Irreversible Electroporation (IRE) Combined With Chemotherapy Increases Survival in Locally Advanced Pancreatic Cancer (LAPC).

OBJECTIVES: Locally advanced pancreatic cancer (LAPC) is found in about 40% of patients with pancreatic cancer. Irreversible electroporation (IRE) is a nonthermal ablative technique that provides an alternative in patients with LAPC and can be safely combined with chemotherapy. MATERIALS AND METHODS: From 2015 until October of 2019, we performed laparotomic IRE in a total of 40 patients with stage III LAPC. The median age of these patients was 65.2 years (range: 46 to 81 y), and the median tumor size was 3.8 cm (range: 2 to 5.2 cm). 33 of 40 patients were treated preoperatively with FOLFIRINOX or nab-paclitaxel plus gemcitabine and in case of disease control, IRE was performed, whereas in 7 patients, IRE was performed without previous chemotherapy. RESULTS: All patients were treated successfully with IRE as the tumor evaluation showed no disease progression after the completion of induction chemotherapy. No IRE-related deaths occurred. Two major grade III complications were reported: pancreatic fistula grade A in 8 patients and 3 patients diagnosed with delayed gastric emptying. Up to October 31, 2019, the median overall survival (OS) of all patients was 24.2 months (range: 6 to 36 mo), and the median progression-free survival was 10.3 months (range: 3 to 24 mo). After the completion of IRE, 30 patients (75%) continued with adjuvant chemotherapy. Fifteen patients (37%) have >24 months OS and 3 patients (8%) have reached 36 months OS and are still alive. CONCLUSION: The combination of chemotherapy with IRE, which is a safe and effective procedure, may result in a survival benefit for patients with LAPC.

Initial experience with neoadjuvant FOLFIRINOX as first line therapy for locally advanced pancreatic cancer.

The prevalence of pancreatic ductal adenocarcinoma (PDAC) is increasing in the western world, being currently on of the leading causes of mortality. Surgical resection provides best chances of cure but, unfortunately, less than 20% of the patients are eligible for curative intent surgery at the time of diagnosis. Chemotherapeutic agents such as FOLFIRINOX have been used in patients with metastatic or locally advanced disease showing survival benefit. METHODS: In this pilot study, we present an early initial experience with neoadjuvant FOLFIRINOX as first line therapy for locally advanced and non resectable PDAC highlighting the toxicity and complete resection rates as well as overall survival. RESULTS: Roughly every patient experienced toxicity according to ECOG criteria with a median recorded event up to 6, most of them grade I and grade II. One third of the patients had downsizing of tumor, however only 43.3% of them ended up having resectable disease. A R0 resection was achieved in 10 of the patients (76.9%). Median follow up for the entire study was 14 months. Fourteen patients (46.6%) had stable disease and 7 (23.3%) had tumor-related death. Approximately 30% of the patients were in remission by the end of follow up. Considering the above results patients that had good response to FOLFIRINOX and underwent R0 surgical treatment had increased their median survival to 30 months compared to those who did not have oncological tumor resection (13 months). CONCLUSIONS: FOLFIRINOX is an effective treatment regimen that manages to convert unresectable -at diagnosis PDAC- to resectable with increased survival. However, due to high toxicity, treatment is only feasible in selected patients and requires close monitoring.

The efficacy and safety of the open approach irreversible electroporation in the treatment of pancreatic cancer: A systematic review.

BACKGROUND: Irreversible Electroporation (IRE) is a novel non-thermal ablation technique used in patients with locally advanced pancreatic cancer (LAPC), in the proximity of sensitive structures such as vessels, intestinal wall and the bile duct. Currently, it is only used in the setting of clinical trials. This systematic review aimed to tackle the knowledge gap in the literature, in relation to the safety and efficacy of the open approach IRE. METHODS: MEDLINE, EMBASE and Cochrane libraries were searched for English language articles published from January 2000 to December 2019. Data related to safety and efficacy were extracted. RESULTS: Nine studies involving 460 patients with LAPC were included. Open approach IRE was associated with high morbidity (29.4%) but with a survival benefit compared to traditional treatment. Median overall survival (OS) was at 17.15 months. Major morbidity was at 10.2% and mortality at 3.4%. CONCLUSIONS: Despite the paucity of literature and the low quality of evidence, the results regarding safety and efficacy appear to be encouraging. The high morbidity seems to be mitigated by a demonstrated improvement in OS. The potential of this technique is more evident when mortality and major morbidity are considered, since they are at acceptable levels. The limitations of this review have made it difficult to extract definitive conclusions. Higher quality evidence is needed in the form of large-scale multicentre randomized controlled trials. It remains to be elucidated whether the rate of adverse events decreases as our experience with this technique increases.

ALPPS for Locally Advanced Intrahepatic Cholangiocarcinoma: Did Aggressive Surgery Lead to the Oncological Benefit? An International Multi-center Study.

BACKGROUND: ALPPS is found to increase the resectability of primary and secondary liver malignancy at the advanced stage. The aim of the study was to verify the surgical and oncological outcome of ALPPS for intrahepatic cholangiocarcinoma (ICC). METHODS: The study cohort was based on the ALPPS registry with patients from 31 international centers between August 2009 and January 2018. Propensity score matched patients receiving chemotherapy only were selected from the SEER database as controls for the survival analysis. RESULTS: One hundred and two patients undergoing ALPPS were recruited, 99 completed the second stage with median inter-stage duration of 11 days. The median kinetic growth rate was 23 ml/day. R0 resection was achieved in 87 (85%). Initially high rates of morbidity and mortality decreased steadily to a 29% severe complication rate and 7% 90-day morbidity in the last 2 years. Post-hepatectomy liver failure remained the main cause of 90-day mortality. Multivariate analysis revealed insufficient future liver remnant at the stage-2 operation (FLR2) to be the only risk factor for severe complications (OR 2.91, p = 0.02). The propensity score matching analysis showed a superior overall survival in the ALPPS group compared to palliative chemotherapy (median overall survival: 26.4 months vs 14 months; 1-, 2-, and 3-year survival rates: 82.4%, 70.5% and 39.6% vs 51.2%, 21.4% and 11.3%, respectively, p < 0.01). The survival benefit, however, was not confirmed in the subgroup analysis for patients with insufficient FLR2 or multifocal ICC. CONCLUSION: ALPPS showed high efficacy in achieving R0 resections in locally advanced ICC. To get the most oncological benefit from this aggressive surgery, ALPPS would be restricted to patients with single lesions and sufficient FLR2.

Bronchobiliary fistula after hepatectomy: A case report and review of the literature.

Bronchobiliary fistula (BBF) is a rare complication following hepatectomy, and consists of an abnormal intercommunication between the biliary tract and bronchial tree. The management of this rare entity is challenging with limited current evidence to date on how to treat this condition. Herein, a case of BBF following a central hepatectomy and the successive steps of the management was presented. Fourteen months postoperatively, the patient presented to the Oncology Department complaining of new onset fever and expectoration. A computerized tomography scan revealed a BBF and the patient was subsequently referred to our department for further treatment. The surgical team decided that a further operation was required. Using the transabdominal approach, a communication between the initial intrahepatic collection and one inferior lobular bronchus was revealed. Transhiatal removal of fistula was performed with closure of the defect through the abdomen. There was no bile leak through the remaining liver parenchyma. Multidisciplinary management should be considered, taking into consideration the underlying pathology leading to this rare complication. Conservative treatment should be considered first, while surgical resection of the BBF remains an option when other therapies have failed. Surgeons should be aware of this rare complication bile duct injuries during hepatic operations can cause.

Associating liver partition and portal vein ligation for staged hepatectomy in patients with primary liver malignancies: A systematic review of the literature.

PURPOSE: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) represents a revolutionary new surgical technique and one of the most promising advances in liver surgery over the last decade, which provides rapid and effective growth of liver remnant volume, allowing surgical resection of hepatic lesions initially considered unresectable. The aim of this review was to address from a critical point of view, the impact of this novel procedure conducted for primary liver malignancies, on tumor biology itself and thus on short and long-term outcomes, as disease free survival and overall survival. METHODS: The present study was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Identification of eligible studies was performed through a systematic search of the literature using Medline/PubMed, Scopus, Cochrane, Google Scholar, and clinicaltrials.gov databases. The end date of the literature search was set to 30th November 2018. The following keywords were used for the search: "Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy", "ALPPS", "Portal Vein Embolization (PVE) And In Situ Split", "Portal Vein Ligation (PVL) And In Situ Split". RESULTS: The 28 studies enrolled in the present analysis incorporated 136 patients who were subjected to ALPPS due to primary liver malignancy. R0 resection status has been documented in 20 studies estimated to be 97.24%. 30-day mortality was 9.55%. Concerning 30-day morbidity graded according to Clavien-Dindo classification, interestingly 7 studies stated no postoperative complications, neither minor (I-II) nor major (III-V). As for the oncological outcomes, median follow up was 10 months (range 0-36), recurrence rate was 36%, disease free survival ranged from 1 to 36 months with a median of 6 months and overall survival ranged from 1 to 36 months with a median of 11 months. CONCLUSIONS: ALPPS offers a reasonable chance of complete resection in patients with unresectable primary liver tumors. Optimal selection of patients, gaining the surgical experience of carrying out this technique and its impact on short and long-term results are issues that still remain under debate while waiting for the final outcomes of the multicenter registries with larger number of cases.

Irreversible electroporation in a case of pancreatic leiomyosarcoma: a novel weapon versus a rare malignancy?

BACKGROUND: Primary pancreatic leiomyosarcoma is an extremely rare entity that needs high clinical suspicion in order to diagnose it at an early stage. Clinical characteristics, diagnosis, and management still remain challenging and controversial, especially in advanced stages, when tumor invades adjacent vessels and organs or gives distant metastases. CASE PRESENTATION: Herein, we describe a case of a 57-year-old woman suffering from advanced pancreatic leiomyosarcoma with thrombosis of the superior mesenteric vein, as well as liver lesions which were suspicious for metastasis. Multidisciplinary team decided for upfront chemotherapy to assess tumor response. Follow-up imaging after the completion of chemotherapy led tumor board to decide for subsequent surgical exploration. The patient underwent exploratory laparotomy and irreversible electroporation ablation of the pancreatic tumor. Postoperative course was uneventful, and she was discharged 10 days later with a plan to receive adjuvant therapy. To the best of our knowledge, this is the first case of pancreatic leiomyosarcoma ever reported, treated with this novel technique of irreversible electroporation that could be an alternative and feasible way for the management of these rare malignancies. CONCLUSIONS: In conclusion, primary pancreatic leiomyosarcoma is a rare and highly malignant tumor associated with poor prognosis. Nowadays, R0 surgical resection remains the cornerstone treatment, combined with adjuvant and/or neoadjuvant chemotherapy prior to resection. In the advanced setting, when major vessel invasion and distant metastases occur, chemotherapy along with irreversible electroporation ablation could be a helpful and possibly effective modality for the management of this highly aggressive tumor.

Weak stromal Caveolin-1 expression in colorectal liver metastases predicts poor prognosis after hepatectomy for liver-only colorectal metastases.

Loss of stromal Caveolin-1 (CAV1) expression is associated with poor prognosis in various cancers. We evaluated the prognostic value of CAV1 expression of both cancer cells and stromal cells in colorectal liver metastases (CRLM) in patients undergoing hepatectomy. In this retrospective study, 109 patients were enrolled. CAV1 expression was studied by immunohistochemistry. The staining was scored semiquantitatively as weak or strong. Disease-free survival (DFS) and overall survival (OS) were calculated using both Kaplan-Meier and multivariate Coxregression methods. Weak stromal CAV1 expression was associated with decreased DFS and OS in univariate and in multivariate analysis (HR 2.00; 95% CI, 1.24-3.22; P = 0.004, and HR 2.47; 95% CI, 1.28-4.76; P = 0.007, respectively). Cancer cell CAV1 expression was not associated with DFS and OS. Five-year DFS and OS rates were 13% and 43%, respectively, in patients with weak stromal CAV1 expression and 40% and 71%, respectively, in patients with strong stromal CAV1 expression. In this study, we indicate that weak stromal CAV1 expression in CRLM is an adverse prognostic factor in patients who undergo liver resection for liver-only colorectal metastases. We suggest validation of this finding in an independent cohort and consideration of risk stratification for post-hepatectomy adjuvant follow-up and therapy.

Irreversible electroporation (Nanoknife® treatment) in the field of hepatobiliary surgery: Current status and future perspectives.

PURPOSE: We aimed to provide an overview of current understanding on the potential use of irreversible electroporation (IRE) in the field of hepatobiliary surgery with a focus on current results in hepatic and pancreatic cancers, its limitations, and its current directions. METHODS: Through a review of the literature we have gathered the key articles and trials that are shaping our understanding of the current status of IRE and its prospective uses, and organized them in an easily understandable format showcasing the most up to date results. RESULTS: IRE appears to be comparable in effectiveness and postoperative pain to the more established thermal ablation methods, while having the benefit of avoiding their detrimental thermal effects. In liver cancer, IRE was shown to be efficacious with low levels of local recurrences and only minimal complications. In pancreatic cancer it proved to have significant survival benefits but more significant (although rare) complications compared to the ones seen when IRE is used in liver cancer. Current evidence suggests a promising future for IRE, but clinical randomized control trials, and further developments of treatment protocols are required to come to more stable conclusions on the effectiveness and safety of IRE. CONCLUSIONS: IRE is proving to be an adequate method for the treatment of tumors of the pancreas and liver in cases where traditional methods are unavailable. It has been proven particularly efficacious in patients with masses in close proximity to vital structures such as vessels, as well as major biliary and hepatic structures where thermal methods of ablation would cause significant complications.

Comprehensive Surgical Treatment as the Mainstay of Management in Retroperitoneal Sarcomas: Retrospective Study from Two Non-sarcoma Specialist Centers.

BACKGROUND/AIM: Complete resection, surgical expertise and individualization of patient management in comprehensive oncology centres result in better clinical outcomes in patients presenting with retroperitoneal sarcomas. PATIENTS AND METHODS: Clinical outcomes of primary and recurrent retroperitoneal sarcoma resections performed between January 2002 and December 2016 in two large surgical oncology, but non-sarcoma specialist centers, were reviewed to determine the efficacy of complete surgical resection as the principle instrument for treatment. The histological type, tumor size and grade, as well as organ resection, were recorded and subsequently reviewed. RESULTS: Our study included 108 cases of sarcoma resection (60 first-time, 38 second-time and 10 third-time laparotomies) in 60 patients (35 males and 25 females). Most patients had complete resection: 57 had a macroscopically complete (R0/R1) resection and three had R2 resection. The 90-day mortality rate was zero and morbidity was minimal. Five- and 10-year overall survival (OS) rates were 88% and 79%, respectively, whereas the corresponding disease-free survival (DFS) rates were 65% and 59%, respectively. High-grade tumors were associated with decreased DFS (hazard ratio(HR)=3.35; 95% confidence interval(CI)=1.23-9.10; p=0.018) and decreased OS (HR=7.18; 95% CI=1.50-34.22; p=0.013). CONCLUSION: Complete surgical resection of retroperitoneal sarcomas combined with individualized patient management when offered by experienced surgical oncology teams, adhering to international guidelines, can succeed in providing patients with good long-term outcomes, comparable to those achieved at sarcoma-specialist centers.

Total robotic pancreaticoduodenectomy: a systematic review of the literature.

BACKGROUND: Pancreaticoduodenectomy (PD) is a complex operation with high perioperative morbidity and mortality, even in the highest volume centers. Since the development of the robotic platform, the number of reports on robotic-assisted pancreatic surgery has been on the rise. This article reviews the current state of completely robotic PD. MATERIALS AND METHODS: A systematic literature search was performed including studies published between January 2000 and July 2016 reporting PDs in which all procedural steps (dissection, resection and reconstruction) were performed robotically. RESULTS: Thirteen studies met the inclusion criteria, including a total of 738 patients. Data regarding perioperative outcomes such as operative time, blood loss, mortality, morbidity, conversion and oncologic outcomes were analyzed. No major differences were observed in mortality, morbidity and oncologic parameters, between robotic and non-robotic approaches. However, operative time was longer in robotic PD, whereas the estimated blood loss was lower. The conversion rate to laparotomy was 6.5-7.8%. CONCLUSIONS: Robotic PD is feasible and safe in high-volume institutions, where surgeons are experienced and medical staff are appropriately trained. Randomized controlled trials are required to further investigate outcomes of robotic PD. Additionally, cost analysis and data on long-term oncologic outcomes are needed to evaluate cost-effectiveness of the robotic approach in comparison with the open technique.

Non-Whipple Operations in the Management of Benign, Premalignant and Early Cancerous Duodenal Lesions.

AIM: We reviewed our 20-year experience with non-Whipple operations (pancreas-preserving duodenectomy and transduodenal ampullectomy) for the treatment of benign, premalignant or early-stage malignant duodenal lesions. PATIENTS AND METHODS: Twenty-four patients who underwent non-Whipple operations between January 1996 and December 2015 were identified from an institutional database and retrospectively analyzed. RESULTS: Between 1996 and 2015, 10 patients underwent pancreas-preserving duodenectomy and 14 patients underwent transduodenal ampullectomy. The mean follow-up was 25.8 months (range=6-54 months) and no patient was lost to follow-up. Eighteen patients had preoperative diagnosis of duodenal adenomatosis, three patients had preoperative diagnosis of duodenal adenocarcinoma, one had a bleeding polyp and two had localized inflammation. Average operative time was 145 min (range=127-168 min) for transduodenal ampullectomy and 183 min (range=173-200 min) for pancreas-preserving duodenectomy (p<0.05). The estimated blood loss for transduodenal ampullectomy was 85 vs. 125 ml for pancreas-preserving duodenectomy (p<0.05). Early postoperative complications were noted in 13 cases (54.17%). There were no postoperative (90-day) deaths observed in this series and there were no recurrences during follow-up for the patients operated on with neoplastic lesions. CONCLUSION: For carefully selected patients, transduodenal ampullectomy and pancreas-preserving duodenectomy may be used in place of the Whipple operation for benign and occasionally early-stage malignant (Tis and T1) duodenal and ampullary disease.

Laparoscopic Approach in Colonic Diverticulitis: Dispelling Myths and Misperceptions.

BACKGROUND/AIM: Diverticular disease is a first-class health care problem and one of the most common gastrointestinal disorders in western industrialized countries, causing significant morbidity and mortality. In this review of the literature, we aim to assess the feasibility and effectiveness of the laparoscopic approach in both elective and emergency setting of diverticular disease. MATERIALS AND METHODS: A bibliographic search of articles was performed using the electronic database Medline from PubMed. Of 341 articles identified, 279 were excluded, resulting in 62 full-text articles for review. Our final review included 16 articles. RESULTS: The 16 articles included in the final review consisted of 6 retrospective studies, 5 prospective studies, 2 randomized controlled trials, 1 systematic review and meta-analysis, and 2 systematic reviews. Seven articles considered elective laparoscopic sigmoid resection, 7 articles evaluated laparoscopic peritoneal lavage, and 2 articles considered emergency laparoscopic sigmoid resection for perforated diverticulitis. The elective laparoscopic approach is feasible and safe. Laparoscopic peritoneal lavage has emerged as a safe and effective minimally invasive procedure for the treatment of perforated diverticulitis. Furthermore, in selected patients, emergency laparoscopic sigmoidectomy could also be feasible for perforated diverticulitis with generalized peritonitis. CONCLUSIONS: Laparoscopic approach can be a safe and effective option in both elective and emergency setting of diverticular disease. Large, prospective, randomized studies should be conducted to confirm these findings.

Anomalous radiological and clinical demonstration of gallbladder duplication in an asymptomatic pregnant female.

Gallbladder duplication is an uncommon congenital anatomical deviation encompassing a number of variants. The morphological difference occurs during budding of the hepatic diverticulum. We report the case of an asymptomatic pregnant woman who was incidentally found to have a large subhepatic cyst on ultrasound. The case highlights the difficulty in diagnosing large gallbladder duplication and the different radiological imaging available to surgeons to aid in mapping such anatomical variants. We propose that this case holds valuable lessons for both radiologists and surgeons when considering the differential diagnosis and management of large hepatobiliary cysts.

Parenchymal-sparing Hepatectomy as the New Doctrine in the Treatment of Liver-metastatic Colorectal Disease: Beyond Oncological Outcomes.

Colorectal cancer is one of the leading causes of mortality in the Western world. Half of patients with colorectal cancer will develop liver-metastatic (CLM) disease, with fewer than 30% having surgically resectable disease at diagnosis. It is well established in the literature that major hepatectomy offers a high rate of R0 resection, however, with concommitant increased rates of mortality and morbidity. Emerging literature during the past two decades has demonstrated the potential superiority of parenchymal-sparing hepatectomy (PSH) in treating CLM disease in terms of oncological outcomes, survival and re-operation in cases of recurrence (salvageability). To date, no data regarding the evaluation of quality of life and cost after PSH have been published. PSH seems to be correlated with less mortality and morbidity, which can be translated in lower re-admission rates, better quality of life and, therefore, reduced relevant cost. Prospective studies and clinical trials evaluating the multiple beneficial role of a PSH surgical strategy in CLM disease are mandatory to support or reject the emerging belief that PSH could be the gold standard of treatment of CLM disease.

Optimization of a green extraction method for the recovery of polyphenols from olive leaf using cyclodextrins and glycerin as co-solvents.

Olive leaf, an agricultural by-product, was studied for the valorization of its biophenols using green extraction techniques; i.e. non-toxic and eco-friendly extraction solvents were used, involving water and glycerol. 2-hydroxypropyl-ß-cyclodextrin (CD), was also employed as an enhancer of the extraction, since cyclodextrins (CD's) are known to improve the extractability of olive leaf polyphenols by forming water soluble inclusion complexes. The process was optimized by implementing a central composite (Box-Behnken) experimental design and response surface methodology, taking into consideration the following independent variables: glycerol concentration (Cgl), CD concentration (CCD) and temperature (T). The evaluation of the extraction model was based on two responses: the total polyphenol yield (YTP) and the antiradical activity (AAR). Optimum values for the extraction process were obtained at 60% (w/v) glycerol content, T = 60 °C and 7% (w/v) CD content. LC-MS analysis was also applied in order to characterize the polyphenolic composition of extracts containing cyclodextrins. The main polyphenols present were oleuropein and oleuropein derivatives. Olive leaf aqueous extracts containing glycerol and cyclodextrins may be used as raw materials/ingredients for several end-users in the food, cosmetic and pharmaceutical industries.

Mechanistic insights of rapid liver regeneration after associating liver partition and portal vein ligation for stage hepatectomy.

AIM: To highlight the potential mechanisms of regeneration in the Associating Liver Partition and Portal vein ligation for Stage hepatectomy models (clinical and experimental) that could unlock the myth behind the extraordinary capability of the liver for regeneration, which would help in designing new therapeutic options for the regenerative drive in difficult setup, such as chronic liver diseases. Associating Liver Partition and Portal vein ligation for Stage hepatectomy has been recently advocated to induce rapid future liver remnant hypertrophy that significantly shortens the time for the second stage hepatectomy. The introduction of Associating Liver Partition and Portal vein ligation for Stage hepatectomy in the surgical armamentarium of therapeutic tools for liver surgeons represented a real breakthrough in the history of liver surgery. METHODS: A comprehensive literature review of Associating Liver Partition and Portal vein ligation for Stage hepatectomy and its utility in liver regeneration is performed. RESULTS: Liver regeneration after Associating Liver Partition and Portal vein ligation for Stage hepatectomy is a combination of portal flow changes and parenchymal transection that generate a systematic response inducing hepatocyte proliferation and remodeling. CONCLUSION: Associating Liver Partition and Portal vein ligation for Stage hepatectomy represents a real breakthrough in the history of liver surgery because it offers rapid liver regeneration potential that facilitate resection of liver tumors that were previously though unresectable. The jury is still out though in terms of safety, efficacy and oncological outcomes. As far as Associating Liver Partition and Portal vein ligation for Stage hepatectomy -induced liver regeneration is concerned, further research on the field should focus on the role of non-parenchymal cells in liver regeneration as well as on the effect of Associating Liver Partition and Portal vein ligation for Stage hepatectomy in liver regeneration in the setup of parenchymal liver disease.

Prognostic indicators following curative pancreatoduodenectomy for pancreatic carcinoma: A retrospective multivariate analysis of a single centre experience.

PURPOSE: Survival after curative resection of pancreatic, ampullary and lower common bile duct cancer remains very poor. The aim of this study was to assess important prognostic factors in patients with resectable pancreatic cancer. METHODS: From 2006 to 2010, 156 patients underwent pancreatoduodenectomy (PD) for malignancies of pancreatic, ampullary or lower common bile duct in our institution. Based on the inclusion criteria 101 patients were selected in our retrospective statistical analysis. Of these 101 cases of malignancies, 65.4% were located in the pancreatic head, 18.8% in the ampulla and 15.8% in the lower bile duct. 48.5% of patients underwent classical PD, and 51.5% pylorus-preserving pancreatoduodenectomy (PPPD). Clinical and pathological data were collected, Kaplan-Meier method and Cox proportional hazard models were used to evaluate prognostic factors. RESULTS: Multivariate analysis revealed that blood transfusion, vascular invasion, T4 vs T1 stage, and R0 resection margins were significant negative predictors of survival. Conversely, ampullary (vs pancreatic ductal) and adjuvant chemotherapy were significantly associated with longer survival. Lymph node ratio (LNR), in all its forms, was not found to have a significant effect on survival. For all patients, tumor grading (p=0.042), resection margins (p=0.004), T stage (p=0.001), perineural invasion (p=0.029), vascular invasion (p=0.007) and age >65 years (p=0.009) were factors that impacted survival. CONCLUSION: Surgical resection margins, tumor grade, T stage, perineural invasion, vascular invasion, age >65 and adjuvant chemotherapy are the strongest predictors of survival after surgical resection of pancreatic, ampullary and lower common bile duct cancer. In this series, lymph node ratio did not impact survival.