J.-R. Delpero

Results of liver transplantation in the treatment of metastatic neuroendocrine tumors. A 31-case French multicentric report.

OBJECTIVEnThe purpose of this study was to assess the value and timing of orthotopic liver transplantation (OLT) in the treatment of metastatic neuroendocrine tumors (NET).nnnSUMMARY BACKGROUND DATAnLiver metastasis from NET seems less invasive than other secondary tumors. This observation suggests that OLT may be indicated when other therapies become ineffective. However, the potential benefit of this highly aggressive procedure is difficult to assess due to the scarcity and heterogeneity of NET.nnnMETHODSnA retrospective multicentric study was carried out, including all cases of OLT for NET performed in France between 1989 and 1994. There were 15 cases of metastatic carcinoid tumor and 16 cases of islet cell carcinomas. Hormone-related symptoms were present in 16 cases (55%). Only 5 patients (16%) had no previous surgical or medical therapy before OLT. Median delay from diagnosis of liver metastasis and OLT was 19 months (range, 2 to 120).nnnRESULTSnThe primary tumor was removed at the time of OLT in 11 cases, by upper abdominal exenteration in 7 cases and the Whipple resection in 3. Actuarial survival rate after OLT was 59% at 1 year, 47% at 3 years, and 36% at 5 years. Survival rates were significantly higher for metastatic carcinoid tumors (69% at 5 years) than for noncarcinoid apudomas (8% at 4 years), because of higher tumor- and non-tumor-related mortality rates for the latter.nnnCONCLUSIONnOLT can achieve control of hormonal symptoms and prolong survival in selected patients with liver metastasis of carcinoid tumors. It does not seem indicated for other NET.

Neoadjuvant chemoradiation and pancreaticoduodenectomy for initially locally advanced head pancreatic adenocarcinoma.

BACKGROUNDnThe most accepted treatment for locally advanced pancreatic adenocarcinoma (LAPA) is chemoradiotherapy (CRT). We sought to determine the benefit of pancreaticoduodenectomy (PD) in patients with LAPA initially treated by neoadjuvant CRT.nnnMETHODSnFrom January 1996 to December 2006, 64 patients with LAPA (borderline, n=49; unresectable, n=15) received 5-fluorouracil-cisplatin-based CRT. Of the 64 patients, 47 had progressive disease at restaging. Laparotomy was performed for 17 patients, and PD was performed in 9 patients (resected group). Fifty-five patients had CRT followed by gemcitabine-based chemotherapy (unresected group).nnnRESULTSnThe median survival and overall 5 years survival duration of all 64 patients were 14 months and 12%, respectively. The mean delay between diagnosis and surgical resection was 5.5 months. Mortality and morbidity from PD were 0% and 33%, respectively. The median survival of the resected group vs. the unresected group was 24 months vs. 13 months. Three specimens presented a major pathological response at histological examination. No involved margins were found and positive lymph nodes were found in one patient. Resected patients developed distant metastases.nnnCONCLUSIONSnPD after CRT was safe and resected patients had interesting survival rates. However, resected patients developed metastatic disease and new neoadjuvant regimens are needed to improve the survival of these patients.

Neoadjuvant docetaxel-based chemoradiation for resectable adenocarcinoma of the pancreas: New neoadjuvant regimen was safe and provided an interesting pathologic response

PURPOSEnTo assess the safety and efficacy of a new neoadjuvant chemoradiation (CRT) docetaxel-based regimen in patients with resectable adenocarcinoma of the pancreatic head or body.nnnPATIENTS AND METHODSn34 patients with histologically-confirmed resectable pancreatic adenocarcinoma were included in this prospective two-center phase II study. Radiotherapy was delivered at the dose of 45xa0Gy in 25 fractions of 1.8xa0Gy per fractions, 5 days/week, over 5 weeks. Docetaxel was administered as a 1-h intravenous (IV) infusion repeated every week during 5 weeks. The dose was 30xa0mg/m(2)/week. All patients were restaged after completion of CRT.nnnRESULTSnTumor progression was documented in 11 patients (32%), stable disease was documented in 20 patients (59%), and partial remission was documented in 3 patients (9%). 23 patients still with local disease at restaging underwent explorative laparotomy. Of this, 17 patients (50%) had a curative pancreaticoduodenectomy with lymphadenectomy. Morbidity and mortality rates were 29% and 0%, respectively. Three patients (17%) had complete histological responses and 5 patients had minimal residual disease. All resected patients (nxa0=xa017) underwent R0 resection. The median and five-year survival times for the resected patients were 32 months and 41%, respectively. Among the resected patients, ten (59%) died as a result of recurrent pancreatic cancer without local tumor bed recurrence.nnnCONCLUSIONSnNeoadjuvant docetaxel-based chemoradiation is well-tolerated. Resected patients had a prolonged survival time. Further studies are needed to confirm our findings and determine the role of such a neoadjuvant approach.

Is port-site resection necessary in the surgical management of gallbladder cancer?

INTRODUCTIONnGallbladder carcinoma is frequently discovered incidentally on pathologic examination of the specimen after laparoscopic cholecystectomy (LC) performed for presumed benign disease. The objective of the present study was to assess the role of excision of port-sites from the initial LC for patients with incidental gallbladder carcinoma (IGBC) in a French registry.nnnMETHODSnData on patients with IGBC identified after LC between 1998 and 2008 were retrospectively collated in a French multicenter database. Among those patients undergoing re-operation with curative intent, patients with port-site excision (PSE) were compared with patients without PSE and analyzed for differences in recurrence patterns and survival.nnnRESULTSnAmong 218 patients with IGBC after LC (68 men, 150 women, median age 64 years), 148 underwent re-resection with curative intent; 54 patients had PSE and 94 did not. Both groups were comparable with regard to demographic data (gender, age > 70, co-morbidities), surgical procedures (major resection, lymphadenectomy, main bile duct resection) and postoperative morbidity. In the PSE group, depth of tumor invasion was T1b in six, T2 in 24, T3 in 22, and T4 in two; this was not significantly different from patients without PSE (P = 0.69). Port-site metastasis was observed in only one (2%) patient with a T3 tumor who died with peritoneal metastases 15 months after resection. PSE did not improve the overall survival (77%, 58%, 21% at 1, 3, 5 years, respectively) compared to patients with no PSE (78%, 55%, 33% at 1, 3, 5 years, respectively, P = 0.37). Eight percent of patients developed incisional hernia at the port-site after excision.nnnCONCLUSIONnIn patients with IGBC, PSE was not associated with improved survival and should not be considered mandatory during definitive surgical treatment.

A reappraisal of preoperative chemoradiation for localized pancreatic head ductal adenocarcinoma in a 5-year single-institution experience.

Resection of localized pancreatic head ductal adenocarcinoma (LPHDA) has a limited impact on survival. Mechanisms of improvement provided by preoperative chemoradiation therapy (CRT) remain under debate. This study analyzes the outcome of patients treated for LPHDA to delineate the benefits of CRT. Among 87 patients with LPHDA, 17 had a pancreaticoduodenectomy alone (group I). Thirtynine with initially resectable cancers received CRT with 5-fluorouracil-based chemotherapy (group II). Thirty-one with initially unresectable cancers were similarly treated by CRT (group III). Patients in groups II and III were restaged after completion of CRT. In patients with resectable disease, resection was planned. Patients in groups I and II were statistically comparable in terms of age, sex, and pretherapeutic stage. Median survival and 2-year overall survival in group I were 13.7 months and 31%, respectively. In group II, 23 patients (59%) had a pancreaticoduodenectomy (group IIa) and 16 patients (41%) did not have resection (group IIb). Median survival and 2-year overall survival were as follows: group IIa, 26.6 months and 51%; and group IIb, 6.1 months and 0%, respectively. In group IIa, pathologic examination revealed eight major responses (35%) including two sterilized specimens, and none of the patients had locoregional recurrence. In group III, none of the patients had resection, and median survival was 8 months with one 2-year survivor. Patient selection appears to play a major role with regard to results achieved with preoperative CRT followed by pancreaticoduodenectomy. However, a high histologic response rate and excellent local control can also be achieved.

Two-stage hepatectomy: who will not jump over the second hurdle?

BACKGROUNDnTwo-stage hepatectomy uses compensatory liver regeneration after a first noncurative hepatectomy to enable a second curative resection in patients with bilobar colorectal liver metastasis (CLM).nnnOBJECTIVEnTo determine the predictive factors of failure of two-stage hepatectomy.nnnMETHODnBetween 2000 and 2010, 48 patients with irresectable CLM were eligible for two-stage hepatectomy. The planned strategy was a) cleaning of the left hepatic lobe (first hepatectomy), b) right portal vein embolisation and c) right hepatectomy (second hepatectomy). Six patients had occult CLM (n = 5) or extra-hepatic disease (n = 1), which was discovered during the first hepatectomy. Thus, 42 patients completed the first hepatectomy and underwent portal vein embolisation in order to receive the second hepatectomy. Eight patients did not undergo a second hepatectomy due to disease progression.nnnRESULTSnUpon univariate analysis, two factors were identified that precluded patients from having the second hepatectomy: the combined resection of a primary tumour during the first hepatectomy (p = 0.01) and administration of chemotherapy between the two hepatectomies (p = 0.03). An independent association with impairment to perform the two-stage strategy was demonstrated by multivariate analysis for only the combined resection of the primary colorectal cancer during the first hepatectomy (p = 0.04).nnnCONCLUSIONnDue to the small number of patients and the absence of equivalent conclusions in other studies, we cannot recommend performance of an isolated colorectal resection prior to chemotherapy. However, resection of an asymptomatic primary tumour before chemotherapy should not be considered as an outdated procedure.

Duodenal gastrointestinal stromal tumors (GISTs): arguments for conservative surgery.

IntroductionGastrointestinal stromal tumors (GISTs) of the duodenum are rare. We sought to evaluate the postoperative courses and long-term outcomes of conservative surgery (CS) versus pancreaticoduodenectomy (PD) for patients with non-metastatic duodenal GISTs.MethodsSeventeen patients underwent surgery for duodenal GISTs between January 2000 and January 2012; 11 patients underwent CS (CS group), and six patients underwent a PD (PD group).ResultsMortality was similar between the two groups. Patients in the PD group had longer operative times, more tumors located on the pancreatic side of the duodenum, higher rates of post-operative complications including postoperative pancreatic fistulas, and a longer hospital stay, when compared with patients of CS group. All tumors were resected with clear surgical margins (R0 resection). The median disease-free survival times were not different.ConclusionCS was safe and provided similar oncologic outcomes as PD. CS should be the procedure of choice in patients with GIST that does not involve the pancreatic side of the duodenum.

Aggressive multimodal therapy of sporadic malignant insulinoma can improve survival: a retrospective 35-year study of 12 patients.

AIMnSporadic malignant insulinoma (SMI) is a rare disease, and the consequent paucity of data in the literature and the development of aggressive treatments for liver metastases have led us to retrospectively analyze a series of 12 cases of SMI.nnnMETHODSnEvery patient presenting with SMI, according to the WHO 2004 histopathology criteria, between 1970 and June 2005 in Marseille was included in the study. Patients with multiple endocrine neoplasia type 1 (MEN-1) and tumours of uncertain malignant potential were excluded.nnnRESULTSnThe ratio of male/female was 4/8, and mean age at diagnosis was 52.5 years. A 48-h fasting test in 10 patients was conclusive in nine, after a mean duration of 12 h 45 min. SMI size ranged from 7-120 mm (mean 30.3mm). Six patients had liver metastases and one had isolated lymph-node invasion. Surgery was performed in 12 patients. Five persisting diseases (mean follow-up of 1.8 years) required other treatments (chemoembolization, radiofrequency thermoablation [RFTA], liver transplantation); one patient relapsed 8.5 years after surgery; six were still in complete remission (mean follow-up of 5.8 years), and one patient had died by the time of the 24-month follow-up.nnnCONCLUSIONnAggressive sequential multimodal therapy can prolong the survival of patients with SMI even in the presence of liver metastases.

Pancreatic neuroendocrine tumor: A multivariate analysis of factors influencing survival

BACKGROUNDnThe outcomes of pancreatic neuroendocrine tumors are extremely diverse, and determining the best strategy, optimal timing of therapy and the therapeutic results depend on understanding prognostic factors. We determined the clinical, radiological and histological factors associated with survival and tumor recurrence for patients with pancreatic neuroendocrine tumor.nnnMETHODSnFrom January 1, 1991 to December 31, 2011, 127 patients with pancreatic neuroendocrine tumor underwent pancreatectomy. The variables including clinical characteristics, surgical data and pathological findings were examined by univariate and multivariate analyses.nnnRESULTSnThere were 103 patients with non-functional tumors (81%). Sixty-four patients (50%) underwent left pancreatectomy, 51 (42%) patients underwent pancreatico-duodenectomy, 12 (9%) patients underwent enucleation and 2 patients (1%) underwent central pancreatectomy. Forty-eight patients (38%) had synchronous liver metastases. Six patients (5%) required portal vein resection, and 19 (15%) patients required enlarged en-bloc resection of adjacent organs. The overall morbidity and mortality rates were 48% and 2.3%, respectively. The 1-, 3- and 5-year overall survival rates were 94%, 84%, and 74%, respectively. In multivariate analyses, synchronous liver metastases (p = 0.02) and portal vein resection (p < 0.01) were independent prognostic factors of survival.nnnCONCLUSIONSnSynchronous liver metastases and portal vein resection were found to be independent factors influencing survival.

Predictors of Survival in Ampullary, Bile Duct and Duodenal Cancers Following Pancreaticoduodenectomy: a 10-Year Multicentre Analysis.

IntroductionPredictors of survival following pancreaticoduodenectomy (PD) are well described for pancreatic cancers but are less detailed in ampullary (AC), bile duct (BDC) and duodenal cancers (DC). We therefore sought to evaluate the long-term results of PD for AC, BDC and DC, and to determine for each tumour the predictive factors of survival.MethodsMedical charts of patients operated on between 2001 and 2011 were retrospectively reviewed. Univariate and multivariate analyses were performed to determine predictors of survival.ResultsOne hundred thirty-five patients were identified. Mean follow-up was 47u2009±u200933xa0months. Median survival was not reached for DC and was 66 and 24xa0months for AC and BDC, respectively. Two-year and five-year survival rates were 80 and 51xa0% for DC and 69 and 51xa0% for AC, respectively. BDC had a significantly poorer prognosis, with two-year and five-year survival rates of 51 and 34xa0%, respectively. Predictors of survival were weight loss, N stage and International Union Against Cancer (UICC) stage for AC, T stage and resection margin status for BDC and N stage for DC.ConclusionAC, BDC and DC display distinctive predictors of survival related to the biological aggressiveness. Preoperative malnutrition worsens the prognosis. The effect of adapted nutritional management on the survival improvement has to be studied.