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Background: Melanoma-intrinsic activated β-catenin pathway, the product of the catenin beta 1 (CTNNB1) gene, has been associated with low/absent tumor-infiltrating lymphocytes, accelerated tumor growth, metastases development, and resistance to anti-PD-L1/anti-CTLA-4 agents in mouse melanoma models. Little is known about the association between the adenomatous polyposis coli (APC) and CTNNB1 gene mutations in stage IV melanoma with immunotherapy response and overall survival (OS).Methods: We examined the prognostic significance of somatic APC/CTNNB1 mutations in the Cancer Genome Atlas Project for Skin Cutaneous Melanoma (TCGA-SKCM) database. We assessed APC/CTNNB1 mutations as predictors of response to immunotherapies in a clinicopathologically annotated metastatic patient cohort from three US melanoma centers.Results: In the TCGA-SKCM patient cohort (n = 434) presence of a somatic APC/CTNNB1 mutation was associated with a worse outcome only in stage IV melanoma (n = 82, median OS of APC/CTNNB1 mutants vs. wild-type was 8.15 vs. 22.8 months; log-rank hazard ratio 4.20, p = 0.011). APC/CTNNB1 mutation did not significantly affect lymphocyte distribution and density. In the 3-melanoma institution cohort, tumor tissues underwent targeted panel sequencing using two standards of care assays. We identified 55 patients with stage IV melanoma and APC/CTNNB1 genetic aberrations (mut) and 169 patients without (wt). At a median follow-up of more than 25 months for both groups, mut compared with wt patients had slightly more frequent (44% vs. 39%) and earlier (66% vs. 45% within six months from original diagnosis of stage IV melanoma) development of brain metastases. Nevertheless, time-to-development of brain metastases was not significantly different between the two groups. Fortunately, mut patients had similar clinical benefits from PD-1 inhibitor-based treatments compared to wt patients (median OS 26.1 months vs. 29.9 months, respectively, log-rank p = 0.23). Less frequent mutations in the NF1, RAC1, and PTEN genes were seen in the mut compared with wt patients from the 3-melanoma institution cohort. Analysis of brain melanoma tumor tissues from a separate craniotomy patient cohort (n = 55) showed that melanoma-specific, activated β-catenin (i.e., nuclear localization) was infrequent (n = 3, 6%) and not prognostic in established brain metastases.Conclusions: APC/CTNNB1 mutations are associated with a worse outcome in stage IV melanoma and early brain metastases independent of tumor-infiltrating lymphocyte density. However, PD1 inhibitor-based treatments provide comparable benefits to both mut and wt patients with stage IV melanoma. [ABSTRACT FROM AUTHOR]

Retrospective case studies in various cancers have shown clinical benefit from chemotherapy following PD-1 inhibitor progression. We asked whether we see a similar clinical benefit with chemotherapy following PD-1 inhibitor progression in metastatic melanoma. We performed a retrospective study in patients with metastatic melanoma, who had received PD-1 inhibitor-based treatments, subsequently progressed, and eventually received chemotherapy. We identified 25 patients (median age 58 years; range 31–77 years; 13 females). Most patients had cutaneous melanoma (72%), were BRAFV600E-negative (75%), and received single-agent temozolomide (84%). At a median follow-up of 21.0 months (range: 4.1–154.2 months), 2 patients had durable response to chemotherapy (progression-free survival is 31.9+ and 21.6+ months, respectively), and 1 patient had a partial, short-term response. We conclude that in this poor prognosis group administration of chemotherapy has a 12% response rate that can be durable. Overall, the clinical benefit is not inferior to that of PD-1 inhibitor-based treatments. [ABSTRACT FROM AUTHOR]

General surgery is one of the more popular career choices among medical students worldwide. An alarming one in five general surgery residents, however, abandon residency training—a rate that is much higher than most other medical and surgical specialities. We believe that additional measures are needed to decrease attrition and increase “grit” among house staff. Specifically, the diversification of the surgery training experience to include global and rural surgery may help mitigate burnout among surgical house staff. [ABSTRACT FROM AUTHOR]

We read with great interest the recent publication by Rao et al[1] on the effect of arteriovenous fistula ligation on cardiac function after kidney transplantation. The striking and possibly practice-changing finding of the study was the clinically and radiographically significant reduction of left ventricular myocardial mass in patients with stable kidney function after kidney transplantation.[1] 1 Rao NN, Stokes MB, Rajwani A, Ullah S, Williams K, King D, Macaulay E, Russell CH, Olakkengil S, Carroll RP, Effects of arteriovenous fistula ligation on cardiac structure and function in kidney transplant recipients. [Extracted from the article]

Metastatic castration-resistant prostate cancer (mCRPC) remains a terminal diagnosis with an aggressive disease course despite currently approved therapeutics. The recent successful development of poly ADP-ribose polymerase (PARP) inhibitors for patients with mCRPC and mutations in DNA damage repair genes has added to the treatment armamentarium and improved personalized treatments for prostate cancer. Other promising therapeutic agents currently in clinical development include the radiotherapeutic 177-lutetium-prostate-specific membrane antigen (PSMA)-617 targeting PSMA-expressing prostate cancer and combinations of immunotherapy with currently effective treatment options for prostate cancer. Herein, we have highlighted the progress in systemic treatments for mCRPC and the promising agents currently in ongoing clinical trials. [ABSTRACT FROM AUTHOR]

Esophageal cancer (EC) and gastric cancer (GC) often have an unfavorable prognosis. Therefore, research is being conducted to identify the molecular mechanisms underlying the tumorigenesis and progression of GC and EC, and to indicate novel therapeutic targets and clinically applicable biomarkers. The dysregulations and roles of long non-coding RNAs (lncRNAs) have been widely reported, and current published literature has shown that lncRNAs play important regulatory roles in the carcinogenesis and progression of EC and GC. The lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been investigated in a number of studies with regard to its pathogenic pathways and association with the prognosis of gastric and esophageal malignancies. As literature on the topic of MALAT1 in EC and GC continues to emerge, the present review aims to summarize all current knowledge on the association between MALAT1 expression and esophagogastric malignancies and to describe the pathogenic pathways and possible prognostic role of MALAT1 in esophagogastric cancer. As research studies on MALAT1 pathways in esophagogastric malignancies are ongoing, new possibilities for the diagnosis, prognosis and therapy of GC and EC are likely to be identified. [ABSTRACT FROM AUTHOR]

Bronchobiliary fistula (BBF) is a rare complication following hepatectomy, and consists of an abnormal intercommunication between the biliary tract and bronchial tree. The management of this rare entity is challenging with limited current evidence to date on how to treat this condition. Herein, a case of BBF following a central hepatectomy and the successive steps of the management was presented. Fourteen months postoperatively, the patient presented to the Oncology Department complaining of new onset fever and expectoration. A computerized tomography scan revealed a BBF and the patient was subsequently referred to our department for further treatment. The surgical team decided that a further operation was required. Using the transabdominal approach, a communication between the initial intrahepatic collection and one inferior lobular bronchus was revealed. Transhiatal removal of fistula was performed with closure of the defect through the abdomen. There was no bile leak through the remaining liver parenchyma. Multidisciplinary management should be considered, taking into consideration the underlying pathology leading to this rare complication. Conservative treatment should be considered first, while surgical resection of the BBF remains an option when other therapies have failed. Surgeons should be aware of this rare complication bile duct injuries during hepatic operations can cause. [ABSTRACT FROM AUTHOR]