Sporadic early-onset colorectal cancer is a specific sub-type of cancer: a morphological, molecular and genetics study.

Sporadic early onset colorectal carcinoma (EOCRC) which has by definition no identified hereditary predisposition is a growing problem that remains poorly understood. Molecular analysis could improve identification of distinct sub-types of colorectal cancers (CRC) with therapeutic implications and thus can help establish that sporadic EOCRC is a distinct entity. From 954 patients resected for CRC at our institution, 98 patients were selected. Patients aged 45-60 years were excluded to help define "young" and "old" groups. Thirty-nine cases of sporadic EOCRC (patients ≤ 45 years with microsatellite stable tumors) were compared to both microsatellite stable tumors from older patients (36 cases, patients>60 years) and to groups of patients with microsatellite instability. Each group was tested for TP53, KRAS, BRAF, PIK3CA mutations and the presence of a methylator phenotype. Gene expression profiles were also used for pathway analysis. Compared to microsatellite stable CRC from old patients, sporadic EOCRC were characterized by distal location, frequent synchronous metastases and infrequent synchronous adenomas but did not have specific morphological characteristics. A familial history of CRC was more common in sporadic EOCRC patients despite a lack of identified hereditary conditions (p = 0.013). Genetic studies also showed the absence of BRAF mutations (p = 0.022) and the methylator phenotype (p = 0.005) in sporadic EOCRC compared to older patients. Gene expression analysis implicated key pathways such as Wnt/beta catenin, MAP Kinase, growth factor signaling (EGFR, HGF, PDGF) and the TNFR1 pathway in sporadic EOCRC. Wnt/beta catenin signaling activation was confirmed by aberrant nuclear beta catenin immunostaining (p = 0.01). This study strongly suggests that sporadic EOCRC is a distinct clinico-molecular entity presenting as a distal and aggressive disease associated with chromosome instability. Furthermore, several signaling pathways including the TNFR1 pathway have been identified as potential biomarkers for both the diagnosis and treatment of this disease.

Recurrence risk after Ivor Lewis oesophagectomy for cancer.

OBJECTIVE: The aim of this study was to analyze the profile of tumor recurrence for patients operated on for cancer of oesophagogastric junction or oesophagus by Ivor-Lewis oesophagectomy. METHODS: Patients undergoing potentially curative Ivor-Lewis oesophageal resection between January 1999 to December 2008 at a single center institution were retrospectively analyzed. Their clinical records, details of surgical procedure, postoperative course, pathological findings, recurrence and long term survival were reviewed retrospectively. Univariate and multivariate survival analyses were performed. RESULTS: One hundred and twenty patients were analyzed. Fifty three patients (44%) presented recurrence during median follow-up of 58 months. Five-year relapse free survival (RFS) rate was 51% (95%CI = [46; 65%]). On multivariate analysis, pT stage > 2 (HR = 2.42, 95%CI = [1.22; 4.79] p = 0.011), positive lymph node status (HR = 3.69; 95% CI = [1.53; 8.96] p = 0.004) and lymph node ratio > 0.2 (HR = 2.57; 95%CI = [1.38; 4.76] p = 0.003) were associated with a poorer RFS and their combination was correlated to relapse risk. Moreover, preoperative tumor stenosis was associated with an increased risk of local recurrence (HR = 3.46; 95% CI = [1.38; 8.70] p = 0.008) whereas poor or undifferentiated tumor was associated with an increased risk of distant recurrence (HR = 3.32; 95% CI = [1.03; 10.04] p = 0.044). CONCLUSION: pT stage > 2, positive lymph node status and lymph node ratio > 0.2 are independent prognostic factors of recurrence after Ivor-Lewis surgery for cancer. Their combination is correlated with an increasing risk of recurrence that may argue favorably, in addition with preoperative tumor stenosis assessment, for adjuvant treatment or reinforced follow-up.

Risk factors for postoperative pancreatic fistulization subsequent to enucleation.

INTRODUCTION: Pancreatectomies increase the risk of postoperative pancreatic fistula (POPF) and pancreatic insufficiency. Pancreatic enucleation preserves pancreatic parenchyma, lowers the risk of pancreatic insufficiency, but may induce specific complications (tumor recurrence or pancreatic fistulization). The aim of this study was to determine the risk factors for POPF following a pancreatic enucleation. METHODS: A retrospective analysis was designed based on data from patients who underwent pancreatic enucleation in five university hospitals (1998-2008). The presence of a pancreatic fistula was determined according to the criteria of the International Study Group of Pancreatic Fistula (Bassi et al. Surgery 138:8-13, 2005). RESULTS: Fifty-two patients (mean age 52 years) were included. Histological analysis revealed 35 endocrine tumors (68.6 %), 6 mucinous and 2 serous cyst adenomas, 2 metastases of renal cancer, and 8 benign tumors. Nineteen patients (36.5%) suffered postoperative complications including 14 POPF (27 %). Median postoperative hospital stay was 12.9 days; 9.1 days without POPF versus 29 days with POPF (p < 0.05). Size of the tumor, its location, histological differentiation, and use of somatostatin analogs were not predictors for POPF. We defined the cutoff for POPF at a distance of 2 mm from the main pancreatic duct based on 60% risk (≤2 mm) versus 19 % (>2 mm) of POPF (p < 0.01). With a mean follow-up of 30.8 months, one patient experienced recurrence of the tumor. No patients exhibited a new onset of diabetes or pancreatic insufficiency. CONCLUSION: Enucleation for resection of pancreatic tumors located at less than or equal to two 2 mm from the main pancreatic duct is a risk factor for POPF. Enucleation is a safe and effective treatment for benign or borderline pancreatic tumors.

Clinical fate of branch duct and mixed forms of intraductal papillary mucinous neoplasia of the pancreas.

AIMS: The aim of the present study was to assess the clinical fate of, and to gain new insights into, branch duct and mixed (predominantly main duct type) forms of intraductal papillary mucinous neoplasia of the pancreas (IPMN). METHODS: During a 17-year period, 99 successive IPMN patients (52 men, 47 women; mean age, 64 years) were included and divided into two groups for further comparison: one group had branch duct IPMN, whereas the other had mixed IPMN. RESULTS: Patients from the mixed IPMN group (n = 52) displayed a greater rate of symptoms (83% vs 55%, P = 0.004), pancreatic resection (67% vs 38%, P = 0.007), malignancy (35% vs 13%, P = 0.017) and death (15% vs 4%, P = 0.09) than those from the branch duct IPMN group. A 38-month follow up of non-operated, symptom-free patients confirmed that more than 85% of branch duct IPMN patients were asymptomatic without evidence of malignancy. Borderline lesions and carcinoma are found in up to 50% of symptomatic resected branch duct IPMN cases. CONCLUSION: Patients with the mixed form of IPMN as well as with symptomatic branch duct IPMN should require pancreatic resection because of symptoms and the risk for malignancy. In silent branch duct IPMN without radiological signs of malignancy, a non-operative watch-and-wait strategy can be discussed.

Spleen-preserving distal pancreatectomy with excision of splenic artery and vein: a case-matched comparison with conventional distal pancreatectomy with splenectomy.

BACKGROUND: The value of spleen preservation during distal pancreatectomy (DP) still remains controversial. Spleen-preserving DP with excision of the splenic artery and vein is a simplified technique for spleen preservation. The aim of this study was to compare the postoperative course of DP with or without splenectomy. PATIENTS AND METHODS: From 1990 to 2005, 38 consecutive patients with benign or low-grade malignant disease underwent a spleen-preserving DP operation with excision of the splenic artery and vein (Conservative Group). They were compared with 38 patients who underwent conventional DP with splenectomy over the same time period (Splenectomy Group) and who had been matched for age, American Society of Anesthesiologists (ASA) score, and pathological diagnosis. Postoperative courses were analyzed and compared between the Conservative Group and Splenectomy Group. RESULTS: Spleen preservation was effective in 36 of the 38 attempts (95%). Postoperative complications - in particular, infectious intra-abdominal complications - were significantly higher in the Splenectomy Group (34 and 18%, respectively) than in the Conservative Group (13 and 3%, respectively) (P = 0.03 and P = 0.02, respectively). The length of the surgery, perioperative blood loss or transfusions, perioperative mortality and length of hospital stay did not differ between the two groups. Univariate analysis showed that splenectomy was the only risk factor for postoperative complication. CONCLUSIONS: Spleen-preserving DP with excision of the splenic artery and vein is a fast, safe and effective procedure associated, in this series, with a reduction of postoperative complications relative to conventional DP with splenectomy. This technique should be considered in patients with benign or low-grade malignant disease of the pancreas.

Is nasogastric or nasojejunal decompression necessary after gastrectomy? A prospective randomized trial.

BACKGROUND: Nasogastric decompression has been routinely used in most major abdominal operations to prevent the consequences of postoperative ileus. The aim of the present study was to assess the necessity for routine prophylactic nasogastric or nasojejunal decompression after gastrectomy. METHODS: A prospective randomized trial included 84 patients undergoing elective partial or total gastrectomy. The patients were randomized to a group with a postoperative nasogastric or nasojejunal tube (Tube Group, n = 43) or to a group without a tube (No-tube Group, n = 41). Gastrointestinal function, postoperative course, and complications were assessed. RESULTS: No significant differences in postoperative mortality or morbidity, especially fistula or intra-abdominal sepsis, were observed between the groups. Passage of flatus (P < 0.01) and start of oral intake (P < 0.01) were significantly delayed in the Tube Group. Duration of postoperative perfusion (P = 0.02) and length of hospital stay (P = 0.03) were also significantly longer in the Tube Group. Rates of nausea and vomiting were similar in the two groups. Moderate to severe discomfort caused by the tube was observed in 72% of patients in the Tube Group. Insertion of a nasogastric or nasojejunal tube was necessary in 5 patients in the No-tube Group (12%). CONCLUSIONS: Routine prophylactic postoperative nasogastric decompression is unnecessary after elective gastrectomy.

Mortality and morbidity after resection for adenocarcinoma of the gastroesophageal junction: predictive factors.

BACKGROUND: Resection for adenocarcinoma of the gastroesophageal junction (AGEJ) is associated with severe mortality and morbidity. This retrospective study aimed to evaluate mortality and morbidity after resection for AGEJ and to determine their predictive factors. STUDY DESIGN: Data from 1,192 patients (mean age 65 +/- 11 years) who underwent resection for AGEJ by members of French Association of Surgery from 1985 to 2000 were collected. A stepwise logistic regression model was built to identify by multivariate analysis the variables independently associated with mortality, morbidity, anastomotic leakage, and major pulmonary complications. RESULTS: Distribution of Siewert's type was: I = 480 (40%), II = 500 (42%), and III = 212 (18%). Most type I and II tumors were treated by esophagectomy and proximal gastrectomy (93% and 58%, respectively), using an approach including a thoracotomy (82% and 64%, respectively); type III tumors were treated mainly by total gastrectomy and distal esophagectomy (83%), through an exclusive transabdominal approach (69%). Seventy-six (6%) patients died postoperatively. Only American Society of Anesthesiologists (ASA) scores III and IV (p < 0.001) and period of study (p = 0.025) were predictive of mortality. Predictive factors of overall morbidity (overall rate = 35%) were high ASA score (p < 0.001), age more than 60 years (p = 0.020), male gender (p = 0.039), and cervical anastomosis (p = 0.001). Factors predictive of anastomotic leakage (overall rate = 9%) were high ASA score (p = 0.006) and manual anastomosis (p = 0.010). Factors predictive of major pulmonary complications (overall rate = 23%) were high ASA score (p = 0.015), age more than 60 years (p < 0.001), anastomotic leakage (p < 0.001), and abdominal complications (p = 0.003). CONCLUSIONS: ASA score is a reliable predictive factor of operative mortality and morbidity after resection of AGEJ.

Octreotide in insulinoma patients: efficacy on hypoglycemia, relationships with Octreoscan scintigraphy and immunostaining with anti-sst2A and anti-sst5 antibodies.

OBJECTIVE: We studied the efficacy of octreotide treatment on hypoglycaemia in patients with insulinoma and its relationships with Octreoscan scintigraphy and the presence of tumoral somatostatin receptors sst2A and sst5. DESIGN AND METHODS: 17 patients with insulinoma were evaluated using (i) evaluation of blood glucose, insulin and C-peptide during a short 100 mug octreotide test in fasting patients and/or treatment over 8 days-8 months with octreotide, (ii) Octreoscan scintigraphy and (iii) immunostaining of the tumor with anti-sst2A and anti-sst5. RESULTS: Octreotide was effective on hypoglycaemia in 10/17 patients. Octreoscan scintigraphy detected 4/17 insulinomas. sst2A receptor was detected in 7/17 insulinomas and sst5 in 15/17 insulinomas. Octreotide was effective on hypoglycaemia in those seven patients with sst2A receptor-expressing insulinoma, and in three patients with undetectable sst2A receptor and detectable sst5; it was ineffective in six patients whose tumor expressed the sst5 receptor with undetectable sst2A and in one patient with undetectable sst2A and sst5 receptor. CONCLUSIONS: Octreotide is an effective treatment of hypoglycaemia in more than 50% of patients with insulinoma. Detection of responsive patients was better based on a positive short test with subcutaneous octreotide than on the results of Octreoscan scintigraphy. Positive anti-sst2 receptor immunostaining is associated with efficacy of octreotide treatment, but does not account for all cases of responsiveness to octreotide. Expression of sst5 receptor does not appear to explain per se the efficacy of octreotide on sst2A-negative insulinomas.

[Non-differentiated carcinoma with osteoclast-like giant cells of the pancreas]. / Carcinome indifférencié avec cellules géantes de type ostéoclastique du pancréas.

We report the case of a 53-year-old man who presented a mass involving the head of the pancreas resulting in isolated jaundice. Histologically, the tumor was an undifferentiated carcinoma with osteoclast-like giant cells of the pancreas. This very rare neoplasm resembles giant cell tumor of bone. An epithelial origin is now established and this tumor has been recently considered as a variant of ductal adenocarcinoma of the pancreas in the last WHO histological classification. The diagnosis requires both morphology and immunohistochemistry. Although the prognosis of these tumors is reported to be poor, our case is unusual because of a favorable outcome without relapse after 2 years.