http://www.swscn.org.uk/wp/wp-content/uploads/2014/11/IPMN_International-consensus-guidelines-20121.pdf

International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas

Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies

Pancreatic cancer is currently one of the most lethal diseases. In recent years, increasing evidence has shown that reprogrammed metabolism may play a critical role in the carcinogenesis, progression, treatment and prognosis of pancreatic cancer. Affected by internal or external factors, pancreatic cancer cells adopt extensively distinct metabolic processes to meet their demand for growth. Rewired glucose, amino acid and lipid metabolism and metabolic crosstalk within the tumor microenvironment contribute to unlimited pancreatic tumor progression. In addition, the metabolic reprogramming involved in pancreatic cancer resistance is also closely related to chemotherapy, radiotherapy and immunotherapy, and results in a poor prognosis. Reflective of the key role of metabolism, the number of preclinical and clinical trials about metabolism-targeted therapies for pancreatic cancer is increasing. The poor prognosis of pancreatic cancer patients might be largely improved after employing therapies that regulate metabolism. Thus, investigations of metabolism not only benefit the understanding of carcinogenesis and cancer progression but also provide new insights for treatments against pancreatic cancer.

/pdf/metabolism-of-pancreatic-cancer-paving-the-way-to-better-3cih26a49e.pdf

Metabolism of pancreatic cancer: paving the way to better anticancer strategies.

The L-type amino acid transporter (LAT) family are Na(+)-independent transporters, which deliver neutral amino acids into cells. The four LATs, LAT1 (SLC7A5), LAT2 (SLC7A8), LAT3 (SLC43A1) and LAT4 (SLC43A2), are responsible for the majority of cellular leucine uptake. They show increased expression in many cancers, and are critical for control of protein translation and cell growth through the mTORC1 pathway. The increased transporter expression observed in cancers is regulated by transcriptional pathways such as hormone receptors, c-myc and nutrient starvation responses. We review the expression and function of the LAT family in cancer, as well as the recent development of specific inhibitors targeting LAT1 or LAT3. These LAT family inhibitors may be useful adjuvant therapeutics in multiple cancers.

L-type amino acid transport and cancer: targeting the mTORC1 pathway to inhibit neoplasia

Background:

Pancreatic resections for benign diseases may lead to long-term endocrine/exocrine impairment. The aim of this study was to compare postoperative and long-term results after different pancreatic resections for benign disease.



Methods:

Between 1990 and 1999, 62 patients underwent pancreaticoduodenectomy (PD), 36 atypical resection (AR) and 64 left pancreatectomy (LP) for benign tumours. Exocrine and endocrine pancreatic function was evaluated by 72-h faecal chymotrypsin and oral glucose tolerance test.



Results:

The incidence of pancreatic fistula was significantly higher after AR than after LP (11 of 36 versus seven of 64; P = 0·028). The long-term incidence of endocrine pancreatic insufficiency was significantly lower after AR than after PD (P < 0·001). Exocrine insufficiency was more common after PD (P < 0·001) and LP (P = 0·009) than after AR. The probability of developing both endocrine and exocrine insufficiency was higher for PD and LP than for AR (32, 27 and 3 per cent respectively at 1 year; 58, 29 and 3 per cent at 5 years; P < 0·001).



Conclusion:

Different pancreatic resections are associated with different risks of developing long-term pancreatic insufficiency. AR represents the best option in terms of long-term endocrine and exocrine function, although it is associated with more postoperative complications. Copyright © 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Pancreatic insufficiency after different resections for benign tumours.

Background/aims The aim of this study was to identify factors that might affect the results of treating benign anastomotic stricture of the esophagus with balloon dilation. Methodology Balloon dilation was performed on 35 patients with benign esophageal anastomotic stricture of the upper (esophageal cancer: 18) or lower (gastric cancer: 15, esophageal varices: 2) esophagus. The procedure was considered effective when patients were able to maintain a solid diet more than 12 months after the last dilation. The follow-up period ranged from 15-130 months (mean: 51 months). Results A total of 245 dilations were performed, with an average of 6.6 dilations per patient. Treatment was effective in 29 patients (83%). Balloon dilation was successful when treating strictures shorter than 12 mm in length. The strictures were significantly shorter in patients treated effectively (5.6 vs. 30.8 mm). The diameter of the stricture did not affect the results. All the strictures in the lower esophagus and all those resulting from stapled anastomoses were treated successfully, while the effectiveness of treating strictures in the upper esophagus or those resulting from hand-sewn anastomoses was 67% and 57%, respectively. Strictures without prior leakage were treated effectively 92% of the time, while the success rate fell to 56% if there was a preceding leak. An average of 4.4 dilations were performed in effective cases, while the average was 17.5 dilations in ineffective cases. The number of repeat dilations was correlated with the length of the stricture. Conclusions Balloon dilation can successfully treat strictures shorter than 12 mm long. The correlation equation may be used to predict the number of repeat dilations and treatment results, and is useful for deciding when to use an alternative method to balloon dilation.

Endoscopic balloon dilation for benign esophageal anastomotic stricture: factors influencing its effectiveness.

Background/aims We modified the surgical procedure for segmental gastrectomy, which is normally used for peptic ulcers, to treat early gastric cancer of the mid-stomach. In this paper, we describe the surgical technique and its results. Methodology The location of the tumor was confirmed by intra-operative endoscopic examination. An area 2 cm proximal and distal to the tumor was marked with sutures. Firstly, the lymph nodes were dissected from around the perigastric and along the left gastric and common hepatic arteries. Then, a segmental gastrectomy was performed. The greater omentum, omental sac, and vagal nerve, including the hepatic, pyloric and celiac rami, were left intact. An end-to-end gastrogastrostomy was performed using Gambee's sutures and 4-0 monofilament polydioxanone. Gastric drainage was not necessary. Results We performed segmental gastrectomies on 30 patients. Tumors less than 1 cm in diameter were found in 4 patients; 1.1-2 cm in 14, 2.1-5 cm in 11, and a tumor exceeding 5.1 cm in one patient. The cancer was confined to the mucosa in 23 patients; in the other 7, it had penetrated the submucosa. No lymph node metastases were found but 2 patients had microscopic invasion or permeation of the lymphatic vessels. One patient required post-operative balloon dilation of the pyloric sphincter for delayed gastric emptying. The remaining patients had no post-operative complications. To date, 29 patients, excluding one who died in a traffic accident, have survived disease-free for a mean of 30 months (range: 7-51). Their body weight and dietary volume returned to pre-operative levels within 12 months of surgery. Conclusions Patients who underwent segmental gastrectomy have had a reasonably good quality of life in the post-operative follow-up to date.

Segmental gastrectomy for early cancer in the mid-stomach.

BACKGROUND/AIMS: Segmental pancreatectomy for benign tumors of the neck of the pancreas was reported in 1993. Mucin-producing carcinomas are generally regarded as low-grade malignancies as compared with ductal cell carcinomas of the pancreas. We report herein our experience with a segmental pancreatectomy for mucin-producing pancreatic tumors. METHODOLOGY: Three patients with mucin-producing tumors of the pancreatic body underwent a segmental pancreatectomy. After the pancreatic tumor had been located with intra-operative ultrasonography (US), the medial pancreas centered on the tumor was resected. The margin of the retained pancreas was submitted for histopathologic inspection intra-operatively to prevent retained disease. A conduit for draining the pancreatic juice consisted of a jejunal Roux-en-Y loop between the left and cephalic portions of the pancreas. Histologically, the 3 tumors were identified as a cystadenocarcinoma, an intraductal papillary adenocarcinoma, and a cystadenoma with a focus of borderline malignancy. The functional result was evaluated with oral glucose tolerance and pancreatic function diagnostic (PFD) testing. Pancreatic juice drainage was confirmed using magnetic resonance cholangiopancreatography (MRCP). RESULTS: Neither technical failure nor operative death occurred in any of the patients. The patients have been followed-up for between 33 months and 77 months after surgery and all are disease free. The oral glucose tolerance test and PFD test results were all within the normal range. MRCP showed good pancreatic juice drainage in the 2 patients examined. CONCLUSIONS: Segmental pancreatectomy may be an appropriate surgical procedure for mucin-producing pancreatic tumors, to prolong survival and to preserve endocrine and exocrine function.

Segmental pancreatectomy for mucin-producing pancreatic tumors.

A 69 year-old man with a history of thoracoplastic surgery for pulmonary tuberculosis, who required a blood transfusion and subsequently tested positive for hepatitis C virus, developed a right hypochondrial mass, swelling of the lower extremities and malaise. A huge hepatocellular carcinoma invading the suprahepatic vena cava with tumor thrombi was diagnosed radiographically. An extended right hepatectomy with supra- to retrohepatic IVC resection was performed in an en bloc fashion using a centrifugal pump for hepatic vascular exclusion (HVE). The supra- to retrohepatic IVC was replaced with an expanded polytetrafluoroethylene (ePTFE) graft, 20 mm x 10 cm in size, and the left hepatic venous confluence was reconstructed. Twenty-one months after surgery, the patient is in good condition without recurrence of tumor.

Extended hepatectomy with ePTFE graft vena caval replacement and hepatic vein reconstruction: a case report.

A 66-year-old man was admitted for an early cancer in the gastric corpus. At laparotomy, the gallbladder was located on the left side of the round ligament and attached to the lateral segment of the liver. This finding was compatible with a left-sided gallbladder. Postoperative ultrasonograms and portograms demonstrated anomalies of the intrahepatic portal vein as follows; The left umbilical portion and the posterior point of the portal branch were lacking. The posterior point was seen as an umbilical portion. An endoscopic retrograde cholangiopancreaticogram showed the cystic duct entering into the right side of the common bile duct confluent to the accessory pancreatic duct. A left-sided gallbladder unassociated with visceral inversion is a rare congenital anomaly. Forty-one cases have been reported in Japan, five with anomalies of the intrahepatic portal vein and two with anomalous junction of the pancreaticobiliary ductal system. To our knowledge, our patient is the only case of the left-sided gallbladder which both congenital anomalies.

Left-sided gallbladder with anomalies of the intrahepatic portal vein and anomalous junction of the pancreaticobiliary ductal system: a case report.

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