Cláudio Bresciani

The prognostic value of CD147/EMMPRIN is associated with monocarboxylate transporter 1 co-expression in gastric cancer

The aim of the present work was to assess the role of monocarboxylate transporters (MCTs), namely MCT1 and MCT4 as well as MCT/CD147 co-expression in gastric tissues and evaluate their clinico-pathological significance in gastric carcinoma. For that, we analysed the immunohistochemical expression of MCT1, MCT4 and CD147, in a large series of gastric samples, including non-neoplastic, tumour and metastatic tissues. A significant decrease in MCT4 plasma membrane expression was observed from non-neoplastic to gastric primary malignant tissues and to lymph-node metastasis and both MCT1 and MCT4 correlated with CD147. Importantly, both MCT4 and CD147 were more frequently expressed in Laurens intestinal-type tumours and MCT1/CD147 co-expression was associated with advanced gastric carcinoma, Laurens intestinal type, TNM staging and lymph-node metastasis. Our results showed that the prognostic value of CD147 was associated with MCT1 co-expression in gastric cancer cells, supporting the view that CD147 plasma membrane activity is dependent on MCT co-expression.

Mucinous colorectal adenocarcinoma : influence of mucin expression (Muc1, 2 and 5) on clinico-pathological features and prognosis

BackgroundMucinous component is associated with distinct clinical and pathological features and poor survival in colorectal cancer. The purpose of this study was to determine differences in outcomes of patients with mucinous colorectal adenocarcinoma according to the type of mucin expressed.Materials and MethodsImmunohistochemistry was performed in all tumors of patients who underwent radical surgery between 1998 and 2003 with mucinous colorectal cancer using antibodies against MUC1, 2, and 5. Correlation between immunoexpression and clinical, pathological features and survival was performed.ResultsOf the 418 patients treated in this period, only 35 had a mucinous adenocarcinoma. Of these, 25 were positive for 1 or more mucin expression. MUC2 expression correlated with tumor site and depth of penetration, while MUC5 expression correlated to tumor site. Overall survival was significantly worse for patients with MUC2 expression, and disease-free survival was significantly worse for patients with MUC1 expression.ConclusionsMucin expression may have significant correlation to specific clinical-pathological features and survival of patients with mucinous-type colorectal adenocarcinoma. These differences may reflect distinct molecular mechanisms involved in carcinogenesis of mucinous colorectal adenocarcinoma.

Complications of gastrectomy with lymphadenectomy in gastric cancer

BackgroundCurrently, gastrectomy and extended lymphadenectomy (LN) is the treatment of choice for gastric cancer. Although a survival rate benefit of D2 LN compared to D1 LN has been shown, the D2 LN procedure is not fully employed, due to possible higher morbidity and mortality rates. These higher rates are being questioned in more recent series, in which D1 and D2 LN complication rates have been similar. The aim of this study was to analyze the immediate postoperative complications of patients submitted to total or subtotal gastrectomy with D1 or D2 LN (according to the Japanese guidelines for gastric cancer) at the Gastrointestinal Surgery Division of the Medical School of São Paulo University, between January 2001 and April 2003.MethodsOne hundred consecutive patients were studied; 61 were men and 39, women. Total gastrectomy was performed in 52 patients (13 with D1 LN and 39 with D2 LN), and subtotal gastrectomy was performed in 48 (11 with D1 LN and 37 with D2 LN). Total or subtotal gastrectomy with D1 or D2 LN was performed according to the tumor extent and histological classification (Lauren’s diffuse or intestinal type), considering the patient’s general condition and the gastric cancer stage. Roux-en-Y reconstruction was performed in almost all patients.ResultsNo difference was observed regarding complications and mortality related to the extent of the gastrectomy. Although morbidity was higher in the D1 group, no significant difference was observed. Mortality was higher in the D1 group, and this was probably related to their poor surgical condition and more advanced tumors.ConclusionAccording to these results, it appears that total or subtotal gastrectomy with D2 LN in gastric cancer treatment, performed according to the Japanese guidelines, can be considered a safe procedure, with acceptable morbidity and mortality, when performed by a trained surgical team.

Laparoscopic versus standard appendectomy outcomes and cost comparisons in the private sector

Minimally invasive surgery has been proposed as the preferred treatment strategy for various gastrointestinal disorders due to shorter hospital stay, less pain, quicker return to normal activities, and improved cosmesis. However, these advantages may not be straightforward for laparoscopic appendectomy, and optimal management of remains controversial. One hundred forty-eight patients with clinical and radiologic diagnoses of acute appendicitis treated in two different hospitals were retrospectively reviewed. Seventy-eight patients underwent laparoscopic appendectomy in hospital A and 70 patients underwent standard appendectomy in hospital B. Patients treated by either type of surgery were compared in terms of clinical and pathologic features, operation characteristics, complications, and costs. There were no significant differences between both groups in terms of clinical features, radiologic studies, complications, and final pathology findings (P > .05). Hospital stay was significantly shorter and bowel movements recovered quicker in the laparoscopy group. However, overall and operating room costs were significantly higher in patients treated by laparoscopy (P < .01). Our series show a subtle difference in terms of hospital stay and bowel movement recovery, favoring patients treated by laparoscopy. However, these results have to be carefully examined and weighed, because overall costs and operating room costs were significantly higher in the laparoscopy group.

Endoscopic management of postoperative stapled colorectal anastomosis hemorrhage

Rectal bleeding following colorectal anastomosis is common but usually self-limited. Continuous hemorrhage is rare, and when it occurs, often requires further treatment. The most frequently used strategies for treatment of stapled anastomotic hemorrhage are clinical observation with or without blood transfusion, rectal packing, angiographic identification of the bleeding site with vasopressin infusion or embolization, and endoscopic eletrocoagulation. We report the case of a 49-year-old man with uncomplicated diverticular disease who was treated by laparoscopic sigmoidectomy, with double-stapled colorectal anastomosis. Six hours later, the patient presented intense rectal bleeding and was taken to the operation room for urgent colonoscopic examination. After complete removal of blood clots inside the rectum, a bleed localized at the anastomotic site was identified and submucosal peri-anastomotic injection of 10 ml adrenaline (1:200 000) in saline was performed with immediate bleeding control.

Are histological alterations observed in the gallbladder precancerous lesions

INTRODUCTION Gallbladder cancer, which is characterized by rapid progression and a poor prognosis, is a complex disease to treat. Unfortunately, little is known currently about its etiology or pathogenesis. A better understanding of its carcinogenesis and determining risk factors that lead to its development could help improve the available treatment options. METHOD Based on this better understanding, the histological alterations (such as acute cholecystitis, adenomyomatosis, xanthogranulomatous cholecystitis, polyps, pyloric metaplasia, intestinal metaplasia, dysplasia, cancer and others) in gallbladders from 1,689 patients who underwent laparoscopic cholecystectomy for cholecystolithiasis were analyzed. The association of these gallbladder histological alterations with clinical data was studied. RESULTS Gender analysis revealed a greater incidence of inflammatory changes in males, while dysplasia and cancer were only found in women. The incidence of cholesterolosis was greater in the patients 60 years of age and under, and the incidence of adenomyomatosis and gangrene was greater in the elderly patients. A progressive increase in the average age was observed as alterations progressed through pyloric metaplasia, intestinal metaplasia, dysplasia and then cancer, suggesting that the metaplasia-dysplasia-carcinoma sequence may occur in gallbladder cancer. Gallbladder histological alterations were also observed in asymptomatic patients. CONCLUSION The results of this study suggest that there could be an association between some histological alterations of gallbladder and cancer, and they also suggest that the metaplasia-dysplasia-carcinoma sequence could in fact be true in the case of gallbladder cancer. Nevertheless, further studies directed towards a perfect understanding of gallbladder carcinogenesis are required.

Laparoscopic versus open splenectomy in the management of hematologic diseases

UNLABELLED Splenectomy is the best available treatment for severe forms of hereditary spherocytosis, idiopathic thrombocytopenic purpura, and other hematologic conditions when these prove refractory to conservative management. It has been employed for many decades with low mortality and favorable remission rates. The use of laparoscopic splenectomy in recent years has been rapidly and even enthusiastically adopted in this field. However, the exact role of laparoscopic versus open surgery for hematologic diseases is still debated. In this study of 58 adult patients, laparoscopic procedures were compared with conventional splenectomies for similar indications. METHODS All patients were operated on within an 8-year period. Subjects underwent similar procedures under the supervision of the same surgical school and were compared regarding age, gender, body mass index, and diagnosis. Laparoscopically managed cases (Group I, n = 30) were prospectively followed according to a written protocol, whereas the same investigation was retrospectively done with regard to traditional laparotomy (Group II, n = 28). Methods included general and demographic findings, duration and technical steps of operation, blood loss, weight of spleen, need for conversion (in minimally invasive subjects), intraoperative and postoperative complications, time until realimentation, postoperative hospitalization, mortality, and late follow-up including recurrence rate. RESULTS Idiopathic thrombocytopenic purpura was the surgical indication in over 50% of the patients in both groups, but familial spherocytosis, thalassemia, myelodysplasia, and lymphomas were also represented in this series. Laparoscopic procedures took more time to perform (P = 0.004), and postoperative hospitalization was 2 days shorter, but this difference was not statistically significant. Postoperative hematocrit and volume of blood transfusions was equivalent, although the laparoscopic cases had a somewhat lower preoperative hematocrit (NS) and displayed better recovery for this measurement (P = 0.03). More patients in Group I were able to accept oral food on the first day than subjects undergoing conventional operations (P < 0.05). Relatively few conversions were necessary during the minimally invasive surgeries (13.3%), and postoperative early and late complications as well as recurrences occurred in similar proportions. Also, the mean weight of the spleen was not statistically different between the groups, although there was a marked numerical tendency toward larger masses in conventional procedures. No spleen in Group I exceeded 2.0 kg, whereas in Group II values up to 4.0 kg occurred, and the mean weight was 50% higher in the latter group. CONCLUSIONS 1) Minimally invasive splenectomy was essentially comparable to open surgery with regard to safety, efficacy, and late results; 2) Advantages concerning shorter postoperative hospitalization could not be shown, despite earlier food intake and a non-significant tendency toward earlier discharge; 3) This new modality should be considered an option in cases of hematologic conditions whenever the spleen is not hugely enlarged.

Microsatellite instability in solitary and sporadic gastric cancer

UNLABELLED Recently, the presence of microsatellite instability (MSI) has been reported in gastric cancer and associated with older age of presentation, distal tumor location, early disease staging, and better overall prognosis. Different characteristics in presentation and in tumor behavior may be explained by different genetic alterations during carcinogenesis of gastric cancer. Identification of specific genetic pathways in gastric cancer may have direct impact on prognosis and selection of treatment strategies. PATIENTS AND METHODS All 24 patients were treated by radical surgery. Fragments of normal and tumor tissues were extracted from the specimen and stored at -80 degrees C before DNA purification and extraction. PCR amplification utilizing microsatellite markers was performed. Tumors presenting PCR products of abnormal sizes were considered positive for microsatellite instability (MSI+). RESULTS Five patients (21%) had tumors that were MSI+ in at least 1 marker. In the group of patients with Laurens intestinal-type gastric carcinoma, 3 had tumors that were MSI+ (23%), while in the group of diffuse-type gastric cancer, 2 patients had tumors that were MSI+ (19%). The mean age of presentation and the male:female ratio was similar in both groups. Tumors that were MSI+ were more frequently located in proximal portion of the stomach compared to microsatellite-stable (MSS) tumors (40% vs. 16%). Although there was a trend of patients with MSI+ tumors towards a proximal gastric tumor location, early staging, and negative lymph node metastasis, there was no statistical significance compared to those with MSS tumors (P >.1). Comparison of overall and disease-free survival between gastric tumors that were MSI+ and those that were MSS found no statistically significant differences (P >.1). CONCLUSIONS Microsatellite instability is a frequent event in gastric carcinogenesis and shows a trend towards distinct clinical and pathological characteristics of gastric cancer.

Phase II trial of etoposide (V), adriamycin (A), and cisplatinum (P) in patients with metastatic gastric cancer.

The efficacy and toxicity of a combination of etoposide (100 mg/m2 i.v. on days 1 to 3), Adriamycin (20 mg/m2 i.v. on days 1 and 8) and cisplatinum (40 mg/m2 i.v. on days 2 and 8) repeated every 4 weeks as an outpatient regimen were assessed in 29 consecutive patients with metastatic gastric cancer with measurable disease. Five of these patients were refractory to 5-Fluorouracil, Adriamycin, and Mitomycin C. Three of these previously treated patients responded to the etoposide, Adriamycin, cisplatinum (VAP) therapy. An overall objective response rate of 72.5% was achieved, including 14% that were complete responses. The median duration of response was 6.0 months; median overall survival was 7.2 months, overall one-year survival was 34.4%. He-matologic toxicity was intense, particularly among patients with lower performance status. Three patients died as a consequence of nadir sepsis episodes.

Distribution of lymph nodes in the mesorectum: how deep is TME necessary?

BackgroundStandardization of total mesorectal excision (TME) had a great impact on decreasing local recurrence rates for the treatment of rectal cancer. However, exact numbers and distribution of lymph nodes (LN) along the mesorectum remains controversial with some studies suggesting that few LNs are present in the distal third of the mesorectum.MethodsEighteen fresh cadavers without a history of rectal cancer were studied. The rectum was removed by TME and then was divided into right lateral, posterior and left lateral sides, which were further subdivided into 3 levels (upper, middle and lower). A pathologist determined the number and sizes of the LNs in each of the nine areas, b linded to their anatomical origin.ResultsOverall, the mesorectum had a mean of 5.7 LNs (SD=3.7) and on average each LN had a maximum diameter of 3.0 mm (SD=2.7). There was no association between the mean number or size of LNs with gender, BMI, or age. There was a significantly higher prevalence of LNs in the posterior location (2.8 per mesorectum) than in the two lateral locations (0.8 and 1.2 per mesorectum; p=0.02). The distribution of LNs in the three levels of the rectum was not significant.ConclusionsThe distribution of LNs reinforces the fact that TME should always include the distal third of the mesorectum. Care must be taken to not violate the posterior aspect of the mesorectum.