Randomised, open-label, phase II study of gemcitabine with and without IMM-101 for advanced pancreatic cancer.

BACKGROUND: Immune Modulation and Gemcitabine Evaluation-1, a randomised, open-label, phase II, first-line, proof of concept study (NCT01303172), explored safety and tolerability of IMM-101 (heat-killed Mycobacterium obuense; NCTC 13365) with gemcitabine (GEM) in advanced pancreatic ductal adenocarcinoma. METHODS: Patients were randomised (2 : 1) to IMM-101 (10 mg ml(-l) intradermally)+GEM (1000 mg m(-2) intravenously; n=75), or GEM alone (n=35). Safety was assessed on frequency and incidence of adverse events (AEs). Overall survival (OS), progression-free survival (PFS) and overall response rate (ORR) were collected. RESULTS: IMM-101 was well tolerated with a similar rate of AE and serious adverse event reporting in both groups after allowance for exposure. Median OS in the intent-to-treat population was 6.7 months for IMM-101+GEM v 5.6 months for GEM; while not significant, the hazard ratio (HR) numerically favoured IMM-101+GEM (HR, 0.68 (95% CI, 0.44-1.04, P=0.074). In a pre-defined metastatic subgroup (84%), OS was significantly improved from 4.4 to 7.0 months in favour of IMM-101+GEM (HR, 0.54, 95% CI 0.33-0.87, P=0.01). CONCLUSIONS: IMM-101 with GEM was as safe and well tolerated as GEM alone, and there was a suggestion of a beneficial effect on survival in patients with metastatic disease. This warrants further evaluation in an adequately powered confirmatory study.

Splenectomy for non-haematological metastatic malignant disease.

PURPOSE: Multiple cases and small series of patients who have undergone splenectomy for metastatic malignant disease have been reported. This study examines the outcome of patients with metastatic malignant disease to the spleen treated by splenectomy at a tertiary oncology centre and a review of cases published in the last 10 years. METHODS: The hospital histopathology database was searched over a 25-year period up to 2004 for patients who had undergone splenectomy for non-haematological malignancy. Medical records of these patients were reviewed and clinical course was examined. The literature review was undertaken using a search of PubMed for the terms "splenectomy" and "metastasis" from 2000 to 2010. RESULTS: Twenty-one cases at our institution were identified. The most common primary site of malignancy was ovary (nine cases), followed by malignant melanoma (three) and pancreas (three). There were two cases of metastatic disease from colonic primary and one each from renal, breast, nasopharyngeal and unknown primary disease. There were two cases of long-term disease-free survival (both primary ovarian tumours) and four cases of patients who survived more than 4 years but had disease recurrence (ovarian and colonic primaries). The literature review provided a further 115 cases. CONCLUSIONS: More favorable outcomes were seen in patients with metachronous disease. There was a trend to improved outcome in ovarian and colorectal primaries over malignant melanoma. It is postulated that improved outcome may be seen in patients for whom there were effective adjuvant chemotherapeutic options, low probability of other metastatic disease and less aggressive tumour biology. However, frequently the presentation is indicative of aggressive widespread disease with a poor prognosis.

Dissecting the stress activating signaling pathways in acute pancreatitis.

BACKGROUND/AIMS: Acute pancreatitis is a severe and frequently a life-threatening disease which can lead to pancreatic necrosis, acute lung injury, SIRS and MODS. The pathophysiologic pattern of acute pancreatitis is being investigated, when guidelines for treatment are being modified often and novel therapeutic strategies have failed to show real benefit in clinical practice. METHODOLOGY: The present paper reviews the role of nuclear factors NF-kappaB and AP-1, TNFalpha, and TLR-4 in acute pancreatitis. CONCLUSION: Understanding the inflammatory mediators expression, regulation of apoptosis and dissecting the stress activating signaling pathways in acute pancreatitis, is of paramount importance in order to achieve in the near future adequate therapeutic interventions.

Pancreaticoduodenectomy for the Management of Pancreatic or Duodenal Metastases from Primary Sarcoma.

BACKGROUND/AIM: Sarcomas are rare and heterogeneous solid tumours of mesenchymal origin and frequently have an aggressive course. The mainstay of management for localized disease is surgical excision. Following excision there is approximately 30-50% risk of developing distant metastases. The role of pancreatic resection for metastatic sarcoma is unclear. Therefore, the aim of this study was to asses the outcome of patients with pancreatic metastases of sarcoma treated with surgical resection. PATIENTS AND METHODS: A retrospective analysis of a prospectively maintained single-surgeon, single-centre database was undertaken. Seven patients were identified who underwent pancreaticoduodenectomy for the management of metastatic disease from sarcoma between 2006-2016. RESULTS: The median age was 59 (range=19-73) years, and there were six females and one male. The primary sites included the uterus, broad ligament, femur and inferior vena cava. One patient died in the early postoperative period. The remaining six patients developed further recurrent disease, with a median disease-free interval of 11 (range=4-27) months and median overall survival of 21 months (range=4 days to 86 months). CONCLUSION: To our knowledge, this is the largest series of patients with pancreatic metastases of sarcoma treated with surgical resection. Despite optimal resection with R0 margins, in the absence of effective adjuvant systemic therapies, the benefit of such an approach in metastatic disease remains unclear.

Appendiceal mucocoeles and pseudomyxoma peritonei.

Mucocoele of the appendix occurs when obstruction of the appendiceal lumen results in mucus accumulation and consequent abnormal dilatation. The most important aetiology, from a surgical perspective, is either mucinous cystadenoma or cystadenocarcinoma. In the latter, a spontaneous or iatrogenic rupture of the mucocoele can lead to mucinous intraperitoneal ascites, a syndrome known as pseudomyxoma peritonei. Optimal management of mucoceles is achieved through accurate preoperative identification and subsequent careful resection. We report two cases and subsequently discuss the clinical presentation of mucocoeles, their association with pseudomyxoma peritonei and an optimal management of both conditions.

Liver regeneration: mechanisms, mysteries and more.

BACKGROUND: Liver regeneration remains a fascinating topic, still partly clouded to many as to the exact cellular and molecular mechanisms that bring about this phenomenon. It is an area, therefore, of active research today. This review looks at the recent published reports that have led to a greater understanding of this process. METHODS: A database search was carried out on Medline search using the terms liver regeneration with no linguistic limitations from 1966 to 2006. RESULTS: There are two randomized controlled trials on the topic and most data and information have come from experimental studies in animals. CONCLUSION: Liver regeneration is a complex, tightly controlled process involving many inflammatory cells growth factors and hormones. More information about it is awaited in studies on humans.

Congenital microgastria with limb defect combined with megaduodenum: case report and review of literature.

Congenital microgastria is a rare developmental disorder with only 59 previously reported cases. Most of the patients undergoing reconstructive surgery are in early infancy, providing gastric augmentation to achieve optimal thrive. The Hunt-Lawrence pouch is the standard surgical treatment in infancy, but late surgery in early adulthood requires different approach. This case demonstrates that duodenojejunostomy is safe and effective in the treatment of congenital, functional duodenal obstruction in adulthood.

Pancreaticoduodenectomy for advanced gastric cancer.

BACKGROUND: Although pancreaticoduodenectomy has been rarely performed for gastric cancer because of frequent morbidity and mortality, some favorable results after this procedure have been reported recently. Our objective was to present our data that might aid in the selection of patients to undergo this procedure. METHODS: Between 1970 and 2001, 23 patients who had pancreaticoduodenectomy for gastric cancer with tumor invading the pancreatic head were identified, and they were the subjects of this study. Clinical, operative, and pathological data, and morbidity and mortality rates were collected and analyzed. Survival outcome was also calculated and analyzed. RESULTS: Five patients underwent this procedure for disease in the gastric remnant, 18 undergoing the procedure for primary tumors. Median operating time was 8 h (range, 6-13 h), and median blood loss was 1600 ml (range, 700-16,000 ml). Regarding extent of gastrectomy, all patients with primary cancer (n = 18) underwent a distal gastrectomy and patients with disease in the gastric remnant (n = 5) underwent a completion gastrectomy. Incurable factors, including paraaortic lymph node metastasis, positive lavage cytology, or peritoneal dissemination were found in 8 patients. The postoperative morbidity rate was 73.9%; however, operation-related death was zero. The overall 5-year survival rate was 34.3%. The 5-year survival rate of the 8 patients with incurable factors was 0%, while that of the 15 patients without incurable factors was 47.4%. CONCLUSION: If an R0 resection can be achieved by pancreaticoduodenectomy, this procedure should be performed for patients with tumor invading the pancreatic head. Patients with incurable factors should not be considered for pancreaticoduodenectomy.