Vascular resection during pancreatectomy for pancreatic head cancer: A technical issue or a prognostic sign?

BACKGROUND: There is an increased interest in venous vascular resection associated with pancreatic resection for pancreatic ductal adenocarcinoma as an upfront procedure or after neoadjuvant treatment. The aim of this study was to evaluate the impact of venous vascular resection for pancreatic ductal adenocarcinoma on postoperative and long-term outcomes. METHODS: The study is a retrospective analysis of patients who underwent pancreatectomy for pancreatic head pancreatic ductal adenocarcinoma with and without venous vascular resection between January 2010 and April 2018. The impact of venous vascular resection on postoperative and pathologic data was analyzed. Univariate and multivariate analyses of predictors of disease-free and disease-specific survival were analyzed for the entire cohort. A propensity-score matched cohort analysis was subsequently performed to remove selection bias and improve homogeneity. RESULTS: Four hundred and eighty-one patients were included, and 126 (26%) underwent a venous vascular resection. Patients undergoing venous vascular resection had higher morbidity (64% vs 54%; P = .026) with no differences in 90-day postoperative mortality (3.1 vs 2.8%; P = .5). Venous vascular resections were also significantly associated with R1 resections (52% vs 37%; P = .002) and perineural invasion (87% vs 77%; P = .017). Five-year disease-free survival in patients with and without venous vascular resection were 7% and 20% (P = .018), respectively. Independent predictors of worse disease-free survival included venous vascular resection, positive lymph node status, and perineural invasion. Independent predictors of worse disease-specific survival were perineural invasion and positive nodal status, while adjuvant treatment was a protective factor. Five-year disease-specific survival in patients with and without venous vascular resection were 19% and 35% (P = .42). CONCLUSION: Pancreatectomy with venous vascular resection can be accomplished safely. Venous vascular resections are associated with poor prognostic factors and with a worse clinical outcome, being a significant predictor of cancer recurrence.

The impact of minimally invasive surgery on hospital readmissions, emergency department visits and functional recovery after distal pancreatectomy.

BACKGROUND: A recent RCT showed similar postoperative outcomes and a reduced time to functional recovery in patients undergoing minimally invasive distal pancreatectomy (DP) compared to open approach. However, it reported very-high post-discharge readmission rates, calling for further investigation. The aim of our study was to evaluate the extent to which minimally invasive surgery impacts on postoperative readmissions following DP. METHODS: Clinical data for patients undergoing DP between 2011 and 2018 were reviewed. Primary outcome was hospital readmission at 90 days after surgery. Secondary outcomes included post-discharge emergency department (ED) visits and time to functional recovery. Regression analyses were performed to evaluate the impact of the laparoscopic approach and other perioperative factors. RESULTS: Overall, 376 consecutive patients underwent DP during the study period. Laparoscopy was successfully performed in 219 (58%) patients. Overall, 62 patients (16.5%) returned to the ED after discharge, 41 (18.7%) of laparoscopically operated patients, and 21 (13.4%) of those undergoing open surgery (p = 0.162). Forty-six (12.2%) of them required readmission, 31 (14.2%) after laparoscopic, and 15 (9.6%) after open procedures (p = 0.179). At multivariate regression, a low preoperative physical status (OR 2.3, 95% CI 1.2-4.7; p = 0.017), occurrence of pancreatic fistula (OR 6.8, 95% CI 2.9-15.9; p < 0.001), and post-pancreatectomy hemorrhage (OR 3.9, 95% CI 1.2-13.1; p = 0.025) were significantly associated with 90-day readmission, while laparoscopy had no impact. Median time to reach functional recovery was 5 (IQR 4-6) days. At multivariate analysis, laparoscopy reduced time to functional recovery by 13% (95% CI - 19 to - 6%; p < 0.001), time to adequate oral intake by 19% (95% CI - 27 to - 10%; p < 0.001), and time to adequate pain control by 12% (95% CI - 18 to - 5%; p < 0.001). CONCLUSION: Hospital readmissions and ED visits following DP were not influenced by the surgical approach. A low preoperative physical status, occurrence of postoperative pancreatic fistula and hemorrhage were significantly associated with post-discharge readmission within 90 days. Laparoscopy reduced time to functional recovery.

Postoperative Outcomes and Functional Recovery After Preoperative Combination Chemotherapy for Pancreatic Cancer: A Propensity Score-Matched Study.

Introduction: Previous studies show encouraging oncologic outcomes for neoadjuvant chemotherapy (NACT) in the setting of pancreatic ductal adenocarcinoma (PDAC). However, recent literature reported an increased clinical burden in patients undergoing pancreaticoduodenectomy (PD) following NACT. Therefore, the aim of our study was to assess the impact of NACT on postoperative outcomes and recovery after PD. Methods: A retrospective propensity score-matched study was performed including all patients who underwent PD for PDAC in a single center between 2015 and 2018. Patients treated with NACT for resectable, borderline resectable or locally advanced PDAC were matched based on nearest neighbor propensity scores in a 1:1 ratio to patients who underwent upfront resection. Propensity scores were calculated using 7 perioperative variables, including gender, age, BMI, ASA score, Charlson-Deyo comorbidity score, fistula risk score (FRS), vascular resection. Primary outcome was the number and severity of complications at 90-days after surgery measured by the comprehensive complication index (CCI). Data are reported as median (IQR) or number of patients (%). Results: Of 283 resected patients, 95 (34%) were treated with NACT. Before matching, NACT patients were younger, had less comorbidities (Charlson-Deyo score 0 vs. 1, p = 0.04), similar FRS [2 (0-3) for both groups], and more vascular resections performed [n = 28 (30%) vs. n = 26 (14%), p < 0.01]. After propensity-score matching, preoperative and intraoperative characteristics were comparable. Postoperatively, CCI was similar between groups [8.7 (0-29.6) for both groups, p = 0.59]. NACT patients had a non-statistically significant increase in superficial incisional surgical site infections [n = 12 (13%) vs. 6 (6%), p = 0.14], while no difference was found for overall infectious complications and organ-space SSI. The occurrence of clinically-relevant pancreatic fistula was similar between groups [10 (11%) vs. 13 (14%), p = 0.51]. No difference was found between groups for length of hospital stay [8 (7-15) vs. 8 (7-14) days, p = 0.62], and functional recovery outcomes. Conclusion: After propensity score adjustment for perioperative risk factors, NACT did not worsen postoperative outcomes and functional recovery following PD for PDAC compared to upfront resection.

Duodeno-jejunal or gastro-enteric leakage after pancreatic resection: a case-control study.

Duodeno-jejunal (DJ) and gastro-jejunal (GJ) anastomosis leakage represents a rare but life-threatening complication after pancreaticoduodenectomy or total pancreatectomy. The aim of this study was to assess its incidence, clinical presentation, and outcomes, and to identify perioperative risk factors for DJ/GJ leak. Prospectively collected perioperative data were reviewed, and a case-control study was performed. Patients who presented with a DJ/GJ leak (cases) were matched in a 1:5 ratio with patients who did not develop it. Match criteria included age, diagnosis, type of surgery, and anastomosis. Perioperative factors and outcomes were compared between groups. From January 2008 to present, 13 cases were observed and compared to 60 controls. Concerning pre-operative variables, cases showed lower pre-operative serum hemoglobin (p = 0.021) and increased pre-operative radiotherapy (p = 0.037). Cases experienced more severe post-operative complications than Controls, according to the CD classification (p < 0.001), with a higher mortality rate (23% vs. 2%; p < 0.016). They also experienced a more demanding intra-operative course including an increased estimated blood loss (median 600 vs. 400 mL; p = 0.002), a higher rate of blood transfusion (n4 31% vs. n5 8%; p = 0.047) with also a longer operative time (median 360 vs. 318 min; p = 0.038). Moreover, the occurrence of a DJ/GJ leak was significantly associated with other post-operative complications: clinically relevant pancreatic fistula (p = 0.006), bile leak (p = 0.021), and bleeding (p = 0.001). In addition, another post-operative finding significantly related to the DJ/GJ occurrence was sepsis (p < 0.001) The DJ/GJ fistula required a surgical treatment in the majority of cases (92.3%), while, in only one patient, a conservative management was accomplished. Length of hospital stay and mortality at 90 days were higher in the DJ/GJ leak group (p = 0.001). DJ/GJ leakage is a severe complication following pancreatic resection. A higher index of suspicion for DJ/GJ fistula should be maintained in case of concomitant relevant pancreatic fistula and post-operative hemorrhage.

A randomised phase 2 trial of nab-paclitaxel plus gemcitabine with or without capecitabine and cisplatin in locally advanced or borderline resectable pancreatic adenocarcinoma.

BACKGROUND: The current trial assessed whether the addition of cisplatin and capecitabine to the nab-paclitaxel-gemcitabine backbone is feasible and active against borderline and locally advanced pancreatic adenocarcinoma (PDAC). METHOD: Fifty-four chemo-naive patients, aged between 18 and 75 years, with a pathological diagnosis of locally advanced or borderline resectable PDAC were randomised to receive either nab-paclitaxel, gemcitabine, cisplatin and oral capecitabine (PAXG; arm A; N = 26) or nab-paclitaxel followed by gemcitabine (AG; arm B; N = 28). The primary end-point was the tumour resection rate. If at least four such resections were performed, the treatment was considered as active. The secondary end-points were progression-free survival (PFS), overall survival (OS), Response Evaluation Criteria in Solid Tumours response rate, Hartman's pathologic response, carbohydrate antigen 19.9 response rate and toxicity. RESULTS: Eight patients (31%) in the PAXG arm and nine (32%) in the AG arm underwent resection. PFS at 1-year was 58% in arm A and 39% in arm B. OS at 18-month was 69% in arm A and 54% in arm B. CONCLUSIONS: In this phase II study, the addition of cisplatin and capecitabine to the AG backbone was feasible and yielded promising results in terms of disease control without detrimental impact on tolerability. The approach warrants further investigation in a phase III study. TRIAL REGISTRATION: NCT01730222.

Safety and efficacy of preoperative or postoperative chemotherapy for resectable pancreatic adenocarcinoma (PACT-15): a randomised, open-label, phase 2-3 trial.

BACKGROUND: Pancreatic ductal adenocarcinoma are known to metastasise early and a rationale exists for the investigation of preoperative chemotherapy in patients with resectable disease. We aimed to assess the role of combination chemotherapy in this setting in the PACT-15 trial. METHODS: We did this randomised, open-label, phase 2-3 trial in ten hospitals in Italy. We report the phase 2 part here. Patients aged 18-75 years who were previously untreated for pancreatic ductal adenocarcinoma, with Karnofsky performance status of more than 60, and pathologically confirmed stage I-II resectable disease were enrolled. Patients were randomly assigned (1:1:1), with a minimisation algorithm that stratified treatment allocation by centre and concentrations of carbohydrate antigen 19-9 (CA19-9 ≤5 × upper limit of normal [ULN] vs >5 × ULN), to receive surgery followed by adjuvant gemcitabine 1000 mg/m2 on days 1, 8, 15 every 4 weeks for six cycles (arm A), surgery followed by six cycles of adjuvant PEXG (cisplatin 30 mg/m2, epirubicin 30 mg/m2, and gemcitabine 800 mg/m2 on days 1 and 15 every 4 weeks and capecitabine 1250 mg/m2 on days 1-28; arm B), or three cycles of PEXG before and three cycles after surgery (arm C). Patients and investigators who gave treatments or assessed outcomes were not masked to treatment allocation. The primary endpoint was the proportion of patients who were event-free at 1 year. The primary endpoint was analysed in the per-protocol population. Safety analysis was done for all patients receiving at least one dose of study treatment. The trial is registered with ClinicalTrials.gov, number NCT01150630. FINDINGS: Between Oct 5, 2010, and May 30, 2015, 93 patients were randomly allocated to treatment. One centre was found to be non-compliant with the protocol, and all five patients at this centre were excluded from the study. Thus, 88 patients were included in the final study population: 26 in group A, 30 in group B, and 32 in group C. In the per-protocol population, six (23%, 95% CI 7-39) of 30 patients in group A were event-free at 1 year, as were 15 (50%, 32-68) of 30 in group B and 19 (66%, 49-83) of 29 in group C. The main grade 3 toxicities were neutropenia (five [28%] of 18 in group A, eight [38%] of 21 in group B, eight [28%] of 29 in group C before surgery, and ten [48%] of 21 in group C after surgery), anaemia (one [6%] in group A, four [19%] in group B, eight [28%] in group C before surgery, and five [24%] in group C after surgery), and fatigue (one [6%] in group A, three [14%] in group B, two [7%] in group C before surgery, and one [5%] in group C after surgery). The main grade 4 toxicity reported was neutropenia (two [11%] in group A, four [19%] in group B, none in group C). Febrile neutropenia was observed in one patient (3%) before surgery in group C. No treatment-related deaths were observed. INTERPRETATION: Our results provide evidence of the efficacy of neoadjuvant chemotherapy in resectable pancreatic ductal adenocarcinoma. Since the trial began, the standard of care for adjuvant therapy has altered, and other chemotherapy regimens developed. Thus, we decided to not continue with the phase 3 part of the PACT-15. We are planning a phase 3 trial of this approach with different chemotherapy regimens. FUNDING: PERLAVITA ONLUS and MyEverest ONLUS.

Early Postoperative Prediction of Clinically Relevant Pancreatic Fistula after Pancreaticoduodenectomy: usefulness of C-reactive Protein.

BACKGROUND: An early recognition of clinically relevant pancreatic fistula (PF) after pancreaticoduodenectomy (PD) is essential. METHODS: All consecutive patients who underwent PD in two institutions were included (2013-2015). In all patients amylase value in drains (AVD) was evaluated in postoperative day 1 (POD1). White-blood cell count (WBC), serum pancreatic amylase (SPA) and C-reactive protein (CRP) were routinely evaluated in POD1, POD2, and POD3. Receiver operator characteristic (ROC) curves were performed. Significant diagnostic cut-offs were tested in a multivariate model. RESULTS: Overall, 463 patients underwent PD. Postoperative morbidity and mortality were 58% and 4%, respectively. Sixty-four patients (14%) had a clinically relevant PF (grade B or C). ROC curve analyses revealed that AVD on POD1 had the greatest area under the curve value (0.881, P < 0.0001) followed by CRP on POD3 (0.796, P < 0.0001). Multivariable analysis identified male gender (OR 2.29 95%CI: 1.12-4.70, P = 0.023), AVD on POD1>500 U/l (OR 21.72, 95%CI: 7.41-63.67, P < 0.0001), CRP on POD2 > 150 mg/l (OR 3.480, 95%CI: 1.21-9.99, P = 0.021), and CRP on POD3 > 185 mg/l (OR 6.738, 95%CI: 1.91-23.78, P = 0.003) as independent predictors of clinically relevant PF. CONCLUSION: The combination of CRP and AVD was effective in the early prediction of clinically relevant POPF after PD.

Enhanced recovery pathway in patients undergoing distal pancreatectomy: a case-matched study.

BACKGROUND: Enhanced recovery (ER) pathways have improved outcomes across multiple surgical specialties, but reports concerning their application in distal pancreatectomy (DP) are lacking. The aim of this study was to assess compliance with an ER protocol and its impact on short-term outcomes in patients undergoing DP. METHODS: Prospectively collected data were reviewed. One hundred consecutive patients undergoing DP were treated within an ER pathway comprising 18 care elements. Each patient was matched 1:1 with a patient treated with usual perioperative care. Match criteria were age, BMI, ASA score, lesion site, and type of disease. RESULTS: Adherence to ER items ranged from 15% for intraoperative restrictive fluids to 100% for intraoperative warming, antibiotic and anti-thrombotic prophylaxis. Patients in ER group experienced earlier recovery of gastrointestinal function (2 vs. 3 days, p < 0.001), oral intake (2 vs. 4 days, p < 0.001), and suspension of intravenous infusions (3 vs. 5 days, p < 0.001). Overall morbidity was similar in the two groups (72% vs. 78%). Length of hospital stay (LOS) was reduced in ER patients without postoperative complications (6.7 ± 1.2 vs. 7.6 ± 1.6 days, p = 0.041). CONCLUSIONS: An ER pathway for DP yielded an earlier postoperative recovery and shortened LOS in uneventful patients. Postoperative morbidity and readmissions were similar in both groups.

Results of 100 consecutive laparoscopic distal pancreatectomies: postoperative outcome, cost-benefit analysis, and quality of life assessment.

BACKGROUND: Laparoscopic distal pancreatectomy (LDP) has been recently proposed as the procedure of choice for lesions of the pancreatic body and tail in experienced centres. The purpose of this study is to assess the potential advantages of LDP in a consecutive series of 100 patients. METHODS: Propensity score matching was used to identify patients for comparison between LDP and control open group. Match criteria were: age, gender, ASA score, BMI, lesion site and size, and malignancy. All patients were treated according to an early feeding recovery policy. Primary endpoint was postoperative morbidity rate. Secondary endpoints were operative time, blood transfusion, length of hospital stay (LOS), hospital costs, and quality of life. RESULTS: Thirty patients of the LDP group had pancreatic adenocarcinoma. Conversion to open surgery was necessary in 23 patients. Mean operative time was 29 min shorter in the open group (p = 0.002). No significant difference between groups was found in blood transfusion rate and postoperative morbidity rate. LDP was associated with an early postoperative rehabilitation and a shorter LOS in uneventful patients. Economic analysis showed 775 extra cost per patient of the LDP group. General health perception and vitality were better in the LDP group one month after surgery. CONCLUSION: Laparoscopic distal pancreatectomy improved short-term postoperative recovery and quality of life in a consecutive series of both cancer and non-cancer patients. Despite the extra cost, the laparoscopic approach should be considered the first option in patients undergoing distal pancreatectomy.

Clinical signature and pathogenetic factors of diabetes associated with pancreas disease (T3cDM): a prospective observational study in surgical patients.

To characterize the clinical signature and etiopathogenetic factors of diabetes associated with pancreas disease [type 3 diabetes mellitus (T3cDM)]. To estimate incidence and identify predictors of both diabetes onset and remission after pancreatic surgery. A prospective observational study was conducted. From January 2008 to December 2012, patients (n = 651) with new diagnosis of pancreatic disease admitted to the Pancreatic Surgery Unit of the San Raffaele Scientific Institute were evaluated. Hospital and/or outpatient medical records were reviewed. Blood biochemical values including fasting blood glucose, insulin and/or C-peptide, glycosylated hemoglobin and anti-islet antibodies were determined. Diabetes onset was assessed after surgery and during follow-up. At baseline, the prevalence of diabetes was 38 % (age of onset 64 ± 11 years). In most cases, diabetes occurred within 48 months from pancreatic disease diagnosis. Among different pancreatic diseases, minor differences were observed in diabetes characteristics, with the exception of the prevalence. Diabetes appeared associated with classical risk factors for type 2 diabetes (i.e., age, sex, family history of diabetes and body mass index), and both beta-cell dysfunction and insulin resistance appeared relevant determinants. The prevalence of adult-onset autoimmune diabetes was as previously reported within type 2 diabetes. Within a few days after surgery, either diabetes remission or new-onset diabetes was observed. In patients with pancreatic cancer, no difference in diabetes remission was observed after palliative or resective surgery. Classical risk factors for type 2 diabetes were associated with the onset of diabetes after surgery. T3cDM appeared as a heterogeneous entity strongly overlapped with type 2 diabetes.

Enhanced recovery after surgery pathway in patients undergoing pancreaticoduodenectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS(®)) pathways have reduced morbidity and length of hospital stay (LOS) in orthopedics, bariatric, and colorectal surgery. New perioperative care protocols have been tested in patients undergoing pancreaticoduodenectomy (PD), with controversial results on morbidity. Incomplete data about ERAS items compliance have been reported. The aim of this study was to assess compliance with an ERAS protocol and its impact on short-term outcome in patients undergoing PD. METHODS: A comprehensive ERAS protocol was applied in 115 consecutive patients undergoing PD. Each ERAS patient was matched with one patient who received standard perioperative care. Match criteria were age, gender, malignant/benign disease, and PD-specific prognostic score. RESULTS: No adverse effect related to ERAS items occurred. Compliance with postoperative items ranged between 38 and 66 %. The ERAS group had an earlier recovery of mobilization (p < 0.001), oral feeding (p < 0.001), gut motility (p < 0.001), and an earlier suspension of intravenous fluids (p = 0.041). No difference between ERAS and control group was found in mortality, overall morbidity, and major complication rates. Subgroup analysis showed that 43/60 (71 %) patients with early postoperative low compliance with the ERAS pathway had complications. The ERAS pathway significantly shortened LOS in uneventful patients or those with minor complications (11.2 vs. 13.7 days, p = 0.001). CONCLUSION: The ERAS pathway was feasible and safe, yielding an earlier postoperative recovery. An ERAS protocol should be implemented in patients undergoing PD; however, patients with early postoperative low compliance should be carefully managed.

Hypofractionated image-guided IMRT in advanced pancreatic cancer with simultaneous integrated boost to infiltrated vessels concomitant with capecitabine: a phase I study.

PURPOSE: To determine the maximum tolerated radiation dose (MTD) of an integrated boost to the tumor subvolume infiltrating vessels, delivered simultaneously with radical dose to the whole tumor and concomitant capecitabine in patients with pretreated advanced pancreatic adenocarcinoma. METHODS AND MATERIALS: Patients with stage III or IV pancreatic adenocarcinoma without progressive disease after induction chemotherapy were eligible. Patients underwent simulated contrast-enhanced four-dimensional computed tomography and fluorodeoxyglucose-labeled positron emission tomography. Gross tumor volume 1 (GTV1), the tumor, and GTV2, the tumor subvolume 1 cm around the infiltrated vessels, were contoured. GTVs were fused to generate Internal Target Volume (ITV)1 and ITV2. Biological tumor volume (BTV) was fused with ITV1 to create the BTV+Internal Target Volume (ITV) 1. A margin of 5/5/7 mm (7 mm in cranium-caudal) was added to BTV+ITV1 and to ITV2 to create Planning Target Volume (PTV) 1 and PTV2, respectively. Radiation therapy was delivered with tomotherapy. PTV1 received a fixed dose of 44.25 Gy in 15 fractions, and PTV2 received a dose escalation from 48 to 58 Gy as simultaneous integrated boost (SIB) in consecutive groups of at least 3 patients. Concomitant chemotherapy was capecitabine, 1250 mg/m(2) daily. Dose-limiting toxicity (DLT) was defined as any treatment-related G3 nonhematological or G4 hematological toxicity occurring during the treatment or within 90 days from its completion. RESULTS: From June 2005 to February 2010, 25 patients were enrolled. The dose escalation on the SIB was stopped at 58 Gy without reaching the MTD. One patient in the 2(nd) dose level (50 Gy) had a DLT: G3 acute gastric ulcer. Three patients had G3 late adverse effects associated with gastric and/or duodenal mucosal damage. All patients received the planned dose of radiation. CONCLUSIONS: A dose of 44.25 Gy in 15 fractions to the whole tumor with an SIB of 58 Gy to small tumor subvolumes concomitant with capecitabine is feasible in chemotherapy-pretreated patients with advanced pancreatic cancer.

Extending indications for islet autotransplantation in pancreatic surgery.

OBJECTIVE: To assess metabolic and oncologic outcomes of islet autotransplantation (IAT) in patients undergoing pancreatic surgery for either benign or malignant disease. BACKGROUND: IAT is performed to improve glycemic control after extended pancreatectomy, almost exclusively in patients with chronic pancreatitis. Limited experience is available for other indications or in patients with pancreatic malignancy. METHODS: In addition to chronic pancreatitis, indications for IAT were grade C pancreatic fistula (treated with completion or left pancreatectomy, as indicated); total pancreatectomy as an alternative to high-risk anastomosis during pancreaticoduodenectomy; and distal pancreatectomy for benign/borderline neoplasm of pancreatic body-neck. Malignancy was not an exclusion criterion. Metabolic and oncologic follow-up is presented. RESULTS: From November 2008 to June 2012, 41 patients were candidates to IAT (accounting for 7.5% of all pancreatic resections). Seven of 41 did not receive transplantation for inadequate islet mass (4 pts), patient instability (2 pts), or contamination of islet culture (1 pt). IAT-related complications occurred in 8 pts (23.5%): 4 bleeding, 3 portal thromboses (1 complete, 2 partial), and 1 sepsis. Median follow-up was 546 days. Fifteen of 34 patients (44%) reached insulin independence, 16 patients (47%) had partial graft function, 2 patients (6%) had primary graft nonfunction, and 1 patient (3%) had early graft loss. Seventeen IAT recipients had malignancy (pancreatic or periampullary adenocarcinoma in 14). Two of them had already liver metastases at surgery, 13 were disease-free at last follow-up, and none of 2 patients with tumor recurrence developed metastases in the transplantation site. CONCLUSIONS: Although larger data are needed to definitely exclude the risk of disease dissemination, the present study suggests that IAT indications can be extended to selected patients with neoplasm.

Preoperative chemotherapy does not adversely affect pancreatic structure and short-term outcome after pancreatectomy.

BACKGROUND: Preoperative chemotherapy (PCHT) has recently been proposed also in patients with resectable pancreatic adenocarcinoma. Few data are currently available on the impact of PCHT on short-term postoperative outcome after pancreatic resection. The objective of this study is to assess the impact of PCHT on pancreatic structure and short-term outcome after surgical resection. METHODS: Fifty consecutive patients successfully underwent resection after PCHT. Each patient was matched with two control patients with pancreatic adenocarcinoma selected from our prospective electronic database. Match criteria were age (±3 years), gender, American Society of Anesthesiologist score, type of resection, pancreatic duct diameter (±1 mm), and tumor size (±5 mm). Primary endpoint was morbidity rate. Secondary endpoints were pancreatic parenchymal structure, mortality rate, and length of hospital stay (LOS). RESULTS: Both degree of fibrosis and fatty infiltration of the pancreas were similar in the two groups. Overall morbidity rate was 48.0 % in the PCHT group vs. 54.0 % in the control group (p = 0.37). Pancreatic fistula rate was 18.0 % in the PCHT group vs. 25.0 % in the control group (p = 0.41). Mortality was 4.0 % in the PCHT group vs. 2.0 % in the control group (p = 0.60). Mean LOS (days) was 12.7 in the PCHT group vs. 12.4 in the control group (p = 0.74). There was no difference in resection margin status, while the rate of patients without nodal involvement was higher in the PCHT group (46.0 vs. 23.0 %, p = 0.004). CONCLUSION: PCHT did not induce significant structural changes in pancreatic parenchyma and did not adversely affect short-term outcome after surgery.

Learning curve for laparoscopic distal pancreatectomy in a high-volume hospital.

Laparoscopic distal pancreatectomy (LDP) for benign and borderline pancreatic lesions is recently becoming the treatment of choice in experienced centres. No data have been published on learning curve so far. The purpose of this study was to identify the learning curve period for performing LDP. Between March 2009 and August 2010 all patients with lesions of pancreatic body or tail were assessed for eligibility for LDP. Exclusion criteria were: major vessels contact in cancer patients, severe organ dysfunction, BMI > 35, and refusing laparoscopic approach. All laparoscopic procedures were carried out by the same surgical team with large experience in open pancreatic surgery. All patients were treated according to an early recovery after surgery protocol. Primary endpoint was conversion rate. Secondary endpoints were operative time, operative blood loss, postoperative morbidity, and length of stay (LOS). Sixty patients were assessed for eligibility. Thirty (50.0 %) patients met the exclusion criteria, while the other 30 patients underwent LDP. Spleen-preserving procedure was planned in the 17 patients with benign lesion and successfully performed in 15 (82.3 %). Overall conversion rate was 23.3 %, but it dropped significantly after the first ten patients (p = 0.01). Mean operative time progressively declined from 254 min in the first subgroup of ten patients to 206 min in the second (p = 0.09 vs. first), and 183 min in the third subgroup (p = 0.006 vs. first). No significant difference was found for operative blood loss, postoperative morbidity rate, and LOS in the different subgroups. Both conversion rate and operative time dropped after the first ten patients who underwent LDP. Strict selection criteria, high-volume hospital, and experienced team in open pancreatic surgery may have played a role in shortening the learning curve.

Analysis of prognostic factors influencing long-term survival after hepatic resection for metastatic colorectal cancer.

BACKGROUND: The aim of this study was to analyze the prognostic factors associated with long-term outcome after liver resection for colorectal metastases. The retrospective analysis included 297 liver resections for colorectal metastases. METHODS: The variables considered included disease stage, differentiation grade, site and nodal metastasis of the primary tumor, number and diameter of the lesions, time from primary cancer to metastasis, preoperative carcinoembryonic antigen (CEA) level, adjuvant chemotherapy, type of resection, intraoperative ultrasonography and portal clamping use, blood loss, transfusions, complications, hospitalization, surgical margins status, and a clinical risk score (MSKCC-CRS). RESULTS: The univariate analysis revealed a significant difference (p < 0.05) in overall 5-year survival rates depending on the differentiation grade, preoperative CEA >5 and >200 ng/ml, diameter of the lesion >5 cm, time from primary tumor to metastases >12 months, MSKCC-CRS >2. The multivariate analysis showed three independent negative prognostic factors: G3 or G4 grade, CEA >5 ng/ml, and high MSKCC-CRS. CONCLUSIONS: No single prognostic factor proved to be associated with a sufficiently disappointing outcome to exclude patients from liver resection. However, in the presence of some prognostic factors (G3-G4 differentiation, preoperative CEA >5 ng/ml, high MSKCC-CRS), enrollment of patients in trials exploring new adjuvant treatments is suggested to improve the outcome after surgery.

[Prognostic factors for long-term outcome of hepatic resection for colorectal liver metastases]. / Fattori prognostici dell'outcome a lungo termine della chirurgia resettiva epatica per metastasi da carcinoma colorettale.

The aim of the study was to analyse the prognostic factors for long-term outcome of liver resections for metastases from colorectal cancer. The retrospective analysis included 297 liver resections for colorectal carcinoma liver metastases. The following prognostic factors were considered: age, gender, stage and grade of differentiation of the primary tumour, node metastases, site of the primary colorectal cancer, number and diameter of the hepatic lesions, time interval from primary cancer to liver metastases, preoperative CEA level, adjuvant chemotherapy after hepatic resection, type of hepatic resection, use of intraoperative ultrasound and portal triad clamping, blood loss and transfusions, postoperative complications and hospital stay, tumour-free surgical margins, clinical risk score (as defined by the Memorial Sloan-Kettering Cancer Centre group, MSKCC-CRS). Overall survival rates were estimated according to the Kaplan-Meier method and were compared at univariate analysis using the log-rank test. Multivariate analysis was performed including significant variables at univariate analysis using the Cox regression model. Differences were considered significant at p < 0.05. The 1, 3, 5 and 10-year overall survival rates were 90.6%, 51%, 27.5%, and 16.9%, respectively. The univariate analysis revealed a statistically significant difference (p < 0.05) in overall survival in relation to: grade of differentiation of the primary cancer (5-year survival of grades G1-G2 vs grades G3-G4: 30.7% vs 14.4%, p = 0.0016), preoperative CEA level > 5 and > 200 ng/ml (5-year survival of CEA < 5 ng/ml vs CEA > 5 ng/ml: 51.1% vs 15.5%, p = 0.0016; 5-year survival of CEA < 200 ng/ml vs CEA > 200 ng/ml: 27.9% vs 17.4%, p = 0.0001), diameter of major lesions > 5 cm (5-year survival of diameter < or = 5 cm vs > 5 cm: 30.0% vs 18.8%, p = 0.0074), disease-free interval between primary tumour and liver metastases longer than 12 months (5-year survival of patients with disease-free interval < or = 12 months vs > 12 months: 23.0% vs 36.1%, p = 0.042), high MSKCC-CRS (5-year survival of MKSCC-CRS 0-1-2 vs 3-4-5: 36.4% vs 1 6.3%, p = 0.017). The multivariate analysis showed three independent negative prognostic factors: G3-G4 primary cancer, CEA level > 5 ng/ml, and high MSKCC-CRS class. No single prognostic factor turned out to be associated with such disappointing outcomes after hepatic surgery for colorectal liver metastases as to permit the identification of specific subgroups of patients to be excluded on principle from undergoing liver resection. However, in the presence of a number of specific prognostic factors (G3-G4 grade of differentiation of the primary tumour, preoperative CEA level > 5 ng/ml, high MSKCC-CRS) enrolment of the patient in trials exploring new diagnostic tools or new adjuvant treatments may be suggested to improve the preoperative staging of the disease and reduce the incidence of tumour recurrence after liver resection.

Successful surgical salvage of pancreas allograft.

BACKGROUND: Early and late complications related to the pancreas after simultaneous kidney-pancreas transplantation (SKPT) frequently result in graft loss. The authors describe a surgical rescue technique that allows salvage of the pancreatic graft when surgical complications appear after the transplant. METHODS: Of 158 patients who underwent SKPT, 7 were identified with posttransplant complications that required surgical salvage of the pancreas allograft. The surgical salvage technique consisted of the following: pancreatoduodenectomy with conversion from whole-pancreas transplant with bladder or enteric diversion to segmental graft with duct injection (three cases) and conversion from whole-pancreas transplant with duct injection (four cases). RESULTS: Five of seven pancreas allografts are still functioning, with a mean follow-up of 28 months (range, 6-42 months). CONCLUSION: The described surgical treatment may be useful for surgical salvage of the pancreatic allograft, without major impairment of endocrine function.

Advantages and disadvantages of enteric versus bladder diversion in simultaneous kidney-pancreas transplantation.

Simultaneous kidney-pancreas transplantation is universally accepted as being the first-choice treatment for insulin-dependent diabetes mellitus in young patients with end stage renal disease. One hundred and fifty-six simultaneous kidney-pancreas transplantations were evaluated, namely, 33 segmental pancreas transplants with duct occlusion using neoprene (group I), 73 whole pancreas transplants with bladder diversion (group II) and 46 whole pancreas transplants with enteric diversion (group III) (37 with systemic venous drainage and 9 with portal diversion). Patient actuarial survival rates at 1, 5 and 10 years were 85%, 78% and 49%, respectively, in group I and 95%, 78% and 65% in group II. In group III the rates were 87% and 72% at 1 and 3 years, respectively. Kidney survival rates at 1, 5 and 10 years were 83%, 72% and 36% in group I and 89%, 78% and 59% in group II. In group III the survival rates were 85% and 72% at 1 and 3 years. Pancreas survival rates at 1, 5 and 10 years were 66%, 37% and 15% in group I and 73%, 67% and 65% in group II. In group III the rates were 87% and 68% at 1 and 3 years. Developments in the fields of organ retrieval technology, clinical immunosuppression and surgical technique have enabled us to improve our success rates, both in terms of organ survival and the quality of life of kidney-pancreas transplant recipients.

Urological complications after simultaneous renal and pancreatic transplantation.

OBJECTIVE: To report the urological complications after simultaneous renal and pancreatic transplantation. DESIGN: Retrospective study. SETTING: Teaching hospital, Italy. SUBJECTS: 143 consecutive patients having simultaneous renal and pancreatic transplantation by one of three techniques. 33 segmental pancreas with duct occlusion, 77 whole pancreas with bladder diversion, and 33 enteric diversion with systemic (n = 26) or portal venous drainage (n = 7). Urological complications were related to the pancreatic transplant, to the renal transplant, or unrelated to the transplant. MAIN OUTCOME MEASURES: Morbidity. RESULTS: After occlusion of the duct and enteric diversion, there were no urological complications related to the pancreatic transplant. On the other hand, among the 77 patients with pancreatic drainage into the bladder, urological complications were common (56/77; 73%). Complications related to the renal transplant were recorded in 6/33 (18%), 26/77 (34%) and 12/33 (36%), respectively. Complications unrelated to the transplant occurred in 6/77 patients (8%) in the bladder drainage group. Five patients after bladder drainage required cystoenteric conversion. CONCLUSIONS: Enteric diversion is a safe alternative to bladder diversion and results in significantly fewer urological complications.