MiRNA-3653 Is a Potential Tissue Biomarker for Increased Metastatic Risk in Pancreatic Neuroendocrine Tumours.

Pancreatic neuroendocrine tumours (PNETs) are relatively uncommon, accounting for 1-2% of all pancreatic neoplasms. Tumour grade (based on the Ki67 proliferative index and mitotic rate) is associated with metastatic risk across large cohorts; however, predicting the behaviour of individual tumours can be difficult. Therefore, any tool which could further stratify metastatic risk may be clinically beneficial. We sought to investigate microRNA (miRNA) expression as a marker of metastatic disease in PNETs. Tumours from 37 patients, comprising 23 with locoregional disease (L) and 14 with distant metastases (DM), underwent miRNA profiling. In total 506 miRNAs were differentially expressed between the L and DM groups, with four miRNAs (miR-3653 upregulated, and miR-4417, miR-574-3p and miR-664b-3p downregulated) showing statistical significance. A database search demonstrated that miRNA-3653 was associated with ATRX abnormalities. Mean survival between the two groups was correlated with mean expression of miRNA-3653; however, this did not reach statistical significance (p = 0.204). Although this is a small study, we conclude that miRNA-3653 upregulation may be associated with an increased risk of metastatic disease in PNETS, perhaps through interaction with ATRX and the alternate lengthening of telomeres pathway.

Pancreatoduodenectomy and the risk of complications from perioperative fluid administration.

BACKGROUND: The dogma of administering sufficient intravenous fluids aggressively to avoid under-resuscitation has recently been challenged. Evidence suggests that excessive perioperative fluid administration may be associated with negative clinical outcomes in gastrointestinal surgery. This study examines the impact of fluid administration on perioperative outcomes in patients undergoing pancreatoduodenectomy (PD). METHODS: A retrospective analysis of 202 patients undergoing PD between January 2004 and August 2015 was performed. A cut-off value of 10 mL/kg/h was applied (low fluid group: <10 mL/kg/h versus high fluid group: ≥10 mL/kg/h). RESULTS: There were 76 patients in the low fluid group and 126 patients in the high fluid group. Both groups had comparable age, American Society of Anesthesiologists score and preoperative morbidity rates. Patients in the high fluid group received significantly more total fluids, crystalloids and colloids intraoperatively (P < 0.0001, P < 0.0001 and P = 0.013, respectively) without a significant difference in estimated blood loss (P = 0.586). The net fluid balance on post-operative day 0 was also significantly higher in the high fluid group (P < 0.0001). The mortality rate was 0% in the cohort. Major morbidity rate was 46.1% and 44.4% in low and high fluid groups, respectively (P = 0.836). Reoperation rate was 5.3% for the low fluid group and 1.6% for the high fluid group (P = 0.136). There were no significant differences between the groups for any of the individual complications. CONCLUSION: This study did not identify a difference in post-operative outcomes between the low and high fluid regime in patients undergoing PD.

Ileocecal Intussusception Caused by an Appendiceal Neoplasm.

Mucinous appendiceal neoplasm occurs in less than 1% of appendicectomies. Majority of what is known in the literature is about pseudomyxoma peritonei, which exists as its disseminated form. Pictorial imagery of its pre-disseminated form is rarely observed. We present in a case report form a case of low-grade mucinous neoplasm of the appendix resulting in focal intussusception including images captured from this unique case that will become a learning case for readers of the journal.

Immunoregulatory Forkhead Box Protein p3-Positive Lymphocytes Are Associated with Overall Survival in Patients with Pancreatic Neuroendocrine Tumors.

BACKGROUND: Forkhead box protein p3-positive (FoxP3(+)) regulatory T cells (Tregs) suppress host T-cell-mediated immune responses, limit surveillance against cancers, and have been associated with a poor prognosis. STUDY DESIGN: This study aims to identify the prognostic significance of FoxP3(+) Tregs in pancreatic neuroendocrine tumors (PNETs). Patients diagnosed with PNETs between 1992 and 2014 (n = 101) were included in this retrospective analysis. Clinical data, histopathology, and expression of FoxP3(+) Tregs and Ki-67 by immunohistochemistry were assessed. The association of these factors with survival was tested by log-rank test and in additional multivariable analysis. RESULTS: A total of 101 patients were included in this study. Mean age was 58.0 years (range 18 to 87 years) and median tumor size was 25 mm (range 8 to 160 mm). The degree of infiltration of tumor by FoxP3(+) Tregs was graded as 0 (n = 75), 1 (n = 15), or 2 (n = 11). Median follow-up was 50 months (interquartile range 123 months; Q1 = 20 months and Q3 = 123 months). In univariate analyses, patient age older than 57 years, TNM stage III or IV, tumor size >25 mm, Ki-67 labeling index >20, and a high number of FoxP3(+) tumor-infiltrating lymphocytes were significantly associated with poorer overall survival. In multivariable analyses, FoxP3(+) expression score of 2 (hazard ratio = 6.9; 95% CI 1.4-34.4) was the only statistically significant predictor for overall mortality. CONCLUSIONS: FoxP3(+) Treg expression is an independent prognostic factor in patients with PNETs, associated with statistically significant shorter overall survival. There is a role for additional research into the immune-mediated role of FoxP3(+) Tregs in PNETs.

Somatostatin Receptor SSTR-2a Expression Is a Stronger Predictor for Survival Than Ki-67 in Pancreatic Neuroendocrine Tumors.

Somatostatin receptors (SSTR) are commonly expressed by neuroendocrine tumors. Expression of SSTR-2a and SSTR-5 may impact symptomatic management; however, the impact on survival is unclear. The aim of this study is to correlate SSTR-2a and SSTR-5 expression in pancreatic neuroendocrine tumors (PNETs) with survival. This study is designed to determine the prognostic significance of somatostatin receptors SSTR-2a and SSTR-5 in PNETs. This retrospective cohort study included cases of resected PNETs between 1992 and 2014. Clinical data, histopathology, expression of SSTR and Ki-67 by immunohistochemistry, and long-term survival were analyzed. A total of 99 cases were included in this study. The mean age was 57.8 years (18-87 years) and median tumor size was 25 mm (range 8-160 mm). SSTR-2a and SSTR-5 expression was scored as negative (n = 19, 19.2%; n = 75, 75.8%, respectively) and positive (n = 80, 80.1%; n = 24, 24.2%). The median follow-up was 49 months. SSTR-2a expression was associated with improved overall survival, with cumulative survival rates at 1, 3, and 5 years being 97.5%, 91.5%, and 82.9%, respectively. Univariate analysis demonstrated better survival in SSTR-2a positive patients (log rank P = 0.04). SSTR-5 expression was not associated with survival outcomes (log rank P = 0.94). Multivariate analysis showed that positive SSTR-2a expression is a stronger prognostic indicator for overall survival [Hazard Ratio (HR): 0.2, 95% Confidence interval (CI): 0.1-0.8] compared to high Ki-67 (HR: 0.8, 95% CI: 0.1-5.7). Expression of SSTR-2a is an independent positive prognostic factor for survival in PNETs.

Tuberculosis: experience in a low endemic area Australian tertiary hospital.

BACKGROUND: Abdominal tuberculosis (ATB) poses a significant diagnostic, management, and resource challenge. In Australia, an increasing number of tuberculosis (TB) cases are being reported, and we describe our experience of ATB in an Australian tertiary institution. METHODS: All diagnosed cases of tuberculosis (TB) at the Royal North Shore tertiary hospital campus of the University of Sydney are entered prospectively into a central registry. Cases of ATB encountered between September 1991 and November 2011 were identified and retrospectively reviewed. RESULTS: In all, 841 cases of TB were identified, of which 20 were abdominal (2.4 %). Median age at presentation was 34 years (range: 22-79 years), and 55 % of patients were women. None of the patients were born in Australia and 11 patients were of South Asian origin. The most common presenting symptom was abdominal pain (65 %). Diagnosis was based primarily on histology (90 % sensitivity), and the sensitivity of PCR analysis in this series was low (44 %). Eleven of the patients required laparoscopy or laparotomy. 40 % of cases involved the peritoneum, and disease was also seen in solid organs (liver, spleen, pancreas, adrenal gland) and bowel (esophagus, small bowel, colon). CONCLUSIONS: In our local experience ATB was seen exclusively in the immigrant population. The presentation of ATB varies greatly, necessitating a high index of suspicion within the context of abdominal symptoms in high-risk groups. The role of surgical involvement is indispensable for both diagnosis and management of ATB-related complications. Surgeons should remain mindful of the diagnosis in an age of increasing worldwide incidence.