May 29, 2017 Accepted November 28, 2017 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved

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Acupuncture May Reduce Treatment-Related Joint Pain for Breast Cancer Patients

Joint pain caused by aromatase inhibitors in postmenopausal women with breast cancer can cause some women to stop taking the drugs. Reducing their symptoms may translate into better adherence to therapy.

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Acupuncture May Reduce Treatment-Related Joint Pain for Breast Cancer Patients

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Dietary habits during the 2 months following the Chernobyl accident and differentiated thyroid cancer risk in a population-based case–control study

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52
Author(s): Constance Xhaard, Carole Rubino, Vincent Souchard, Stéphane Maillard, Yan Ren, Françoise Borson-Chazot, Geneviève Sassolas, Claire Schvartz, Marc Colonna, Brigitte Lacour, Anne Sophie Woronoff, Michel Velten, Emilie Marrer, Laurent Bailly, Eugènia Mariné Barjoan, Martin Schlumberger, Vladimir Drozdovitch, Andre Bouville, Jacques Orgiazzi, Elisabeth Adjadj, Florent de Vathaire
BackgroundThe Chernobyl nuclear power plant accident occurred in Ukraine on April 26th 1986. In France, the radioactive fallout and thyroid radiation doses were much lower than in highly contaminated areas. However, a number of risk projections have suggested that a small excess in differentiated thyroid cancer (DTC) might occur in eastern France due to this low-level fallout. In order to investigate this potential impact, a case–control study on DTC risk factors was started in 2005, focusing on cases who were less than 15 years old at the time of the Chernobyl accident. Here, we aim to evaluate the relationship between some specific reports of potentially contaminated food between April and June 1986 – in particular fresh dairy products and leafy vegetables – and DTC risk.MethodsAfter excluding subjects who were not born before the Chernobyl accident, the study included 747 cases of DTC matched with 815 controls. Odds ratios were calculated using conditional logistic regression models and were reported for all participants, for women only, for papillary cancer only, and excluding microcarcinomas.ResultsThe DTC risk was slightly higher for participants who had consumed locally produced leafy vegetables. However, this association was not stronger in the more contaminated areas than in the others. Conversely, the reported consumption of fresh dairy products was not statistically associated with DTC risk.ConclusionBecause the increase in DTC risk associated with a higher consumption of locally produced vegetables was not more important in the most contaminated areas, our study lacked power to provide evidence for a strong association between consumption of potentially contaminated food and DTC risk.

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An in-depth prognostic analysis of baseline blood lipids in predicting postoperative colorectal cancer mortality: The FIESTA study

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52
Author(s): Feng Peng, Dan Hu, Xiandong Lin, Gang Chen, Binying Liang, Ying Chen, Chao Li, Hejun Zhang, Yan Xia, Jinxiu Lin, Xiongwei Zheng, Wenquan Niu
BackgroundDyslipidaemia is key to colorectal carcinogenesis, and the prediction of baseline triglycerides (TG), total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDLC and LDLC) for postsurgical colorectal cancer mortality has not been researched.ObjectivesWe attempted to re-analyse the FIESTA database to assess the prognostic value of three informative lipid derivatives − AI (atherogenic index: (TC − HDLC)/HDLC), THR (TG/HDLC) and LHR (LDLC/HDLC) in predicting colorectal cancer mortality.MethodsBased on the FIESTA database, 1318 patients received radical resection from 2000 to 2008, with the latest follow-up completed in December 2015. Median follow-up time was 58.6 months.ResultsTotal 1318 patients were randomly evenly divided into the derivation and validation groups. Overall, baseline AI and LHR were associated with the significantly increased risk of colorectal cancer mortality in both derivation (hazard ratio (HR): 1.41 and 1.35, respectively) and validation (HR: 1.37 and 1.32, respectively) groups (all P < 0.001). The predictive performance of AI and LHR was remarkably enhanced in patients with female gender, former/current smoking, colon cancer, early stage, positive vein tumor embolus, normal weight, preoperative hypertension or diabetes comorbidities. Calibration/discrimination analyses revealed that adding AI or LHR to the traditional model had a better fit in both groups. A prognostic nomogram was finally constructed with good predictive accuracy and discriminative capability (C-index = 0.814, P < 0.001).ConclusionWe consolidated the prognostic superiority of AI and LHR in predicting colorectal cancer mortality over TNM stage.

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Dietary habits during the 2 months following the Chernobyl accident and differentiated thyroid cancer risk in a population-based case–control study

An in-depth prognostic analysis of baseline blood lipids in predicting postoperative colorectal cancer mortality: The FIESTA study

Local therapy of stage IV renal cell cancer: a case report

Summary

This mini-review and case report demonstrates how systemic and local treatments work synergistically for patients with metastatic renal cell carcinoma (mRCC). Although new targeted and immunotherapies have revolutionized the treatment armamentarium of mRCC and dramatically improved patients' prognosis, local treatment remains an important part of therapy. Here, we report on a patient who benefitted enormously from the combination and interaction of both therapeutic approaches, and we summarize the literature and guidelines that supported our treatment decisions in this case.

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Report from the WCLC 2017 Congress, Yokohama, 8th–12th September, 2017

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Prognostic Value of c-MET Expression in Patients With Pancreatic Cancer Receiving Adjuvant and Neoadjuvant Chemoradiation Therapy

Publication date: 1 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 2
Author(s): Kyle C. Cuneo, Meredith A. Morgan, Kent A. Griffith, Peter G. Hawkins, Joel K. Greenson, Edgar Ben-Josef, Theodore S. Lawrence, Mark M. Zalupski
PurposeTo determine the prognostic significance of c-MET expression and develop a predictor of distant failure in patients with resectable pancreatic cancer treated with chemoradiation.Methods and MaterialsWe used a tissue microarray to study protein expression by immunohistochemistry in 102 patients treated surgically for pancreatic cancer. Two cores per patient were blindly scored from 0 (no staining) to 3 (strong staining) by a single pathologist. The Kaplan-Meier method was used to determine time to local and distant failure, overall survival, and progression-free survival. P values were calculated with the log–rank test.ResultsHigh tumor expression of c-MET was associated with a shorter time to distant failure in patients receiving neoadjuvant (n=23) or neoadjuvant therapy (n=73) (median 8.9 months vs 22.0 months, P=.0010). We then examined the ability of incorporating 2 known biomarkers, thymidylate synthase and DPC4 (SMAD4), with c-MET to risk-stratify patients. This multi-protein predictor divided our cohort into groups of similar numbers and was predictive of distant failure (median 13.4 months vs 24.2 months, P=.0094) but not of local control.Conclusionc-MET is potentially predictive of distant failure. Using c-MET, DPC4, and thymidylate synthase, we developed a multi-protein predictor that could be used to risk-stratify patients and guide decisions regarding the sequencing of locoregional and systemic therapies in pancreatic cancer.

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Cardiac Morbidity and Radiation Therapy for Breast Cancer

Publication date: 1 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 2
Author(s): Jean Wright, Rachel Blitzblau

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Erratum to: Wang SY, Kelly G, Gross C, et al. Information needs of older women with early-stage breast cancer when making radiation therapy decisions. Int J Radiat Oncol Biol Phys 2017;98:733-740.

Publication date: 1 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 2

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Chemo-radiation, Then on to Surgery

Publication date: 1 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 2
Author(s): Junzo Chino

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Issue Highlights

Publication date: 1 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 2

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Rescuing Spanish Radiation Therapy: The Role of Leadership and Opportunity

Publication date: 1 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 2
Author(s): Pedro C. Lara, Aurora Rodríguez, Carlos Ferrer, Jose Javier Aristu, Pedro Jose Prada, Julia Muñoz, Meritxell Arenas, Hector Perez-Montero

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Effect of CD4 Count on Treatment Toxicity and Tumor Recurrence in Human Immunodeficiency Virus–Positive Patients With Anal Cancer

Publication date: 1 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 2
Author(s): Alex K. Bryant, Ross Mudgway, Minh-Phuong Huynh-Le, Daniel R. Simpson, Loren K. Mell, Samir Gupta, Andrew B. Sharabi, James D. Murphy
PurposeTo study the effects of immunosuppression on treatment toxicity, long-term cancer recurrence risk, and survival among human immunodeficiency virus (HIV)-positive anal cancer patients.Methods and MaterialsFrom a nationwide retrospective cohort of veterans with anal cancer we identified 142 HIV-positive patients with stage I-III disease, diagnosed between 2000 and 2015 and treated with definitive-intent chemotherapy and radiation. We used regression models to study the impact of pretreatment CD4 counts and longitudinal posttreatment CD4 counts on outcomes including acute toxicity, long-term ostomy rates, cancer recurrence, cancer-specific survival, and overall survival. All models were adjusted for potential confounders.ResultsThe median pretreatment CD4 count was 375 cells/mm³, which dropped to 157 cells/mm³ after treatment. Each 100-cell/mm³ decrease in pretreatment CD4 count was associated with an increased risk of acute hematologic toxicity (odds ratio 1.19, 95% confidence interval [CI] 1.01-1.42, P=.04) and hospitalization for hematologic toxicity (odds ratio 1.24, 95% CI 1.00-1.54, P=.049) but not gastrointestinal toxicity, tumor recurrence, or cancer-specific mortality (P>.05). Each 100-cells/mm³ decrease in posttreatment CD4 count increased the risk of recurrence by 54% (hazard ratio 1.54, 95% CI 1.09-2.17, P=.01) and cancer mortality by 46% at a trend level (hazard ratio 1.46, 95% CI 0.99-2.14, P=.06). Neither pre- nor posttreatment CD4 count influenced long-term ostomy rates or overall survival (all P>.05).ConclusionsLower pretreatment CD4 counts were associated with acute hematologic toxicity, and lower posttreatment CD4 count levels were associated with an increased risk of tumor recurrence. These results suggest that immune surveillance may play an important role in long-term disease control in anal cancer.

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Quantifying the Effect of 3T Magnetic Resonance Imaging Residual System Distortions and Patient-Induced Susceptibility Distortions on Radiation Therapy Treatment Planning for Prostate Cancer

Publication date: 1 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 2
Author(s): Mary Adjeiwaah, Mikael Bylund, Josef A. Lundman, Camilla Thellenberg Karlsson, Joakim H. Jonsson, Tufve Nyholm
PurposeTo investigate the effect of magnetic resonance system- and patient-induced susceptibility distortions from a 3T scanner on dose distributions for prostate cancers.Methods and MaterialsCombined displacement fields from the residual system and patient-induced susceptibility distortions were used to distort 17 prostate patient CT images. VMAT dose plans were initially optimized on distorted CT images and the plan parameters transferred to the original patient CT images to calculate a new dose distribution.ResultsMaximum residual mean distortions of 3.19 mm at a radial distance of 25 cm and maximum mean patient-induced susceptibility shifts of 5.8 mm were found using the lowest bandwidth of 122 Hz per pixel. There was a dose difference of <0.5% between distorted and undistorted treatment plans. The 90% confidence intervals of the mean difference between the dCT and CT treatment plans were all within an equivalence interval of (−0.5, 0.5) for all investigated plan quality measures.ConclusionsPatient-induced susceptibility distortions at high field strengths in closed bore magnetic resonance scanners are larger than residual system distortions after using vendor-supplied 3-dimensional correction for the delineated regions studied. However, errors in dose due to disturbed patient outline and shifts caused by patient-induced susceptibility effects are below 0.5%.

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Prognostic Value of c-MET Expression in Patients With Pancreatic Cancer Receiving Adjuvant and Neoadjuvant Chemoradiation Therapy

Radiation Is the Place to Start

Publication date: 1 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 2
Author(s): Ann Klopp

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Chemo First, Then Radiation, and Perhaps Surgery

Publication date: 1 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 2
Author(s): Alexander B. Olawaiye

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Issue Highlights

Publication date: 1 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 2

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Rescuing Spanish Radiation Therapy: The Role of Leadership and Opportunity

Effect of CD4 Count on Treatment Toxicity and Tumor Recurrence in Human Immunodeficiency Virus–Positive Patients With Anal Cancer

In Regard to Chowdhary et al

Publication date: 1 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 2
Author(s): Trevor J. Royce

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MRI-based Assessment of 3D Intrafractional Motion of Head and Neck Cancer for Radiation Therapy

Publication date: 1 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 2
Author(s): Oliver J. Gurney-Champion, Dualta McQuaid, Alex Dunlop, Kee H. Wong, Liam C. Welsh, Angela M. Riddell, Dow-Mu Koh, Uwe Oelfke, Martin O. Leach, Christopher M. Nutting, Shreerang A. Bhide, Kevin J. Harrington, Rafal Panek, Kate L. Newbold
PurposeTo determine the 3-dimensional (3D) intrafractional motion of head and neck squamous cell carcinoma (HNSCC).Methods and MaterialsDynamic contrast-enhanced magnetic resonance images from 56 patients with HNSCC in the treatment position were analyzed. Dynamic contrast-enhanced magnetic resonance imaging consisted of 3D images acquired every 2.9 seconds for 4 minutes 50 seconds. Intrafractional tumor motion was studied in the 3 minutes 43 seconds of images obtained after initial contrast enhancement. To assess tumor motion, rigid registration (translations only) was performed using a region of interest (ROI) mask around the tumor. The results were compared with bulk body motion from registration to all voxels. Motion was split into systematic motion and random motion. Correlations between the tumor site and random motion were tested. The within-subject coefficient of variation was determined from 8 patients with repeated baseline measures. Random motion was also assessed at the end of the first week (38 patients) and second week (25 patients) of radiation therapy to investigate trends of motion.ResultsTumors showed irregular occasional rapid motion (eg, swallowing or coughing), periodic intermediate motion (respiration), and slower systematic drifts throughout treatment. For 95% of the patients, displacements due to systematic and random motion were <1.4 mm and <2.1 mm, respectively, 95% of the time. The motion without an ROI mask was significantly (P<.0001, Wilcoxon signed rank test) less than the motion with an ROI mask, indicating that tumors can move independently from the bony anatomy. Tumor motion was significantly (P=.005, Mann-Whitney U test) larger in the hypopharynx and larynx than in the oropharynx. The within-subject coefficient of variation for random motion was 0.33. The average random tumor motion did not increase notably during the first 2 weeks of treatment.ConclusionsThe 3D intrafractional tumor motion of HNSCC is small, with systematic motion <1.4 mm and random motion <2.1 mm 95% of the time.

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Quantifying the Effect of 3T Magnetic Resonance Imaging Residual System Distortions and Patient-Induced Susceptibility Distortions on Radiation Therapy Treatment Planning for Prostate Cancer

Radiation Dose, Local Disease Progression, and Overall Survival in Patients With Inoperable Non-Small Cell Lung Cancer After Concurrent Chemoradiation Therapy

Publication date: 1 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 2
Author(s): RongRong Zhou, Ting Xu, Quynh-Nhu Nguyen, Ying Liu, Ju Yang, Ritsuko Komaki, Daniel R. Gomez, Zhongxing Liao
PurposeTo identify predictors of local control and overall survival (OS) for patients with inoperable non-small cell lung cancer treated with concurrent chemoradiation therapy.Methods and MaterialsWe identified 491 patients with newly diagnosed stage IIIA-IIIB non-small cell lung cancer who had received 60 to 74 Gy (with concurrent chemotherapy) from January 2005 through December 2013 and grouped them by radiation dose received: 60 to 63 Gy, 64 to 66 Gy, 67 to 70 Gy, or 71 to 74 Gy. Local progression (LP) was that appearing within the high-dose volume (planning target volume plus 1-cm margin). Times to events were calculated from the completion of radiation therapy. Potential predictors of LP and OS were analyzed with a Cox regression model.ResultsRates of LP for all patients were 16.2% at 1 year, 26.2% at 2 years, 31.0% at 3 years, 32.9% at 4 years, and 32.9% at 5 years; corresponding OS rates were 85.3%, 61.2%, 44.5%, 37.0%, and 31.6%. Median OS time was 21 months (range, 2.9-99.9 months). In multivariate analysis, receipt of 67 to 70 Gy was associated with improved LP-free survival (LPFS) relative to 60 to 63 Gy (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.062-3.150, P=.030) or 64 to 66 Gy (HR 2.14, 95% CI 1.159-3.969, P=.015). Non-squamous histology (HR 0.23, 95% CI 0.114-0.478, P=.000), gross tumor volume (HR 1.00, 95% CI 1.000-1.003, P=.018) and induction chemotherapy (HR 1.86, 95% CI 1.239-2.778, P=.003) were independent predictors of LPFS. Local progression–free survival was the only independent predictor of OS (HR 2.71, 95% CI 1.331-5.512, P=.006). Incidence of grade ≥3 radiation pneumonitis was no different among dose groups (P=.307).ConclusionsSquamous histology, large tumor volumes, and receipt of induction chemotherapy all predicted worse LPFS. Doses of 67 to 70 Gy were associated with improved LP-free survival after chemoradiotherapy. The link between LP and reduced OS suggests that more effective local control strategies are warranted.

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A Single Intraperitoneal Injection of Endotoxin Changes Glial Cells in Rats as Revealed by Positron Emission Tomography Using [ 11 C]PK11195

Abstract

Purpose

Intracranial administration of lipopolysaccharide (LPS) is known to elicit a rapid innate immune response, activate glial cells in the brain, and induce depression-like behavior. However, no study has focused on the changes in glial cells induced by intraperitoneal injection of LPS in vivo.

Methods

Ten adult male Fischer F344 rats underwent [¹¹C]PK11195 PET before and 2 days after intraperitoneal injection of LPS to evaluate the changes in glial cells. The difference in standardized uptake values (SUV) of [¹¹C]PK11195 between before and after injection was determined.

Results

There was a cluster of brain regions that showed significant reductions in SUV. This cluster included the bilateral striata and bilateral frontal regions, especially the somatosensory areas.

Conclusions

Changes in activity of glial cells induced by the intraperitoneal injection of LPS were detected in vivo by [¹¹C]PK11195 PET. Intraperitoneal injection of LPS is known to induce depression, and further studies with [¹¹C]PK11195 PET would clarify the relationships between neuroinflammation and depression.

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The Two Faces of Adjuvant Glucocorticoid Treatment in Ovarian Cancer

Abstract

Adjuvant glucocorticoid treatment is routinely used in the treatment of ovarian cancer to mitigate the undesirable side effects of chemotherapy, thereby enhancing tolerability to higher cytotoxic drug doses and frequency of treatment cycles. However, in vitro and preclinical in vivo and ex vivo studies indicate that glucocorticoids may spare tumor cells from undergoing cell death through enhanced cell adhesion, promotion of anti-inflammatory signaling, and/or inhibition of apoptotic pathways. The implications of laboratory studies showing potential negative impact on the efficacy of chemotherapy have been long overlooked since clinical investigations have found no apparent survival detriment attributable to adjuvant glucocorticoid use. Importantly, these clinical studies were not randomized and most did not consider glucocorticoid receptor status, a vital determinant of tumor response to glucocorticoid administration. Additionally, the clinically beneficial elements of increased chemotherapy treatment adherence and dosing afforded by adjuvant glucocorticoids may offset and therefore mask their anti-chemotherapy activities. This review summarizes the current evidence on the impact of glucocorticoids in ovarian cancer and discusses the need for further research and development of alternative strategies to ameliorate untoward side effects of chemotherapy.

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Ultrasound-Guided Restaging and Localization of Axillary Lymph Nodes After Neoadjuvant Chemotherapy for Guidance of Axillary Surgery in Breast Cancer Patients: Experience with Activated Charcoal

Abstract

Objective

The aim of this study was to review our experience with ultrasound (US)-guided localization of axillary lymph nodes using activated charcoal for the guidance of axillary surgery after neoadjuvant chemotherapy (NAC) in clinically node-positive breast cancer patients.

Methods

Between April 2016 and April 2017, US-guided localization of the most suspicious axillary lymph nodes at restaging US using activated charcoal (Charcotrace™) was performed in 45 consecutive, clinically node-positive breast cancer patients who had less than two suspicious nodes after NAC and axillary surgery with sentinel node biopsy. Sentinel nodes were defined as radioactive nodes or nodes containing blue dye. The concordance between final pathological results for both the tattooed and sentinel nodes was analyzed.

Results

Sentinel node biopsy failed in five patients (11%) in whom axillary surgery was performed under the guidance of the tattooed node. The tattooed nodes were identified in the surgical field in 44 patients (98%). Of the 44 tattooed nodes, 25 (57%) were concordant with the sentinel nodes and 19 (43%) were non-sentinel nodes, including the five nodes with failed sentinel node biopsy. In the final pathological results, 18 patients (40%) had metastatic nodes. The sensitivities for detecting axillary metastasis of the sentinel node biopsy, tattooed node biopsy, and the sentinel and/or tattooed node biopsy were 61% (11/18), 67% (12/18), and 78% (14/18), respectively.

Conclusion

US-guided localization of axillary lymph nodes using activated charcoal at restaging after NAC in clinically node-positive breast cancer patients is a useful technique to guide axillary surgery, with a high identification rate.

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Prospective Assessment of First-Year Quality of Life After Pelvic Exenteration for Gynecologic Malignancy: A French Multicentric Study

Abstract

Background

Pelvic exenteration remains one of the most mutilating procedures, with important postoperative morbidity, an altered body image, and long-term physical and psychosocial concerns. This study aimed to assess quality of life (QOL) during the first year after pelvic exenteration for gynecologic malignancy performed with curative intent.

Methods

A French multicentric prospective study was performed by including patients who underwent pelvic exenteration. Quality of life by measurement of functional and symptom scales was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 (version 3.0) and the EORTC QLQ-OV28 questionnaires before surgery, at baseline, and 1, 3, 6, and 12 months after the procedure.

Results

The study enrolled 97 patients. Quality of life including physical, personal, fatigue, and anorexia reported in the QLQ-C30 was significantly reduced 1 month postoperatively and improved at least to baseline level 1 year after the procedure. Body image also was significantly reduced 1 month postoperatively. Global health, emotional, dyspnea, and anorexia items were significantly improved 1 year after surgery compared with baseline values. Unlike younger patients, elderly patients did not regain physical and social activities after pelvic exenteration.

Conclusions

Therapeutic decision on performing a pelvic exenteration can have a severe and permanent impact on all aspects of patients' QOL. Deterioration of QOL was most significant during the first 3 months after surgery. Elderly patients were the only group of patients with permanent decreased physical and social function. Preoperative evaluation and postoperative follow-up evaluation should include health-related QOL instruments, counseling by a multidisciplinary team to cover all aspects concerning stoma care, sexual function, and long-term concerns after surgery.

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Metastasectomy for Tumor-Infiltrating Lymphocytes: An Emerging Operative Indication in Surgical Oncology

Abstract

Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TILs) is an emerging immunotherapy for metastatic cancer. Surgeons play a central role in ACT treatments by performing resection of tumors from which TILs are isolated. It is important that surgeons have familiarity with this emerging treatment method because it is increasingly performed for an expanding variety of solid tumors at institutions around the world. This report offers a brief introduction to ACT for cancer, highlights historical milestones in its development, and provides patient selection and operative considerations for surgeons called upon to perform metastasectomy for the purpose of isolating TILs.

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Treatment and Outcome of Synchronous Colorectal Carcinomas: A Nationwide Study

Abstract

Background

Synchronous colorectal carcinomas (CRC) occur in 1–8% of patients diagnosed with CRC. This study evaluated treatment patterns and patient outcomes in synchronous CRCs compared with solitary CRC patients.

Methods

All patients diagnosed with primary CRC between 2008 and 2013, who underwent elective surgery, were selected from the Netherlands Cancer Registry. Using multivariable regressions, the effects of synchronous CRC were assessed for both short-term outcomes (prolonged postoperative hospital admission, anastomotic leakage, postoperative 30-day mortality, administration of neoadjuvant or adjuvant treatment), and 5-year relative survival (RS).

Results

Of 41,060 CRC patients, 1969 patients (5%) had synchronous CRC. Patients with synchronous CRC were older (mean age 71 ± 10.6 vs. 69 ± 11.4 years), more often male (61 vs. 54%), and diagnosed with more advanced tumour stage (stage III–IV 54 vs. 49%) compared with solitary CRC (all p < 0.0001). In 50% of the synchronous CRCs, an extended surgery was conducted (n = 934). Synchronous CRCs with at least one stage II–III rectal tumour less likely received neoadjuvant (chemo)radiation [78 vs. 86%; adjusted OR 0.6 (0.48–0.84)], and synchronous CRCs with at least one stage III colon tumour less likely received adjuvant chemotherapy [49 vs. 63%; adjusted OR 0.7 (0.55–0.89)]. Synchronous CRCs were independently associated with decreased survival [RS 77 vs. 71%; adjusted RER 1.1 (1.01–1.23)].

Conclusions

The incidence of synchronous CRCs in the Dutch population is 5%. Synchronous CRCs were associated with decreased survival compared with solitary CRC. The results emphasize the importance of identifying synchronous tumours, preferably before surgery to provide optimal treatment.

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Prognostic Value of Tumor Volume in Glioblastoma Patients: Size Also Matters for Patients with Incomplete Resection

Abstract

Background

Incomplete resection of glioblastoma is discussed controversially in the era of combined radiochemotherapy.

Objective

The aim of this study was to analyze the benefit of subtotal tumor resection for glioblastoma patients as this was recently questioned in the era of radiochemotherapy.

Methods

Overall, 209 patients undergoing surgery for newly diagnosed WHO grade IV gliomas were retrospectively analyzed, and pre- and postoperative tumor volumes were manually segmented (cm³). Survival analyses were performed, including prognostic factors such as age, Karnofsky performance score (KPS), O⁶-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status, and adjuvant treatment regimen.

Results

Pre- and postoperative tumor volume is significantly associated with pre- and postoperative KPS, as well as age (p < 0.001). Postoperative tumor volume remained a significant prognostic factor in a multivariate analysis, independent of other prognostic factors (hazard ratio 1.0365, 95% confidence interval 1.0235–1.0497, p < 0.001).

Conclusions

In the era of molecularly-driven radiochemotherapy, glioblastoma surgery remains a major prognostic factor. Even in situations in which a gross total resection cannot be achieved, maximum safe reduction of tumor burden should be attempted.

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Molecular Genomic Testing for Breast Cancer: Utility for Surgeons

Abstract

Molecular genomic testing provides clinicians with both prognostic and (sometimes) predictive information that can help individualize treatment and decrease the risk of over- or under-treatment. We review the genomic tests that are currently available for clinical use in management of breast cancer, discuss ongoing research related to validating and expanding their utility in different patient populations, and explain why it is important for surgeons to know how to incorporate these tools into their clinical practice in order to individualize patient treatment, reduce unnecessary morbidity, and, accordingly, improve outcomes.

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Major Amputations for Extremity Soft-Tissue Sarcoma

Abstract

Introduction

With modern techniques facilitating limb conservation, amputation for extremity soft-tissue sarcoma (ESTS) is now rare. We sought to determine the indications and outcomes following major amputation for ESTS and whether amputation is prognostic of oncological outcomes in primary disease.

Patients and Methods

Patients undergoing major amputations for ESTS from 2004 to 2014 were identified from electronic patient records.

Results

The amputation rate in primary localized disease was 4.1%. Overall, 69 patients were identified, including 23 (33.3%) amputations for primary localized disease, 36 (52.2%) amputations for recurrent disease, and 10 (14.5%) amputations for metastatic disease. The local recurrence rate for localized disease at 3 years was 10.4%. Three-year overall survival (OS) was 50.3% following curative amputation, with a median survival of 41 months, and median OS following palliative amputation was 6 months. In the context of primary, localized disease, patients undergoing amputation had a greater proportion of high-grade tumors (69.6% vs. 41.1%; p = 0.009) of greater size (median 16.0 vs. 9.0 cm; p = 0.003) when compared with patients undergoing limb-conserving surgery. The rates of systemic relapse and disease-specific survival were poorer following amputation compared with limb-conserving surgery, however mode of surgery (amputation vs. limb conservation) was only prognostic for OS.

Conclusions

Amputation maintains an important role in ESTS and achieves durable local control in those unsuitable for limb-conserving surgery. Survival following amputation in the presence of metastatic disease is poor and should be reserved for patients with significant symptoms.

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Effectiveness of Hepatic Artery Infusion (HAI) Versus Selective Internal Radiation Therapy (Y90) for Pretreated Isolated Unresectable Colorectal Liver Metastases (IU-CRCLM)

Abstract

Background

In the era of modern effective systemic chemotherapy, the comparative effectiveness of hepatic artery infusion (HAI) versus selective internal radiation therapy (yttrium-90 [Y90]) for pretreated patients with isolated unresectable colorectal liver metastasis (IU-CRCLM) remains unknown. This study sought to compare the overall survival (OS) after HAI versus Y90 for IU-CRCLM patients treated with modern chemotherapy and to perform a cost analysis of both regional methods.

Methods

This study retrospectively reviewed patients receiving HAI or Y90 in combination with modern chemotherapy as second-line therapy for IU-CRCLM. Overall survival was calculated from the time of IU-CRCLM diagnosis. Uni- and multivariate models were constructed to identify independent predictors of survival.

Results

The inclusion criteria were met by 97 patients (48 HAI patients and 49 Y90 patients). Both groups were similar in terms of age, gender, body mass index (BMI), synchronous disease, carcinoembryonic antigen (CEA), liver tumor burden, and chemotherapy-related characteristics including use of biologics and lines of chemotherapy (all p > 0.05). The HAI group had a better OS than the Y90 group (31.2 vs. 16.3 months; p < 0.001). A trend toward reduced cost favored the HAI group (median, $29,479 vs. $39,092; p = 0.296). The multivariate analysis showed that receipt of HAI (hazard ratio 0.465) and number of chemotherapy lines (HR 0.797) were associated with improved OS from the date of IU-CRCLM diagnosis.

Conclusions

This is the first study to evaluate the comparative effectiveness of HAI versus Y90 in the era of modern chemotherapy, and the findings suggests that HAI is associated with better survival than Y90 for patients with pretreated IU-CRCLM.

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How Low Can We Go—and Should We? Risk Reduction for Minimal-Volume DCIS

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A Novel T-Stage Classification System for Adrenocortical Carcinoma: Proposal from the US Adrenocortical Carcinoma Study Group

Abstract

Background

The 7th AJCC T-stage system for adrenocortical carcinoma (ACC), based on size and extra-adrenal invasion, does not adequately stratify patients by survival. Lymphovascular invasion (LVI) is a known poor prognostic factor. We propose a novel T-stage system that incorporates LVI to better risk-stratify patients undergoing resection for ACC.

Method

Patients undergoing curative-intent resections for ACC from 1993 to 2014 at 13 institutions comprising the US ACC Group were included. Primary outcome was disease-specific survival (DSS).

Results

Of the 265 patients with ACC, 149 were included for analysis. The current T-stage system failed to differentiate patients with T2 versus T3 disease (p = 0.10). Presence of LVI was associated with worse DSS versus no LVI (36 mo vs. 168 mo; p = 0.001). After accounting for the individual components of the current T-stage system (size, extra-adrenal invasion), LVI remained a poor prognostic factor on multivariable analysis (hazard ratio 2.14, 95% confidence interval 1.05–4.38, p = 0.04). LVI positivity further stratified patients with T2 and T3 disease (T2: 37 mo vs. median not reached; T3: 36 mo vs. 96 mo; p = 0.03) but did not influence survival in patients with T1 or T4 disease. By incorporating LVI, a new T-stage classification system was created: [T1: ≤ 5 cm, (−)local invasion, (+/−)LVI; T2: > 5 cm, (−)local invasion, (−)LVI OR any size, (+)local invasion, (−)LVI; T3: > 5 cm, (−)local invasion, (+)LVI OR any size, (+)local invasion, (+)LVI; T4: any size, (+)adjacent organ invasion, (+/−)LVI]. Each progressive new T-stage group was associated with worse median DSS (T1: 167 mo; T2: 96 mo; T3: 37 mo; T4: 15 mo; p < 0.001).

Conclusions

Compared with the current T-stage system, the proposed T-stage system, which incorporates LVI, better differentiates T2 and T3 disease and accurately stratifies patients by disease-specific survival. If externally validated, this T-stage classification should be considered for future AJCC staging systems.

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The Impact of Primary Tumor Location on Long-Term Survival in Patients Undergoing Hepatic Resection for Metastatic Colon Cancer

Abstract

Background

The impact of primary tumor location on overall survival (OS), recurrence-free survival (RFS), and long-term outcomes has not been well established in patients undergoing potentially curative resection of colorectal liver metastases (CRLM).

Methods

A single-institution database was queried for initial resections for CRLM 1992–2004. Primary tumor location determined by chart review (right = cecum to transverse; left = splenic flexure to sigmoid). Rectal cancer (distal 16 cm), multiple primaries, and unknown location were excluded. Kaplan–Meier and Cox regression methods were used. Cure was defined as actual 10-year survival with either no recurrence or resected recurrence with at least 3 years of disease-free follow-up.

Results

A total of 907 patients were included with a median follow-up of 11 years; 578 patients (64%) had left-sided and 329 (36%) right-sided primaries. Median OS for patients with a left-sided primary was 5.2 years (95% confidence interval [CI] 4.6–6.0) versus 3.6 years (95% CI 3.2–4.2) for right-sided (p = 0.004). On multivariable analysis, the hazard ratio for right-sided tumors was 1.22 (95% CI 1.02–1.45, p = 0.028) after adjusting for common clinicopathologic factors. Median RFS was marginally different stratified by primary location (1.3 vs. 1.7 years; p = 0.065). On multivariable analysis, location of primary was not significantly associated with RFS (p = 0.105). Observed cure rates were 22% for left-sided and 20% for right-sided tumors.

Conclusions

Among patients undergoing resection of CRLM, left-sided primary tumors were associated with improved median OS. However, long-term survival and recurrence-free survival were not significantly different stratified by primary location. Patients with left-sided primary tumors displayed a prolonged clinical course suggestive of more indolent biology.

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Proposal of a New Preoperative Prognostic Model for Solitary Hepatocellular Carcinoma Incorporating 18 F-FDG-PET Imaging with the ALBI Grade

Abstract

Background

Existing prognostic systems were not developed using only objective variables available preoperatively, and therefore do not provide ideal prognostication for patients undergoing hepatectomy for hepatocellular carcinoma (HCC). We aimed to develop a preoperative prognostic model using objective variables involving two parameters: ¹⁸F-fluorodeoxyglucose-positron emission tomography (¹⁸F-FDG-PET) and the albumin-bilirubin (ALBI) grade.

Methods

This study included 207 consecutive patients with solitary HCC who underwent ¹⁸F-FDG-PET prior to hepatectomy. The tumor to non-tumor maximum standardized uptake value ratio (TNR) was used as an ¹⁸F-FDG PET imaging parameter.

Results

The 5-year overall survival (OS) and disease-free survival (DFS) rates were 58.6% and 28.8%, respectively. Multivariate analysis of OS identified TNR ≥ 2 (hazard ratio [HR] 1.743, 95% confidence interval [CI] 1.114–2.648, p = 0.016) and ALBI grade 2 (HR 1.966, 95% CI 1.349–2.884, p < 0.001) as the only significant prognostic factors; tumor diameter and tumor markers were not significant. Patients were divided into low- (TNR < 2 and ALBI grade 1), intermediate- (TNR < 2 and ALBI grade 2, or TNR ≥ 2 and ALBI grade 1), and high-risk (TNR ≥ 2 and ALBI grade 2) groups, which differed significantly in terms of survival (5-year OS: 75.7, 49.6, and 27.3%, respectively, p < 0.001; 5-year DFS: 37.0, 24.9, and 13.6%, respectively, p < 0.001). Compared with other staging systems, our model had the best discriminatory ability (corrected Akaike information criteria 1054.8, p < 0.001) and homogeneity (likelihood ratio Chi square value 27.6, p < 0.001).

Conclusion

A preoperative prognostic model incorporating ¹⁸F-FDG-PET imaging with the ALBI grade may be useful for estimating the prognosis of selected patients with solitary HCC.

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Comparison of Recurrence Between Pancreatic and Duodenal Neuroendocrine Neoplasms After Curative Resection: A Single-Institution Analysis

Abstract

Background

The primary site of a neuroendocrine neoplasms (NEN) around the head of the pancreas is sometimes difficult to assess before resection, and the characteristics of the primary site around this region have not been elucidated for recurrence after curative resection. In this study, the clinicopathologic characteristics of pancreatic NEN (PanNEN) and duodenal NEN (DuNEN) were evaluated, and the risk factors as well as the recurrence types after resection were investigated.

Methods

Consecutively diagnosed NEN patients at the authors' hospital from January 2000 to July 2016 were evaluated in this study. For 117 PanNEN patients and 31 non-ampullary DuNEN patients, R0 resection was achieved. The median follow-up period was 8.1 years.

Results

In this study, 27 PanNEN patients (23.1%) had recurrences, with a median disease-free survival (DFS) of 133 months, whereas 11 DuNEN patients (35.5%) had recurrences, with a median DFS of 156 months. The PanNEN patients tended to have primary recurrence in the liver (85.2%), followed by lymph nodes (11.1%). The independent risk factors for short DFS were lymph node metastasis at resection (p = 0.001) and microvascular invasion (p = 0.048). In contrast, the DuNEN patients were likely to have lymph node metastasis (81.8%). The independent risk factors for short DFS were lymph node metastasis at resection (p = 0.003) and large diameter (p = 0.013).

Conclusions

Most initial recurrences of PanNEN occurred in the liver, whereas those of DuNEN appeared in lymph nodes, suggesting that proper diagnosis of the primary site and appropriate imaging methods for surveillance after resection are necessary.

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Correlation Between Biomarker Candidate Proteins with the Effect of Neoadjuvant Chemoradiation Therapy on Esophageal Squamous Cell Carcinoma

Abstract

Background

While chemoradiation therapy (CRT) is one of the most useful treatments for esophageal squamous cell carcinoma (ESCC), it is important to predict response prior to treatment by using markers because some patients respond well and others do not.

Methods

Fifty-nine patients with ESCC were treated with neoadjuvant CRT at the Kagoshima University Hospital. The expression of seven types of biomarker candidate proteins in biopsy specimens of untreated primary tumors was evaluated to determine whether it correlated with response and prognosis.

Results

The positive expression rates were 47% for p53, 83% for CDC25B, 68% for 14-3-3sigma, 76% for p53R2, 75% for ERCC1, 32% for Gli-1, and 54% for Nrf2. In terms of histological response, tumor grade of the 59 patients was 48.8% for grade 1 as the non-responder, 29.2% for grade 2, and 22.0% for grade 3 as the responder. CRT was significantly effective in p53(−), p53R2(−), ERCC1(−), and Nrf2(−) tumors, while p53(−), p53R2(−), and ERCC1(−) were factors independently correlated with effective histological response. Their combined expression of two or three negative expressions had 100% effective response and was a significant prognostic factor.

Conclusion

Our results suggest that two or three negative expressions of p53, p53R2, and ERCC1 in biopsy specimens of primary tumors were associated with a favorable response to CRT for ESCC. Assessment of tumor suppressor and DNA repair protein expressions in biopsy specimens may be useful for the potential utility of CRT therapy for patients with ESCC prior to treatment.

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Ultrasound-Guided Restaging and Localization of Axillary Lymph Nodes After Neoadjuvant Chemotherapy for Guidance of Axillary Surgery in Breast Cancer Patients: Experience with Activated Charcoal

Abstract

Objective

Methods

Results

Conclusion

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Prospective Assessment of First-Year Quality of Life After Pelvic Exenteration for Gynecologic Malignancy: A French Multicentric Study

Abstract

Background

Methods

Results

Conclusions

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Metastasectomy for Tumor-Infiltrating Lymphocytes: An Emerging Operative Indication in Surgical Oncology

Abstract

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Treatment and Outcome of Synchronous Colorectal Carcinomas: A Nationwide Study

Abstract

Background

Methods

Results

Conclusions

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Morbidity and Outcomes Following Axillary Lymphadenectomy for Melanoma: Weighing the Risk of Surgery in the Era of MSLT-II

Abstract

Background

Limited data exist characterizing complications after axillary lymphadenectomy for melanoma. With high rates of complications reported after dissection for breast cancer and data suggesting that completion lymphadenectomy may have limited therapeutic benefit, this study characterized morbidity to facilitate clinical decision-making.

Methods

Using a broad definition for complications, patients who underwent axillary dissection for melanoma at a single center (from 2003 to 2015) were assessed through retrospective chart review. Patients were stratified by potential risk factors for complications; outcomes were compared.

Results

Two hundred fifty-four axillary dissections in 239 patients were identified. Assessed risk factors for complications included age > 55 years (n = 133, 52%), body mass index (BMI) ≥ 30 kg/m² (n = 90, 40%), diabetes (n = 40, 16%), smoking (n = 81, 32%), extremity primary (n = 71, 28%), therapeutic lymphadenectomy (n = 105, 41%), and adjuvant radiation (n = 33, 13%). Wound complications were observed in 51 patients with 38 (15%) seromas, 3 (1%) dehiscences, and 10 (4%) hematomas. There were 5 (2%) reoperations, all for hematoma. Thirty-day readmission rate was 6% (n = 14). Importantly, lymphedema occurred in only 13 (5%) patients. Wound dehiscence occurred only in smokers (p = 0.03) and was associated with adjuvant radiation (p = 0.04). Twenty-eight (11%) patients developed frozen shoulder, which was related to smoking (p = 0.02). Lymphedema was more likely in patients after therapeutic dissection (p = 0.04). All other risk factors were not associated with increased complications.

Conclusions

This analysis supports historical data that axillary dissection for melanoma is a low-risk procedure, with smoking, therapeutic lymphadenectomy, and adjuvant radiation associated with increased morbidity. Although morbidity of lymphadenectomy is often cited as a reason to alter surgical approach or even forgo intervention, this may be less of a concern for axillary dissection.

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Prognostic Value of Tumor Volume in Glioblastoma Patients: Size Also Matters for Patients with Incomplete Resection

Abstract

Background

Incomplete resection of glioblastoma is discussed controversially in the era of combined radiochemotherapy.

Objective

The aim of this study was to analyze the benefit of subtotal tumor resection for glioblastoma patients as this was recently questioned in the era of radiochemotherapy.