Alfonso Díaz

Mitochondrial DNA Mutation at the D310 (Displacement Loop) Mononucleotide Sequence in the Pathogenesis of Gallbladder Carcinoma

Purpose: Mutations in the mitochondrial DNA (mtDNA) have been observed frequently in human neoplasia, in both coding and noncoding regions. A mononucleotide repeat (poly-C) between 303 and 315 nucleotides (D310) within the regulatory displacement loop has been identified recently as a frequent hot spot of deletion/insertion mutations in tumors. We investigated the frequency and pattern of D310 abnormalities in the pathogenesis of gallbladder carcinoma (GBC). Experimental Design: DNA extracted from neoplastic and nonneoplastic archival gallbladder tissue including 123 tumors, 53 dysplastic areas, and 90 histologically normal epithelia adjacent to GBC, chronic cholecystitis, and 15 normal gallbladders were examined by PCR-based assay for D310 mutations, followed by sequencing in a subset of cases. Results: D310 mutation was a relatively frequent (47 of 123; 38%) abnormality in GBC. A very high frequency of mutations were detected in dysplastic (8 of 14; 57%) and normal-appearing gallbladder epithelia (10 of 22; 46%) accompanying GBC, showing a clonal relationship compared with the corresponding tumors. D310 mutations were also detected in dysplastic (8 of 39; 21%) and normal (17 of 68; 25%) epithelia obtained from chronic cholecystitis. A single case of 15 normal gallbladders showed a D310 abnormality. Overall, deletions (67 of 91; 74%) at D310 were more frequent than insertions. Conclusions: D310 mutation at the mtDNA displacement loop is a relatively frequent and early event in the sequential pathogenesis of GBC, being detected in normal-appearing epithelium from chronic cholecystitis. Our findings suggest that mtDNA mutations should be additionally investigated in GBC pathogenesis, and D310 mononucleotide abnormalities could be included in a panel of molecular biomarkers for GBC early detection strategy.

Total esophagogastrectomy plus extended lymphadenectomy with transverse colon interposition: A treatment for extensive esophagogastric junction cancer

AIM To review the post-operative morbidity and mortality of total esophagogastrectomy (TEG) with second barrier lymphadenectomy (D2) with interposition of a transverse colon and to determine the oncological outcomes of TEG D2 with interposition of a transverse colon. METHODS This study consisted of a retrospective review of patients with a cancer diagnosis who underwent TEG between 1997 and 2013. Demographic data, surgery protocols, complications according to Clavien-Dindo classifications, final pathological reports, oncological follow-ups and causes of death were recorded. We used the TNM 2010 and Japanese classifications for nodal dissection of gastric cancer. We used descriptive statistical analysis and Kaplan-Meier survival curves. A P-value of less than 0.05 was considered statistically significant. RESULTS The series consisted of 21 patients (80.9% men). The median age was 60 years. The 2 main surgical indications were extensive esophagogastric junction cancers (85.7%) and double cancers (14.2%). The mean total surgery time was 405 min (352-465 min). Interposition of a transverse colon through the posterior mediastinum was used for replacement in all cases. Splenectomy was required in 13 patients (61.9%), distal pancreatectomy was required in 2 patients (9.5%) and resection of the left adrenal gland was required in 1 patient (4.7%). No residual cancer surgery was achieved in 75.1% of patients. A total of 71.4% of patients had a postoperative complication. Respiratory complications were the most frequently observed complication. Postoperative mortality was 5.8%. Median follow-up was 13.4 mo. Surgery specific survival at 5 years of follow-up was 32.8%; for patients with curative surgery, it was 39.5% at 5 years. CONCLUSION TEG for cancer with interposition of a transverse colon is a very complex surgery, and it presents high post-operative morbidity and adequate oncological outcomes.

Gastrectomía totalmente laparoscópica por neoplasias gástricas: Experiencia en un centro público

Background: The laparoscopic approach for the treatment of gastric tumors has many advantages. Aim: To evaluate the results of a laparoscopic gastrectomy program developed in a public hospital. Patients and Methods: Retrospective review of epidemiological, perioperative and follow-up data of patients who were treated with a laparoscopic gastrectomy due to gastric tumors between 2006 and 2013. A totally laparoscopic technique was used for all cases. Complications were evaluated according to the Clavien-Dindo classification. Results: Fifty one patients, aged 65 (36-85) years, underwent a laparoscopic gastrectomy. In 22 patients a total gastrectomy was performed. Conversion rate to open surgery was 8%. Operative time was 330 (90-500) min and bleeding was 200 (20-500) ml. Median hospital stay was 7 (3-37) days. Postoperative morbidity was present in 17 (33%) patients, 3 (6%) patients had complications grade 3 or higher and one patient died (1.9%). Tumor pathology was adenocarcinoma in 39 patients. A complete resection was achieved in 97%. Twenty nine patients (74%) with gastric adenocarcinoma had early gastric cancer and 84% of patients were in stage one. Median lymph node count was 24. Median follow-up was 26 (1-91) months. There was no cancer related mortality among patients subjected to a curative resection. Overall survival for patients with adenocarcinoma was 92% at 3 years. Conclusions: This study supports the feasibility and safety of a laparoscopic gastrectomy program in a public hospital; with low morbidity, adequate lymph node dissection and long-term survival. This approach must be considered an option for selected patients with gastric cancer.BACKGROUND The laparoscopic approach for the treatment of gastric tumors has many advantages. AIM To evaluate the results of a laparoscopic gastrectomy program developed in a public hospital. PATIENTS AND METHODS Retrospective review of epidemiological, perioperative and follow-up data of patients who were treated with a laparoscopic gastrectomy due to gastric tumors between 2006 and 2013. A totally laparoscopic technique was used for all cases. Complications were evaluated according to the Clavien-Dindo classification. RESULTS Fifty one patients, aged 65 (36-85) years, underwent a laparoscopic gastrectomy. In 22 patients a total gastrectomy was performed. Conversion rate to open surgery was 8%. Operative time was 330 (90-500) min and bleeding was 200 (20-500) ml. Median hospital stay was 7 (3-37) days. Postoperative morbidity was present in 17 (33%) patients, 3 (6%) patients had complications grade 3 or higher and one patient died (1.9%). Tumor pathology was adenocarcinoma in 39 patients. A complete resection was achieved in 97%. Twenty nine patients (74%) with gastric adenocarcinoma had early gastric cancer and 84% of patients were in stage one. Median lymph node count was 24. Median follow-up was 26 (1-91) months. There was no cancer related mortality among patients subjected to a curative resection. Overall survival for patients with adenocarcinoma was 92% at 3 years. CONCLUSIONS This study supports the feasibility and safety of a laparoscopic gastrectomy program in a public hospital; with low morbidity, adequate lymph node dissection and long-term survival. This approach must be considered an option for selected patients with gastric cancer.

Resultados actuales de la pancreatoduodenectomía para el tratamiento de los tumores periampulares y análisis de factores pronósticos de sobrevida

Background: The diagnosis and treatment of periampullary tumors represents a challenge for current medicine. Aim: To review the results of pancreaticoduodenectomy (PDD) in the treatment of periampullary tumors and to identify risk factors that impact the long-term survival. Patients and Methods: We performed a retrospective study of patients who underwent a PDD for periampullary tumors between 1993 and 2009. We reviewed perioperative results and long term survival. We performed a multivariate analysis for long-term survival. Results: A PDD was performed in 181 patients aged 58 ± 12 years (98 females). Piloric preservation was done in 53% and a pancreatogastric anastomosis was used in 94% of cases. Morbidity was 62% and postoperative mortality was 5.5%. Pancreatic cancer was the most frequent pathological finding in 41%, followed by ampullary cancer in 28% and distal bile duct cancer in 16%. Median survival was 17 months, with a five years survival of 24%. Survival for ampullary tumors was 28 months with a five years survival of 32%. The median and five years survival were 14 months and 16% for bile duct cancer and 11 months and 14% for pancreatic cancer. Multivariate analysis identified tumor type (pancreas /bile duct) and lymph node dissemination as independent predictors of mortality. Conclusions: One quarter of patients experienced long term survival. Mortality predictors were tumor type and lymph node dissemination.

Lipoma gástrico gigante sintomático tratado con gastrectomía subtotal laparoscópica: caso clínico

Gastric lipoma is a rare benign gastric tumor. We report a 62-year-old man, who presented with abdominal pain, vomiting and weight loss. An upper gastrointestinal endoscopy showed a gastric antral, submucosal tumor. Abdominal ultrasound and computed tomography revealed a large antral lesion with content of high echogenicity and fat density, measuring 11 x 6 cm. The patient was treated with a laparoscopic distal subtotal gastrectomy, and a Roux-en-Y reconstruction. The patient had no postoperative morbidity, was started on a liquid diet on the third postoperative day and was discharged on the third postoperative day. The pathological study revealed a gastric lipoma with clear margins. This laparoscopic procedure represents a good alternative in the treatment of this benign gastric tumor.

Results of a Population-Based Gastric Cancer Screening Program Conducted in Chile 1996-2008

Background Chile presents the second highest stomach cancer (SC) incidence and mortality in the Americas. Since 1980 the SC mortality rate has stabilized at around 20 per 100,000, reaching a level of 18.6 per 100,000 in 2008 (males 24.4, females 12.9). Beginning in 2006 the public and the private health insurance systems cover a secondary prevention program consisting of upper gastrointestinal endoscopy (UGE) for all symptomatic cases (epigastric pain with or without symptoms of poor prognosis) aged 40 and above; it also covers medical and surgical treatments of SC detected. This prevention program has been piloted since 1996 in La Florida County (66,412 beneficiaries 40 years and older). This is the largest SC detection program conducted in Chile so far. Its goals are to decrease SC mortality through early detection and treatment. Our aim is to evaluate the 12 years of experience using this strategy. Methods Patients consulting in the primary care clinics of the study area who satisfied the above mentioned criteria were referred to the secondary level for UGE. Any suspicious lesions at UGE were biopsied and detected SC cases were referred to the base hospital for treatment. We entered all SC patients detected in the screening program from 1996 to 2008. We describe SC cases by sex, age, and staging -TNM classification system-, calculate their 5 year survival rate using the Kaplan Maier method and identify prognostic factors using the Log rank test and Cox model. Results In the study period, 11,978 individuals were referred for UGE 29.7% males (mean age 53.3: 14-93 years) and 70.3% females (mean age 52.2: 14-95 years). We identified 234 SC cases (67.1% males; 32.9% females); mean age of SC patients was 65.7 years (males 65.2 yrs, females 66.9 yrs). Detection rate of SC was 4.4% and 0.9% for males and females respectively (p<0.00001). SC staging for all patients and for males and females were: stage I 39% (35%, 45%), stage II 5% (2%, 12%), stage III 15.8% (15%, 17%), and stage IV 40% (48%, 26%). At the 5-year follow-up, 64 (27.3%) patients remained alive, 132 (56.41%) had died from SC, 12 (5.1%) died from other causes and 26 (11.1%) were censored; the 5-year survival was 41.5% (35.9% and 52.8% for males and females, p=0.002). The only prognostic factors in multivariate analysis were stage (p<0.0001) and age (p=0.001). Discussion The 5-year survival rate for SC in the program (42%) was higher than previously reported in Chile in population-based studies (11%), although the survival range of hospital-based reports has been between12-49%. We needed 212 endoscopies to detect one early cancer. It is necessary to review the current strategy to focus the UGE on populations at higher risk of early cancers -people under 50 years of age-and to include biomarkers to triage the population.