The increased angiogenic capacity and decreased inflammatory response when a mesh is used in combination with an omental flap. A prospective experimental study.

BACKGROUND: The use of a surgical mesh for abdominal wall reconstruction is well established and has been used for long with minor complications, whereas the omental flap has been used for decades in reconstructive surgery. AIM: To demonstrate the increased angiogenic capacity and the reduced inflammatory markers of a synthetic mesh when used in combination with an omental flap. Furthermore, we compare two independent meshes when used alone or in combination with the omental flap. MATERIALS AND METHODS: Twenty-eight rats were included in the study. To determine the effect of using an omental flap under two different meshes, the animals were separated into four groups, i.e., group A (flap + mesh 1), group B (flap + mesh 1 + silicone), group C (flap + mesh 2), and group D (flap + mesh 2 + silicone). A silicone sheet was placed as a barrier between the mesh and the flap. All groups were sacrificed 8 weeks post-operatively. RESULTS: The use of a silicone sheet barrier between any of the two synthetic meshes and the omental flap in an abdominal wall defect is accompanied by a markedly reduced angiogenesis in terms of a cluster of differentiation (CD)-34 (p < 0.001) and factor VIII (p = 0.0012) and by increased inflammatory response CD-68 (p = 0.0024) and visual scoring (p < 0.001). CONCLUSIONS: Τhe increased angiogenic capacity and the reduced inflammatory markers of a synthetic surgical mesh when used in combination with an omental flap make it a useful option in the reconstruction of an abdominal wall defect on a large or contaminated wound.

Similar immunity profiles in patients with meningioma and glioma tumors despite differences in the apoptosis and necrosis of circulating lymphocyte and monocyte populations.

AIM: The present study aims to compare the host immune responses induced by benign (meningiomas) and malignant (gliomas) brain tumors. METHODS: Peripheral blood samples from 8 meningioma and 7 glioma patients collected pre- and post operatively were assessed for cell-mediated immunity, humoral immunity and IL-6, IL-8 and TNF-a expression. Apoptosis and necrosis of circulating lymphocytes and monocytes were evaluated by Annexin/PI, while DNA analysis was applied to trace circulating cells with an abnormal DNA content. RESULTS: Cell-mediated immunity was similar in the two groups either pre- or post- operatively. However, differences in the apoptosis and necrosis of circulating lymphocytes and monocytes were observed. Menigioma patients were characterized by increased percentage of apoptotic lymphocytes and necrotic monocytes pre-operatively and apoptotic monocytes postoperatively. In contrast glioma patients showed an increase in necrotic monocytes postoperatively. Humoral immunity and cytokine expression were at comparable levels both pre- and post-operatively. IL-6 expression was significant elevated after surgery in both groups. Circulating aneuploid cells were identified in three glioma patients pre-operatively, by DNA analysis. CONCLUSION: The presented data indicate that meningioma and glioma tumors trigger comparable systemic host immunity response mediated by impairments in cell-mediated immunity due to alternations in apoptosis and necrosis that also influence their shift towards the Th2 immunity profile. Moreover, the presented evidences on the circulation of aneuploid cells in glioma patients may substantiate further the immunosuppressive phenotype detected in these patients and offer a mechanism for the rare cases that extra- neural dissemination was observed without previous surgical intervention.

Metastatic melanoma: case report of a patient with seventeen months of complete remission, five years survival and review of the literature.

Melanoma, an aggressive, therapy-resistant malignancy of melanocytes, is the most serious type of skin cancer affecting young and middle-aged people. Therapy for early disease is predominantly surgical, with a minor benefit noted with the use of adjuvant therapy. Management of systemic melanoma is a challenge because of a paucity of active treatment modalities. The authors present the case of a patient with advanced-stage melanoma who underwent surgery for metastatic disease. He then received cisplatin-based combination chemotherapy, with disease stabilization. However, after different regimen modifications complete remission (CR) was finally achieved, until the disease progressed once more. Five years after surgery, the patient is still alive and continuing chemotherapy.

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.

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.

Sealed perforated duodenal ulcer discovered during elective laparoscopic cholecystectomy.

During laparoscopic cholecystectomy (LC) there is possibility of discovering concomitant occult intra-abdominal pathology and the surgeon must be prepared to undertake the appropriate procedure. We evaluated the incidence of latent perforated duodenal ulcer in 5539 patients who underwent LC for gallstone disease at our unit between November 1991 and November 2001. Seven (0.13 %) cases of perforated duodenal ulcer were discovered. Following the diagnosis of the perforation, laparoscopic suturing and omental patch repair was carried out in four patients, open repair with selective vagotomy and pyloroplasty in two patients and an open suture and omental patch repair in one patient. In all cases the cholesystectomy was completed successfully.

Incidental finding of gallbladder carcinoma detected during or after laparoscopic cholecystectomy.

AIM: Carcinoma of the gallbladder is a rare neoplasm with a dismal prognosis. With the increase of cholecystectomies due to the wide acceptance of laparoscopic cholecystectomy, the incidental diagnosis of gallbladder carcinoma is more frequent. We report our experience with gallbladder cancer diagnosed during or after the performance of laparoscopic cholecystectomy. METHODS: We evaluated 11 patients with gallbladder cancer out of 5539 patients who underwent laparoscopic cholecystectomy. Patient clinical and demographic characteristics were reviewed. RESULTS: Intraoperatively in 297 patients there was the suspicion of adenocarcinoma and frozen sections were performed. In four of them the diagnosis of adenocarcinoma was confirmed. In two of them the procedure was converted to open with gallbladder liver bed resection and regional lymph node dissection while the other two were considered inoperable. Of the remaining 5242 patients, seven were diagnosed postoperatively at the pathologic examination. Of these, five patients refused to undergo a repeat operation. We did not observe port site metastasis in any of our patients. Survival was low and ranged from 3-14 months. CONCLUSION: Gallbladder cancer runs a short course, with a poor prognosis. The use of a meticulous laparoscopic technique seems to be important for the diagnosis and the avoidance of early complications of the disease.

Common prognostic factors for stage III melanoma patients and for stage I and II melanoma patients with recurrence to their regional lymph nodes.

This study was undertaken in order to identify the prognostic factors for stage III malignant melanoma patients. In addition we compared the survival data of these patients with data from patients presenting with stage I and II disease who subsequently developed a regional nodal recurrence, in order to identify common prognostic factors and to compare the biological behaviour of the two groups. We retrospectively examined two groups of patients. The first consisted of 116 patients with stage III malignant melanoma and the second consisted of 57 patients with stage I and II malignant melanoma that were found to have regional lymph node metastases diagnosed at least 6 months after surgical treatment of their primary lesion. The age of the patients, the number of disease-involved lymph nodes, the site of the primary lesion and the presence or not of palpable lymph nodes proved to be significant prognostic factors of the first group. We also analysed the survival data of the second group and compared it with data from the stage III patients. The 5 year survival starting from the time after diagnosis of the primary lesion was 47.37% compared with 25.86% in stage III patients; however, this difference was not statistically significant. Patients who present with stage III malignant melanoma seem to have a more aggressive phenotype than stage I and II malignant melanoma patients who present with recurrent disease in their regional lymph nodes. Disease behaviour is dictated by the number of disease-involved lymph nodes, the site of the primary lesion and the type of surgical procedure performed (elective or therapeutic lymph node dissection).

Latent adenocarcinoma of the colon discovered during or after laparoscopic cholecystectomy.

BACKGROUND: The wide acceptance of laparoscopic cholecystectomy has resulted in the performance of increased numbers of cholecystectomies, hence increasing the number of patients discovered with concomitant malignancy or other pathological states. PATIENTS AND METHODS: A total of 3751 patients who underwent laparoscopic cholecystectomy between January 1995 and December 2000 were included in this study. Nine cases of coexisting malignant colonic neoplasm were discovered. All of these patients but one underwent therapeutic resection. RESULTS: The survival rate of these nine patients was the same as that of 62 consecutive colonic cancer patients who were treated in our department over the same period. The rate of postoperative complications in the study group was higher than in the control group (21 % vs. 9.5 %). The hospital stay in these patients was also greater (17 days vs. 10 days). CONCLUSION: The rate of incidental discovery of colorectal carcinomas during laparoscopic cholecystectomy in our department was 0.24 %. These patients had higher complication rates and a longer hospital stay.

Can expression of apoptosis genes, bcl-2 and bax, predict survival and responsiveness to chemotherapy in node-negative breast cancer patients?

BACKGROUND: Although the status of the axillary lymph nodes is widely accepted to be associated with prognosis in breast cancer patients, there is a need for biomarkers to be analyzed as indicators of responsiveness to treatment. The objective of this study was to test the hypothesis that the expression of apoptosis genes, bcl-2 and bax, predicts survival and responsiveness to chemotherapy in node-negative breast cancer patients. METHODS: One hundred thirty premenopausal women with primary breast carcinoma were studied for the expression of bcl-2 and bax genes. The relationship between the expression of bcl-2 and bax proteins and a series of markers of known prognostic value [such as tumor size, nuclear grade, receptors of the steroid hormones estrogen (ER) and progesterone (PgR)]. The association of these proteins with survival and responsiveness to chemotherapy was also examined. RESULTS: Sixty (46%) and sixty-four (49%) breast cancer cases were found positive for bcl-2 and bax, respectively, as indicated by immunohistochemistry. A statistically significant association was found between expression of bcl-2 and tumor size (P = 0.001), low grade (grade I) (P = 0.002), positivity of ER (P = 0.001), positivity of PR (P = 0.03), and superior disease-free survival (DFS) (P = 0.04), and superior overall survival (OS) (P = 0.03). In contrast, no similar associations were observed for the bax gene. Overall, there was a trend toward an association between adjuvant chemotherapy and DFS (P = 0.08) and OS (P = 0.07). This trend became statistically significant when the patients were analyzed by individual gene expression. In bax-positive patients, chemotherapy improves 6-year DFS (P = 0.01) and OS (P = 0.03) while similar effects were not observed in the other subgroups of patients. CONCLUSION: Our results indicated that bcl-2 expression is associated with a number of favorable prognostic factors and better clinical outcome, while bax expression seems to have positive predictive value for responsiveness to chemotherapy in lymph node-negative breast cancer patients.

Reconstruction of the pancreatic duct after pancreaticoduodenectomy: a modification of the Whipple procedure.

BACKGROUND AND OBJECTIVES: Pancreaticoduodenectomy is still associated with high morbidity and mortality even though there has been significant progress in the field of pancreatic surgery and postoperative follow-up. The pancreatoenteric anastomosis, regardless of the technique used, is a major cause for both morbidity and mortality after Whipple procedure. To overcome all problems resulting from anastomotic leakage, we used external drainage of the pancreatic duct. METHODS: In 24 patients who underwent pancreaticoduodenectomy in our Department from 1986 to 1995, a modification to the standard Whipple procedure was performed. Instead of pancreaticoenteric anastomosis, external drainage of the pancreatic duct remnant was performed. The pancreatic duct was intubated with a silastic tube, the external end of which was sutured to the skin. All patients received substitution therapy with pancreatic enzymes. RESULTS: Mortality in our group of patients was 4%. No complications due to the external drainage of the pancreatic duct were reported, while no patient developed diabetes mellitus after surgery. CONCLUSIONS: External drainage of the pancreatic duct remnant can be used alternatively to pancreatoenteric anastomosis after pancreatoduodenectomy. The technique is safe and simple to perform and appears to reduce overall operative time. It may be an option for patients with significant comorbidity and/or intraoperative hemodynamic instability which mandates expeditious completion of the operation.

Apoptosis in cells of bronchoalveolar lavage: a cellular reaction in patients who die with sepsis and respiratory failure.

OBJECTIVE: Apoptosis represents a physiologic clearance mechanism in human tissues. The role of apoptosis has not been examined in lung cell populations, such as alveolar macrophages of septic patients, an organ frequently insulted in these patients. This study was designed to examine the effect of sepsis on the apoptosis of alveolar macrophages. DESIGN: Prospective study. SETTING: Intensive care unit and surgical intensive care and trauma unit of a large university hospital in Athens, Greece. PATIENTS: Bronchoalveolar lavage was obtained from 20 consecutive patients who met the criteria for sepsis, admitted to two intensive care units. Bronchoalveolar lavage was obtained from nine volunteers without lung disease who served as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The specimens were analyzed by using annexin V binding, terminal deoxynucleotidyl transfer-mediated deoxyuridine 5-triphosphate nick end labeling (TUNEL), DNA laddering, light microscopy, and immunohistochemistry. Spontaneous apoptosis of bronchoalveolar lavage cells and particularly of alveolar macrophages was significantly decreased in septic patients compared with nonseptic controls. This finding was confirmed by using morphologic criteria and the TUNEL method. Furthermore, gel electrophoresis of DNA obtained from bronchoalveolar cells revealed that DNA fragmentation was not necessarily associated with apoptotic cell death. The bcl-2 gene was minimally expressed in the control group. An inverse correlation was found between the percentage of apoptotic alveolar macrophages and the severity of sepsis. CONCLUSIONS: The prolonged survival of lung cells in septic patients and especially of alveolar macrophages may be attributable to the inhibition of apoptosis. This seems to represent an initial attempt of the host to increase the defense capacity to kill the invading microorganism, resulting in an unbalanced tissue load of cells and an uncontrolled release of toxic metabolites. Furthermore, the inhibition of apoptosis in septic patients may explain why lung function is impaired, leading to sepsis-induced acute respiratory distress syndrome and death.

A phase II study of 9-nitrocamptothecin in patients with advanced pancreatic adenocarcinoma.

PURPOSE: Preclinical and phase I clinical data suggest that 9-nitrocamptothecin (9NC) is an agent with potential anticancer activity. A phase II study was undertaken in order to evaluate the potential benefit of oral 9NC administration in patients with advanced pancreatic cancer. This was the first clinical study of 9NC in Europe. METHODS: A total of 19 consecutive patients with locally advanced or metastatic adenocarcinoma were enrolled (8 males and 11 females, aged 37-73 years). The patients were given 9NC orally five times a week, once a day. The end-points of this study were toxicity, objective response rate, subjective response rate (i.e. pain control, performance status and body weight), and survival. RESULTS: An objective response was documented in 4 of the 14 evaluable patients (28.6%), while a subjective response was observed in 13 patients (92.9%). Overall median survival was 21 weeks (31 weeks in the group of 14 patients evaluable for response), and the 1-year survival was 16.7% and 23.1%, respectively. Toxicity leading to temporary discontinuation of 9NC was encountered in seven patients (36.8%), all related to a prior dose increase, while milder toxicity was observed in eight patients (42.1%). CONCLUSIONS: 9NC administered orally to patients with advanced pancreatic cancer gave promising results, while the toxicity of the therapy was mild and readily overcome. A larger scale clinical trial should be organized in order to establish the potential benefit of 9NC in patients with pancreatic adenocarcinoma.

Circulating anti-CEA antibodies in the sera of patients with breast cancer.

AIM: The aim of this study was to detect circulating anti-carcinoembryonic antigen antibodies (anti-CEA) in breast cancer patients and to evaluate their clinical and prognostic significance. METHODS: Fifty-two breast cancer patients and 28 controls were included in this study. Detection of anti-CEA antibodies was performed using a modified enzyme linked immunoassay (ELISA). Sensitivity, specificity and usefulness index of anti-CEA antibodies were compared to those of CEA. The correlation of anti-CEA antibodies with survival and recurrence-free survival was tested with univariate and multivariate analysis. RESULTS: Anti-CEA was present in 57% of breast cancer patients and in 11% of controls. The sensitivity and usefulness index of anti-CEA were significantly better than those of CEA. The specificity of anti-CEA antibodies was less than that of CEA, the difference not being statistically significant. Anti-CEA antibodies were an independent statistically significant, favourable factor in recurrence-free survival. CONCLUSION: Anti-CEA antibodies circulate in breast cancer patients. They could be used as a more sensitive tumour marker than CEA. Their presence is associated with improved recurrence-free survival. These results should be confirmed in a larger series.

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.

Risk of basal cell and squamous cell carcinoma in persons with prior cutaneous melanoma.

BACKGROUND: Melanoma has been associated with an overall increase in actinic tumors, including actinic keratoses, as well as with noncutaneous malignancies. OBJECTIVE: Determine the risk of developing basal cell and squamous cell skin cancer in patients with prior cutaneous melanoma (actinic keratoses not encountered). METHODS: This retrospective study included 1396 white patients with prior cutaneous melanoma followed at the Roswell Park Cancer Institute in the period 1977-1978. The control group was the white population of the Detroit area in the same period (1977-1978). RESULTS: A total of 25 patients (18 males, 7 females) developed 35 basal cell and/or squamous cell carcinomas: 18 developed basal cell carcinomas, 2 squamous cell carcinomas, and 5 both. The calculated odds ratio was 3.49 (males 3.67, females 2.86, 95% confidence interval 1.52-8.00). No correlations were found with age, type, anatomic site, and length of follow-up of cutaneous melanoma. CONCLUSION: A history of cutaneous melanoma significantly increases the risk of basal cell and squamous cell skin cancer.

Reflections on the European Conference "Molecular Screening of Individuals at High Risk for Developing Cancer: Medical, Ethical, Legal, and Social Issues".

The fascinating progress of molecular biology in the last decades has made possible the early identification of persons at risk of developing malignant neoplasms, such as thyroid, colon, and breast cancer. This has changed conventional medical practice and has raised a number of ethical questions. Despite the fact that there has been substantial development throughout the Western countries in legislation dealing with medical information, there is an acute need for further exploration and assessment of the moral and social dimensions of medical practices to achieve more precise and uniform regulations. These topics were discussed in a multidisciplinary European Conference entitled "Molecular Screening of Individuals at High Risk of Developing Cancer: Medical, Ethical, Legal, and Social Issues," which took place in March, 1999, in Athens, Greece.