Prognostic Role of Mismatch Repair Status, Histotype and High-Risk Pathologic Features in Stage II Small Bowel Adenocarcinomas.

BACKGROUND: Small bowel adenocarcinoma is a relatively rare cancer, often diagnosed in an advanced stage. In localized and resectable disease, surgery alone or in combination with adjuvant chemotherapy is the mainstay of treatment. In the recently published National Comprehensive Cancer Network Clinical Practice guidelines, criteria for selecting patients with stage II small bowel adenocarcinoma to receive adjuvant chemotherapy are provided, and they are mainly extrapolated from studies on colorectal cancer. PATIENTS AND METHODS: In the present study, we aimed to verify whether mismatch repair deficiency phenotype, high-risk pathologic features (including T4, positive resection margins and a low number of lymph nodes harvested), as well as tumor histologic subtype, were associated with cancer-specific survival in 66 stage II non-ampullary small bowel adenocarcinoma patients, collected through the Small Bowel Cancer Italian Consortium. A central histopathology review was performed. Mismatch repair deficiency was tested by immunohistochemistry for MLH1, MSH2, MSH6 and PMS2, and confirmed by polymerase chain reaction for microsatellite instability. RESULTS: We identified mismatch repair deficiency, glandular/medullary histologic subtype, and celiac disease as significant predictors of favorable cancer-specific survival using univariable analysis with retained significance in bivariable models adjusted for pT stage. Among the high-risk features, only T4 showed a significant association with an increased risk of death; however, its prognostic value was not independent of mismatch repair status. CONCLUSIONS: Mismatch repair protein expression, histologic subtype, association with celiac disease, and, in the mismatch repair proficient subset only, T stage, may help identify patients who may benefit from adjuvant chemotherapy.

Sorafenib treatment has the potential to downstage advanced hepatocellular carcinoma before liver resection.

Sorafenib is acknowledged as the standard therapy for advanced hepatocellular carcinoma (HCC) but in the clinical practice the treatment of these patients is extremely complex and needs to be personalized. New evidence suggests that surgical resection-based multimodal treatments may improve outcome in these patients. There is no strong evidence supporting the ability of sorafenib in downstage HCC before surgery. We presented a case of a 53-year-old man with well-compensated HCV-cirrhosis complicated with HCC and neoplastic portal vein thrombosis. The patient was treated initially with sorafenib with optimal radiological and serological response and subsequently with liver resection. Pathological examination showed necrotic portal thrombosis and massive necrosis of a metastatic regional node confirming radiological evidence. This finding suggests that sorafenib exhibits a potential to downstage advanced HCC which is not irrelevant. A possible combination of different modalities has to be considered in the view of a personalized medicine.

Glutathione S-transferase P1 Ile105Val polymorphism is associated with haematological toxicity in elderly rectal cancer patients receiving preoperative chemoradiotherapy.

BACKGROUND: Increasing evidence suggests that common gene polymorphisms may influence the toxicity of various cytotoxic agents used in the treatment of cancer. OBJECTIVE: To evaluate the predictive value of acute toxicity of methylenetetrahydrofolate reductase 677T polymorphism, glutathione S-transferase P1 (GSTP1) substitution of isoleucine with valine at codon 105 (Ile105Val) polymorphism and the tandem repeat polymorphism in the thymidylate synthase gene promoter in elderly patients with rectal cancer receiving preoperative chemoradiotherapy (CRT). METHOD: From 1994 to 2002, 166 Caucasian patients underwent surgery following CRT for mid-low rectal cancer at a single institution, 42 (male-to-female ratio, 25 : 17) of whom were aged > or =65 years (median age 70 years, range 65-79). The pre-treatment clinical stage was tumour (T) stage 3-4 in 38 patients and node (N)-positive in 29 patients. Patients received external-beam radiotherapy with conventional fractionation and fluorouracil-based chemotherapy. Blood samples were used to extract and amplify DNA. Gene polymorphisms were determined by polymerase chain reaction and restriction enzyme digestion. Acute toxicity to preoperative therapy was reported according to the National Cancer Institute Common Toxicity Criteria, version 2. Univariate and multivariate analyses were performed using one-way analysis of variance and linear regression, respectively. RESULTS: Haematological toxicity (grade 1-2) was observed in 15 of 40 patients for whom toxicity data were available and gastrointestinal toxicity (grade 1-4) in 24 of these same 40 patients. At univariate analysis, female sex (p = 0.036) and GSTP1 Ile105Val (p = 0.0376) were associated with haematological toxicity. At multivariate analysis, GSTP1 Ile105Val polymorphism (p = 0.041) was the only factor found to be associated with haematological toxicity. Patients carrying the Val/Val genotype in the GSTP1 gene had a lower risk of haematological toxicity (odds ratio = 0.322, 95% CI 0.101, 0.957) than patients with the Ile/Ile genotype. CONCLUSION: GSTP1 Ile105Val polymorphism is a promising marker of potential haematological toxicity in elderly patients with rectal cancer receiving preoperative CRT.