Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas).

OBJECTIVES: Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. DESIGN: Retrospective multinational study including SCN diagnosed between 1990 and 2014. RESULTS: 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2-200)), 9% had resection beyond 1 year of follow-up (3 years (1-20), size at diagnosis: 25 mm (4-140)) and 39% had no surgery (3.6 years (1-23), 25.5 mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). CONCLUSIONS: After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. TRIAL REGISTRATION NUMBER: IRB 00006477.

High serum CA 19-9 but not tumor size should select patients for staging laparoscopy in radiological resectable pancreas head and peri-ampullary cancer.

BACKGROUND: The objective of this study was to validate current recommendations for the selective use of staging laparoscopy in patients with radiological resectable pancreas head and peri-ampullary tumors. METHODS: Data from a prospectively collected database (2007-2013) of 136 patients with peri-pancreatic head cancer were analyzed. RESULTS: Over a 6 year time period, 136 patients were evaluated, 126 patients were deemed radiological resectable and underwent laparotomy and 10 patients were characterized radiological unresectable. There were 111 patients with pancreas head resection and 15 without resection (8 due to extensive vascular involvement and 3 due to peritoneal/liver metastases). The sensitivity, specificity, PPV and NPV of pre-operative radiological imaging in determining unresectability due to liver/peritoneal metastases were 42%, 100%, 100% and 94.7% respectively. There was a significant difference in CA 19-9 values between metastatic and non-metastatic disease (p = 0.020). ROC curve analysis calculated the optimal CA 19-9 cutoff point for predicting metastasis at 215.37 U/ml with a sensitivity of 72.7%, a specificity of 58.3%, PPV of 15.1% and NPV of 95.5%. Tumor diameter was not a significant factor in predicting resectability. Laparoscopy would have been useful in only 5.3% of patients in the present series. CONCLUSION: High CA 19-9 values (>215 U/ml) and not tumor size should select patients with radiological resectable peri-pancreatic cancer for staging laparoscopy.

Plasma VEGF levels in breast cancer patients with and without metastases.

Vascular endothelial growth factor (VEGF) is a key mediator of angiogenesis since it stimulates the formation of new blood vessels. Basic fibroblast growth factor (bFGF) is related to the promotion of endothelial cells into tube-like structures, and it is therefore expected to promote angiogenesis with a greater potency than VEGF. VEGF and bFGF are considered to be biomarkers that predict treatment effectiveness. Elevated plasma VEGF and bFGF levels have been reported in a variety of different malignant tumors, and patients with metastatic disease have also been reported to present with higher serum VEGF and bFGF levels. Other studies have documented controversial results with respect to the prognostic and predictive value of the aforementioned biomarkers. This study aimed to determine the plasma VEGF and bFGF levels in breast cancer patients without metastatic disease compared with breast cancer patients with advanced metastatic disease. The study included 93 patients with breast cancer, 46 without recurrent disease (group A) and 47 with metastatic disease (group B), as well as 21 healthy individuals. The median age was 58 years (range 34-78) for group A and 59 years (range 37-75) for group B. All 93 patients underwent chemotherapy, adjuvant for group A, and adjuvant plus chemotherapy for group B patients with advanced disease. Plasma VEGF and bFGF levels were determined using a quantitative sandwich immunoassay, and samples were tested in triplicate (ELISA). The plasma levels of VEGF and bFGF varied greatly, i.e., from extremely low to extremely high in the two groups, as well as in the healthy individuals. No statistically significant difference was found between the two groups or between the patients and healthy individuals. Data of the present study therefore showed that VEGF and bFGF levels are not valuable biomarkers for predicting treatment outcome.

The Mount Sinai experience with orthotopic liver transplantation for benign tumors: brief report and literature review: case reports.

Orthotopic liver transplantation (OLT) is performed for benign hepatic lesions that are symptomatic, too large to be resected, have a malignant transformation potential, cause debilitating/life-threatening manifestations, or in patients experiencing posthepatectomy acute liver failure. Among benign tumors, polycystic liver disease (PLD) is the most common indication for OLT alone, or combined liver-kidney transplantation. Our 10-year experience with OLT for benign tumors includes two patients with PLD and one with a benign giant fibrous tumor. In this report, we present our experience with OLT for benign liver tumors, commenting on relevant published studies.

Use of fogarty catheter to limit hemorrhage and hematoma after vacuum-assisted breast biopsy.

A 42-year-old woman underwent vacuum-assisted breast biopsy (VABB, 11G) due to a nonpalpable, BI-RADS 4A lesion without microcalcifications. During the procedure, an extraordinarily large amount of blood was lost. In an attempt to stop the hemorrhage and limit the imminent hematoma, a thin intravascular Fogarty catheter was inserted adjacent to the VABB probe (through the same incision). The catheter was maintained in its position for 2 days. At clinical examination 9 days after VABB, no hematoma was present. The use of a Fogarty catheter seems capable of limiting any severe bleeding after VABB and may also possibly prevent subsequent hematoma formation.

The role of host immune response and apoptosis in patients with laryngeal squamous cell carcinoma.

PURPOSE: To determine whether the combined use of markers of host immune response (HLA-DR) and apoptosis (bax and bcl-2) can predict prognosis in laryngeal carcinoma patients. PROCEDURES: Immunohistochemical staining for HLA-DR, bax and bcl-2 proteins was investigated retrospectively in 37 patients with laryngeal squamous cell carcinoma. Seven healthy adult males were used as the control group. RESULTS: HLA-DR antigen expression was detected in the tumor cells of 18 patients (48.6%). Another 18 patients (48.6%) expressed HLA-DR antigen in the peritumoral inflammatory infiltrate, while bax and bcl-2 protein expressions were detected in 17 (45.9%) and 9 (24.3%) patients, respectively. None of the controls expressed any of the proteins studied. bcl-2 and HLA-DR protein expressions of the tumor infiltrate were statistically significant independent prognostic factors suggesting improved survival (p = 0.0272 and p = 0.0285, respectively). bax+/bcl-2- patients demonstrated an unfavorable clinical outcome (p = 0.0298), followed by a significantly increased mean HLA-DR antigen expression observed both in the tumor and the stroma cells (p = 0.024 and p = 0.045, respectively). CONCLUSIONS: bcl-2 and HLA-DR proteins independently predict a dismal prognosis among laryngeal carcinoma patients. The bax+/bcl-2- protein coexpression pattern correlates with elevated immunohistochemical expression of HLA-DR antigen both by tumor and peritumoral stromal cells. MESSAGE: bcl-2 and HLA-DR are significant prognostic markers in laryngeal carcinoma patients. Further prospective investigation is required to validate our findings.

HLA-DR antigen and bax protein expression in patients with primary non-Hodgkin's gastric lymphoma.

Primary gastric lymphoma represents a rare gastrointestinal malignancy with an unclear prognosis. The aim of this study was to determine the prognostic significance of HLA-DR antigen and bax expression in patients with primary non-Hodgkin's gastric lymphoma. We immunohistochemically studied bax protein and HLA-DR antigen expression in 36 B-cell, MALT-type primary gastric lymphoma patients diagnosed and treated in our department from 1990 to 1995. Ten non-malignant gastric tissue specimens were used as benign controls. Clinicopathological and survival data were correlated with the staining results. HLA-DR antigen expression was observed in 33 gastric lymphoma patients (91.7%). Positive bax staining was found in 24 gastric lymphomas (66.7%) and in none of the benign cases studied. In the univariate analysis, those gastric lymphoma patients who expressed HLA-DR antigen in more than 15% of their tumor cells, presented a significantly improved 5-year survival rate (75% vs. 37.5%, p = 0.04). Furthermore, gastric lymphoma patients who were bax(+)/HLA-DR(+) had a statistically better overall survival compared to those who were bax(-)/HLA-DR(-) (82.4% vs. 25%, p = 0.01). HLA-DR antigen expression was associated with a favorable clinical outcome. Its expression improved the predictive value of bax protein expression in non-Hodgkin's gastric lymphoma patients. The combined use of these markers permits the identification of a high-risk group of patients that may benefit from a more aggressive therapeutic approach.

Common pathways for primary hypertrophic and dilated cardiomyopathy.

Testing the hypothesis that hypertrophic and dilated cardiomyopathy as well as viral myocarditis share a common mitogenic growth response pathway with mitotically competent cell types are the aims of this study. The expression of the c-fos, H-ras and c-myc genes was immunohistochemically determined in biopsies from 12 patients with dilated cardiomyopathy, 24 patients with hypertrophic cardiomyopathy, and 4 patients with myocarditis. Normal myocardium from 9 subjects was used as the control group. Staining results were correlated with patient's demographic data. C-fos, H-ras and c-myc protein overexpression was seen in 15 patients (62.5%) with primary hypertrophic and 4 patients (33.3%) with dilated cardiomyopathy. The majority of hypertrophic and dilated cardiomyopathy patients expressed at least one of the genes studied compared with the control group (p = 0.006). Primary cardiomyopathy patients also showed a statistically significant difference in the gene co-expression compared with the control group (p = 0.042). C-fos, H-ras, and C-myc protein expression did not differ substantially between patients with hypertrophic and dilated cardiomyopathy. Patients with myocarditis expressed only the C-fos protein (n = 2, 50%). C-fos, h-ras and c-myc genes are overexpressed in patients with cardiac hypertrophy and cardiac dilation. Cardiac myocytes respond to biomechanical stress by initiating several different processes. One of them is oncogene expression. This results in a hypertrophy of the myocytes proportional in length and width (hypertrophic cardiomyopathy or with a relatively greater increase in length than in the width (dilated cardiomyopathy).

Prognostic significance of p53, bax and bcl-2 gene expression in patients with laryngeal carcinoma.

AIM: This study was designed to examine the prognostic significance of the coexpression of three genes (bax, bcl-2 and p53) which play a critical role in the apoptotic mechanisms in patients with squamous cell laryngeal carcinoma. MATERIALS AND METHODS: The immunohistochemical expression of bcl-2, bax and p53 genes was retrospectively examined in 38 patients with squamous cell laryngeal carcinoma and in five controls (necrotomic tissue). Tissue specimens were obtained both during the diagnostic biopsy and at the time of surgery. Clinicopathological and survival data were correlated with the staining results. RESULTS: Bcl-2 protein expression (P=0.0472), stage (P=0.0087) and lymph-node involvement (P=0.0488) were found to be independent prognostic factors. Increased bcl-2 protein expression correlated with a better 5-year survival (P=0.0472). Patients who were bcl-2(-)/p53(-) (n=25) or bax(+)/bcl-2(-) (n=13) had a significantly worse overall survival (P=0.0305 and P=0.0482, respectively). Similarly, patients who were bax(+)/bcl-2(-)/p53(-) (n=11) also had a worse 5-year survival compared with the rest of the group (P=0.0088). Changes that were noticed in bax and p53 protein expression from the time of biopsy until the time of surgery did not correlate with a significant increase in the overall survival. CONCLUSIONS: The expression of bcl-2 gene appears to be an independent prognostic factor for patients with laryngeal carcinoma. The coexpression of the genes studied can be used to determine aggressive clinical phenotypes.

Laparoscopic or open cholecystectomy in patients with sickle cell disease: which approach is superior?

OBJECTIVE: To compare laparoscopic with open cholecystectomy in patients with sickle cell disease. DESIGN: Retrospective clinical study. SETTING: University hospital, Greece. SUBJECTS: 41 patients (22 men and 19 women) with sickle cell disease had laparoscopic cholecystectomy between September 1991 and June 1998. Each patient was matched for age, sex, year of operation, and number of preoperative transfusions with control patients with sickle cell disease who had open cholecystectomy. MAIN OUTCOME MEASURES: Duration of operation, postoperative stay in hospital, incidence of complications, and conversion to open operation. RESULTS: The mean operation time was 81.4 min (range 55-125) for open cholecystectomy and 64.2 min (range 45-90) for laparoscopic cholecystectomy (p < 0.01). Complications occurred in 5% (2/41) of the patients in the laparoscopic group and in 20% (8/41) of the patients in the open group (p = 0.04). The mean length of stay in hospital was 5.6 days (range 3-9) in the open group and 2.7 days (range 2-5) in the laparoscopic group (p < 0.01). Conversion to open operation was necessary in 2 (5%) patients. CONCLUSIONS: Laparoscopic cholecystectomy resulted in a shorter hospital stay with fewer postoperative complications than open operation in patients with sickle cell disease and may be the procedure of choice in the treatment of cholelithiasis in such patients.

Protein expression of bax, bcl-2, and p53 in patients with non-Hodgkin's gastric lymphoma: prognostic significance.

The biologic significance of bcl-2, bax, and p53 gene expression in patients with non-Hodgkin's gastric lymphoma is unknown. We examined the prognostic value of these genes in 36 patients with gastric lymphoma treated in our clinic between 1990 and 1995. Paraffin-embedded specimens from 36 patients who underwent primary resection of the stomach for gastric lymphoma were analyzed immunohistochemically for p53, bax, and bcl-2 gene expression. Expression of bax was seen in 24 of 36 patients (66.7%), p53 expression was found in 8 of 36 tumors (22.2%), and bcl-2 cytoplasmic staining was detected in 6 of 36 patients (16.7%). We performed a univariate analysis to examine the possible correlation between the expression of these genes and the survival of our patients. Expression of bax protein proved to be a statistically significant prognostic factor (p = 0.049). Protein expression of p53 and bcl-2 did not statistically correlate with survival. In the bcl-2-negative (-) patient group (30 patients), those who were bax-positive had a statistically significant better survival than those who were bax-negative (63.3% vs. 36.7%, p = 0.03). There was also a statistically significant correlation between p53 expression and the grade of the tumor (p = 0.0014). P53 protein expression increased along with the grade. Expression of bax is a significant prognostic factor in patients with gastric lymphoma. Its prognostic value increases significantly when studied in bcl-2-negative patients; but expression of bax failed to be an independent prognostic factor. Expression of bcl-2 and p53 has no prognostic significance. Expression of p53 seems to represent a marker for loss of differentiation.