Comparison of tumor-infiltrating lymphocytes of breast cancer in core needle biopsies and resected specimens: a retrospective analysis

Abstract

Purpose

Neoadjuvant chemotherapy (NAC) is being increasingly used to treat locally advanced breast cancer and to conserve the breast. In triple-negative breast cancer and HER2-positive breast cancer, a high density of tumor-infiltrating lymphocytes (TILs) is an important predictor of NAC response. Thus far, it remains unclear whether the TIL scores in core needle biopsies (CNBs) are closely representative of those in the whole tumor section in resected specimens. This study aimed to evaluate the concordance between the TIL scores of CNBs and resected specimens of breast cancer.

Methods

A total of 220 matched pairs of CNBs and resected specimens of breast cancer were included. Stromal TILs were scored on slides stained with hematoxylin and eosin. Clinicopathologic parameters and the agreement of the TIL scores between CNBs and resected specimens were statistically analyzed.

Results

The average TIL score was approximately 4.4% higher for the resected specimens than for the CNBs. When the tumors were divided into two groups according to a 60% TIL score cut-off (low and intermediate TIL vs. high TIL), 8.2% showed discordance between the CNB and resected specimen. The overall intraclass correlation coefficient (ICC) value of the TIL score was 0.895 (95% confidence interval, 0.864–0.920, P < 0.001), and all molecular subtypes showed ICC values over 0.8 (P < 0.001). The ICC values were > 0.9 when ≥ 5 cores were included in the CNBs. Tumors with discordant TILs were characterized by histologic grade III, ER negativity, high proliferative index, and HER2 and triple-negative subtypes. A high proliferative index was an independent risk factor for TIL discordance.

Conclusions

The TIL score in CNB specimens is a reliable value that reflects the TIL status of the entire tumor in resected specimens of breast cancer. More than five CNB cores may accurately predict the TIL score of the entire tumor.

https://ift.tt/2kQiLqB

Long-term outcomes of total body irradiation plus cyclophosphamide versus busulfan plus cyclophosphamide as conditioning regimen for acute lymphoblastic leukemia: a comparative study

Abstract

The role of total body irradiation (TBI) in allogeneic hematopoietic stem cell transplantation (HCT) for adult acute lymphoblastic leukemia (ALL) remains controversial. Therefore, we investigated long-term treatment outcomes of transplanted ALL patients aiming to identify prognostic factors and the impact of conditioning. We enrolled consecutive ALL patients transplanted from 1990 to 2016, following TBI- or busulfan (Bu)-based conditioning regimen. We studied 151 ALL patients transplanted in first complete remission (CR) (60), other CR (33), or relapsed/refractory disease (58) from sibling (87), and HLA-matched (42) or mismatched (17) unrelated and alternative donors (5). High-dose fractionated TBI-based conditioning was administered in 84. No differences were observed in baseline characteristics, except for disease stage at transplant, donor type, and graft source. With a follow-up of 19.0 (0.5–170.5) in TBI and 14.5 (1.2–319.1) months in non-TBI patients, there was no difference in acute (grades II–IV) or chronic GVHD, thrombotic microangiopathy, and bacterial or fungal infections. Only viral infections were significantly increased in the non-TBI group. There was no significant difference in the cumulative incidence (CI) of treatment-related or relapse mortality and disease-free or overall survival (OS). In the multivariate analysis, unfavorable pre-transplant predictors of OS were age (p = 0.024), advanced disease stage (p = 0.007), and female-to-male donor (p = 0.006). Interestingly, TBI patients younger than 40 years had significantly higher OS (55.1%, p = 0.023) and DFS (48.6%, p = 0.020). In conclusion, high-dose TBI is feasible in younger patients providing better survival. The choice between TBI- or Bu-conditioning regimens remains challenging.

https://ift.tt/2Lo4YT8

Extent of regional lymph node surgery and impact on outcomes in patients with early-stage breast cancer and limited axillary disease undergoing mastectomy

Abstract

Purpose

Management of the axilla in patients with early-stage breast cancer (ESBC) has evolved. Recent trials support less extensive axillary surgery in patients undergoing mastectomy. We examine factors affecting regional lymph node (RLN) surgery and outcomes in patients with ESBC undergoing mastectomy.

Methods

Women with clinical T1/2 N0 M0 invasive BC who underwent mastectomy with 1–2 positive nodes were selected from the National Cancer Database (2004–2015). Axillary surgery was defined by number of RLNs examined: 1–5 sentinel LN dissection (SLND), and ≥ 10 axillary LND (ALND). Binary logistic regression and survival analyses were performed to assess the association between axillary surgery and clinical characteristics, and overall survival (OS), respectively.

Results

34,243 patients were included: 13,821 SLND (40%) and 20,422 ALND (60%). SLND significantly increased from 21% (2004) to 45% (2015) (p < .001). Independent factors associated with SLND were treatment year, non-Academic centers, geographic region, tumor histology, and postmastectomy radiotherapy (PMRT). Multivariable survival analysis showed that ALND was associated with better OS (HR 0.78, 95% CI 0.72–0.83, p < .001) relative to SLND; however, there was no difference in patients with LN micrometastases treated without RT (HR 0.87, 95% CI 0.73–1.05, p = .153) or patients receiving PMRT (HR 0.92, 95% CI 0.76–1.13, p = .433).

Conclusions

SLND has significantly increased in patients undergoing mastectomy with limited axillary disease and is influenced by patient, tumor, and treatment factors. Survival outcomes did not differ by axillary treatment for patients with LN micrometastases treated without RT or patients who received PMRT. SLND may be considered in select patients with ESBC and limited axillary disease undergoing mastectomy.

https://ift.tt/2Hk7aJg

Development of MGD007, a gpA33 x CD3 bispecific DART(R) protein for T-cell immunotherapy of metastatic colorectal cancer

We have developed MGD007 (anti-glycoprotein A33 x anti-CD3), a DART® protein designed to redirect T-cells to target gpA33 expressing colon cancer. The gpA33 target was selected based on an antibody-based screen to identify cancer antigens universally expressed in both primary and metastatic CRC specimens, including putative cancer stem cell populations. MGD007 displays the anticipated bispecific binding properties and mediates potent lysis of gpA33-positive cancer cell lines, including models of colorectal cancer stem cells, through recruitment of T-cells. Xenograft studies showed tumor growth inhibition at doses as low as 4 µg/kg. Both CD8 and CD4 T cells mediated lysis of gpA33-expressing tumor cells, with activity accompanied by increases in granzyme and perforin. Notably, suppressive T-cell populations could also be leveraged to mediate lysis of gpA33 expressing tumor cells. Concomitant with CTL activity, both T-cell activation and expansion are observed in a gpA33-dependent manner. No cytokine activation was observed with human PBMC alone, consistent with the absence of gpA33 expression on peripheral blood cell populations. Following prolonged exposure to MGD007 and gpA33 positive tumor cells, T cells express PD 1 and LAG-3 and acquire a memory phenotype but retain ability to support potent cell killing. In cynomolgus monkeys, 4 weekly doses of 100 µg/kg were well tolerated, with prolonged PK consistent with that of an Fc-containing molecule. Taken together MGD007 displays potent activity against colorectal cancer cells consistent with a mechanism of action endowed in its design and support further investigation of MGD007 as a potential novel therapeutic treatment for colorectal cancer.

https://ift.tt/2JdPJf0

The XPO1 inhibitor Selinexor inhibits translation and enhances the radiosensitivity of glioblastoma cells grown in vitro and in vivo

Analysis of the radiation-induced translatome of glioblastoma stem-like cells (GSCs) identified an interacting network in which XPO1 serves as a major hub protein. To determine whether this nuclear export protein provides a target for radiosensitization, we defined the effects of the clinically relevant XPO1 inhibitor Selinexor on the radiosensitivity of glioblastoma cells. As determined by clonogenic survival analysis, Selinexor enhanced the radiosensitivity of GSCs but not normal fibroblast cell lines. Based on H2AX foci and neutral comet analyses, Selinexor inhibited the repair of radiation-induced DNA double strand breaks in GSCs suggesting that the Selinexor-induced radiosensitization is mediated by an inhibition of DNA repair. Consistent with a role for XPO1 in the nuclear to cytoplasm export of rRNA, Selinexor reduced 5S and 18S rRNA nuclear export in GSCs, which was accompanied by a decrease in gene translation efficiency, as determined from polysome profiles, as well as in protein synthesis. In contrast, rRNA nuclear export and protein synthesis were not reduced in normal cells treated with Selinexor. Orthotopic xenografts initiated from a GSC line were then used to define the in vivo response to Selinexor and radiation. Treatment of mice bearing orthotopic xenografts with Selinexor decreased tumor translational efficiency as determined from polysome profiles. Although Selinexor treatment alone had no effect on the survival of mice with brain tumors, it significantly enhanced the radiation-induced prolongation of survival. These results indicate that Selinexor enhances the radiosensitivity of glioblastoma cells and suggest that this effect involves a global inhibition of gene translation.

https://ift.tt/2xHw3yW

Glucuronide-linked antibody-tubulysin conjugates display activity in MDR+ and heterogeneous tumor models

While antibody-drug conjugates (ADCs) find increasing applications in cancer treatment, de novo or treatment-emergent resistance mechanisms may impair clinical benefit. Two resistance mechanisms that emerge under prolonged exposure include upregulation of transporter proteins that confer multidrug resistance (MDR+) and loss of cognate antigen expression. New technologies that circumvent these resistance mechanisms may serve to extend the utility of next generation ADCs. Recently, we developed the quaternary ammonium linker system to expand the scope of conjugatable payloads to include tertiary amines and applied the linker to tubulysins, a highly potent class of tubulin binders that maintain activity in MDR+ cell lines. In this work, tubulysin M, which contains an unstable acetate susceptible to enzymatic hydrolysis, and two stabilized tubulysin analogues, were prepared as quaternary ammonium-linked glucuronide-linkers and assessed as ADC payloads in preclinical models. The conjugates were potent across a panel of cancer cell lines and active in tumor xenografts, including those displaying the MDR+ phenotype. The ADCs also demonstrated potent bystander activity in a co-culture model comprised of a mixture of antigen-positive and -negative cell lines, and in an antigen-heterogeneous tumor model. Thus, the glucuronide-tubulysin drug-linkers represent a promising ADC payload class, combining conjugate potency in the presence of the MDR+ phenotype and robust activity in models of tumor heterogeneity in a structure-dependent manner.

https://ift.tt/2LY9zg9

Synthetic Lethal Strategy Identifies a Potent and Selective TTK and CLK2 Inhibitor for Treatment of Triple-negative Breast Cancer with a Compromised G1/S Checkpoint

Historically, phenotypic-based drug discovery has yielded a high percentage of novel drugs while uncovering new tumor biology. CC-671 was discovered using a phenotypic screen for compounds that preferentially induced apoptosis in triple negative breast cancer cell lines while sparing luminal breast cancer cell lines. Detailed in vitro kinase profiling shows CC-671 potently and selectively inhibits two kinases-TTK and CLK2. Cellular mechanism of action studies demonstrate that CC-671 potently inhibits the phosphorylation of KNL1 and SRp75, direct TTK and CLK2 substrates, respectively. Furthermore, CC-671 causes mitotic acceleration and modification of pre-mRNA splicing leading to apoptosis, consistent with cellular TTK and CLK inhibition. Correlative analysis of genomic and potency data against a large panel of breast cancer cell lines identifies breast cancer cells with a dysfunctional G1/S checkpoint as more sensitive to CC-671, suggesting synthetic lethality between G1/S checkpoint and TTK/CLK2 inhibition. Furthermore, significant in vivo CC-671 efficacy was demonstrated in two cell line-derived and one patient tumor-derived xenograft models of TNBC following weekly dosing. These findings are the first to demonstrate the unique inhibitory combination activity of a dual TTK/CLK2 inhibitor that preferably kills TNBC cells and shows synthetic lethality with a compromised G1/S checkpoint in breast cancer cell lines. Based on these data, CC-671 was moved forward for clinical development as a potent and selective TTK/CLK2 inhibitor in a subset of TNBC patients.

https://ift.tt/2M1qChh

Surgical treatment of pulmonary metastasis in colorectal cancer patients: Current practice and results

Publication date: July 2018
Source:Critical Reviews in Oncology/Hematology, Volume 127
Author(s): Matthieu Zellweger, Etienne Abdelnour-Berchtold, Thorsten Krueger, Hans-Beat Ris, Jean Yannis Perentes, Michel Gonzalez
Colorectal cancer (CRC) is a frequently occurring disease, yet diagnosed at a local stage in only 40% of cases. Lung metastases (LM) appear in 5–15% of patients and, left untreated, carry a very poor prognosis. Some CRC patients may benefit from a potentially curative LM resection, but success and benefit are difficult to predict. We discuss prognostic factors of survival after lung metastasectomy in CRC patients under several scenarios (with/ without prior liver metastases; repetitive pulmonary resections).We reviewed all studies (2005–2015) about pulmonary metastases surgical management with curative intent in CRC patients, with a minimum threshold on the number of patients reported (without prior liver metastases: n ≥ 100; with prior resection of liver metastases: n ≥ 50; repetitive thoracic surgery: n ≥ 30).The picture of the prognostic factors of survival is nuanced: surgical management demonstrates clear successes and steady progress, yet there is no single success criterion; stratification of patients and selection bias impact the conclusions. Surgical management of liver and lung metastases may prolong life or cure CRC patients, provided the lesions are fully resected and patients carefully selected. Repeat lung metastasectomy is a safe approach to treat patients in selected cases.In conclusion, there is no standard for surgical management in CRC patients with pulmonary metastases. Patients with isolated unilateral lung metastasis with normal CEA level and no lymph node involvement benefit the most from surgery. Most series report good results in highly selected patients, but instances of long-term disease-free survival remain exceptional.



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Identification of clonal hematopoiesis mutations in solid tumor patients undergoing unpaired next-generation sequencing assays

Purpose: In this era of precision-based medicine, for optimal patient care, results reported from commercial next-generation sequencing assays should adequately reflect the burden of somatic mutations in the tumor being sequenced. Here, we sought to determine the prevalence of clonal hematopoiesis leading to possible misattribution of tumor mutation calls on unpaired FoundationMedicine® next-generation sequencing assays. Experimental Design: This was a retrospective cohort study of individuals undergoing next-generation sequencing of solid tumors from two large cancer centers. We identified and quantified mutations in genes known to be frequently altered in clonal hematopoiesis (DNMT3A, TET2, ASXL1, TP53, ATM, CHEK2, SF3B1, CBL, JAK2) that were returned to physicians on clinical FoundationMedicine® reports. For a subset of patients, we explored the frequency of true clonal hematopoiesis by comparing mutations on FoundationMedicine® reports with matched blood sequencing. Results: Mutations in genes that are frequently altered in clonal hematopoiesis were identified in 65% (1139/1757) of patients undergoing next-generation sequencing. When excluding TP53, which is often mutated in solid tumors, these events were still seen in 35% (619/1757) of patients. Utilizing paired blood specimens, we were able to confirm that 8% (18/226) of mutations reported in these genes were true clonal hematopoiesis events. The majority of DNMT3A mutations (64%, 7/11) and minority of TP53 mutations (4%, 2/50) were clonal hematopoiesis. Conclusion: Clonal hematopoiesis mutations are commonly reported on unpaired next-generation sequencing testing. It is important to recognize clonal hematopoiesis as a possible cause of misattribution of mutation origin when applying next-generation sequencing findings to a patient's care.

https://ift.tt/2HlIT5f

BRCA1/2 testing: therapeutic implications for breast cancer management

BRCA1/2 testing: therapeutic implications for breast cancer management

<i>BRCA</i>1/2 testing: therapeutic implications for breast cancer management, Published online: 05 June 2018; doi:10.1038/s41416-018-0127-5

BRCA1/2 testing: therapeutic implications for breast cancer management

https://ift.tt/2kPM8cG

RIPK4 promotes bladder urothelial carcinoma cell aggressiveness by upregulating VEGF-A through the NF-κB pathway

RIPK4 promotes bladder urothelial carcinoma cell aggressiveness by upregulating VEGF-A through the NF-κB pathway

RIPK4 promotes bladder urothelial carcinoma cell aggressiveness by upregulating VEGF-A through the NF-κB pathway, Published online: 05 June 2018; doi:10.1038/s41416-018-0116-8

RIPK4 promotes bladder urothelial carcinoma cell aggressiveness by upregulating VEGF-A through the NF-κB pathway

https://ift.tt/2HkIFeP

Safety, pharmacokinetics, and preliminary efficacy of E6201 in patients with advanced solid tumours, including melanoma: results of a phase 1 study

Safety, pharmacokinetics, and preliminary efficacy of E6201 in patients with advanced solid tumours, including melanoma: results of a phase 1 study

Safety, pharmacokinetics, and preliminary efficacy of E6201 in patients with advanced solid tumours, including melanoma: results of a phase 1 study, Published online: 05 June 2018; doi:10.1038/s41416-018-0099-5

Safety, pharmacokinetics, and preliminary efficacy of E6201 in patients with advanced solid tumours, including melanoma: results of a phase 1 study

https://ift.tt/2kPoexW

Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer

Breast cancer is the most common cancer in women in the United States and worldwide. Hormone-receptor–positive, axillary node–negative disease accounts for approximately half of all cases of breast cancer in the United States. Adjuvant chemotherapy reduces the risk of recurrence, with effects that…

https://ift.tt/2LgH7oC

Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer

Breast cancer is the most common cancer in women in the United States and worldwide. Hormone-receptor–positive, axillary node–negative disease accounts for approximately half of all cases of breast cancer in the United States. Adjuvant chemotherapy reduces the risk of recurrence, with effects that…

https://ift.tt/2LgH7oC

MiR-23b-3p induces the proliferation and metastasis of esophageal squamous cell carcinomas cells through the inhibition of EBF3

Abstract

MicroRNAs (miRNAs), some small non-coding RNAs that regulate gene expression at the posttranscriptional level, are always aberrantly expressed in carcinomas. In this study, we found that miR-23b-3p was remarkably up-regulated in human esophageal squamous cell carcinoma cells and tissues. Moreover, miR-23b-3p could induce the proliferation, invasion, and metastasis in vitro. EBF3 was identified as the direct downstream target gene of miR-23b-3p and ectogenic EBF3 could strongly inhibit the proliferation, invasion, and metastasis in vitro. Furthermore, it was found that miR-23b-3p could regulate epithelial-to-mesenchymal transition progress by blocking EBF3. Therefore, it was concluded that miR-23b-3p targeted EBF3 to accelerate the proliferation, invasion, and metastasis in ESCC.

https://ift.tt/2JhqEQz

BRCA1/2 testing: therapeutic implications for breast cancer management

https://ift.tt/2JaMOb2

RIPK4 promotes bladder urothelial carcinoma cell aggressiveness by upregulating VEGF-A through the NF-κB pathway

https://ift.tt/2sGO2Q3

Safety, pharmacokinetics, and preliminary efficacy of E6201 in patients with advanced solid tumours, including melanoma: results of a phase 1 study

https://ift.tt/2kMEU99

Testing criterion-based benchmarking for the appropriate use of radiotherapy

Planning for radiotherapy (RT) services requires information on the proportion of patients who should be given radiotherapy. Criterion-Based Benchmark (CBB) has been proposed in Canada to estimate the proportion of cancer patients who should be treated with radiotherapy.The aim of this study was to assess CBB in a health system outside of Canada.

https://ift.tt/2xHkUhx

Bowel morbidity following radiochemotherapy and image-guided adaptive brachytherapy for cervical cancer: Physician- and patient reported outcome from the EMBRACE study

This study describes late bowel morbidity prospectively assessed in the multi-institutional EMBRACE study on MRI-guided adaptive brachytherapy in locally advanced cervical cancer (LACC).

https://ift.tt/2LX8uVP

Internal biliary drainage for isolated posterior segmental biliary obstruction: a case report

Biliary system anatomical abnormalities can be preoperatively detected on magnetic resonance imaging; therefore, some presume that the number of bile duct injuries should decline. However, once a bile duct inj...

https://ift.tt/2kMgvR6

Response Prediction of Altered Thyroglobulin Levels After Radioactive Iodine Therapy Aided by Recombinant Human Thyrotropin in Patients with Differentiated Thyroid Cancer

Abstract

Purpose

Thyroglobulin (Tg) may be released from damaged residual thyroid tissues after radioactive iodine (RAI) therapy in patients with differentiated thyroid carcinoma (DTC). We investigated whether altered levels of serum Tg after recombinant human thyrotropin (rhTSH)-aided RAI therapy could be a prognostic marker in patients with DTC.

Methods

We evaluated 68 patients who underwent RAI therapy after total thyroidectomy. Serum Tg levels were measured just before RAI administration (D0Tg) and 7 days after RAI therapy (D7Tg). Patients with a D0Tg level greater than 2.0 ng/mL were excluded to more precisely evaluate the injury effect of RAI in small remnant tissues. The ratioTg was defined as the D7Tg level divided by that on D0Tg. The therapeutic responses were classified as acceptable or non-acceptable. Finally, we investigated which clinicopathologic parameters were associated with therapeutic response.

Results

At the follow-up examination, an acceptable response was observed in 50 patients (73.5%). Univariate analysis revealed significant differences in N stage (P = 0.003) and ratioTg (acceptable vs. non-acceptable responses, 21.9 ± 33.6 vs. 3.8 ± 6.5; P = 0.006). In multivariate analysis, only ratioTg significantly predicted an acceptable response (odds ratio 1.104; 95% confidence interval 1.005–1.213; P = 0.040). A ratioTg above 3.5 predicted an acceptable response with a sensitivity of 66.0%, specificity of 83.3%, and accuracy of 70.6% (area under the curve = 0.718; P = 0.006).

Conclusions

Altered levels of serum Tg after RAI therapy, calculated as the ratioTg (D7Tg/D0Tg), significantly predicted an acceptable response in patients with DTC.

https://ift.tt/2Jj3jOs

Bispecific light T-cell engagers for gene-based immunotherapy of epidermal growth factor receptor (EGFR)-positive malignancies

Abstract

The recruitment of T-cells by bispecific antibodies secreted from adoptively transferred, gene-modified autologous cells has shown satisfactory results in preclinical cancer models. Even so, the approach's translation into the clinic will require incremental improvements to its efficacy and reduction of its toxicity. Here, we characterized a tandem T-cell recruiting bispecific antibody intended to benefit gene-based immunotherapy approaches, which we call the light T-cell engager (LiTE), consisting of an EGFR-specific single-domain V_HH antibody fused to a CD3-specific scFv. We generated two LiTEs with the anti-EGFR V_HH and the anti-CD3 scFv arranged in both possible orders. Both constructs were well expressed in mammalian cells as highly homogenous monomers in solution with molecular weights of 43 and 41 kDa, respectively. In situ secreted LiTEs bound the cognate antigens of both parental antibodies and triggered the specific cytolysis of EGFR-expressing cancer cells without inducing T-cell activation and cytotoxicity spontaneously or against EGFR-negative cells. Light T-cell engagers are, therefore, suitable for future applications in gene-based immunotherapy approaches.

https://ift.tt/2LUUUCm

Cancers, Vol. 10, Pages 182: Cancer Metastases to Bone: Concepts, Mechanisms, and Interactions with Bone Osteoblasts

Cancers, Vol. 10, Pages 182: Cancer Metastases to Bone: Concepts, Mechanisms, and Interactions with Bone Osteoblasts

Cancers doi: 10.3390/cancers10060182

Authors: Alison B. Shupp Alexus D. Kolb Dimpi Mukhopadhyay Karen M. Bussard

The skeleton is a unique structure capable of providing support for the body. Bone resorption and deposition are controlled in a tightly regulated balance between osteoblasts and osteoclasts with no net bone gain or loss. However, under conditions of disease, the balance between bone resorption and deposition is upset. Osteoblasts play an important role in bone homeostasis by depositing new bone osteoid into resorption pits. It is becoming increasingly evident that osteoblasts additionally play key roles in cancer cell dissemination to bone and subsequent metastasis. Our laboratory has evidence that when osteoblasts come into contact with disseminated breast cancer cells, the osteoblasts produce factors that initially reduce breast cancer cell proliferation, yet promote cancer cell survival in bone. Other laboratories have demonstrated that osteoblasts both directly and indirectly contribute to dormant cancer cell reactivation in bone. Moreover, we have demonstrated that osteoblasts undergo an inflammatory stress response in late stages of breast cancer, and produce inflammatory cytokines that are maintenance and survival factors for breast cancer cells and osteoclasts. Advances in understanding interactions between osteoblasts, osteoclasts, and bone metastatic cancer cells will aid in controlling and ultimately preventing cancer cell metastasis to bone.

https://ift.tt/2HgR4A0

Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK): An Abridged Explanation and Elaboration

Abstract

The Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) were developed to address widespread deficiencies in the reporting of such studies. The REMARK checklist consists of 20 items to report for published tumor marker prognostic studies. A detailed paper was published explaining the rationale behind checklist items, providing positive examples and giving empirical evidence of the quality of reporting. REMARK provides a comprehensive overview to educate on good reporting and provide a valuable reference for the many issues to consider when designing, conducting, and analyzing tumor marker studies and prognostic studies in medicine in general. Despite support for REMARK from major cancer journals, prognostic factor research studies remain poorly reported. To encourage dissemination and uptake of REMARK, we have produced this considerably abridged version of the detailed explanatory manuscript, which may also serve as a brief guide to key issues for investigators planning tumor marker prognostic studies. To summarize the current situation, more recent papers investigating the quality of reporting and related reporting guidelines are cited, but otherwise the literature is not updated. Another important impetus for this paper is that it serves as a basis for literal translations into other languages. Translations will help to bring key information to a larger audience world-wide. Many more details can be found in the original paper.

https://ift.tt/2LW0SDb

HIPEC: HOPE or HYPE in the fight against advanced ovarian cancer?

https://ift.tt/2sBZsVr

Reply to the Letter to the Editor "Reporting of HRQOL results from the PALOMA-2 trial: unfounded conclusions due to highly biased analyses" by T. Kaiser, et al.

https://ift.tt/2kLEyzB

Impact of age on the efficacy of oxaliplatin in the preoperative chemoradiotherapy and adjuvant chemotherapy of rectal cancer: A post hoc analysis of the CAO/ARO/AIO-04 phase 3 trial

Abstract

Background

The German rectal cancer trial CAO/ARO/AIO-04 has shown a significant benefit in 3-year disease-free survival (DFS) of adding oxaliplatin to a standard preoperative 5-fluorouracil-based chemoradiotherapy (CRT) and adjuvant chemotherapy in patients with locally advanced rectal cancer. The use of oxaliplatin as adjuvant treatment in elderly patients with colon cancer is controversial . We therefore investigated the impact of age on clinical outcome in the CAO/ARO/AIO-04 phase 3 trial.

Patients and Methods

We performed a post hoc analysis of the CAO/ARO/AIO-04 phase 3 trial evaluating primary and secondary endpoints according to age. Patient and tumor characteristics, adverse events grades of 3-4, dose intensities as well as survival and recurrence data were analyzed in three specified age groups (<60, 60-70, and ≥70 years). The influence of age as a continuous variable on DFS was modeled using a subpopulation treatment effect pattern plot (STEPP) analysis.

Results

A total of 1,232 patients were evaluable. With the exception of ECOG status (p < 0.001), no differences in patient and tumor characteristics were noticed between age groups. Likewise, toxicity pattern, dose intensities of CRT and surgical results were similar in all age groups. After a median follow-up of 50 months, in patients aged <60 years a significant benefit of adding oxaliplatin to 5-FU-based CRT and adjuvant chemotherapy was observed for local (p = 0.013) and systemic recurrences (p = 0.023), DFS (p = 0.011) and even overall survival (OS; p = 0.044. The STEPP analysis revealed improved hazard ratios for DFS in patients aged 40-70 years compared with elderly patients treated with oxaliplatin.

Conclusion

The addition of oxaliplatin significantly improved DFS and OS in younger patients aged <60 years with advanced rectal cancer. Patients aged ≥70 years had no benefit.

Clinical Trials Number

NCT00349076

https://ift.tt/2sCzZv2

Anti-EGFR therapy in oesophagogastric cancer: precise but not enough

https://ift.tt/2swyK1b

Reporting of HRQOL results from the PALOMA-2 trial: unfounded conclusions due to highly biased analyses

https://ift.tt/2HkYdz9

Mediastinal lymph node clearance and anti-PD-1 induction in resected NSCLC

https://ift.tt/2kLEsYL

Bone and Calcified Soft Tissue Metastases of Medullary Thyroid Carcinoma Better Characterized on 18 F-Fluoride PET/CT than on 68 Ga-Dotatate PET/CT

Abstract

Herein, we report a case of a 19-year-old man with multiple endocrine neoplasia type 2B (MEN2B) and medullary thyroid carcinoma (MTC) diagnosed when he was 12 years of age. The patient had previously undergone total thyroidectomy, cervical radiotherapy, and chemotherapy. He progressed with known bone, pulmonary, and lymph node metastases and was scanned with ¹⁸F-fluoride (¹⁸F-NaF) and ⁶⁸Ga-dotatate whole-body positron emission tomography/computed tomography (PET/CT) for metastatic disease monitoring. We found that the MTC bone metastases and soft tissue calcified metastases were better characterized on ¹⁸F-NaF PET/CT than on ⁶⁸Ga-dotatate PET/CT. This case illustrates that the ¹⁸F-NaF PET/CT could be helpful not only to the detection of bone metastases but also to the detection of calcified soft tissue metastases in patients with MTC.

https://ift.tt/2J91Huj

MR-only brain radiotherapy: Dosimetric evaluation of synthetic CTs generated by a dilated convolutional neural network

Publication date: Available online 4 June 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Anna M. Dinkla, Jelmer M. Wolterink, Matteo Maspero, Mark H.F. Savenije, Joost J.C. Verhoeff, Enrica Seravalli, Ivana Išgum, Peter R. Seevinck, Cornelis A.T. van den Berg
PurposeThis work aims to facilitate a fast MR-only workflow for radiotherapy of intracranial tumors. Here, we evaluate whether synthetic computed tomography (sCT) images generated with a dilated convolutional neural network (CNN) enable accurate magnetic resonance (MR)-based dose calculations in the brain.MethodsWe conducted a retrospective study on 52 patients with brain tumors who underwent both CT and MR imaging for radiotherapy treatment planning. To generate the sCTs, a T1-weighted gradient echo MR sequence was selected from the clinical protocol for multiple types of brain tumors. sCTs were created for all 52 patients with a dilated CNN using two-fold cross validation, in each fold 26 patients were used for training and the remaining 26 for evaluation. For each patient, the clinical CT-based treatment plan was recalculated on sCT. We calculated dose differences and gamma pass rates between CT- and sCT-based plans inside body and planning target volume (PTV). Geometric fidelity of the sCT and differences in beam depth and equivalent path length were assessed between both treatment plans.ResultssCT generation took 1 minute per patient. The mean absolute error (MAE) over the patient population of the sCT within the intersection of body contours was 67±11 Hounsfield Units (HU) (±1SD, range: 51-117 HU), and the mean error (ME) was 13±9 HU (±1SD, range:-2 to 38 HU). Dosimetric analysis showed mean deviations of 0.00±0.02% (±1SD, range:-0.05-0.03) for dose within the body contours and -0.13±0.39% (±1SD, range:-1.43-0.80) inside the PTV. Mean γ1mm/1% was 98.8±2.2% for doses larger than 50% of the prescribed dose.ConclusionsThe presented dilated CNN generated sCTs from conventional MR images without adding scan time to the acquisition. Dosimetric evaluation suggests that dose calculations performed on the sCTs are accurate, and can therefore be used for MR-only intracranial radiotherapy treatment planning.

Teaser

Synthetic CTs of 52 patients treated with intracranial radiotherapy were generated from a conventional MR sequence using a convolutional neural network. Recalculation of clinical treatment plans on the synthetic CTs showed that dose calculation was accurate. A wide range of tumor locations was analyzed, validating the synthesized CTs for implementation of MR-only treatment planning for the brain.


https://ift.tt/2LkyWaR

Long Term Late Toxicity, Quality Of Life and Emotional Distress In Nasopharyngeal Carcinoma Patients Treated With Intensity-Modulated Radiotherapy

Publication date: Available online 4 June 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Lachlan J. McDowell, Kathy Rock, Wei Xu, Biu Chan, John Waldron, Lin Lu, Shereen Ezzat, David Pothier, Lori J. Bernstein, Nathaniel So, Shao Hui Huang, Meredith Giuliani, Andrew Hope, Brian O'Sullivan, Scott V. Bratman, John Cho, John Kim, Raymond Jang, Andrew Bayley, Jolie Ringash
PurposeTo report long-term (> 4 year) toxicity and quality of life (QOL) in nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT) in a non-endemic center.Materials/Methods.A cross-sectional cohort study enrolled NPC patients who were disease-free and ≥4 years post-IMRT ± chemotherapy. Physician-reported adverse events (CTCAE v4.03) and patient-reported QOL (FACT-H&N, FACIT-F), utilities (EuroQOL-5D), head and neck symptoms (MDASI-HN) and emotional distress (HADS), were collected. Consenting patients also underwent endocrine screening and audiometry.ResultsAmong 107 patients enrolled, median age at enrollment and time since treatment were 57 (32-81) and 7.5 years (4.2-11.1) respectively. Most patients (99%) received 70Gy/35#; the majority (93%) received concurrent chemotherapy. Mean scores for the FACT-H&N, FACIT-F, and EQ-5D were 105.0 (46-148), 116.6 (44-160), and 0.85 (0.29-1.00) respectively. Dry mouth, mucus, swallowing/chewing, memory and teeth/gum problems scored highest on the MDASI-HN; mean symptom severity and symptom interference scores were 2.3 and 2.4, respectively. Grade 3 or higher physician-reported adverse events were noted in 50 patients (47%); most frequently hearing (46, 43%). Audiometry revealed significant bilateral hearing loss (≥Grade 3) in 68 patients (72%). Depression (25%), anxiety (37%), and fatigue (28%) were common and strongly correlated with QOL. The majority (69%) of patients developed hypothyroidism; one patient (1%) developed pituitary dysfunction requiring hormone replacement. V50>90 and V45>99 to the thyroid correlated with significantly higher rates of hypothyroidism.ConclusionsDespite the implementation of IMRT, NPC survivors still experience many physical symptoms which impact long-term QOL many years after treatment. Depression, anxiety and fatigue remain common in long-term survivors and are highly correlated with QOL.



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Association of severe and therapy-refractory systemic lupus erythematosus and neuromyelitis optica: a management challenge

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disorder. Neuromyelitis optica (NMO) is an infrequent neuroinflammatory disorder, whose association with SLE remains rare. The authors report the case of an 18-year-old woman, with SLE refractory to multiple immunosuppressive therapies and novel biological agents. Under immunosuppressive therapy, the patient presented with transverse myelitis with contiguous spinal cord lesions and urinary incontinence, having been diagnosed with seropositive NMO, which was also proven to be refractory to common treatments. Partial recovery of the neurological deficits occurred with plasmapheresis, although not averting the brain involvement by NMO that ensued. The patient was listed nationally for allogeneic bone marrow transplant, but, unfortunately, no match was found and the patient died of severe cerebral NMO flare with coma due to brain swelling and consequent respiratory failure. Although the association of SLE and NMO is very rare, early diagnosis is crucial to facilitate initiation of immunosuppressive therapy.

https://ift.tt/2JhICSV

Prospective analysis of psychological differences between adult and elderly cancer patients during postoperative adjuvant chemotherapy

Abstract

Purpose

Despite the burgeoning geriatric population with cancer and the importance of understanding how age may be related to mental adjustment and quality of life so far, differences in coping strategies and psychological harm between the elderly and adults are hardly being taken into account to modify the approach to this population. The aim of this prospective study is to describe the differences in psychological characteristics between older and adult cancer patients and examine dissimilarities in their psychological evolution during adjuvant chemotherapy.

Methods

Adults (18–69 years old) and older patients (≥ 70) with newly diagnosed non-metastatic resected cancer admitted to receive adjuvant chemotherapy were recruited. Patients completed the following questionnaires: mini-mental adjustment to cancer, brief symptom inventory, shared decision-making questionnaire–patient's version, multidimensional scale of perceived social support, EORTC quality-of-life instrument, life orientation test-revised, and satisfaction with life scale.

Results

500 cancer patients (394 adults and 106 older) were evaluated. The impact of the diagnosis was less negative among older patients, with no differences in coping strategies, quality of life, or search for support. Regarding psychological changes from the beginning to the end of the adjuvant treatment, both age groups reported more somatic symptoms, increased psychological difficulty, reduced coping strategies, and a significant decrease in quality of life at the end of postoperative chemotherapy.

Conclusion

Although there were clear psychological differences between adults and senior cancer patients, their evolution during adjuvant chemotherapy was similar, with deterioration in quality of life and coping. This negative psychological impact of adjuvant chemotherapy should be taken into account when considering interventions.

https://ift.tt/2J9Ezw0

New physical approaches to treat cancer stem cells: a review

Abstract

Cancer stem cells (CSCs) have been identified as the main center of tumor therapeutic resistance. They are highly resistant against current cancer therapy approaches particularly radiation therapy (RT). Recently, a wide spectrum of physical methods has been proposed to treat CSCs, including high energetic particles, hyperthermia (HT), nanoparticles (NPs) and combination of these approaches. In this review article, the importance and benefits of the physical CSCs therapy methods such as nanomaterial-based heat treatments and particle therapy will be highlighted.

https://ift.tt/2sDOSND

Choice of antiepileptic drugs affects the outcome in cancer patients with seizures

Abstract

Background

Seizures in cancer patients may occur as a result of CNS primary or metastatic tumor, brain surgery, vascular disease, pharmacologic treatment (including chemotherapy), radiation therapy, or metabolic disorders. The aims of the study were to a) determine whether seizures in cancer patients have prognostic implications and b) study patient outcome based on the antiepileptic drug used.

Method

This is a prospective comparative study that included adult cancer patients with and without seizures from May 2010 to November 2016 seen by the neuro-oncology unit at a cancer referral center. Variables included age, gender, oncologic characteristics, seizure features, treatment, and outcome. Parametric and non-parametric tests were used to compare groups, and Kaplan–Meier curves with the log-rank test were used to analyze survival. Cox multivariate regression tests were used to describe survival and compare groups.

Results

A total of 823 patients were included; 419 (51%) patients had at least one seizure and were compared with 404 (49%) who did not experience seizures. Of the seizure group, 53% had brain metastases, 36% did not have a brain tumor, and 11% had a primary brain tumor. No survival differences were noted among patients with brain metastases or primary tumor with or without seizures. In the seizure group, 249 (59%) required only one antiepileptic drug, whereas 134 (32%) required 2 or more. A better overall survival was identified for patients prescribed carbamazepine (p = 0.02), lamotrigine (p = 0.015), levetiracetam (p = 0.03), and valproic acid (p = 0.009).

Conclusions

Patients with primary or metastatic brain tumors have the same overall survival with or without seizures. However, patients with seizures not treated with antiepileptics exhibit worse overall survival.

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Cancers, Vol. 10, Pages 180: KIAA0100 Modulates Cancer Cell Aggression Behavior of MDA-MB-231 through Microtubule and Heat Shock Proteins

Cancers, Vol. 10, Pages 180: KIAA0100 Modulates Cancer Cell Aggression Behavior of MDA-MB-231 through Microtubule and Heat Shock Proteins

Cancers doi: 10.3390/cancers10060180

Authors: Zhenyu Zhong Vaishali Pannu Matthew Rosenow Adam Stark David Spetzler

The KIAA0100 gene was identified in the human immature myeloid cell line cDNA library. Recent studies have shown that its expression is elevated in breast cancer and associated with more aggressive cancer types as well as poor outcomes. However, its cellular and molecular function is yet to be understood. Here we show that silencing KIAA0100 by siRNA in the breast cancer cell line MDA-MB-231 significantly reduced the cancer cells&rsquo; aggressive behavior, including cell aggregation, reattachment, cell metastasis and invasion. Most importantly, silencing the expression of KIAA0100 particularly sensitized the quiescent cancer cells in suspension culture to anoikis. Immunoprecipitation, mass spectrometry and immunofluorescence analysis revealed that KIAA0100 may play multiple roles in the cancer cells, including stabilizing microtubule structure as a microtubule binding protein, and contributing to MDA-MB-231 cells Anoikis resistance by the interaction with stress protein HSPA1A. Our study also implies that the interaction between KIAA0100 and HSPA1A may be targeted for new drug development to specifically induce anoikis cell death in the cancer cell.

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Cancers, Vol. 10, Pages 181: The Glucose-Regulated MiR-483-3p Influences Key Signaling Pathways in Cancer

Cancers, Vol. 10, Pages 181: The Glucose-Regulated MiR-483-3p Influences Key Signaling Pathways in Cancer

Cancers doi: 10.3390/cancers10060181

Authors: Felice Pepe Rosa Visone Angelo Veronese

The hsa-mir-483 gene, located within the IGF2 locus, transcribes for two mature microRNAs, miR-483-5p and miR-483-3p. This gene, whose regulation is mediated by the the CTNNB1/USF1 complex, shows an independent expression from its host gene IGF2. The miR-483-3p affects the Wnt/&beta;-catenin, the TGF-&beta;, and the TP53 signaling pathways by targeting several genes as CTNNB1, SMAD4, IGF1, and BBC3. Accordingly, miR-483-3p is associated with various tissues specific physiological properties as insulin and melanin production, as well as with cellular physiological functions such as wounding, differentiation, proliferation, and survival. Deregulation of miR-483-3p is observed in different types of cancer, and its overexpression can inhibit the pro-apoptotic pathway induced by the TP53 target effectors. As a result, the oncogenic characteristics of miR-483-3p are linked to the effect of some of the most relevant cancer-related genes, TP53 and CTNNB1, as well as to one of the most important cancer hallmark: the aberrant glucose metabolism of tumor cells. In this review, we summarize the recent findings regarding the miR-483-3p, to elucidate its functional role in physiological and pathological contexts, focusing overall on its involvement in cancer and in the TP53 pathway.

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Effects of the combination of As2O3 and AZT on proliferation inhibition and apoptosis induction of hepatoma HepG2 cells following silencing of Egr-1

https://ift.tt/2J7pIlA

Obesity-associated miR-27a upregulation promotes hepatocellular carcinoma metastasis through suppressing SFRP1

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Delayed Diagnosis of Acute Rheumatic Fever in a Patient with Multiple Emergency Department Visits

While the incidence of acute rheumatic fever (ARF) in the United States has declined over the past years, the disease remains one of the causes of severe cardiovascular morbidity in children. The index of suspicion for ARF in health care providers may be low due to decreasing incidence of the disease and clinical presentation that can mimic other conditions. We present the case of a 5-year-old boy with a history of intermittent fevers, fatigue, migratory joint pain, and weight loss following group A Streptococcus pharyngitis. The patient presented to the emergency department twice with the complaints described above. On his 3rd presentation, the workup for his symptoms revealed the diagnosis of acute rheumatic fever with severe mitral and aortic valve regurgitation. The patient was treated with penicillin G benzathine and was started on glucocorticoids for severe carditis. The patient was discharged with recommendations to continue secondary prophylaxis with penicillin G benzathine every 4 weeks for the next 10 years. This case illustrates importance of primary prevention of acute rheumatic fever with adequate antibiotic treatment of group A Streptococcus pharyngitis. Parents should also receive information and education that a child with a previous attack of ARF has higher risk for a recurrent attack of rheumatic fever. This can lead to development of severe rheumatic heart disease. Prevention of recurrent ARF requires continuous antimicrobial prophylaxis. Follow-up with a cardiologist every 1-2 years is essential to assess the heart for valve damage.

https://ift.tt/2supxq6

Atypical mandibular metastasis as the first presentation of a colorectal cancer

We describe a case of a 70-year-old man presenting with a mandibular metastasis as the first sign of a mucinous adenocarcinoma of the rectum. After 6 months of a protracted toothache, the patient presented with a palpable mandibular mass and trismus, precluding adequate clinical evaluation. A CT scan was performed, and imaging findings suggested an aggressive primary jawbone tumour, most likely an osteosarcoma. However, biopsy and further patient's management proved to be a metastasis. Metastasis to the oral cavity account for only 1%–3% of all malignant oral tumours, and the mandible is the most frequent site. Clinical presentation can be quite variable, and most often a primary malignancy is already known. Jawbone metastases are a sign of disseminated malignant neoplasms, with poor prognosis and usually an indication for palliative therapy.

https://ift.tt/2J8oYwr

Micro-fragmented adipose tissue for treatment of knee osteoarthritis with Bakers cyst: a case study

Adipose-derived therapies have increased in popularity for treatment of painful orthopaedic conditions, such as osteoarthritis. We report the passage of fat into a Baker's cyst after injection of micro-fragmented adipose tissue in a patient with bilateral knee arthritis. Following fat grafting, the patient required drainage of fatty fluid from within the Baker's cyst on multiple occasions. Approximately 3 months postprocedure, she began to notice an improvement in her knee pain with no further recurrence of pain or swelling from her Baker's cyst.

https://ift.tt/2sFg5iX

Testicular plasmacytoma misdiagnosed as orchitis

Testicular plasmacytomas are rare, accounting for only 1.3% of all extramedullary plasmacytomas. The infrequency in which it is encountered, coupled with its non-specific clinical and sonographic presentation, makes its diagnosis a challenge. We present a case of a 70-year-old man with multiple myeloma, which was systemically responding to chemotherapy, who developed testicular swelling, erythema and pain. Ultrasound findings were concerning for infection, although urine and serum testing were unremarkable. The patient did not improve after several rounds of antibiotics prompting further evaluation. The patient underwent radical orchiectomy which revealed testicular plasmacytoma. Fluorescent in situ hybridisation (FISH) of the testicular tissue noted mutations which had not been present in the FISH analysis of bone marrow. Positron emission tomography scan later revealed new retroperitoneal plasmacytomas involving the new clone and his chemotherapy regimen needed to be adjusted for treatment.

https://ift.tt/2J551GS

Management of cervical root fracture by reattachment using fibre post

Description

Tooth fractures are commonly reported emergencies in dental practise. They can vary in severity from a simple enamel fracture to complete avulsion of tooth. Among these injuries, crown-root fractures are considered to be the most common cause of tooth loss.1 They are clinically challenging cases to treat as management of such cases requires a multidisciplinary approach for complete rehabilitation. Reattachment of the tooth fragment is the most conservative and biological treatment available in case of crown-root fractures if the fractured tooth fragments are available and reported early in a clean and hydrated state.2 Reattachment can be done with the help of fibre-reinforced posts which provides increased retention of fractured crown segment and is less subjected to root fracture due to adhesive and elastic properties.3 In cases of fractures extending subgingivally, an envelope flap helps to achieve the desired isolation and visibility....

https://ift.tt/2sBzQbl

Rare paratesticular aggressive angiomyxoma with negative oestrogen and progesterone receptors in a male patient

Aggressive angiomyxoma (AAM) is a rare mesenchymal myxoid tumour localised to the pelvis and/or perineum in adult females in reproductive age group. AAM is very rare in males, with <50 cases described in literature, and involves scrotum, spermatic cord and perineum. It is slow growing, with a marked tendency for local recurrence after excision, but without metastatic potential. We present a rare case of a paratesticular AAM in a man aged 53 years. Tumour cells were immunoreactive for desmin, smooth muscle actin (SMA), vimentin, CD34 and were negative for S100. Unlike AAMs in females which express oestrogen receptor (ER) and/or progesterone receptor (PR) in >90% cases, the tumour cells in our case were negative for ER and PR, suggesting that the hypothesis that these markers play a role in tumour development and pathogenesis, does not apply in males. Androgen receptor positivity was noted in 2%–5% tumour cells.

https://ift.tt/2kLSpWv

Ciprofloxacin-induced generalised non-bullous fixed drug eruption

Ciprofloxacin, a very common antibiotic used in our day-to-day practice can cause adverse cutaneous reactions in 1–2% of patients. Photosensitivity, urticaria and maculopapular rash are the usual skin reactions. Fixed drug eruption (FDE) is an uncommon side effect of ciprofloxacin. Ciprofloxacin-induced generalised bullous FDEs have been very rarely reported in the literature. We report one such case of a young man who developed generalised non-bullous FDEs after treatment with ciprofloxacin.

https://ift.tt/2sBzO3d

Unusual presentation of primary cutaneous melanoma of the forearm with epitrochlear and axillary lymphadenopathy

In patients with primary cutaneous melanomas of the distal upper limb, metastatic involvement of the epitrochlear lymph nodes is uncommon. It belongs to a particular category of nodal metastasis termed as interval or in-transit lymphadenopathies often encountered by tumour cells as they spread from the primary sites. We describe the case of a 41-year-old woman who presented with a right forearm melanoma that was metastatic to both the epitrochlear and axillary lymph nodes. She underwent wide excision of the primary lesion as well as epitrochlear and axillary nodal clearances in the same sitting. Although uncommon, It is prudent to search for the presence of sentinel lymph nodes in the epitrochlear region although uncommon, and where positive, a completion axillary clearance should be undertaken at the same time as the epitrochlear clearance. Failure to detect the presence of interval lymph nodes along the melanoma spread pathways may be a cause of tumour recurrence.

https://ift.tt/2kKmdmz

Primary cardiac angiosarcoma: a rare cause of diffuse alveolar haemorrhage

Primary cardiac angiosarcoma is a rare disease with a dismal prognosis. We report a case of a 50-year-old man who presented with haemoptysis, cough and worsening dyspnoea. An intracardiac mass was visualised on echocardiogram. He was treated for diffuse alveolar haemorrhage and acute respiratory distress syndrome but died from refractory hypoxaemic respiratory failure leading to cardiac arrest. The diagnosis of primary cardiac angiosarcoma with haemorrhagic pulmonary metastases leading to diffuse alveolar damage was confirmed on autopsy.

https://ift.tt/2sFfU7h

Management of acute lower extremity deep venous thrombosis in a patient with duplicated inferior vena cava and contraindication to anticoagulation: case and review of the literature

Duplication of the inferior vena cava (DIVC) is an uncommon embryological anatomic phenomenon.

We report a 63-year-old woman with extensive right leg deep vein thrombosis who required an IVC filter due to contraindications for anticoagulation, but was found to have DIVC which required the placement of two IVC filters with good result. This report will review and summarise past reports of DIVC management to provide a guide for future clinicians, and review the embryological development, diagnosis and IVC filter placement options as they are based on the type of anatomic malformation encountered.

https://ift.tt/2kKzbkb

Unusual cause of pneumomediastinum

Description 

A 25-year-old man presented to the emergency department reporting a 6-hour history of progressive neck swelling associated with a single episode of chest pain. He had no significant medical history. He initially denied any illicit drug use.

On examination, the neck was visibly distended with palpable crepitus that extended to the upper torso. Cardiorespiratory examination was otherwise unremarkable. He was systemically well and routine observations were normal. The ECG showed widespread concave ST elevation suggestive of pericarditis. The chest radiograph demonstrated pneumomediastinum. A CT scan of the neck and thorax revealed widespread surgical emphysema along the thoracic wall, extending through the mediastinum, upwards into the neck involving both superficial and deep compartments (figure 1) up to the skull base (figure 2). No pneumothorax was seen. The white blood cell count was mildly raised at 17.7x10⁹/L, C reactive protein was 24 mg/L and troponin was...

https://ift.tt/2Hifzg0

Cause of irreducible dislocation of a re-revision THR

Instability or recurrent dislocations are a common reason for revision of total hip replacements (THRs). Dual-mobility constructs can help improve stability by increasing the femoral head jump distance. These constructs are used to decrease the risk of re-revision in the setting of recurrent dislocation. This case describes an unusual case of irreducible dislocation of a re-revision THR due to intraprosthetic dislocation. The patient required open reduction and revision of this construct to a tripolar implant. This is important to appreciate from an emergency medicine point of view as repeated attempts at reduction will be fruitless and may result in a femur fracture. This particular type of dislocation is very rare. Perioperative considerations should include early referral to the orthopaedic team for reduction in theatre, and having a low threshold for open reduction. Revision options should be available when bringing a case like this to the operating theatre.

https://ift.tt/2kKvJpK

Management of a late breast implant rupture in the setting of previous radiation

Management of ruptured breast implants is scarcely discussed in the literature, especially in the setting of previous breast cancer and radiation. The authors present an uncommon presentation of late breast implant rupture with seroma and history of prior radiation. It is important to acknowledge the increased risk of wound healing complications in patients who are several years' postradiation therapy for breast cancer and should be an important factor when discussing treatment options with the patient.

https://ift.tt/2sFfMoj

Successful use of subcutaneous ivermectin for the treatment of Strongyloides stercoralis hyperinfection in the setting of small bowel obstruction and paralytic ileus in the immunocompromised population

Severe Strongyloides stercoralis, such as hyperinfection syndrome, carries a high mortality risk. Even with appropriate treatment, patients may experience infectious complications and failure of therapy. Currently, there are no Food and Drug Administration–approved parenteral therapies available for treatment in patients who develop gastrointestinal complications from hyperinfection, including small bowel obstruction. A veterinary form of ivermectin is available as a subcutaneous injection, although current literature in humans is limited. We report on the successful treatment of two surviving immunocompromised patients with S. stercoralis hyperinfection syndrome after prompt recognition and initiation of veterinary subcutaneous ivermectin therapy.

https://ift.tt/2J9bxfR

Testicular toxoplasmosis in a 26-year-old immunocompetent man

Testicular toxoplasmosis is a very rare presentation of Toxoplasma gondii. A 26-year-old immunocompetent man presented to us with right testicular pain and a right epididymal mass. Ultrasound was concerning for malignancy and a radical orchiectomy was performed. Surgical pathology revealed chronic granulomatous inflammation which stained positive for T. gondii.

https://ift.tt/2sEKJJ9

Case of primary Sjogrens syndrome preceded by dystonia

There are only six cases in literature that describe development of dystonia with Sjogren's syndrome (SS). We describe a case of a 43-year-old woman who presented with symptoms including movement disorder, sensory neurogenic bladder, sensory loss and neuropathic pain, migraine like headaches, musculoskeletal pain, Raynaud's phenomenon and dysautonomia. Symptoms started in 2000, with weakness that progressed to dystonia in 2003. Diagnostic work-up was inconclusive with negative inflammatory serologies, cerebrospinal fluid and MRI for many years. After patient developed sicca syndrome with dry eyes and mouth in 2009, her rheumatoid factor titre was elevated (550 IU/mL), erythrocyte sedimentation rate, anti-Sjogrens syndrome-related antigen A (anti-Ro/SSA) and anti-SSB/La: anti-Sjogrens syndrome-related antigen B (anti-La/SSB) became positive. Lip biopsy confirmed diagnosis of SS. She was diagnosed with primary SS with neurological involvement. Her symptoms responded well to intravenous methylprednisolone. Symptoms stabilised with trials of immune-suppressive therapy. This is a case that demonstrates the delay of diagnosing SS with preceding unique neurological association.

https://ift.tt/2J7fAcy

Ophthalmomyiasis in a case of basal cell carcinoma of eyelid

Ocular myiasis is a rare disease with invasion of the lids, conjunctiva, cornea and, rarely, orbit or globe of the mammalian eye by dipteral larvae.

We report a case of a 74-year-old woman with chronic, infiltrating, ulcerative lesion of the left lower eyelid, which was confirmed as basal cell carcinoma subsequently, having ophthalmomyiasis.

She was a destitute, living in unhygienic environmental conditions and having poor general health. She developed permanent blindness as a result of ophthalmomyiasis of the left eye. Proper wound care, hygiene and adequate nutrition helped her recover from the illness.

https://ift.tt/2HiKHMv

Hyperkalaemic periodic paralysis in pregnancy

Hyperkalaemic periodic paralysis is a rare skeletal muscle disorder which is characterised by episodic muscle paralysis associated with hyperkalaemia. Although it is an autosomal-dominant disease, cases of de novo mutations have been reported. We report the case of a 30-year-old woman, gravida 5 para 3+1, who was planned for an elective repeated caesarean section at 38 weeks and 3 days of pregnancy. She developed recurrent episodes of hyperkalaemic periodic paralysis after receiving corticosteroids. Intravenous calcium gluconate was administered to normalise potassium levels (from 6.3 mmol/L to 4.1 mmol/L). Extra anaesthetic precautions were taken during the caesarean delivery. Postoperatively, she was well and discharged from the ward. She encountered similar symptoms in her third pregnancy, and there was no family history of muscle weakness which suggested a de novo mutation. Pregnancy seemed to result in vulnerability to hyperkalaemic attacks as she was never symptomatic outside pregnancy.

https://ift.tt/2kNbNmg

Crescent sign in abdominal aortic aneurysm

Description

A 70-year-old man referred to emergency department with acute onset of severe flank pain. In initial examinations, the patient was pale, with pulse rate of 120/min and blood pressure of 95/65. In abdominal palpation a pulsatile mass was detectable. Urgent resuscitation was done.

The patient had been known to have hypertension and abdominal aortic aneurysm (AAA) since 7 years ago. Abdominal CT scan without and with contrast injection (figures 1 and 2) showed a large fusiform abdominal aorta with crescentic focus of hyperdensity (black arrow) within the mural thrombus (white arrow), known as high-attenuating crescent sign. Retroperitoneal haematoma was also observed anterior to psoas muscles bilaterally (asterisks). Endovascular repair was chosen as an emergent surgical procedure. The patient was discharged on postoperative day 7, and recovery was uneventful.

Figure 1

Non-contrast enhanced abdominal CT scan shows an abdominal aorta aneurysm with mural thrombosis...

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Unusual case of anorexia

We report the case of a 15-year-old female patient suffering from progressive anorexia, weight loss and recurrent abdominal pain, initially diagnosed as anorexia nervosa. She eventually presented with severe malnutrition and acute bowel obstruction, revealing a mass of the transverse colon. A well-differentiated Lieberkühn adenocarcinoma was established by histology. The patient underwent transverse and right colectomy and was treated with adjuvant chemotherapy. Colorectal cancer (CRC) is predominantly a disease of older adults and is extremely rare in children and adolescents. Seldom suspected, it is more likely to be diagnosed at an advanced stage, with unfavourable tumour histology and poor outcome. Young patients diagnosed with CRC should receive genetic counselling regardless of their family history or tumour type. This reports' take-home message is that recurrent and persistent digestive symptoms in the young should alert physicians and lead to further investigations.

https://ift.tt/2kMEHmz

A promising response to osimertinib in a patient with erlotinib-resistant lung adenocarcinoma with an uncommon EGFR mutation

Most patients with non-small cell lung cancer with common epidermal growth factor receptor (EGFR) mutations respond dramatically to EGFR tyrosine kinase inhibitors (TKIs), but data are limited on the response of tumours with uncommon mutations. We present the case of a 68-year-old man with stage IV lung adenocarcinoma with an uncommon EGFR mutation in exon 21 (L861Q). The disease progressed 2 years after he started erlotinib (150 mg daily). Using a transbronchial lung biopsy, we detected additional mutations in exon 20 (T790M) and exon 21 (L858R). He was treated with osimertinib (80 mg daily) and achieved a partial remission. This case demonstrates the value of repeating a biopsy after EGFR-TKI therapy in patients with uncommon EGFR mutations.

https://ift.tt/2HijJon

Clinical and Histopathologic Correlates and Management Strategies for Inflammatory Myofibroblastic tumor of the lung. A case series and review of the literature

Abstract

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm that may arise in soft tissues of nearly every organ. Although IMTs are the most common lung tumors in pediatric populations, these tumors are extremely rare in adults, constituting less than 1% of adult lung tumors. IMTs are characterized by proliferating spindle cells with variable inflammatory component. The biological behavior of lung IMTs in adults is highly unpredictable, which confounds diagnosis and treatment. We retrospectively investigated patients with pulmonary lesions and the histopathologic diagnosis of inflammatory myofibroblastic tumor or its synonymous names (Plasma Cell Granuloma, xanthogranuloma, inflammatory pseudotumor, fibroxanthoma, and fibrous histiocytoma) at the MD Anderson Cancer Institute in the period between August 2000 and August 2016. We describe 7 adult cases of IMT of the lung that were diagnosed at MD Anderson Cancer Center. These cases highlight the tumor's variability in terms of clinical presentation, histopathology, and biologic behavior, and underscore the challenges in the management of these rare lung neoplasms.

https://ift.tt/2Jr2ne0