Gastric cancer is the second most important neoplasm in the world. Surgical resection is the treatment of choice for gastric cancer, and recognized by the International Union against Cancer (International Union Against Cancer - UICC) TNM classification of the parameters of the tumor and lymph node. Prognostic factors related to characteristics of the tumor by histopathologic findings have an impact on the planning of the operation. According to the results of most studies it is possible to predict survival and recurrence based on histological type and TNM classification of tumors on the one hand and the surgical procedure on the other.

Epithelial downgrowth is an uncommon complication of ocular surgery or adverse consequence of accidental trauma, caused by surface squamous epithelium that has gained access to the inner compartments of the eye. Once embedded in the eye, squamous epithelium spreads over contiguous structures, interfering with normal aqueous outflow and vision. The pursuit of improved therapies is ongoing, but the greatest chance of preventing blindness is with early recognition. Two cases of epithelial downgrowth diagnosed from a corneal button and an iris biopsy are presented to familiarize pathologists with this disorder. In the appropriate clinical setting, the presence of stratified squamous epithelium, with or without goblet cells, is diagnostic of epithelial downgrowth. Other than congenital epithelial inclusion cyst (choristoma), stratified squamous epithelium is not found inside the eye. Surface epithelium introduced surgically or traumatically needs to be differentiated histologically from ectopic corneal endothelium and metastatic carcinoma.

Cancer of the gastroesophageal junction (GEJ), although rare, is now considered a separate entity with a distinct pathophysiological and molecular profile. Although much progress has been made over the past decades in delineating the multiple environmental and genetic pathways involved GEJ carcinoma, the exact molecular mechanisms underlying disease initiation and progression are still poorly understood. This is of paramount importance for the treating physician as the disease bears a poor therapeutic response. This review defines the GEJ and types of GEJ carcinoma, and provides useful insight in its pathophysiology. Future aspects include better understanding of GEJ oncogenesis, early detection of precursor lesions, the use of biomarkers and targeted therapy (through molecular profiling) so as to increase overall survival. (Acta gastroenterol. belg., 2016, 79, 471-479).

Pericardial effusions can cause considerable morbidity and potentially may lead to mortality. Malignant pericardial effusions are uncommon, and data on malignancies encountered in pericardial effusion cytology specimens are limited.

Intrahepatic cholangiocarcinoma (ICC) is classified according to the following subtypes: massforming (MF), periductal infiltrating (PI), and intraductal growth (IG). The aim of this study is to measure the association between ICC subtypes and patient survival after surgical resection. Data were abstracted on all patients treated with definitive resections of ICC at a single institution between 2000 and 2011 with at least three years follow-up. Survival estimates were quantified using Kaplan-Meier curves and compared using the log-rank test. There were 37 patients with ICC treated with definitive partial hepatectomies with a median survival of 33.5 months. Tumor stage (P < 0.0001), satellitosis (P < 0.001), lymphovascular space invasion (P = 0.003), and macroscopic subtype (P = 0.003) were predictive of postoperative survival. Disease-free survivals for MF, PI, and IG subtypes, respectively, were 30 per cent, 0 per cent, and 57 per cent (P = 0.017). Overall survivals among ICC macroscopic subtypes were as follows: MF 37 per cent, PI 0 per cent, and IG 71 per cent (P = 0.003). Although limited by the small sample size of this rare cancer, this study demonstrates significant differences among macroscopic subtypes of ICC in both disease-free survivals and overall survivals after definitive partial hepatectomy.

The surgical management of duodenal pathology is challenging because of its retroperitoneal position and shared blood supply with the pancreas. We present three types of limited resection of the duodenum for the removal of superficial or small nonampullary duodenal (NADL) lesions, and also a review of the English literature regarding management, such as endoscopic resection and limited duodenal resection. Ten cases underwent limited resections of the duodenum for superficial or small NADL lesions from 2011 to 2015. Pancreas-preserving segmental duodenectomy was performed in three cases, local full-thickness resection was performed in three and transduodenal submucosal dissection was performed in four. One patient experienced pancreatic fistula as a postoperative complication. Postoperative pathological diagnosis were adenoma (n = 2), mucosal adenocarcinomas (n = 5), and neuroendocrine tumor (n = 3). Surgical margin was negative in all cases, and no patient has experienced postoperative recurrence or metastasis. Limited resections of the duodenum were feasible and safe procedures for patients with superficial or small NADL lesions. Laparoscopic surgery may be considered in treatment for these tumors. However, the optimal surgical management for superficial or small nonampullary duodenal lesions remains controversial.

We present the case of a 76-year-old male found to have a large tumor involving the left lateral lobe of the liver, presumed to be hepatocellular carcinoma (HCC). After resection, pathologic features demonstrated both high-grade HCC and high-grade neuroendocrine carcinoma (NEC). Areas of NEC stained strongly for synaptophysin, which was not present in HCC component. The HCC component stained strongly for Hep-Par 1, which was not present in the NEC component. The patient underwent genetic analysis for biomarkers common to both tumor cell types. Both tumor components contained gene mutations in CTNNB1 gene (S33F located in exon 3). They also shared mutations in PD-1, PGP, and SMO. Mixed HCC/NEC tumors have been rarely reported in the literature with generally poor outcomes. This patient has been referred for adjuvant platinum-based chemotherapy; genetic biomarker analysis may provide some insight to guide targeted chemotherapy.

The prognosis of patients with gastrointestinal (GI) melanoma metastases is poor. Surgery renders select patients disease free and/or palliates symptoms. We reviewed our single-institution experience of resection with GI melanoma metastases. A retrospective review was performed on patients who underwent surgery for GI melanoma metastases from 2007 to 2013. Fifty-four patients were identified and separated based on completeness of resection into curative 13 (24%) and palliative 41 (75.9%) groups. Thiry-six (63.2%) were symptomatic preoperatively with bleeding and/or obstruction/pain with 91.7 per cent achieving objective symptom relief. Thirty-day operative mortality was 0 per cent. The most common complication was wound infection (n = 5); major complications like anastomotic leak (n = 1) were uncommon. With a median follow-up of 9.5 months (range 0.2-75.8), median overall survival was not reached (curative) versus 9.53 months (palliative group). Median recurrence-free and progression-free survival after resection were 18.89 and 1.97 months in the curative versus palliative groups, respectively. On multivariate analysis, resection to no clinical evidence of disease (P = 0.012) and presence of single metastases (P = 0.031) were associated with improved overall survival. Surgery for GI metastases from melanoma provides symptomatic relief without major morbidity. Fewer metastases and curative resection were associated with improved survival.

The Ferguson Operating Anoscope (FOA) is a surgical instrument, which can facilitate transanal excision of appropriate rectal tumors within 15 cm of the anal verge. Previous work showed low recurrence (4.3%) for favorable T1 tumors (no lymphovascular invasion, well/moderate differentiation, negative margins). This follow-up study evaluates outcomes in rectal cancer excised with FOA at a tertiary care center. T1 rectal cancer patients were identified in a prospectively maintained database. Tumor pathology and patient characteristics were reviewed. Primary outcomes include tumor recurrence and patient and disease-free survival. Secondary outcomes are quality of excision (intact specimen). Twenty-eight patients had pathologic stage T1 rectal cancer (average 8 ± 2.6 cm from the anal verge). Final path demonstrated 14 per cent to be well differentiated, 82 per cent moderately differentiated, and 93 per cent without angiolymphatic invasion. All specimens removed were intact. One patient had a true local recurrence and underwent a salvage operation 24 months after her index operation. Patient survival was 96.4 per cent (n = one death from primary lung cancer) at median follow-up 64 ± 35 months. With appropriate tumor selection and quality of initial resection, FOA has demonstrated utility in achieving optimal oncologic resection of T1 rectal tumors.

With the increasing popularity of sleeve gastrectomy, many stomach specimens are being evaluated. Understanding the significance and treatment for unexpected pathology is important. This study examines the incidence of relevant histopathology of sleeve gastrectomy specimens. It evaluates previous data for each histopathology and provides recommendations for treatment. In this study, a retrospective review was performed for 241 patients who underwent sleeve gastrectomy from 2009 to 2014 at a single institution. Of the specimens, 122 had no significant histopathology, 91 had gastritis, 13 had lymphoid aggregates, 5 had hyperplasia, 3 had intestinal metaplasia, 3 had gastrointestinal stromal tumors (GISTs), and 3 had gastric polyps. Of the GISTs all had a low mitotic rate and the size of the tumor ranged from 1.5 to 4.5 cm. The findings of metaplasia may be a marker for increased risk of malignancy and may require additional surveillance. The findings of GIST may warrant interval imaging to survey for recurrence, though the likelihood of recurrence for the tumors in this study is less than 2 per cent based on previous studies.

This study investigated disparities between patients who had local excision versus radical resection for T1 rectal cancer. A retrospective analysis was performed using the National Cancer Data Base, 2004 to 2011. Inclusion criteria consisted of patients with T1, N0 rectal adenocarcinoma that were <3 cm, well or moderately differentiated without perineural invasion. Patients were stratified based on local excision and radical surgery. The primary outcome was overall survival (OS). Secondary outcomes included 30-day mortality, unplanned readmission rates, and postoperative length of stay. A total of 2235 patients were identified; 1335 (59.7%) underwent local excision and 900 (40.3%) had radical surgery. Overall, radical surgery was associated with an improved 5-year OS rate compared to local excision (0.86 vs 0.78, P = 0.009), increased unplanned readmission (6.5% vs 2.7%, P < 0.001), and longer postoperative length of stay (6.9 days vs 3.1 days, P < 0.001). For patients who had local excision, insurance status was an independent predictor of OS. Compared to patients with private insurance, those with government plans or no insurance had poorer OS (hazard ratio = 1.77 and 17.45, respectively, P = 0.006). Further study is warranted to understand the reasons accounting for this disparity in surgical approach to T1 rectal cancer.

Small (2 cm) peripheral lung lesions and ground glass opacities remain a difficult subset of lung lesions for the diagnosis and management of lung cancer. Surgical biopsy is more difficult for these lesions because intraoperative localization has to be made without the aid of direct visualization or manual palpation. Electromagnetic navigation bronchoscopy can be used in the operating room to identify a small peripheral lesion and marked using an injection of methylene blue, which can be seen on the visceral pleura of the lung. We present our initial experience using this technique. The sample was eight patients who had peripheral lesions with an average size of 19 mm. Surgical wedge biopsy was diagnostic in all cases, with an average procedure time of 28 minutes. There were no complications from this procedure. In conclusion, these data suggest that electromagnetic navigation bronchoscopy can be performed safely with high diagnostic accuracy by the operating thoracic surgeon, but further data are needed to establish its utility and safety.

Pancreatic cancer is the fourth most common cause of cancer-related mortality. Novel molecular biomarkers need to be identified for personalized medicine and to improve survival. The aim of this study was to examine chloride intracellular channel 4 (CLIC4) and Indian Hedgehog (Ihh) expression in benign and malignant lesions of the pancreas and to examine the eventual association between CLIC4 and Ihh expression, with clinicopathological features and prognosis of pancreatic cancer. A retrospective study of specimens collected from January 2000 to December 2011 at the Department of Pathology of the Second and Third Xiangya Hospitals, Central South University was undertaken to explore this question. Immunohistochemistry of CLIC4 and Ihh was performed with EnVision™ in 106 pancreatic ductal adenocarcinoma specimens, 35 paracancer samples (2 cm away from the tumour, when possible or available), 55 benign lesions and 13 normal tissue samples. CLIC4 and Ihh expression in pancreatic ductal adenocarcinoma were significantly higher than in paracancer tissue and benign lesions (CLIC4: P = 0.009 and Ihh: P < 0.0001; CLIC4: P = 0.0004 and Ihh: P = 0.0001 respectively). CLIC4 and Ihh expression was negative in normal pancreatic tissues. The expression of CLIC4 and Ihh was associated significantly with tumour grade, lymph node metastasis, tumour invasion and poor overall survival. Thus CLIC4 and Ihh could serve as biological markers for the progression, metastasis and/or invasiveness of pancreatic ductal adenocarcinoma.

Purpose Cabozantinib is an oral potent inhibitor of vascular endothelial growth factor receptor 2, MET, and AXL and is a standard second-line therapy for metastatic renal cell carcinoma (mRCC). This randomized phase II multicenter trial evaluated cabozantinib compared with sunitinib as first-line therapy in patients with mRCC. Patients and Methods Eligible patients had untreated clear cell mRCC and Eastern Cooperative Oncology Group performance status of 0 to 2 and were intermediate or poor risk per International Metastatic Renal Cell Carcinoma Database Consortium criteria. Patients were randomly assigned at a one-to-one ratio to cabozantinib (60 mg once per day) or sunitinib (50 mg once per day; 4 weeks on, 2 weeks off). Progression-free survival (PFS) was the primary end point. Objective response rate (ORR), overall survival, and safety were secondary end points. Results From July 2013 to April 2015, 157 patients were randomly assigned (cabozantinib, n = 79; sunitinib, n = 78). Compared with sunitinib, cabozantinib treatment significantly increased median PFS (8.2 v 5.6 months) and was associated with a 34% reduction in rate of progression or death (adjusted hazard ratio, 0.66; 95% CI, 0.46 to 0.95; one-sided P = .012). ORR was 33% (95% CI, 23 to 44) for cabozantinib versus 12% (95% CI, 5.4 to 21) for sunitinib. All-causality grade 3 or 4 adverse events were 67% for cabozantinib and 68% for sunitinib and included diarrhea (cabozantinib, 10% v sunitinib, 11%), fatigue (6% v 15%), hypertension (28% v 22%), palmar-plantar erythrodysesthesia (8% v 4%), and hematologic adverse events (3% v 22%). Conclusion Cabozantinib demonstrated a significant clinical benefit in PFS and ORR over standard-of-care sunitinib as first-line therapy in patients with intermediate- or poor-risk mRCC.

Purpose Women receiving trastuzumab with chemotherapy are at risk for trastuzumab-related cardiac dysfunction (TRCD). We explored the prognostic value of cardiac markers (troponins I and T, N-terminal prohormone of brain natriuretic peptide [NT-proBNP]) to predict baseline susceptibility to develop TRCD. We examined whether development of cardiac end points or significant left ventricular ejection fraction (LVEF) drop was associated with markers' increases. Patients and Methods Cardiac marker assessments were coupled with LVEF measurements at different time points for 533 patients from the Herceptin Adjuvant (HERA) study who agreed to participate in this study. Patients with missing marker assessments were excluded, resulting in 452 evaluable patients. A primary cardiac end point was defined as symptomatic congestive heart failure of New York Heart Association class III or IV, confirmed by a cardiologist, and a significant LVEF drop, or death of definite or probable cardiac causes. A secondary cardiac end point was defined as a confirmed significant asymptomatic or mildly symptomatic LVEF drop. Results Elevated baseline troponin I (> 40 ng/L) and T (> 14 ng/L), occurring in 56 of 412 (13.6%) and 101 of 407 (24.8%) patients, respectively, were associated with an increased significant LVEF drop risk (univariate analysis: hazard ratio, 4.52; P < .001 and hazard ratio, 3.57; P < .001, respectively). Few patients had their first elevated troponin value recorded during the study (six patients for troponin I and 25 patients for troponin T). Two patients developed a primary and 31 patients a secondary cardiac end point (recovery rate of 74%, 23 of 31). For NT-proBNP, higher increases from baseline were seen in patients with significant LVEF drop. Conclusion Elevated troponin I or T before trastuzumab is associated with increased risk for TRCD. A similar conclusion for NT-proBNP could not be drawn because of the lack of a well-established elevation threshold; however, higher increases from baseline were seen in patients with TRCD compared with patients without.