Impact of cirrhosis in patients undergoing laparoscopic liver resection in a nationwide multicentre survey.

BACKGROUND: The aim was to analyse the impact of cirrhosis on short-term outcomes after laparoscopic liver resection (LLR) in a multicentre national cohort study. METHODS: This retrospective study included all patients undergoing LLR in 27 centres between 2000 and 2017. Cirrhosis was defined as F4 fibrosis on pathological examination. Short-term outcomes of patients with and without liver cirrhosis were compared after propensity score matching by centre volume, demographic and tumour characteristics, and extent of resection. RESULTS: Among 3150 patients included, LLR was performed in 774 patients with (24·6 per cent) and 2376 (75·4 per cent) without cirrhosis. Severe complication and mortality rates in patients with cirrhosis were 10·6 and 2·6 per cent respectively. Posthepatectomy liver failure (PHLF) developed in 3·6 per cent of patients with cirrhosis and was the major cause of death (11 of 20 patients). After matching, patients with cirrhosis tended to have higher rates of severe complications (odds ratio (OR) 1·74, 95 per cent c.i. 0·92 to 3·41; P = 0·096) and PHLF (OR 7·13, 0·91 to 323·10; P = 0·068) than those without cirrhosis. They also had a higher risk of death (OR 5·13, 1·08 to 48·61; P = 0·039). Rates of cardiorespiratory complications (P = 0·338), bile leakage (P = 0·286) and reoperation (P = 0·352) were similar in the two groups. Patients with cirrhosis had a longer hospital stay than those without (11 versus 8 days; P = 0·018). Centre expertise was an independent protective factor against PHLF in patients with cirrhosis (OR 0·33, 0·14 to 0·76; P = 0·010). CONCLUSION: Underlying cirrhosis remains an independent risk factor for impaired outcomes in patients undergoing LLR, even in expert centres.

ANTECEDENTES: El objetivo de este estudio fue analizar el impacto de la cirrosis en los resultados a corto plazo después de la resección hepática laparoscópica (laparoscopic liver resection, LLR) en un estudio de cohortes multicéntrico nacional. MÉTODOS: Este estudio retrospectivo incluyó todos los pacientes sometidos a LLR en 27 centros entre 2000 y 2017. La cirrosis se definió como fibrosis F4 en el examen histopatológico. Los resultados a corto plazo de los pacientes con hígado cirrótico (cirrhotic liver CL) (pacientes CL) y los pacientes con hígado no cirrótico (non-cirrhotic liver, NCL) (pacientes NCL) se compararon después de realizar un emparejamiento por puntaje de propension del volumen del centro, las características demográficas y del tumor, y la extensión de la resección. RESULTADOS: Del total de 3.150 pacientes incluidos, se realizó LLR en 774 (24,6%) pacientes CL y en 2.376 (75,4%) pacientes NCL. Las tasas de complicaciones graves y mortalidad en el grupo de pacientes CL fueron del 10,6% y 2,6%, respectivamente. La insuficiencia hepática posterior a la hepatectomía (post-hepatectomy liver failure, PHLF) fue la principal causa de mortalidad (55% de los casos) y se produjo en el 3,6% de los casos en pacientes CL. Después del emparejamiento, los pacientes CL tendieron a tener tasas más altas de complicaciones graves (razón de oportunidades, odds ratio, OR 1,74; i.c. del 95% 0,92-0,41; P = 0,096) y de PHLF (OR 7,13; i.c. del 95% 0,91-323,10; P = 0,068) en comparación con los pacientes NCL. Los pacientes CL estuvieron expuestos a un mayor riesgo de mortalidad (OR 5,13; i.c. del 95% 1,08-48,6; P = 0,039) en comparación con los pacientes NCL. Los pacientes CL presentaron tasas similares de complicaciones cardiorrespiratorias graves (P = 0,338), de fuga biliar (P = 0,286) y de reintervenciones (P = 0,352) que los pacientes NCL. Los pacientes CL tuvieron una estancia hospitalaria más larga (11 versus 8 días; P = 0,018) que los pacientes NCL. La experiencia del centro fue un factor protector independiente de PHLF (OR 0,33; i.c. del 95% 0,14-0,76; P = 0,010) pacientes CL. CONCLUSIÓN: La presencia de cirrosis subyacente sigue siendo un factor de riesgo independiente de peores resultados en pacientes sometidos a resección hepática laparoscópica, incluso en centros con experiencia.

FOLFOX4 versus sequential dose-dense FOLFOX7 followed by FOLFIRI in patients with resectable metastatic colorectal cancer (MIROX): a pragmatic approach to chemotherapy timing with perioperative or postoperative chemotherapy from an open-label, randomized phase III trial.

BACKGROUND: Perioperative FOLFOX4 (oxaliplatin plus 5-fluorouracil/leucovorin) chemotherapy is the current standard in patients with resectable metastases from colorectal cancer (CRC). We aimed to determine whether a sequential chemotherapy with dose-dense oxaliplatin (FOLFOX7) and irinotecan (FOLFIRI; irinotecan plus 5-fluorouracil/leucovorin) is superior to FOLFOX4. The chemotherapy timing was not imposed, and was perioperative or postoperative. PATIENTS AND METHODS: In this open-label, phase III trial, patients with resectable or resected metastases were randomly assigned either to 12 cycles of FOLFOX4 (oxaliplatin 85 mg/m(2)) or 6 cycles of FOLFOX7 (oxaliplatin 130 mg/m(2)) followed by 6 cycles of FOLFIRI (irinotecan 180 mg/m(2)). Randomization was done centrally, with stratification by chemotherapy timing, type of local treatment (surgery versus radiofrequency ablation with/without surgery), and Fong's prognostic score. The primary end point was 2-year disease-free survival (DFS). RESULTS: A total of 284 patients were randomized, 142 in each treatment group. Chemotherapy was perioperative in 168 (59.2%) patients and postoperative in 116 (40.8%) patients. Perioperative chemotherapy was preferentially proposed for synchronous metastases, whereas postoperative chemotherapy was more frequently used for metachronous metastases. Two-year DFS was 48.5% in the FOLFOX4 group and 50.0% in the FOLFOX7-FOLFIRI group. In the multivariable analysis, more than one metastasis [hazard ratio (HR) = 2.15] and synchronous metastases (HR = 1.63) were independent prognostic factors for shorter DFS. Five-year overall survival (OS) rate was 69.5% with FOLFOX4 versus 66.6% with FOLFOX7-FOLFIRI. CONCLUSIONS: FOLFOX7-FOLFIRI is not superior to FOLFOX4 in patients with resectable metastatic CRC. Five-year OS rates observed in both groups are the highest ever reported in this setting, possibly reflecting the pragmatic approach to chemotherapy timing. CLINICAL TRIALS NUMBER: NCT00268398.

Distal pancreatectomy for pancreatic carcinoma in the era of multimodal treatment.

BACKGROUND: Recent publications have suggested improvements in the outcome of distal pancreatectomy (DP) for cancer, but the series were small and heterogeneous. The aim of the present study was to assess perioperative and long-term outcomes of DP for pancreatic adenocarcinoma in the era of multimodal treatment in a major European country. METHODS: This was a nationwide study of all patients undergoing DP for pancreatic adenocarcinoma between 2004 and 2009 in 28 centres in France. Postoperative and long-term outcomes were assessed retrospectively and outcome predictors were explored by multivariable analysis. RESULTS: A total of 278 patients were enrolled. Multivisceral resections were performed in 58 patients (20·9 per cent), venous resections in 33 (11·9 per cent) and arterial resections in 11 (4·0 per cent). Neoadjuvant chemoradiotherapy was used in 20 patients. Postoperative complications occurred in 96 patients (34·5 per cent) and pancreatic fistulas developed in 76 (27·3 per cent). The postoperative 90-day mortality rate was 5·0 per cent. In univariable analysis, multivisceral resection was the only factor associated with postoperative morbidity (P = 0·048). Age 65 years or less, body mass index of at least 30 kg/m(2) and absence of preoperative chemoradiotherapy were associated with an increased risk of pancreatic fistula in multivariable analysis. Overall survival rates at 3 and 5 years were 44·9 and 29·5 per cent respectively. In multivariable analysis, only the presence of lymph node metastases was associated with poorer overall survival. CONCLUSION: Postoperative morbidity and mortality associated with pancreatic fistula remain considerable after DP, but both short- and long-term survival have improved markedly.

Para-aortic lymph node sampling in pancreatic head adenocarcinoma.

BACKGROUND: The significance of positive para-aortic nodes in patients with resectable pancreatic carcinoma is unclear. This study sought to evaluate the accuracy of intraoperative detection and prognostic significance of these lymph nodes in patients with resected adenocarcinoma of the pancreatic head. METHODS: From 2000 to 2010, para-aortic node sampling was performed prospectively in all patients before pancreatoduodenectomy. Frozen sections were created and nodes categorized as positive or negative for metastases. Surgeons were blinded to the frozen-section results. This was followed by standard histopathological assessment of corresponding paraffin-embedded, haematoxylin and eosin-stained material. Nodes considered uninvolved by this analysis were examined immunohistochemically for micrometastases. RESULTS: A total of 111 consecutive patients were included, with a median follow-up of 20·8 (range 1·5-126) months. The 1-, 2- and 5-year overall survival (OS) and disease-free survival (DFS) rates were 73·6, 54·0 and 24·7 per cent, and 51·8, 28·1 and 18·8 per cent respectively. Para-aortic node involvement was always associated with peripancreatic lymph node metastasis, and was detected by frozen-section analysis in 12 patients and by haematoxylin and eosin staining in 17. Sensitivity and specificity of frozen-section examination for detecting para-aortic lymph node metastases were 71 and 100 per cent respectively. Median OS for patients with and without para-aortic node involvement on frozen-section analysis was 9·7 versus 28·5 months respectively (P = 0·012), and 15·7 versus 27·2 months (P = 0·050) when assessed by haematoxylin and eosin staining. Median DFS for patients with and without para-aortic node involvement on frozen-section examination was 5·6 versus 12·9 months respectively (P = 0·041), and 8·4 versus 12·9 months (P = 0·038) for haematoxylin and eosin analysis. The presence of micrometastases in para-aortic nodes was not significantly associated with altered OS or DFS. CONCLUSION: Para-aortic node sampling with frozen-section examination detects distant lymphatic involvement reliably. It should be performed systematically. When metastases are found, they should be considered a contraindication to pancreatic resection.

Influence of bile duct obstruction on the results of Frey's procedure for chronic pancreatitis.

OBJECTIVES: To evaluate the influence of a biliary obstruction (BO) requiring biliary bypass on both short and long-term outcomes of patients undergoing Frey's procedure for chronic pancreatitis (CP). METHODS: From 1999 to 2010, 33 consecutive patients underwent Frey's procedure for CP in two centers. Seventeen (54%) patients underwent biliary bypass to treat an associated BO. Characteristics and outcomes of these patients were compared to those of 16 others without BO. RESULTS: Patients with BO had more severe disease including lower BMI and larger pancreatic head (4 cm vs. 6 cm, p = 0.021). The operative mortality was nil. Patients with BO experienced more overall postoperative complications (71% vs. 31%, p = 0.024) but similar major complication rates (18% vs. 6%, p = 0.316) compared to those without BO. After a median follow-up of 51 (1-96) months, 91% of the patients experienced either partial or complete relief of their symptoms and 36% exhibited deterioration of their endocrine function. Multivariate analysis revealed preoperative BO to be associated with long-term impairment of endocrine function (OR: 43.249; 95% CI 2.221-84.277; p = 0.013). CONCLUSION: In patients undergoing Frey's procedure for CP, associated BO can be safely managed using biliary bypass. However, the severity of CP in these patients is responsible for a higher risk of long-term endocrine insufficiency.

Combined HER2 analysis of biopsies and surgical specimens to optimize detection of trastuzumab-eligible patients in eso-gastric adenocarcinoma: a GERCOR study.

BACKGROUND: HER2 is overexpressed in 10 to 20% of gastro-esophageal adenocarcinoma (GE-ADK), and is a target for trastuzumab in metastatic patients. We conducted a study to compare HER2 expression between diagnostic biopsies (DBs) and surgical specimens (SSs) of GE-ADK, and to determine the influence of non-trastuzumab containing neoadjuvant chemotherapy (NAC) on this expression. PATIENTS AND METHODS: Pathological specimens from biopsies of 228 patients operated on between 2004 and 2011 were collected. Two cohorts treated (n = 141) or not (n = 87) with a NAC were constituted. Two blind independent pathological HER2 analyses on DB and on SS were carried out using immunohistochemistry (IHC) and colorimetric in situ hybridization (CISH). HER-2 overexpression (HER2+) was defined by a score 3+ in IHC, or 2+ with a positive CISH test, according to the specific HER2 scoring guidelines for GE-ADK. RESULTS: Paired HER2 status could be determined for 218 out of the 228 patients (95.6%). HER2+ rates were 13.3% on DB (29/218) and 14.7% on SS (32/218). HER2+ tumors were mainly cardial or esophageal adenocarcinomas, with a well-differentiated, intestinal histological type. HER2 status differed between DB and SS in 6% of cases. When DB analyses were added to SS analyses, the relative increase in HER2+ cases was 13.5% (17.1% for patients with NAC and 23.5% for patients with histological response to NAC, versus 7.1% for patients without NAC, P = 0.4, NS). Differences between DB and SS HER2 expression could be explained by intratumoral heterogeneity and by a HER2 expression decrease in SS after NAC in responding patients possibly due to a higher chemosensitivity of HER2-positive clones. CONCLUSION: The determination of HER2 status on DB provides results that complete those obtained with SS. Combining the analysis of DB and of SS enables to optimize the selection of trastuzumab-eligible patients in case of metastatic relapse, and particularly in previously NAC-responding patients.

Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma.

BACKGROUND: Prognosis of patients with pancreatic adenocarcinoma is poor. Many prognostic biomarkers have been tested, but most studies included heterogeneous patients. We aimed to investigate the prognostic and/or predictive values of four relevant biomarkers in a multicentric cohort of patients. PATIENTS AND METHODS: A total of 471 patients who had resected pancreatic adenocarcinoma were included. Using tissue microarray, we assessed the relationship of biomarker expressions with the overall survival: Smad4, type II TGF-ß receptor, CXCR4, and LKB1. RESULTS: High CXCR4 expression was found to be the only independent negative prognostic biomarker [hazard ratio (HR) = 1.74; P < 0.0001]. In addition, it was significantly associated with a distant relapse pattern (HR = 2.19; P < 0.0001) and was the strongest prognostic factor compared with clinicopathological factors. In patients who did not received adjuvant treatment, there was a trend toward decrease in the overall survival for negative Smad4 expression. Loss of Smad4 expression was not correlated with recurrence pattern but was shown to be predictive for adjuvant chemotherapy (CT) benefit (HR = 0.59; P = 0.002). CONCLUSIONS: CXCR4 is a strong independent prognostic biomarker associated with distant metastatic recurrence and appears as an attractive target to be evaluated in pancreatic adenocarcinoma. Negative SMAD4 expression should be considered as a potential predictor of adjuvant CT benefit.

[A rare cause of acute small bowel obstruction: incarcerated Spieghelian hernia. Case-report and literature review]. / Une cause rare d'occlusion aiguë du grêle : la hernie de Spiegel étranglée. Description d'un cas et revue de la littérature.

A 73-year-old man, who previously underwent laparotomy for pancreatic adenocarcinoma, was admitted in the emergency room for acute small bowel obstruction related to a strangulated Spieghelian hernia. On CT-scan, the hernia was located at the lateral border of the right rectus abdominis muscle below the external oblique muscle, among the transverse abdominis and internal oblique muscles layers. Spieghelian hernias (or hernia of the linea semilunaris) often occur at the level of a weak spot where the linea accurata crosses the linea semilunaris, when the posterior layer of the rectus gain changes its conformation. This weak spot is limited underneath by the inferior epigastric artery. When examining a patient with a previous history of laparotomy presenting with acute small bowel obstruction, it is mandatory to exclude a possible strangulated Spieghelian hernia before concluding to postoperative intra-abdominal adhesions. Spieghelian hernias are asymptomatic in approximately 90% of cases but entail a high risk of strangulation. Consequently, herniorrhaphy through a local approach route or open/laparoscopic mesh repair is always required.

The value of 18F-FDG positron emission tomography to differentiate benign from malignant intraductal papillary mucinous neoplasms: A prospective multicenter study.

OBJECTIVE: To assess the value of 18F-FDG PET/CT in differentiating between benign and malignant intraductal papillary mucinous neoplasms (IPMN) of the pancreas. SUMMARY BACKGROUND DATA: Malignant or high-risk IPMN require surgical resection but surgery should be avoided in patients with IPMN carrying a low risk of malignancy. 18F-FDG PET has been studied mostly in small, single center, retrospective series. METHODS: Prospective, non-comparative, multicenter French study. The primary endpoint was the specificity of PET/CT for identifying malignant IPMN (in situ or invasive carcinoma). Final diagnosis was obtained from pathological examination of the resected specimen. RESULTS: Among 120 patients analyzed, 99 had confirmed IPMN, including 24 with malignant lesions, namely 9 with carcinoma in situ and 15 with invasive carcinoma. The 18F-FDG PET/CT was positive in 44 and 31 patients in the overall and IPMN populations respectively. In the 99 IPMN patients, PET/CT showed 13 true positive, 18 false positive, 57 true negative and 11 false negative results. The sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) for the diagnosis of malignancy were 54.2%, 76.0%, 83.8% and 41.9% respectively, versus 64.9%, 75.9%, 82.9% and 54.5% in the overall population. We could not identify a cut-off value for SUVmax to distinguish benign from malignant lesions. Conventional imaging included computed tomography, magnetic resonance cholangiopancreatography and endoscopic ultrasound. In IPMN patients who underwent the 3 techniques, sensitivity, specificity, NPV and PPV were 66.7%, 84.4%, 84.4% and 66.7% respectively. CONCLUSIONS: In this study, 18F-FDG PET/CT did not perform better than conventional imaging to differentiate malignant from benign IPMN.

Predictors of long-term survival after liver transplantation for metastatic endocrine tumors: an 85-case French multicentric report.

Liver transplantation (LTx) for metastatic endocrine tumors (MET) remains controversial due to the lack of clear selection criteria. From 1989 to 2005, 85 patients underwent LTx for MET. The primary tumor was located in the pancreas or duodenum in 40 cases, digestive tract in 26 and bronchial tree in five. In the remaining 14 cases, primary location was undetermined at the time of LTx. Hepatomegaly (explanted liver > or =120% of estimated standard liver volume) was observed in 53 patients (62%). Extrahepatic resection was performed concomitantly with LTx in 34 patients (40%), including upper abdominal exenteration (UAE) in seven. Postoperative in-hospital mortality was 14%. Overall 5-year survival was 47%. Independent factors of poor prognosis according to multivariate analysis included UAE (relative risk (RR): 3.72), primary tumor in duodenum or pancreas (RR: 2.94) and hepatomegaly (RR: 2.63). After exclusion of cases involving concomitant UAE, the other two factors were combined into a risk model. Five-year survival rate was 12% for the 23 patients presenting both unfavorable prognostic factors versus 68% for the 55 patients presenting one or neither factor (p < 10(-7)). LTx can benefit selected patients with nonresectable MET. Patients presenting duodeno-pancreatic MET in association with hepatomegaly are poor indications for LTx.

[Autoimmune pancreatitis mimicking an intra-ductal papillary mucinous neoplasm of the pancreas: an original case]. / Pancréatite auto-immune mimant une tumeur intracanalaire papillaire et mucineuse : une observation originale et trompeuse.

In recent years, autoimmune pancreatitis (AIP) has been increasingly recognized. It can be associated with diabetes mellitus and other systemic autoimmune diseases, or with bile ducts lesions, which are also responsive to steroid therapy as pancreatic lesions. We report the case of a 34-year-old man with a history of a first acute pancreatitis, attributed to an intraductal papillary-mucinous neoplasm of the pancreas (IPMN) with segmental involvement of the main pancreatic duct. A spleno-pancreatectomy was performed, and pathological examination of the specimen diagnosed autoimmune pancreatitis. A treatment with corticosteroids was carried out. To our knowledge, this is the first reported case of AIP mimicking IPMN of the main pancreatic duct.

Contribution of solid-phase hexapeptide ligand libraries to the repertoire of human bile proteins.

Proteins in bile may have important physiological functions and serve as disease biomarkers. Here, the protein composition of human gallbladder bile was analyzed using a recently described chromatography-like technology capable to enhance the signal of low-abundance species. First, proteins present in bile fluid were treated with immobilized peptide ligand libraries to concentrate dilute and very dilute species while concomitantly diluting the high-abundance proteins. The analysis of resulting protein mixture was then performed using LC-MS/MS after having classically separated proteins by a mini preparative gel electrophoresis. Overall 222 gene products were found; 143 of them were not reported before in proteomics studies. Ligand libraries by themselves contributed to find 81 new gene products distributed throughout different categories. The described chromatographic approach provides a significant contribution to the bile protein repertoire and opens new perspectives for the discovery of markers for specific biliary tract diseases.

Resectable invasive IPMN versus sporadic pancreatic adenocarcinoma of the head of the pancreas: Should these two different diseases receive the same treatment? A matched comparison study of the French Surgical Association (AFC).

PURPOSE: To compare survival and impact of adjuvant chemotherapy in patients who underwent pancreaticoduodenectomy (PD) for invasive intraductal papillary mucinous neoplasm (IIPMN) and sporadic pancreatic ductal adenocarcinoma (PDAC). METHODS: From 2005 to 2012, 240 patients underwent pancreatectomy for IIPMN and 1327 for PDAC. Exclusion criteria included neoadjuvant treatment, pancreatic resection other than PD, vascular resection, carcinoma in situ, or <11 examined lymph nodes. Thus, 82 IIPMN and 506 PDAC were eligible for the present study. Finally, The IIPMN group was matched 1:2 to compose the PDAC group according to TNM disease stage, perineural invasion, lymph node ratio, and margin status. RESULTS: There was no difference in patient's characteristics, intraoperative parameters, postoperative outcomes, and histologic parameters. Overall survival and disease-free survival times were comparable between the 2 groups. In each group, overall survival time was significantly poorer in patients who did not achieve adjuvant chemotherapy (p = 0.03 for the IIPMN group; p = 0.03 for the PDAC group). In lymph-node negative patients of the IIPMN group, adjuvant chemotherapy did not have any significant impact on overall survival time (OR = 0.57; 95% CI [0.24-1.33]). Considering the whole population (i.e. patients with IIPMN and PDAC; n = 246), patients who did not achieve adjuvant chemotherapy had poorer survival (p < 0.01). CONCLUSIONS: The courses of IIPMN and PDAC were similar after an optimized stage-to-stage comparison. Adjuvant chemotherapy was efficient in both groups. However, in lymph node negative patients, adjuvant chemotherapy seemed not to have a significant impact.

Ciliated hepatic foregut cyst with extensive squamous metaplasia: report of a case.

Ciliated hepatic foregut cysts (CHFC) are rare cystic lesions of the liver composed of a ciliated pseudostratified columnar epithelium with mucous cells, connective tissue, and smooth muscles bundles. We report the first case of CHFC with extensive squamous metaplasia without dysplasia or carcinoma. A unilocular, avascular, hypoechoic 60-mm liver lesion located in segment IV was detected by ultrasonography in a 31-year-old woman. The cyst was surgically removed and was lined mainly by a regular squamous epithelium without keratin formation. After extensive sampling, a ciliated pseudostratified columnar epithelium with some alcian blue-positive goblet cells was identified. The lesion was totally examined and there was no epithelial dysplasia or carcinoma. Squamous epithelium is very rare in hepatic foregut cysts and may degenerate into squamous carcinoma. Squamous epithelium is also described in biliary cysts. When squamous epithelium is identified in a liver cyst, an extensive sampling is recommended to identify possible foci of squamous carcinoma and to classify more precisely the histological type of the lesion. Because some cases of squamous carcinoma have been described in CHFC, surgical removal of the lesion may be more appropriate than close follow-up or sclerosing therapy.

Prognostic score for recurrence after Whipple's pancreaticoduodenectomy for ampullary carcinomas; results of an AGEO retrospective multicenter cohort.

BACKGROUND: Ampullary carcinoma (AC) is a relatively rare entity often managed as a biliopancreatic carcinoma. AC has a better prognosis than peri ampullary tumors after resection, but more than a third of patients relapse. Factors predictive of recurrence are controversial, mainly because the relevant studies are very small or also included non AC tumors. There are no guidelines on the use of adjuvant or neoadjuvant chemotherapy. The aim of this study was to identify prognostic factors for recurrence after AC resection in a large multicentric cohort, and to establish a simple, practical, predictive score for recurrence in order to guide multidisciplinary decisions. METHODS: We included 152 consecutive patients who underwent Whipple's pancreaticoduodenectomy for ampullary carcinoma from January 2000 to December 2010 in 10 gastrointestinal oncology departments. RESULTS: The estimated overall 5-year disease-free survival rate (DFS) was 47.1%. In multivariate analysis, age≥ 75 years at diagnosis (p < 0.0001), poor general condition (p = 0.01), poorly (p = 0.005) or moderately differentiated tumors (p = 0.01) and TNM stage IIb or III (p = 0.05) were associated with poor DFS. Based on this multivariate analysis, we developed a prognostic score with three levels of risk: DFS at 5 years was 73.5% in the low-risk group and 20.1% in the high-risk group. CONCLUSION: This simple score based on age, general condition, tumor differentiation and TNM stage can classify patients into subgroups with different risks of recurrence and could help with therapeutic decisionmaking.

Intraductal papillary mucinous tumors of the pancreas confined to secondary ducts show less aggressive pathologic features as compared with those involving the main pancreatic duct.

Intraductal papillary mucinous tumors (IPMTs) of the pancreas are rare tumors characterized by a malignant potential. Because of the progress of imaging procedures, smaller cystic pancreatic lesions are now detected and some of them correspond to IPMTs that involve ectatic pancreatic branch ducts but spare the main pancreatic duct. To investigate differences in morphology and clinical behavior of branch and main duct types of IPMT, a surgical series of 43 cases was studied. All pathologic specimens of IPMT, surgically resected in our institution between October 1987 and July 1998, were analyzed. In all cases, the entire pancreatic specimen was systematically examined. IPMT of the branch type was found in 13 (30%) patients, whereas IPMT of main pancreatic duct type that involved the main pancreatic duct and branch ducts was observed in 30 (70%) patients. Patients with IPMT of the branch type were younger (median age, 55 yrs vs 64 yrs), and all but one of the lesions were located in the head and neck of the pancreas (vs 17 of 30 patients with the main duct type). The size of the cysts ranged from 4 to 55 mm, and the major duct showed a mild dilation in most cases. In contrast to the main pancreatic duct type, which showed invasive carcinoma and in situ carcinoma in 11 (37%) of 30 patients and 6 (20%) of 30 patients, respectively, IPMT of the branch type showed significantly less aggressive histologic lesions with five (39%) patients with simple hyperplasia, six (46%) patients with atypical hyperplasia, and two (15%) patients with in situ carcinoma. No invasive carcinoma was observed in this group. IPMT of the branch type occurs in younger patients and is associated with less aggressive histologic features than is the main pancreatic duct type. Our findings raise the difficult issue of clinical management of IPMT of the branch type as a distinctive group.

Intraductal papillary mucinous tumors of the pancreas: pancreatic resections guided by preoperative morphological assessment and intraoperative frozen section examination.

BACKGROUND: We undertook this study to assess the results of a policy of limited pancreatic resections for intraductal papillary-mucinous tumors (IPMT), guided by a standardized preoperative morphological assessment and the frozen section histologic examination of pancreatic resection margins. METHODS: From 1991 to 1998, there were 41 patients who underwent resection of IPMT in our center after standardized morphological preoperative assessment, including abdominal computed tomography scans, endoscopic retrograde cholangiopancreatography, and endoscopic ultrasonography. All patients but one underwent a partial pancreatic resection. RESULTS: Preoperative assessment had an 89% diagnostic accuracy for IPMT. It detected malignant transformation with a 67% sensitivity and a 95% specificity, but failed to correctly assess ductal extension of the disease in 17 cases (41%). The diagnostic accuracy of frozen section histologic examination of the pancreatic resection margin was 92%. There was no recurrence in case of in situ carcinoma when epithelial lesions were completely resected (8 cases) nor in lower grades of dysplasia (23 cases). Conversely, recurrence was constant in invasive carcinoma (10 cases) regardless of the status of the pancreatic margin. CONCLUSIONS: Frozen section histologic examination of the pancreatic resection margin is useful and reliable to ensure a complete resection of IPMT by a partial resection that prevents recurrence of noninvasive lesions.

Preoperative chemoembolization of hepatocellular carcinoma: a comparative study.

OBJECTIVE: To assess the efficacy and adverse effects of preoperative transcatheter chemoembolization (CE) on surgical resection, postoperative outcome, and recurrence of hepatocellular carcinoma. DESIGN: A before-after trial comparing a group of patients undergoing liver resection after CE (CE group) with a group of patients undergoing liver resection without prior CE (control group), matched for tumor size and underlying liver disease. SETTING: A tertiary care university hospital in a metropolitan area. PATIENTS: Twenty-four patients in each group, treated between 1986 and 1992. INTERVENTIONS: A mean of 1.6+/-0.2 preoperative CE procedures were performed per patient in the CE group. Tumorectomies, segmentectomies, and major liver resections were performed with a comparable frequency in each group. RESULTS: Overall, CE was not associated with a significant reduction of tumor size (7.8+/-1 cm prior to CE vs 7.1+/-1 cm after CE) or alpha-fetoprotein levels (2560+/-2091 microg/L prior to CE vs 1788+/-1270 microg/L after the last CE). Chemoembolization promoted tumor necrosis but did not influence tumor encapsulation, invasion of the capsule, venous permeation, presence of daughter nodules, or surgical margins. Liver resection was rendered more difficult by preoperative CE as a result of pediculitis and gallbladder lesions in 37% of patients, but the postoperative course was not altered. Disease-free survival (33%+/-12% vs 32%+/-12% at 3 years) and overall survival were comparable. CONCLUSIONS: Convincing evidence is lacking to support systematic preoperative CE in patients with initially resectable hepatocellular carcinoma. Further studies should aim to identify the subgroup of patients who may benefit from this neoadjuvant treatment.