Armando Antinori

Prognostic factors after surgical resection for pancreatic carcinoma.

Surgical resection offers the only potential cure for pancreatic carcinoma. Several recent series have reported an encouraging increase in 5‐year survival rate exceeding 20% and have emphasized the importance of patient selection based on reproducible prognostic factors. The impact on survival of demographic, intraoperative, and histopatologic factors are investigated in this study.

Choledochocele : Changing Trends in Diagnosis and Management

Eighty-four patients with choledochocele collected from the world literature and one personal observation are reviewed. The main issues regarding clinical presentation, diagnostic work-up, and the treatment of this uncommon lesion are discussed. Abdominal pain was the most common clinical feature (91% of cases), followed by pancreatitis (38%), nausea or vomiting (35%), and jaundice (26%). In addition, associated lithiasis was found in 43% of the cases. Endoscopic retrograde cholangiopancreatography was the most useful diagnostic procedure and resulted in a correct diagnosis in all but one of the patients investigated by this method. Surgical excision of the duodenal luminal portion of the choledochocele was the treatment most commonly used (65% of cases). In recent years, operative endoscopy has also been increasingly used, with good results.

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.

Prognostic value of Bax, Bcl-2, p53, and TUNEL staining in patients with radically resected ampullary carcinoma

Background: There is a lack of data in the literature concerning the identification of potential prognostic factors in ampullary adenocarcinoma. Aims: To examine the prognostic significance of Bax, Bcl-2, and p53 protein expression and the apoptotic index in a large cohort of uniformly treated patients with radically resected ampullary cancer. Methods: All patients with a pathological diagnosis of ampullary cancer and radical resection were evaluated. Expression analysis for p53, Bax, and Bcl-2 was performed by immunohistochemistry. Apoptotic cells were identified by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). Results: Thirty nine tumour specimens from patients with radically resected ampullary adenocarcinoma were studied. A positive significant correlation between Bax and p53 expression was found by rank correlation matrix (p < 0.001). A trend towards a positive correlation was found between the apoptotic index and p53 expression (p  =  0.059). By univariate analysis, overall survival was influenced by Bax expression, p53 expression, and TUNEL staining (p  =  0.001, p  =  0.01, and p  =  0.03, respectively). Bcl-2 expression did not influence overall survival in these patients (p  =  0.55). By multivariate Cox regression analysis, the only immunohistochemical parameter that influenced overall survival was Bax expression (p  =  0.020). Conclusions: These results provide evidence that apoptosis may be an important prognostic factor in patients with radically resected ampullary cancer. This study is the first to assess the clinical usefulness of Bax expression in radically resected ampullary cancer.

COX-2 expression in ampullary carcinoma: correlation with angiogenesis process and clinicopathological variables.

Background: There is evidence that the anti-neoplastic effect of non-steroidal anti-inflammatory drugs is attributable to cyclooxygenase-2 (COX-2) inhibition, but the exact mechanisms whereby COX-2 can promote tumour cell growth remain unclear. One hypothesis is the stimulation of tumour angiogenesis by the products of COX-2 activity. To data, there have been few clinicopathological studies on COX-2 expression in human ampullary carcinoma and no data have been reported about its relation with tumour angiogenesis. Objective: To investigate by immunohistochemistry the expression of COX-2 and the angiogenesis process in a series of primary untreated ampullary carcinomas. Methods: Tissue samples from 40 archival ampullary carcinomas were analysed for COX-2, vascular endothelial growth factor (VEGF), and an endothelial cell marker von Willebrand factor (vWF) by immunohistochemistry, using specific antibodies. Results: COX-2 expression was detected in 39 tissue samples (97.5%), of which two (5%) were graded as weak, 26 (65%) as moderate, and 11 (27.5%) as strong. Only one lesion (2.5%) was negative for COX-2 expression. VEGF expression was detected in 36 tissue samples (90%). A significant positive correlation was found between COX-2 and VEGF expression. No statistic correlation was found between COX-2 expression and microvessel density. Conclusions: COX-2 is highly expressed in ampullary carcinomas. This suggests an involvement of the COX-2 pathway in ampullary tumour associated angiogenesis, providing a rationale for targeting COX-2 in the treatment of ampullary cancer.

External Beam Radiotherapy Plus 24-Hour Continuous Infusion of Gemcitabine in Unresectable Pancreatic Carcinoma: Long-Term Results of a Phase II Study

PURPOSE To evaluate the efficacy of gemcitabine-based chemoradiation (CT-RT) in treating patients (pts) affected by locally advanced pancreatic cancers (LAPC). METHODS AND MATERIALS Weekly gemcitabine (100 mg/m(2)) was given as a 24-hour infusion during the course of three-dimensional radiotherapy (50.4 Gy to the tumor, 39.6 Gy to the nodes). After CT-RT, pts received five cycles of sequential chemotherapy with gemcitabine (1000 mg/m(2); 1, 8, q21). Response rate was assessed according to World Health Organization criteria 6 weeks after the end of CT-RT. Local control (LC), time to progression (TTP), metastases-free survival (MFS), and overall survival (OS) were analyzed by the Kaplan Meier method. RESULTS Forty pts (male/female 22/18; median age 62 years, range, 36-76) were treated from 2000 to 2005. The majority had T4 tumour (n = 34, 85%), six pts (15%) had T3 tumour. Sixteen pts (40%) were node positive at diagnosis. Grade 3-4 acute toxicity was observed in 21 pts (52.5%). Thirty pts (75%) completed the treatment schedule. A clinical response was achieved in 12 pts (30%). With a median follow-up of 76 months (range, 32-98), 2-year LC was 39.6% (median, 12 months), 2-year TTP was 18.4% (median, 10 months), and 2-year MFS was 29.7% (median, 10 months). Two-year OS (25%; median, 15.5 months) compared with our previous study on 5-fluorouracil-based CT-RT (2.8%) was significantly improved (p <0.001). CONCLUSIONS Gemcitabine CT-RT seems correlated with improved outcomes. Healthier patients who are likely to complete the treatment schedule may benefit most from this therapy.

Gastric adenocarcinoma associated with granulomatous gastritis. Case report and review of the literature.

Aims We describe the fourth reported case of granulomatous gastritis associated with gastric adenocarcinoma, with a review of the literature and considerations about the prognostic implications of this association. Results A 48-year-old woman who had been suffering from gastritis for ten years was admitted to our institute for increasing left epigastric pain associated with vomiting. After an endoscopic biopsy had revealed an ulcerated signet ring cell carcinoma, the patient was submitted to subtotal gastrectomy with regional lymph node dissection. Pathological examination of the resected specimen revealed a superficial signet ring cell carcinoma (early cancer) associated with multiple granulomas. The granulomas, which were observed within the mucosa and the submucosa at the periphery of the carcinoma, were composed of CD68-positive, CD15-negative epithelioid and giant cells of the Langhans type, confirming their true histiocytic nature, and were also extensively found within the dissected lymph nodes. Since no ocular, skin, pulmonary or other gastrointestinal lesions were found and the granulomas were negative for acid-fast and fungal stain, a diagnosis of granulomatous gastritis was made. Conclusions To the best of our knowledge this is the fourth example of gastric adenocarcinoma and granulomatous gastritis. These cases suggest an association between granulomatous gastritis and early gastric cancer.

Breast cancer in women 70 years of age or older

OBJECTIVES: To investigate the impact of age as a prognostic factor in older patients with breast cancer and to discuss the role of surgery in this category of patients.

Case of Rectal GI Stromal Tumor Demonstrating that KIT and PDGFRA Mutations Are Not Always Mutually Exclusive

Case Report A 52-year-old woman presented with complaints of anal pain/ constipation/tenesmus for 3 months before being referred to our hospital. There were no relevant prior illnesses. Rectal digital examination revealed a 6-cm smooth elastic mass on the rectal posterior left side 2 cm from the anal verge. Colonoscopy showed a rectal submucosal bulging. Computed tomography (CT) scan and magnetic resonance imaging confirmed the presence of a single 6-cm well-delimited mass, compressing and infiltrating the wall of the medium to low rectum. The tumor was completely removed, although ruptured, by transanal excision to save the organ. The specimen (2to 22-mm fragments) was almost entirely composed of tumor, highly cellular and with necrosis, consisting of spindle cells with perinuclear vacuolization and several mitoses (80/50 high-power fields; Fig 1A, magnification 400). Scarce rectal wall smooth muscle was present (Fig 1B, left, magnification 100). The tumor stained for CD117 (Fig 1C, magnification 400), DOG1 (Fig 1D, magnification 400), CD34, and S100 (patchy cytoplasmic pattern); desmin, melan-A, and HMB45 were negative. The diagnosis was spindle-cell GI stromal tumor (GIST). The patient’s disease was considered high-risk because of the fragmentation during removal, morphology, and site. Given thatasubsequentpositronemissiontomography/CTscanwasnegative, a conservative approach was maintained, leaving additional surgery as an option in case of relapse. By using polymerase chain reaction direct sequencing on independent DNA templates from four different tumor fragments, two mutations were consistently found: a 6-nucleotide– insertion GCCTAT between 1509-1510 nucleotides (CDS mutation: c. 1509_1510insGCCTAT)causinganinsertionof twoaminoacids:alanine and tyrosine (p.Y503_F504insAY) in KIT exon 9 (Fig 2A; arrow indicates thestartpointof theGCCTATinsertion),andapointmutation(A3Tat 2525)determiningaValforAspsubstitutionat842(D842V)ofexon18of platelet-derived growth factor receptor alpha (PDGFRA; Fig 2B; arrow indicates point mutation). KIT and PDGFRA were wild type in the rectal wall smooth muscle.

MUC2 but not MUC5 expression correlates with prognosis in radically resected pancreatic cancer patients

Introduction: Pancreatic cancer is one of the most aggressive gastrointestinal cancer with less than 10% long-term survivors. The apoptotic pathway deregulation is a postulated mechanism of carcinogenesis of this tumour. The present study investigated the prognostic role of MUC2 and MUC5 apomucin expression in a series of surgically resected pancreatic cancer patients. Material and Methods: All patients affected by pancreatic ductal adenocarcinoma and treated with surgical resection from 1988 to 2003 were considered for the study. MUC2 and MUC5 expression were evaluated by immunohistochemical staining. Tumour specimens of 59 resected patients were included in the study. Results: By univariate analysis, survival was influenced by MUC2 expression but not by MUC5 expression. The MUC2 overexpression was associated with better prognosis (P=0.003). By a multivariate Cox regression analysis, MUC2 overexpression maintained the prognostic statistical value. In particular, patients with high MUC2 staining showed a longer survival. Moreover the present study does report the absence of a prognostic role of MUC5 expression in this type of cancer. Conclusions: the study demoinstrated the prognostic relevance of MUC2 expression in pancreatic cancer and underlined its potential role as target gene in the field of therapy research.