Gennaro Nappo

Complete pathological response after FOLFIRINOX for locally advanced pancreatic cancer. The beginning of a new era? Case report and review of the literature.

Neoadjuvant treatments (chemo or chemoradiation therapy) are used for patients with locally advanced Pancreatic Ductal Adeno-Carcinoma (PDAC). FOLFIRINOX is now considered an effective treatment modality for patients with metastatic pancreatic cancer and a promising option for patients with locally advanced PDAC. Complete pathologic response after neoadjuvant therapies is anecdotic and its prognostic impact is completely unclear. We report the case of a complete pathological response after treatment with FOLFIRINOX in a patient affected by a locally advanced PDAC with a review of the literature regarding the use of FOLFIRINOX for locally advanced PDAC.

Minimally Invasive Pancreatic Resection: Is It Really the Future?

The introduction and widespread application of minimally invasive surgery has been one of the most important innovations that radically changed the practice of surgery during the last few decades. The application to pancreatic surgery of minimally invasive approach has only recently emerged: both laparoscopic distal pancreatectomy (LDP) and laparoscopic pancreaticoduodenectomy (LPD) can be competently performed. LDP and LPD are advocated to improved perioperative outcomes, including decreased blood loss, shorter length of stay, reduced postoperative pain and expedited time to functional recovery. However, the indication to minimally invasive approach for pancreatic surgery is often benign or low-grade malignant pathologies. In this review, we summarize the current data on minimally invasive pancreatic surgery, focusing on indication, perioperative and oncological outcomes.

hERG1 channels drive tumour malignancy and may serve as prognostic factor in pancreatic ductal adenocarcinoma

Background:hERG1 channels are aberrantly expressed in human cancers. The expression, functional role and clinical significance of hERG1 channels in pancreatic ductal adenocarcinoma (PDAC) is lacking.Methods:hERG1 expression was tested in PDAC primary samples assembled as tissue microarray by immunohistochemistry using an anti-hERG1 monoclonal antibody (α-hERG1-MoAb). The functional role of hERG1 was studied in PDAC cell lines and primary cultures. ERG1 expression during PDAC progression was studied in Pdx-1-Cre,LSL-KrasG12D/+,LSL-Trp53R175H/+ transgenic (KPC) mice. ERG1 expression in vivo was determined by optical imaging using Alexa-680-labelled α-hERG1-MoAb.Results:(i) hERG1 was expressed at high levels in 59% of primary PDAC; (ii) hERG1 blockade decreased PDAC cell growth and migration; (iii) hERG1 was physically and functionally linked to the Epidermal Growth Factor-Receptor pathway; (iv) in transgenic mice, ERG1 was expressed in PanIN lesions, reaching high expression levels in PDAC; (v) PDAC patients whose primary tumour showed high hERG1 expression had a worse prognosis; (vi) the α-hERG1-MoAb could detect PDAC in vivo.Conclusions:hERG1 regulates PDAC malignancy and its expression, once validated in a larger cohort also comprising of late-stage, non-surgically resected cases, may be exploited for diagnostic and prognostic purposes in PDAC either ex vivo or in vivo.

Effects of Reactive Oxygen Species on Mitochondrial Content and Integrity of Human Anastomotic Colorectal Dehiscence: A Preliminary DNA Study

BACKGROUND: Anastomotic dehiscence is one of the most severe complications of colorectal surgery. Gaining insight into the molecular mechanisms responsible for the development of anastomotic dehiscence following colorectal surgery is important for the reduction of postoperative complications.

The Standardization of Pancreatoduodenectomy: Where Are We?

Abstract Pancreaticoduodenectomy (PD) represents an important challenge for surgeons due to the complexity of the operation, requirement for technical skills and experience, and postoperative management involving important and life-threatening complications. Despite efforts to reduce mortality in high-volume centers, the morbidity rate is still high (approximately 40–50%). The PD standardization process of surgical aspects and preoperative and postoperative settings is essential to permit pancreatic surgeons to communicate in the same language, compare experiences and results, and to improve the short- and long-term outcomes. The aim of this article is to assess the state of the art practices for important matters of debate for PD (the role of mini invasive approach, the definition and the role of mesopancreas, the extent of lymphadenectomy, the different methods of reconstructions, the prophylactic drainage of the abdominal cavity), and to suggest possible future studies.

Locally advanced pancreatic duct adenocarcinoma: pancreatectomy with planned arterial resection based on axial arterial encasement

SummaryPancreatectomy with arterial resection for locally advanced pancreatic duct adenocarcinoma (PDA) is associated with high morbidity and is thus considered as a contraindication. The aim of our study was to report our experience of pancreatectomy with planned arterial resection for locally advanced PDA based on specific selection criteria.Material and methodsAll patients receiving pancreatectomy for PDA between October 2008 and July 2014 were reviewed. The patients were classified into group 1, pancreatectomy without vascular resection (66 patients); group 2, pancreatectomy with isolated venous resection (31 patients), and group 3, pancreatectomy with arterial resection for locally advanced PDA (14 patients). The primary selection criteria for arterial resection was the possibility of achieving a complete resection based on the extent of axial encasement, the absence of tumor invasion at the origin of celiac trunk (CT) and superior mesenteric artery (SMA), and a free distal arterial segment allowing reconstruction. Patient outcomes and survival were analyzed.ResultsSix SMA, two CT, four common hepatic artery, and two replaced right hepatic artery resections were undertaken. The preferred arterial reconstruction was splenic artery transposition. Group 3 had a higher preoperative weight loss, a longer operative time, and a higher incidence of intraoperative blood transfusion. Ninety-day mortality occurred in three patients in groups 1 and 2. There were no statistically significant differences in the incidence, grade, and type of complications in the three groups. Postoperative pancreatic fistula and postpancreatectomy hemorrhage were also comparable. In group 3, none had arterial wall invasion and nine patients had recurrence (seven metastatic and two loco-regional). Survival and disease-free survival were comparable between groups.ConclusionPlanned arterial resection for PDA can be performed safely with a good outcome in highly selected patients. Key elements for defining the resectability is based on the extent of the axial arterial encasement with two criteria: the origin of the CT and SMA are free from tumor invasion and the possibility of distal reconstruction.

Microscopic Residual Tumor After Pancreaticoduodenectomy: Is Standardization of Pathological Examination Worthwhile?

ObjectivesR1 resection rate after pancreaticoduodenectomy (PD) for cancer is highly variable. The aim of this study was to verify if a standardized histopathological work-up of the specimen affects the rate of R1 resection after PD for cancer. MethodsTwo groups of specimens were managed with (standardized method [SM] group) or without (non-standardized method [NSM] group) a SM of histopathological work-up. Each group included 50 cases of PD for periampullary cancer. Differences in terms of R1 resection rate between the 2 groups were evaluated. Correlation between R1 status and local recurrence was also evaluated. ResultsThe cohort of 100 patients consisted of 66 pancreatic ductal adenocarcinoma, 15 cholangiocarcinoma, and 19 ampullary cancer. The R1 resection rate resulted statistically higher in the SM group (66% vs 10%). Local recurrence was more frequently related to R1 resection in the SM group (34.3% of cases) than in NSM group (20% of cases). ConclusionsThe use of the SM of pathological evaluation of the specimen after PD for cancer determines a significant increase of R1 resection. This remarkable difference seems to be due to the different definition of minimum clearance. The SM seems to better discriminate patients in terms of risk of local recurrence.

Liver transplantation for hereditary hemorrhagic telangiectasia: a systematic review

AIM To evaluate the indications, timing and results of liver transplantation in patients affected by hereditary hemorrhagic telangiectasia (HHT), by undertaking a systematic review of the current literature. METHODS Electronic bibliographical databases were searched on MEDLINE and Pubmed according to the PRISMA criteria. A total of 58 articles were initially found, 11 have been excluded because of single center series later included in the European Liver transplant Registry (ELTR), already reported in this study. Thirty-eight articles have been excluded because they did not report specifically new cases of liver transplantation for hereditary hemorrhagic telangiectasia. Finally 9 articles were included in the analysis. RESULTS A total of 56 patients who underwent liver transplantation for HHT are present in the English literature. One additional patient is presented in this article, for a total of 57 patients worldwide. To date, the most consistent published series is the one of the ELTR, including patients from 15 liver transplantation centers in the period 1985-2003 with a mean follow-up of 69 months. Ten-year patient and graft survival is 82.5% CONCLUSION: Liver transplantation should be considered as a radical but definitive treatment option in patients affected by HHT with liver or cardiac involvement not responsive to medical treatment.

Survivals of distal cholangiocarcinoma and pancreatic adenocarcinoma after pancreaticoduodenectomy: post-operative complications really matter?

Introduction: Pancreaticoduodenectomy (PD) has been established as the standard surgical procedure for ampullary cancer. Alternatively, ampullectomy (PR) has also been performed for benign tumors and early cancers (T1). The aim of this study was to evaluate the prognostic indicators for recurrence and survival after curative resection for ampullary cancer and to investigate whether PR can substitute for PD in T1 ampullary cancer. Methods: Eighty-eight consecutive patients with ampullary cancer underwent initial curative resection (73 PD, 15 PR) between 1985 and 2016. Clinicopathologic factors for recurrence and survival were evaluated retrospectively. Results: In univariate analysis, preoperative biliary drainage, high level of CA19-9, non-exposed protruded type, moderate or poor differentiation, pT2-4, lymph node metastasis (pN1), microvascular invasion, lymphovascular invasion, and perineural invasion were significant factors for both recurrence and survival (p < 0.05). In multivariate analysis, high CA19-9 (p = 0.036), moderate or poor differentiation (p = 0.041), pT2-4 (p = 0.040), and pN1 (p = 0.008) were independent factors for recurrence, and high CA19-9 (p = 0.030) and pN1 (p = 0.006) for survival. High CA19-9 (p = 0.030) and pT2-4 (p = 0.048) predicted pN1. Of the 37 patients with pT1, four (10.8%) had pN1. Six (40.0%) of 15 patients (12 pT1, 3 pT2) undergoing PR had recurrence. Conclusions: High CA19-9 and pN1 were the most important predictor for poor prognosis after radical surgery for ampullary cancer, therefore, more effective systemic adjuvant therapy should be considered in such patients. We suggest that PD is the optimal surgical procedure even for T1 cancer. PR should be selected carefully due to the high rate of recurrence.

The borderline resectable/locally advanced pancreatic ductal adenocarcinoma: What should be the surgeon's choice?

In 2006, MD Anderson group published a new classification of pancreatic ductal adenocarcinoma (PDAC) that took into account the degree of neoplastic involvement of peripancreatic vessels.[1] According to that, PDAC was classified as resectable, borderline resectable (BR), or locally advanced (LA).[1] From its introduction, this classification has been universally adopted, allowing a standardization of terminology used by different pancreatic centers. If, in case of resectable PDAC, upfront radical surgery followed by adjuvant chemotherapy is the gold standard treatment,[2] on the other hand, the optimal treatment strategy of patients with BR and LA-PDAC is complex, and it is still matter of debate.