Carlos Eduardo Jacob

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.

Does the intraoperative peritoneal lavage cytology add prognostic information in patients with potentially curative gastric resection

Peritoneal recurrence is the foremost pattern of failure after potentially curative resection for gastric cancer. Our aim was to evaluate the prognostic value of intraperitoneal free cancer cells (IFCCs) in peritoneal lavage of patients who underwent potentially curative resection for gastric carcinoma. Two hundred twenty patients with gastric cancer stage I, II, or III were prospectively evaluated with peritoneal lavage and cytologic examination. Aspirated fluid from the abdominal cavity was centrifuged and subjected to Papanicolaou staining. The mean age was 60.9 years (range, 21–89 years), and 63.6% were men. IFCCs were detected in 6.8% of the patients; suspicious in 2.7%, and negative in 84.5%. No judgment could be given in 5.9% of the cases. Invasion of the gastric serosa (pT3) was observed in all positive cytology patients. Patients with IFCCs had a mean survival time of 10.5 months, while those with negative IFCC had a mean survival time of 61 months (P = 0.00001). There was no correlation between the presence of IFCCs and tumor size, histology, pN, or tumor site. Our conclusions are that (1) positive cytology indicates a poor prognosis in patients who underwent potentially curative gastric resection and (2) peritoneal lavage cytology improves staging in assessing these patients and may alter their therapeutic approach.

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.

Alterações metabólicas e digestivas no pós-operatório de cirurgia bariátrica

BACKGROUND: Changes in digestion and nutrients losses are relevant aspects in weight reduction and maintenance of the nutritional status of patients undergoing gastroplasty, but few studies are available in the literature. AIM: To study the systemic changes arising from the reduction in weight over time after surgery. METHOD: A prospective cohort study with 44 morbid obese patients operated on between July 2001 and April 2005. The operation performed was a gastric by pass Roux-en-Y with silicon ring. Medical tests were conducted at different times: preoperatively, six months after the operation and during the years 2006 and 2007. The examinations performed were: fasting glucose, serum albumin, total cholesterol, hemoglobin, fecal fat, reducing substance in stool, occult blood in the stool. Endoscopy was also performed to measure the ring in centimeters. Also studied were the gender, age, height, weight, BMI, diabetes, and time after operation. RESULTS: The initial weight ranged from 91 to 216 kg (Md = 141 kg) and BMI at this stage was between 36,3 and 80,3 kg/m2 (Md = 49,28 kg/m2). Anemia manifested in eight patients (18,2%) and 13 (29,5%) had albumin with reduced values. Follow-up ranged from 32 to 79 months (X = 52,5 months, SD = 8,8). The final weight ranged from 60,3 to 122,9 kg (mean = 83,95 kg, 1o and 3o quartile = 75,7 and 83,95) and BMI was between 24,62 and 45,54 kg/m2 (mean = 31,69 kg/m2, 1o and 3o quartile = 28,93 and 35,89). The percentage of weight reduction at this stage was 36,31% (p>0,001), one patient had weight gain, in three (6,8%) patients the albumin level was reduced and nine had anemia. The faecal fat was positive in 16 patients (36,4%), reducing substance in stool was positive in one patient and the presence of faecal occult blood was positive in 13 patients (29,5%). The internal diameter of the silicon ring was between 0,45 and 1,4 cm (mean 0,75, SD = 0,22). CONCLUSION: After surgery there is a significant weight loss, but the BMI is still above 35 kg/m2 in 26 patients (59%), followed for a long time. There is a substantial improvement in cholesterol and glucose blood levels. The diameter of ring in the small stomach showed no significant association with weight reduction, while patients with greater than 1 cm ring did not show anemia or low levels of albumin, clinically better than those with rings smaller than 1 cm.

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.

Gastric cancer trends in epidemiology

Stomach cancer is a very malignant challenge being the forth most common cancer worldwide. In Brazil the incidence is still important mainly among men(2). Its incidence varies widely around the world in a way that our current understanding of etiology cannot fully explain. It is admitted and described that its incidence has been decreasing in most industrialized countries over the past 3 decades. In spite of this favorable trend, a large geographical variability in both incidence and mortality rates still persists. There is a substantial variation in patients’ survival among Eastern (Japan, Korea, and China) and Western countries. Even in the West world different survival rates are reported when we compare the results in the United States and European countries, like Italy and Germany where the Japanese rules were been accepted over the last decades. It is important to emphasize that the results of surgical treatment are better in some US high volume centers dedicated to gastric cancer research. All those findings are due to the enormous difference not only in etiology but also in early detection, specialized treatment and for sure prevention. In fact, etiology is a challenge in understanding and improving the prevention and surveillance programs. Over the last 2 decades, an evolutionary approach to the introduction of early diagnosis strategies, surveillance programs, different types of surgery, and adjuvant treatments has been adopted(1, 5). Gastric cancer has a multifactorial etiology. The incidence thought to be strongly influenced by both exogenous and unknown endogenous factors. Several risk factors have been described as important to disease development. Among risk factors can be mentioned blood type A, familial history of gastric cancer, pernicious anemia, histological modifications of gastric remnant after resection for benign diseases, genetic or genes modifications, and environmental factors(8). Gastric carcinogenesis is also correlated with high sodium chloride diets, water and food consumptions with high amounts of nitrous compounds, poor consumption of vitamins C, E and beta-caroten diets, and for sure one of the most greater villain, the inflammatory response to Helicobacter pylori infection. Those influences were well established studying migratory populations who have changed their alimentary habits and where gastric cancer incidence decreased. The influence of H pylori infection and other exogenous factors, such as nutrition, food conservation, additives, and a low socio-economic status are specially important in high incidence areas like Latin America and Asia. GASTRIC CANCER TRENDS IN EPIDEMIOLOGY

Termo de consentimento livre e esclarecido (TCLE): fatores que interferem na adesão

BACKGROUND: The written informed consent form (WICF) provides information that must be written in simple, easily understood language, highlighting voluntary participation safeguards, risks, possible benefits, and procedures. Currently, the possibility that research subjects do not fully understand the text of the WICF or their rights as participants, despite having signed the WICF and agreed to participate in the study, has been a point of discussion. AIM: To evaluate the readability of the WICFs, as well as to correlate research subject acceptance of the WICF with demographic status, social factors, risk-benefit relationship, and education level. METHODS: The study involved 793 patients treated in public or private hospitals and asked to give informed consent for their inclusion. Were reviewed patient medical charts in order to obtain demographic and social data, and was used the Flesch Reading Ease and the Flesch-Kincaid Readability Indices to evaluate the reading level of the WICF texts. RESULTS: Acceptance was higher (99.7%) among patients treated in public health care facilities and among patients (99.73%) who participated in protocols involving lower risk. Although acceptance was not influenced by education level, 462 patients (58.26%) had eight or less years of schooling. The obtained readability index ranged from 9.9 to 12 on the Flesch-Kincaid test, and from 33.1 to 51.3 on the Flesch Reading Ease test. CONCLUSION: The WICFs had high degree of reading difficulty. Although patient acceptance was not found to be related to demographic or social factors, it was found to be influenced by the risk-benefit relationship.

Consenso brasileiro sobre câncer gástrico: diretrizes para o câncer gástrico no Brasil

BACKGROUND: In Brazil, gastric cancer is the fourth most common malignancy among men and sixth among women. The cause is multivariate and the risks are well known. It has prognosis and treatment defined by the location and staging of the tumor and number of lymph nodes resected and involved. AIM: The Brazilian Consensus on Gastric Cancer promoted by ABCG was designed with the intention to issue guidelines that can guide medical professionals to care for patients with this disease. METHODS: Were summarized and answered 43 questions reflecting consensus or not on diagnosis and treatment that may be used as guidance for its multidisciplinary approach. The method involved three steps. Initially, 56 digestive surgeons and related medical specialties met to formulate the questions that were sent to participants for answers on scientific evidence and personal experience. Summaries were presented, discussed and voted in plenary in two other meetings. They covered 53 questions involving: diagnosis and staging (six questions); surgical treatment (35 questions); chemotherapy and radiotherapy (seven questions) and anatomopathology, immunohistochemistry and perspective (five questions). It was considered consensus agreement on more than 70% of the votes in each item. RESULTS: All the answers were presented and voted upon, and in 42 there was consensus. CONCLUSION: It could be developed consensus on most issues that come with the care of patients with gastric cancer and they can be transformed in guidelines.

Resultados da gastrectomia D2 para o câncer gástrico: dissecção da cadeia linfática ou ressecção linfonodal múltipla?

BACKGROUND: Eastern literature is remarkable for presenting survival rates for surgical treatment of gastric adenocarcinoma superior to those presented in western countries. AIM: To analyze the long-term result after D2 gastrectomy for gastric cancer. METHODS: Two hundred seventy four underwent gastrectomy with D2 lymph node dissection as exclusive treatment. The inclusion criteria were: 1) lymph node removal according to Japanese standardized lymphatic chain dissection; 2) potentially curative surgery described in medical records as D2 or more lymph node dissection; 3) tumoral invasiveness of gastric wall restricted to the organ (T1 - T3); 4) absence of distant metastasis (N0-N2/M0); 5) a minimum of five years follow-up. Clinical pathological data included sex, age, tumor location, Borrmanns macroscopic tumor classification, type of gastrectomy, mortality rates, hystological type, TNM classification and staging according to UICC TNM 1997. RESULTS: Total gastrectomy was performed in 77 cases (28.1%) and subtotal gastrectomy in 197 (71.9%). The tumor was located in the upper third in 28 cases (10.2%), in the middle third in 53 (19.3%), and in the lower third in 182 (66.5%). Among patients that had their Borrmanns classification assigned, five cases (1.8%) were BI, 34 (12.4%) BII, 230 (84.0%) BIII and 16 (5.9%) BIV. Tumors were histologically classified as Lauren intestinal type in 119 cases (43.4%) and as diffuse type in 155 (56.6%). According to UICC TNM 1997 classification, early gastric cancer (T1) was diagnosed in 68 cases (24.8 %); 51 (18.6%) were T2, and 155 (56.6%) were T3. No lymph node involvement (N0) was observed in 129 cases (47.1%), whereas 100 (36.5%) were N1 (1-6 lymph nodes), and 45 (16.4%) were N2 (7-15 lymph nodes).The median number of lymph nodes dissected was 35. The overall long-term (five-year) survival rate, for stages I to IIIb was 70.4%. CONCLUSION: Digestive surgeons must be stimulated in performing D2 gastrectomies to avoid wasting the only treatment to gastric adenocarcinoma that has proven to be efficient up to this days. It must be emphasized that standardized lymph nodes dissection according to tumor location is more important that only the number of removed nodes