FOLFIRI3-aflibercept in previously treated patients with metastatic colorectal cancer.

AIM: To evaluate the efficacy and safety of the modified FOLFIRI3-aflibercept as second-line therapy in patients with metastatic colorectal cancer. METHODS: This is a retrospective multicenter cohort, evaluating the efficacy and safety of the association of aflibercept with FOLFIRI3 (day 1: aflibercept 4 mg/kg, folinic acid 400 mg/m2, irinotecan 90 mg/m2, 5-fluorouracil infusion 2400 mg/m2 per 46 h; day 3: irinotecan 90 mg/m2) in patients with previously treated metastatic colorectal cancer. The primary endpoint was overall response rate (ORR). Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Among 74 patients treated in four French centers, nine were excluded due to prior use of aflibercept (n = 3), more than one prior treatment line in irinotecan-naïve patients (n = 3), and inadequate liver function (n = 3). In the "irinotecan-naïve" patients (n = 30), ORR was 43.3% and DCR was 76.7%. Median PFS and OS were 11.3 mo (95%CI: 6.1-29.0) and 17.0 mo (95%CI: 13.0-17.3), respectively. The most common (> 5%) grade 3-4 adverse events were diarrhea (37.9%), neutropenia (14.3%), stomatitis and anemia (10.4%), and hypertension (6.7%). In the "pre-exposed irinotecan" patients (n = 35), 20 (57.1%) received ≥ 2 prior lines of treatment. ORR was 34.3% and DCR was 60.0%. Median PFS and OS were 5.7 mo (95%CI: 3.9-10.4) and 14.3 mo (95%CI: 12.8-19.5), respectively. CONCLUSION: Minimally modified FOLFIRI has improvement dramatically the FOLFIRI3-aflibercept efficacy, whatever prior use of irinotecan. A prospective randomized trial is warranted to compare FOLFIRI-aflibercept to FOLFIRI3-aflibercept.

Therapeutic strategy in unresectable metastatic colorectal cancer: an updated review.

Systemic therapy is the standard care for patients with unresectable advanced colorectal cancer (CRC), but salvage surgery of metastatic disease should be considered in the case of adequate tumor shrinkage. Several drugs and combinations are now available for use in treating patients with advanced CRC, but the optimal sequence of therapy remains unknown. Moreover, the administration of antitumor therapy can be modulated by periods of maintenance or treatment breaks rather than delivered as full therapy until disease progression or unacceptable toxicity, followed by reintroduction of prior full therapy when required, before switching to other drugs. Consequently, randomized strategy trials are needed to define the optimal treatment sequences. Molecular testing for Kirsten rat sarcoma viral oncogene homolog (KRAS) and neuroblastoma RAS viral oncogene homolog (NRAS) is mandatory but not sufficient to select appropriate patients for epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb) therapy.

Ileal patch duodenoplasty after right colectomy extended to the duodenal wall.

After radical resection of cancer of the right colonic flexure, a parietal defect can be created in case of duodenal invasion. In this paper the authors describe an "easy and safe" duodenoplasty surgical technique using an ileal patch.

Impaired E-cadherin expression and glutamine synthetase overexpression in solid pseudopapillary neoplasm of the pancreas.

OBJECTIVES: To analyze in solid pseudopapillary neoplasm of the pancreas (SPNP) the consequences of the deregulated Wnt pathway by studying the expression of Wnt target glutamine synthetase (GLUL), cyclin D1, and E-cadherin, which is one of the beta-catenin binding partner in cell adhesion. METHODS: The expression of cyclin D1 and GLUL was studied at the protein and/or messenger RNA levels, and the immunolocalization for E-cadherin was analyzed in 28 SPNPs screened for beta-catenin mutations. Expression of cyclin D1, GLUL, and beta-catenin was also assessed in pancreatic endocrine tumors as controls. RESULTS: Cytosolic and/or nuclear accumulation of beta-catenin was observed in all tumors; an activating beta-catenin mutation was identified in 21 (91%) of 23 tumors analyzed. E-cadherin expression is lost from the membrane and is observed in intracytosolic "dotlike" structures. Whereas cyclin D1 expression is observed widely in SPNP and endocrine tumors, GLUL expression is restricted to SPNP (100%) and rare endocrine tumors (10%) displaying Wnt activation. CONCLUSIONS: The activation of the Wnt/beta-catenin pathway in SPNP has 2 main consequences. First, E-cadherin expression moved from membranous to intracytoplasmic localization. Second, GLUL expression is highly correlated with Wnt/beta-catenin activation, demonstrating its faithfulness as a Wnt target gene.

Prognostic factors after resection for hepatocellular carcinoma in nonfibrotic or moderately fibrotic liver. A 116-case European series.

The purpose of this study was to identify factors influencing prognosis after resection for hepatocellular carcinoma in the noncirrhotic liver and to measure the impact of moderate fibrosis on presentation and prognosis. A series of 116 primary procedures were performed for hepatocellular carcinoma in the noncirrhotic liver. These cases accounted for 42% of hepatic resections performed for hepatocellular carcinoma during the study period (1987-2005). Seventy-seven cases (58%) occurred in patients with nonfibrotic livers (Metavir score F0). The mean age was 61 years. The sex ratio was 3.5, with a female predominance before 50 years. Hepatitis B virus (HBV) or hepatitis C virus infection was found in 30% of patients. Symptoms were present in 64% of cases. Elevated serum alpha fetoprotein levels were observed in 44% of cases. Procedures involved minor hepatectomy in 40 cases, major hepatectomy in 72 cases, and transplantation in 4 cases. Postoperative mortality was 6% and morbidity was 31%. Complete resection was achieved in 90% of cases. The tumor was isolated in 72% of cases. The mean tumor diameter was 10.6 cm. Vascular invasion was observed in 48% of cases. Hepatocellular carcinoma in the nonfibrotic liver was associated with younger age and female sex, but there was no difference with other hepatocellular carcinoma with regard to histological or prognostic features. With a median follow-up of 79 months, overall survival was 40% for a median of 41 months. Multivariate analysis identified incomplete resection, vascular invasion, and HBV infection as independent factors of poor prognosis. In case of recurrence, repeat resection was feasible in 30% of cases with 69% survival at 5 years. Although hepatocellular carcinoma in the noncirrhotic liver is generally diagnosed at an advanced stage, its resectability remains high. As a result, hepatocellular carcinoma in the noncirrhotic liver accounts for a large proportion of cases in surgical series and has a better prognosis than hepatocellular carcinoma in the cirrhotic liver. Vascular invasion, incomplete resection, and HBV infection are independent factors of poor prognosis.

[Ileosigmoid knot is an unusual and severe cause of bifocal bowel strangulation]. / Le noeud iléosigmoïde: une cause improbable d'occlusion intestinale primitive par strangulation bifocale.

Ileosigmoid knot is an unusual and severe cause of bifocal bowel strangulation. Prompt surgery is necessary to prevent widespread intestinal infarction and high mortality rate. We report a clinical case and present a literature review to precise the features that should lead to prompt preoperative diagnosis. There are no clinical features specific for this diagnosis. Abdominal CT scan with contrast enema appears to be the fastest way to show the association of small bowel ischemia and sigmoid volvulus that signs ileosigmoid knotting.

Resection of hepatocellular carcinoma with tumor thrombus in the major vasculature. A European case-control series.

Tumor thrombus in major vasculature is a frequent finding with a poor long-term prognosis in patients with hepatocellular carcinoma (HCC). The utility of surgical resection is still controversial. This study compared morbidity and survival after resection for HCC with and without tumor thrombus. Data of 108 patients who underwent major hepatic resection for HCC were prospectively recorded. Patients were divided into two groups. The venous thrombectomy (VT) group included 26 patients who had HCC with tumor thrombus in the portal or hepatic veins. The matched control group included 82 patients who had HCC without tumor thrombus. Surgical technique, early outcome, and late survival were analyzed in each group. Multivariate analysis was performed to assess the prognostic value of this feature. Surgical technique was comparable in the VT and control group with regard to extent of hepatectomy, procedure duration, and transfusion requirements. Early postoperative outcome was also comparable. Actuarial survival at 1, 3, and 5 years was 38%, 20%, and 13%, respectively, in the VT group (median: 9 months) versus 74%, 56%, and 33%, respectively, in the control group (median: 41 months). In the subgroup of patients with tumor thrombus limited to the portal vein, actuarial survival at 1, 3, and 5 years was 50%, 26%, and 17%, respectively, (median: 12 months) and two patients lived longer than 5 years. Multivariate analysis showed that incomplete resection, alphafetoprotein level greater than 100 N, more than two tumor nodules, and tumor thrombus in major vasculature were independent factors of poor prognosis. Survival after resection for HCC with tumor thrombus in the major vasculature is poorer than after resection for HCC without tumor thrombus. However, an aggressive surgical strategy can provide significant survival with comparable morbidity in selected cases, that is, tumor thrombus located in the portal vein only and expected complete resection of the lesions.