Sergio Valeri

Apoptotic index or a combination of Bax/Bcl‐2 expression correlate with survival after resection of pancreatic adenocarcinoma

In the present study, the prognostic impact of factors involved in the apoptosis pathway were tested on 67 consecutive patients treated with surgical resection. Included in the study were all patients resected for pancreatic adenocarcinoma from 1988 to 2003. Expression analysis for p53, Bax, and Bcl‐2 were performed by immunohistochemical staining. Apoptotic cells were identified by the TUNEL method. These data were correlated with survival. Sixty‐seven tumor specimens were included in the study. A strong positive correlation was recorded between p53 overexpression and Bax expression levels (P < 0.001). By univariate analysis, overall survival seemed to be improved with Bcl‐2 and Bax expression (respectively, P = 0.0379 and 0.0311). The median survival time in patients with low apoptotic index was better versus those with a high index (P = 0.0127). Lymph node involvement was the only clinico‐pathologic parameter that significantly correlated with overall survival (P = 0.0202). By a multivariate Cox regression analysis, the only immunohistochemical parameter that influenced overall survival was the apoptotic index (P = 0.040). Tumors overexpression of both Bax and Bcl‐2 resulted the strongest independent prognostic factor (P = 0.013). This is the first study to report a statistically significant association of apoptosis to overall survival for pancreatic cancer patients treated with surgical resection. The contemporary overexpression of Bax and Bcl‐2 represents the strongest prognostic factor. J. Cell. Biochem.

Bevacizumab in association with de Gramont 5-fluorouracil/folinic acid in patients with oxaliplatin-, irinotecan-, and cetuximab-refractory colorectal cancer: a single-center phase 2 trial.

The aim of the current study was the investigation of the value of bevacizumab + 5‐fluorouracil(5–FU)/folinic acid in patients with advanced colorectal cancers who have exhausted standard chemotherapy options.

Percutaneous ultrasound-guided ablation of BW7756-hepatoma using ethanol or acetic acid in a rat model

BackgroundTo compare tumor necrosis in hepatoma induced in rats by a single percutaneous injection of ethanol (PEI) or acetic acid (PAI).MethodsBW7756 hepatomas of 1 mm3 were implanted in the liver of 40 male healthy rats. After 14 days, the 36 surviving rats were treated, in a single session, by ultrasound-guided injection of 300 μl of 95% ethanol (n = 17) or 100 μl of 50% acetic acid (n = 19). They were sacrificed 14 days after treatment and explanted tumoral livers were examined. The same PAI procedure was repeated on 13 additional rats to exclude a suspected occurrence of technical failures during the experiment, due to a surprisingly high rate of deaths within 30 minutes after PAI.ResultsFour rats died within four days after tumor implantation; after PEI, 1/17 (6%) died, whereas after PAI 9/19 (47%) died. The remaining 26 rats, after 14 days post-percutaneous ablation, were sacrificed. Gross and microscopic examinations showed that the hepatomas nodules treated with PEI had 45.3 ± 19.4% tumor necrosis compared to 49 ± 23.3% (P = NS) for those treated with PAI. Complete tumor necrosis was not found in any animal. Peritoneal invasion was present in 4/16 (25%) and 2/10 (20%) rats treated with PEI or PAI, respectively (P = NS). Autopsy was performed in the 5 additional rats that died within 30 minutes after PAI.ConclusionOur results show that there is no significant difference in the percentage of tumor necrosis between two local ablation methods in spite of the different dosages used. However, mortality in the PAI-treated group was greater than in PEI-treated group, presumably due to greater acetic acid systemic diffusion and its metabolic side effects. In human subjects, HCC occurs in the setting of cirrhosis, where the non-tumoral tissue is firmer than the tumor structure, with consequent reduction of drug diffusion. This could be the reason why some human studies have concluded similar or even better safety and efficacy with PAI compared to PEI.

Recurrent peptic stenosis of the esophagus: treatment with a self-expanding metallic stent.

A 12-year-old neurologically impaired boy with recurrent peptic stenosis of the esophagus was treated successfully with use of a self-expanding metallic stent that remained for 3 months.

Phase II study of induction chemotherapy followed by chemoradiotherapy in patients with borderline resectable and unresectable locally advanced pancreatic cancer

There is not a clear consensus regarding the optimal treatment of locally advanced pancreatic disease. There is a potential role for neoadjuvant therapy to treat micrometastatic disease with chemotherapy, as well as for the treatment of local disease with radiotherapy. We evaluated the safety and efficacy of induction chemotherapy with oxaliplatin and gemcitabine followed by a high weekly dose of gemcitabine concurrent to radiation therapy in patients with borderline resectable and unresectable locally advanced pancreatic cancer. In our study, 41 patients with pancreatic cancer were evaluated. In all cases an accurate pre-treatment staging was performed. Patients with evidence of metastatic disease were excluded, and thus a total of 34 patients were consequently enrolled. Of these, twenty-seven patients (80%) had locally advanced unresectable tumours, seven patients (20%) had borderline resectable disease. This protocol treatment represents a well-tolerated promising approach. Fifteen patients (55.5%) underwent surgical radical resection. With a median follow-up of 20 months, the median PFS and OS were 20 months and 19.2 months, respectively. The median OS for borderline resectable patients was 21.5 months compared with 14 months for unresectable patients (p = 0.3). Continued optimization in multimodality therapy and an accurate patient selection remain crucial points for the appropriate treatment of these patients.

Microscopic Residual Tumor After Pancreaticoduodenectomy: Is Standardization of Pathological Examination Worthwhile?

ObjectivesR1 resection rate after pancreaticoduodenectomy (PD) for cancer is highly variable. The aim of this study was to verify if a standardized histopathological work-up of the specimen affects the rate of R1 resection after PD for cancer. MethodsTwo groups of specimens were managed with (standardized method [SM] group) or without (non-standardized method [NSM] group) a SM of histopathological work-up. Each group included 50 cases of PD for periampullary cancer. Differences in terms of R1 resection rate between the 2 groups were evaluated. Correlation between R1 status and local recurrence was also evaluated. ResultsThe cohort of 100 patients consisted of 66 pancreatic ductal adenocarcinoma, 15 cholangiocarcinoma, and 19 ampullary cancer. The R1 resection rate resulted statistically higher in the SM group (66% vs 10%). Local recurrence was more frequently related to R1 resection in the SM group (34.3% of cases) than in NSM group (20% of cases). ConclusionsThe use of the SM of pathological evaluation of the specimen after PD for cancer determines a significant increase of R1 resection. This remarkable difference seems to be due to the different definition of minimum clearance. The SM seems to better discriminate patients in terms of risk of local recurrence.

Imatinib rechallenge in patients with advanced gastrointestinal stromal tumors following progression with imatinib, sunitinib and regorafenib

Background: Rechallenge with imatinib is an option in advanced gastrointestinal stromal tumor (GIST) patients following progression with standard tyrosine-kinase inhibitors (TKIs), imatinib, sunitinib and regorafenib. We retrospectively collected data from metastatic Italian GIST patients treated with imatinib resumption after progression to conventional TKIs. Methods: A total of 104 eligible advanced GIST patients, previously treated with imatinib, sunitinib and regorafenib, were collected from six referral Italian institutions. Mutational analysis was recorded and correlated with survival and response according to RECIST 1.1 or CHOI criteria. Results: Overall, 71 patients treated with imatinib 400 mg as rechallenge were included. Mutational status was available in all patients. The median follow up was 13 months. In patients who received a rechallenge therapy, the median time to progression (TTP) was 5.4 months [95% confidence interval (CI) 1.9–13.5] and overall survival (OS) was 10.6 months (95% CI 2.8–26.9). A correlation between mutational status, response rate, TTP and OS was not found but comparing deleted versus nondeleted KIT exon 11 patients, a significant difference was identified in terms of TTP and OS (p = 0.04 and p = 0.02, respectively). Conclusions: Our retrospective data confirm that imatinib rechallenge is a reasonable option in advanced GIST. The prognostic value of the specific KIT mutations was confirmed in our series.

Body Mass Index as a Risk Factor for Toxicities in Patients with Advanced Soft-Tissue Sarcoma Treated with Trabectedin

Objectives: Low body mass index (BMI) and/or low lean body mass have been shown to be risk factors for chemotherapy-related toxicities in a number of different cancers. However, no data are available regarding the role of BMI as a risk factor for developing toxicities related to the novel anticancer agent, trabectedin, in patients with soft-tissue sarcoma (STS). We evaluated the role of BMI as a risk factor for trabectedin-related toxicity in patients with STS. Methods: Data from 51 patients with metastatic/advanced STS treated with trabectedin after progression on ≥1 anthracycline ± ifosfamide regimen were retrospectively reviewed. Results: Eighteen patients (35.3%) were underweight, and the remainder were of normal bodyweight (45.1%) or overweight (19.6%). Neutropenia of any grade (77.8 vs. 33.3%) and grade 3–4 neutropenia (50.0 vs. 18.2%) occurred more frequently in the underweight versus normal/overweight patients (p = 0.025). Febrile neutropenia also occurred more frequently in underweight patients. Differences remained statistically significant after adjusting for other predictors of toxicity. There were no significant differences in other hematological and nonhematological toxicities between the groups. Conclusions: The data suggest for the first time that BMI should be considered a risk factor for neutropenia in patients with STS treated with trabectedin.