Management of Pancreatic Cystic Lesions

Background: The prevalence of undefined pancreatic cystic neoplasms (PCNs) is high in the general population, increasing with patient age. PCNs account for different biological entities with different potential for malignant transformation. The clinician must balance his or her practice between the risk of surgical overtreatment and the error of keeping a malignant lesion under surveillance. Methods: We review and discuss the clinical management of PCNs. Specifically, we analyze the main features of PCNs from the surgeon's point of view, as they present in the outpatient clinic. We also review the different consensus guidelines, address recent controversies in the literature, and present the current clinical practice at 4 different European Centers for pancreatic surgery. Results: The main features of PCNs were analyzed from the surgeon's point of view as they present in the outpatient clinic. All aspects of surgical management were discussed, from indications for surgery to intraoperative management and surveillance strategies. Conclusions: Management of PCNs requires a selective approach with the aim of minimizing clinically relevant diagnostic mistakes. Through the evaluation of clinical and radiological features of a PCN, the surgeon can elaborate on a diagnostic hypothesis and assess malignancy risk, but the final decision should be tailored to the individual patient's need

Middle Segment Pancreatectomy: A Useful Tool in the Management of Pancreatic Neoplasms

Small, benign, or low-grade malignant tumors located in the neck of the pancreas are usually treated with enucleation. However, if enucleation is too risky because of possible damage of the main pancreatic duct, standard pancreatic resections are performed. Such operations can lead to impaired long-term exocrine–endocrine function. Middle segment pancreatectomy consists of a limited resection of the midportion of the pancreas and can be performed in selected patients affected by tumors of the pancreatic neck. Middle segment pancreatectomy is a safe and feasible procedure for treating tumors of the pancreatic neck; in experienced hands it is associated with no mortality but with high morbidity, even if the rate of “clinical” pancreatic fistula is about 20%. Moreover, it allows a surgeon to preserve pancreatic parenchyma and consequently long-term endocrine and exocrine pancreatic function

Effect of hyperbaric oxygenation and gemcitabine on apoptosis of pancreatic ductal tumor cells in vitro.

Gemcitabine is first-line therapy for advanced pancreatic ductal adenocarcinoma (PDAC) with a poor survival and response rate. Hyperbaric oxygenation (HBO) enhances delivery of oxygen to hypoxic tumor cells and increases their susceptibility to cytotoxic effects of chemotherapy. We hypothesized that the anticancer activity of gemcitabine (GEM) may be enhanced if tumor cells are placed in an oxygen-rich environment. The present study evaluated the effects of gemcitabine, HBO and their combination on apoptosis of tumor cells. Materials and Methods: PANC-1 and AsPc-1 PDAC tumor cell lines wereused. Cultured tumor cells were treated with GEM at its growth-inhibitory concentration (IC50) and HBO at 2.5 ATA for 90 min or a combination of both (HBO then GEM and GEM then HBO). Twenty-four hours later, apoptotic cells ineach group were analyzed and the apoptotic index (AI) wascalculated. Results: PANC-1 cell line: HBO alone had noeffect on AI: 6.5\ub10.1 vs. 5.9\ub10.1. HBO before and aftergemcitabine did not further increase AI: 8.2\ub10.1 (HBOGEM),8.5\ub10.1 (GEM-HBO) vs. 8.1\ub10.1 (GEM). The combination of HBO and gemcitabine significantly increased AI: 10.7\ub10.02 (p<0.001 vs. all groups). AsPc-1 cell line: HBO-alone had no effect on AI: 5.9\ub10.1 vs. 5.9\ub10.1. HBO before and after gemcitabine did not further increase AI:8.2\ub10.1 (HBO-GEM), 8.4\ub10.1 (GEM-HBO) vs. 8.0\ub10.1 (GEM). The combination of HBO and gemcitabine significantly increased AI: 9.7\ub10.1 (p<0.001 vs. all groups). Conclusion: HBO-alone, whether administered before and after gemcitabine has no effect on apoptosis of PDAC cellsin vitro. HBO significantly enhanced gemcitabine-induced apoptosis when administered during gemcitabine. Our findings suggest that the time window would be critical for using HBO as adjuvant to chemotherapy

MALAT1 and HOTAIR long non-coding RNAs play opposite role in estrogen-mediated transcriptional regulation in prostate cancer cells

In the complex network of nuclear hormone receptors, the long non-coding RNAs (lncRNAs) are emerging as critical determinants of hormone action. Here we investigated the involvement of selected cancer-associated lncRNAs in Estrogen Receptor (ER) signaling. Prior studies by Chromatin Immunoprecipitation (ChIP) Sequencing showed that in prostate cancer cells ERs form a complex with the endothelial nitric oxide synthase (eNOS) and that in turn these complexes associate with chromatin in an estrogen-dependent fashion. Among these associations (peaks) we focused our attention on those proximal to the regulatory region of HOTAIR and MALAT1. These transcripts appeared regulated by estrogens and able to control ERs function by interacting with ER\u3b1/ER\u3b2 as indicated by RNA-ChIP. Further studies performed by ChIRP revealed that in unstimulated condition, HOTAIR and MALAT1 were present on pS2, hTERT and HOTAIR promoters at the ERE/eNOS peaks. Interestingly, upon treatment with17\u3b2-estradiol HOTAIR recruitment to chromatin increased significantly while that of MALAT1 was reduced, suggesting an opposite regulation and function for these lncRNAs. Similar results were obtained in cells and in an ex vivo prostate organotypic slice cultures. Overall, our data provide evidence of a crosstalk between lncRNAs, estrogens and estrogen receptors in prostate cancer with important consequences on gene expression regulatio

Definition and classification of chyle leak after pancreatic operation: A consensus statement by the International Study Group on Pancreatic Surgery

Recent literature suggests that chyle leak may complicate up to 10% of pancreatic resections. Treatment depends on its severity, which may include chylous ascites. No international consensus definition or grading system of chyle leak currently is available. The International Study Group on Pancreatic Surgery, an international panel of pancreatic surgeons working in well-known, high-volume centers, reviewed the literature and worked together to establish a consensus on the definition and classification of chyle leak after pancreatic operation. Chyle leak was defined as output of milky-colored fluid from a drain, drain site, or wound on or after postoperative day 3, with a triglyceride content ≥110 mg/dL (≥1.2 mmol/L). Three different grades of severity were defined according to the management needed: grade A, no specific intervention other than oral dietary restrictions; grade B, prolongation of hospital stay, nasoenteral nutrition with dietary restriction, total parenteral nutrition, octreotide, maintenance of surgical drains, or placement of new percutaneous drains; and grade C, need for other more invasive in-hospital treatment, intensive care unit admission, or mortality. This classification and grading system for chyle leak after pancreatic resection allows for comparison of outcomes between series. As with the other the International Study Group on Pancreatic Surgery consensus statements, this classification should facilitate communication and evaluation of different approaches to the prevention and treatment of this complicatio

International cancer of the pancreas screening (CAPS) consortium summit on the management of patients with increased risk for familial pancreatic cancer

Background Screening individuals at increased risk for pancreatic cancer (PC) detects early, potentially curable, pancreatic neoplasia. Objective To develop consortium statements on screening, surveillance and management of high-risk individuals with an inherited predisposition to PC. Methods A 49-expert multidisciplinary international consortium met to discuss pancreatic screening and vote on statements. Consensus was considered reached if ≥75% agreed or disagreed. Results There was excellent agreement that, to be successful, a screening programme should detect and treat T1N0M0 margin-negative PC and high-grade dysplastic precursor lesions (pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm). It was agreed that the following were candidates for screening: first-degree relatives (FDRs) of patients with PC from a familial PC kindred with at least two affected FDRs; patients with Peutz–Jeghers syndrome; and p16, BRCA2 and hereditary non-polyposis colorectal cancer (HNPCC) mutation carriers with ≥1 affected FDR. Consensus was not reached for the age to initiate screening or stop surveillance. It was agreed that initial screening should include endoscopic ultrasonography (EUS) and/or MRI/magnetic resonance cholangiopancreatography not CT or endoscopic retrograde cholangiopancreatography. There was no consensus on the need for EUS fine-needle aspiration to evaluate cysts. There was disagreement on optimal screening modalities and intervals for follow-up imaging. When surgery is recommended it should be performed at a high-volume centre. There was great disagreement as to which screeni

Diagnostic strategy and timing of intervention in infected necrotizing pancreatitis: an international expert survey and case vignette study

AbstractBackgroundThe optimal diagnostic strategy and timing of intervention in infected necrotizing pancreatitis is subject to debate. We performed a survey on these topics amongst a group of international expert pancreatologists.MethodsAn online survey including case vignettes was sent to 118 international pancreatologists. We evaluated the use and timing of fine needle aspiration (FNA), antibiotics, catheter drainage and (minimally invasive) necrosectomy.ResultsThe response rate was 74% (N = 87). None of the respondents use FNA routinely, 85% selectively and 15% never. Most respondents (87%) use a step-up approach in patients with infected necrosis. Walled-off necrosis (WON) is considered a prerequisite for endoscopic drainage and percutaneous drainage by 66% and 12%, respectively. After diagnosing infected necrosis, 55% routinely postpone invasive interventions, whereas 45% proceed immediately to intervention. Lack of consensus about timing of intervention was apparent on day 14 with proven infected necrosis (58% intervention vs. 42% non-invasive) as well as on day 20 with only clinically suspected infected necrosis (59% intervention vs. 41% non-invasive).DiscussionThe step-up approach is the preferred treatment strategy in infected necrotizing pancreatitis amongst expert pancreatologists. There is no uniformity regarding the use of FNA and timing of intervention in the first 2–3 weeks of infected necrotizing pancreatitis