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

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

Evaluation of the combination of oxaliplatin and 5-fluorouracil or gemcitabine in patients with sporadic metastatic pulmonary carcinoid tumors.

OBJECTIVES: The aim of this retrospective study was to analyse the efficacy of gemcitabine-oxaliplatin (gemox) or 5-fluorouracil-oxaliplatin (folfox) in the treatment of metastatic pulmonary carcinoid tumors. PATIENTS AND METHODS: 45 patients were included in two tertiary referral centers between January 1999 and January 2013. Typical, atypical carcinoids or not otherwise specified carcinoids were diagnosed according to WHO criteria in 19%, 57%, and 24% of cases by two expert pathologists. Patients had synchronous (38%) or metachronous (62%) metastastic disease (median of 2 (1-5) metastatic sites). Seventy-nine percent had progressive disease before start of chemotherapy. Treatment consisted of: gemcitabine 1000mg/m(2) and oxaliplatin 100mg/m(2) every 2 weeks (gemox regimen, n=24) or 5-fluorouracil (5-FU) (400mg/m(2) in bolus injection and 5-FU 2400mg/m(2) in 46h-infusion) and oxaliplatin 85mg/m(2) (folfox regimen, n=21) every 2 weeks. Tumor response was assessed according to RECIST criteria every 8-12 weeks. Progression free survival and overall survival were assessed using Kaplan Meier curves. RESULTS: Patients received oxaliplatin-based chemotherapy in first-line (20%), second-line (33%), or post-second-line (47%) systemic treatment. The median number of cycles was 8 (1-12). Nine (20%) stopped oxaliplatin before 8 cycles because of toxicity. Nine patients (20%) had a partial response and 29 (64%) had stable disease. Median progression free survival (PFS) was 15 (6-25) months. Median overall survival (OS) was 34 (21-49) months. No significant difference was observed in response and PFS between either regimens. CONCLUSIONS: Our results suggest that either gemcitabine-oxaliplatin or 5-fluorouracil-oxaliplatin combinations are attractive chemotherapy regimen in metastatic pulmonary carcinoid tumors.

O6-Methylguanine-DNA methyltransferase status in neuroendocrine tumours: prognostic relevance and association with response to alkylating agents.

BACKGROUND: O(6)-Methylguanine-DNA methyltransferase (MGMT) loss of expression has been suggested to be predictive of response to temozolomide in neuroendocrine tumours (NETs), but so far, only limited data are available. We evaluated the prognostic and predictive value of MGMT status, assessed by two molecular methods and immunohistochemistry, in a large series of NETs of different origins. METHODS: A total of 107 patients, including 53 treated by alkylants (temozolomide, dacarbazine or streptozotocin), were retrospectively studied. In each case, we used methyl-specific PCR (MS-PCR) and pyrosequencing for evaluation of promoter methylation and immunohistochemistry for evaluation of protein status. RESULTS: MGMT promoter methylation was detected in 12 out of 99 (12%) interpretable cases by MS-PCR and in 24 out of 99 (24%) by pyrosequencing. O(6)-Methylguanine-DNA methyltransferase loss of expression was observed in 29 out of 89 (33%) interpretable cases. Status of MGMT was not correlated with overall survival (OS) from diagnosis. Progression-free survival and OS from first alkylant use (temozolomide, dacarbazine and streptozotocin) were higher in patients with MGMT protein loss (respectively, 20.2 vs 7.6 months, P<0.001 and 105 vs 34 months, P=0.006) or MGMT promoter methylation assessed by pyrosequencing (respectively, 26.4 vs 10.8 months, P=0.002 and 77 vs 43 months, P=0.026). CONCLUSIONS: Our results suggest that MGMT status is associated with response to alkylant-based chemotherapy in NETs.

Epstein-Barr virus-associated smooth muscle tumors in a composite tissue allograft and a pediatric liver transplant recipient.

Epstein-Barr virus (EBV) is known to establish latent infections in B-lymphocytes that can cause lymphoproliferative disorders particularly in immunocompromised patients. More recently, the development of rare EBV-associated smooth muscle tumors has been reported in transplant recipients. We herein describe 2 new cases of EBV-associated post-transplant smooth muscle tumors (EBV-PTSMT), including the first in a facial composite tissue graft recipient. Among the striking features shared by these 2 patients were their young ages, the fact that they were naïve for EBV before the transplantation, that they developed a post-transplant lymphoproliferative disorder before the diagnosis of EBV-PTSMT, and that they responded favorably to reduction of immunosuppression. Radiological and histologic features of EBV-PTSMT are shown. Finally, pathophysiology and therapeutic management of EBV-PTSMT are discussed based on a comprehensive review of the literature.

Pain as the only consistent sign of acute appendicitis: lack of inflammatory signs does not exclude the diagnosis.

BACKGROUND: The clinical diagnosis of acute appendicitis in adults remains tricky, but radiological examinations are very helpful to determine the diagnosis even when the adult patient presents atypically. This study was designed to quantify the proportion of patients with a preoperative diagnosis of acute appendicitis that had isolated right lower quadrant pain without biological inflammatory signs and then to determine which imaging examination led to the determination of the diagnosis. METHODS: In this monocentric study based on retrospectively collected data, we analyzed a series of 326 patients with a preoperative diagnosis of acute appendicitis and isolated those who were afebrile and had isolated right lower quadrant pain and normal white blood cell counts and C-reactive protein levels. We determined whether the systematic ultrasonography examination was informative enough or a complementary intravenous contrast media computed tomography scan was necessary to determine the diagnosis, and whether the final pathological diagnosis fit the preoperative one. RESULTS: A total of 15.6% of the patients with a preoperative diagnosis of acute appendicitis had isolated rebound tenderness in the right lower quadrant, i.e., they were afebrile and their white blood cell counts and C-reactive protein levels were normal. In 96.1% of the cases, the ultrasonography examination, sometimes complemented by an intravenous contrasted computed tomography scan if the ultrasonography result was equivocal, fit the histopathological diagnosis of acute appendicitis. CONCLUSIONS: The diagnosis of acute appendicitis cannot be excluded when an adult patient presents with isolated rebound tenderness in the right lower quadrant even without fever and biological inflammatory signs. In our study, ultrasonography and computed tomography were very helpful when making the final diagnosis.

Long-term survival (superior to 20 years) after pancreaticoduodenectomy for pancreatic duct adenocarcinoma: report of two cases.

Pancreatic duct adenocarcinoma (PDA) is associated with dismal survival. This study reports two cases of very long survival after pancreatectomy for PDA. These were two male patients with pT30M0 and pT2N0M0 tumour. Both received adjuvant treatment and are currently alive after 21y 6 months and 22 y 2 months respectively. Very long term survival for PDA can be achieved for some patients who benefit from R0 resection.

[Bile duct involvement in autoimmune pancreatitis: classification and treatment]. / Atteinte biliaire au cours d'une pancréatite auto-immune: quel cadre nosologique et quel traitement?

Autoimmune pancreatitis is a rare disease characterized by inflammation of the pancreatic parenchyma, irregular narrowing of the pancreatic duct, periductal lymphoplasmacytic infiltration and fibrosis at histological examination, the presence of autoantibodies and hypergammaglobulinemia, as well as the possible association of cholangitis and other autoimmune diseases. There is a favorable response to steroid therapy. We report the case of a patient with autoimmune pancreatitis with bile duct involvement and peripheral eosinophilia, requiring long-term immunosuppressant treatment. The diagnosis of a diffuse form of AIP was made without direct histological evidence and based on indirect imaging, clinical and laboratory findings in an autoimmune context. The histological and imaging studies of bile duct involvement and the favourable response to steroids were additional arguments.

Rejection under alpha interferon therapy in liver transplant recipients.

Interferon alpha (IFN) is the corner stone drug for the treatment of recurrent hepatitis C (HCV) in liver transplant (LT) recipients. One of its serious potential adverse effects is acute and chronic rejection. The aim of this study was to review our experience using IFN-based therapy, in order to examine the incidence and the risk factors for rejection, and the outcome of patients who developed rejection. Between September 1990 and December 2004, 70 LT recipients were treated. Patients started antiviral treatment 16 (1-137) months after LT. Histological follow-up was available in all patients according to protocol biopsies. Rejection was diagnosed and graded according to Banff classification. Twenty-one percent of patients developed acute rejection (5 mild, 9 moderate and 1 severe) during IFN-based therapy. Patients were treated for 8 (1-15) months prior to rejection. Previous history of acute rejection before IFN therapy and treatment with pegylated-IFN was significantly associated with rejection (p = 0.04 and p = 0.02, respectively). The rejection was successfully treated in 87% of patients. No chronic rejection or graft losses were observed. Acute rejection under IFN-based therapy often occurs in LT recipients, but early diagnosis with protocol biopsies and early treatment can lead to a favorable outcome.

Endoscopic mucosal resection for squamous premalignant and early malignant lesions of the esophagus.

UNLABELLED: BACK AND STUDY AIMS: Endoscopic mucosal resection (EMR) is used to treat premalignant and malignant digestive tract lesions. This report presents the efficacy and safety of EMR for squamous superficial neoplastic esophageal lesions. PATIENTS AND METHODS: A retrospective cohort study presented data from 51 patients with 54 lesions over an 8-year period, between November 1997 and September 2005. Dysplasas or mucosal (m) T1 carcinomas were treated with repeated EMR until there was a complete local remission. Patients with submucosal (sm) T1 carcinomas were treated with repeated EMR until there was a complete local remission. Patients with submucosal (sm) T1 carcinomas or more advanced stage were offered surgery or chemoradiotherapy. RESULTS: There was no mortality, perforation, or major hemorrhage, and there were three easily dilated stenoses. Of the patients, 16 had lesions graded as T1sm or more advanced and one patient was found to have normal tissue post EMR. Complete local remission was achieved in 31 of the 34 patients with dysplasia or T1 m cancers (91%). There was no distant relapse and there was local disease recurrence in eight of the 31 patients (26%). The 5-year survival rate was 95%. CONCLUSIONS: EMR for squamous superficial neoplastic lesions of the esophagus is safe and provides satisfactory survival results.

Expression of beta-catenin in gastroenteropancreatic endocrine tumours: a study of 229 cases.

AIMS: To clarify the role of beta-catenin in digestive endocrine carcinogenesis, a large and representative series of gastroenteropancreatic endocrine tumours was analysed in order to determine the incidence and pattern of beta-catenin changes and to analyse the clinical and histological characteristics of the tumours presenting immunohistochemically detectable changes in beta-catenin expression. METHODS: 229 cases of gastroenteropancreatic endocrine tumours (stomach, 11; duodenum and ampulla, 29; jejunum and ileum, 51; appendix, 13; colon and rectum, 17; and pancreas, 108) were studied by immunohistochemistry to assess the pattern of distribution of beta-catenin (membranous, cytoplasmic or nuclear). DNA was analysed to detect mutations in exon 3 of the CTNNB1 gene. RESULTS: The distribution of immunoreactive beta-catenin protein was membranous in 164 cases, cytoplasmic in 58 cases and nuclear in seven cases. No mutation was detected in exon 3 of the CTNNB1 gene in any case. The seven cases with nuclear accumulation of beta-catenin were large tumours (mean size 44 (standard deviation (SD) 18.5) mm) with metastases, including liver metastases in five cases, high Ki-67 index (mean 34% (SD 16.5%)) and cyclin D1 overexpression; p53 accumulation was detected in six cases. Five patients died of disease; the mean (SD) survival was 13.6 (4.8) months. CONCLUSIONS: Immunohistochemically detectable nuclear accumulation of beta-catenin is infrequent in gastroenteropancreatic endocrine tumours and is usually not associated with mutations in CNNTB1 exon 3. Changes in beta-catenin expression are late events in digestive endocrine carcinogenesis, associated with tumour progression and dissemination.

Unusual cystic presentation of an endocrine carcinoma of the jejunum.

The cystic presentation of endocrine tumours is rare and raises difficult diagnostic problems. So far, the only cases of cystic digestive endocrine tumours reported in the literature are of pancreatic origin. We report the unusual observation of a jejunal endocrine carcinoma presenting as a cystic abdominal mass. A 59-year-old woman was referred for chest and abdominal pain. Imaging studies revealed multiple cystic nodules in the liver and a large sus-mesocolic cystic lesion of probable intestinal origin. Biopsies of the extra-hepatic mass and liver nodules showed endocrine tumour. Surgical resection of the jejunal mass and of liver segment III were performed. Histological examination confirmed the diagnosis of jejunal endocrine carcinoma metastatic to the liver. Large areas of the primary and secondary tumours presented an unusual vesicular architecture, responsible for the cystic presentation. No adjuvant treatment was attempted. This observation underlines the difficult diagnostic problems raised by the cystic presentation of digestive endocrine tumours.

Preaortic paraganglioma mimicking a hypervascular tumor of the pancreas.

Paragangliomas are rare tumors that arise from neuroepithelial cells. They are most frequently located in the para-aortic region and they may be confused with other retroperitoneal tumors, especially pancreatic tumors. We present a case of a secreting preaortic paraganglioma in a young patient which was mimicking a hypervascular tumor of the pancreas, and that was completely resected 5 years after the failure of a first attempt to remove the tumor.

Drug resistance associated with loss of p53 involves extensive alterations in microtubule composition and dynamics.

In the present study, we compared the dynamics and composition of microtubules in cell lines derived from the human breast adenocarcinoma MCF-7 containing either the wild-type p53 (wt-p53; MN1) or a dominant-negative variant of p53 gene (mut-p53; MDD2). Mut-p53 cells were significantly resistant to the cytotoxicity of the microtubule-targeted drugs (vinca alkaloids and taxanes), as compared with wt-p53 cells. Studies by high-resolution time-lapse fluorescence microscopy in living cells indicated that the dynamics of microtubules of mut-p53 cells were altered in complex ways and were significantly increased as compared with microtubules in wt-p53 cells. The percentage of time microtubules spent in growing and shortening phases increased significantly, their catastrophe frequency increased, and their overall dynamicity increased by 33%. In contrast, their shortening rate and the mean length shortened decreased. Cells containing mut-p53 displayed increased polymerisation of tubulin, increased protein levels of the class IV beta-tubulin isotype, STOP and survivin, and reduced protein levels of class II beta-tubulin isotype, MAP4 and FHIT. We conclude that p53 protein may contribute to the regulation of microtubule composition and function, and that alterations in p53 function may generate complex microtubule-associated mechanisms of resistance to tubulin-binding agents.