Prognostic significance of thymidylate synthase polymorphisms in rectal cancer patients treated with neoadjuvant chemoradiotherapy.

AIM: There is a lack of prognostic factors of preoperative chemoradiation for locally advanced rectal cancer. Thymidylate synthase (TS) is the most important target of 5-fluorouracil; three main genetic polymorphisms of TS have been described. We analysed the prognostic value of these in patients with locally advanced rectal cancer treated with fluoropyrimidine-based chemoradiation. METHOD: Ninety-nine patients treated between November 2001 and March 2009 were included. All were treated by radiotherapy (5040 cGy) and concomitant fluoropyrimidine-based chemotherapy. Three polymorphisms were analysed: (i) a double (2R) or triple (3R) repeat of a 28 base pair (bp) tandem sequence upstream of the ATG codon initiation site in the 5'-terminal regulatory region, (ii) a functional G > C single nucleotide polymorphism present in the second repeat of the 3R alleles and (iii) a 6 bp deletion at nucleotide 1494 in the 3'-untranslated region. DNA was extracted from paraffin-embedded core biopsies taken from the tumour and the genotype was analysed using polymerase chain reaction restriction fragment length polymorphism. RESULTS: The 6 bp polymorphism was significantly associated with disease-free survival (+ 6 bp/+ 6 bp vs-6 bp/-6 bp, P = 0.032 logistic regression). No differences were found in disease-free survival according to the other polymorphisms studied. No relationship was observed between the different TS genotypes and pathological regression. CONCLUSION: The study suggests that the TS 6 bp polymorphism may be a predictor of disease-free survival in patients with locally advanced rectal cancer treated with fluoropyrimidine-based chemoradiation.

Pathologic response assessed by Mandard grade is a better prognostic factor than down staging for disease-free survival after preoperative radiochemotherapy for advanced rectal cancer.

OBJECTIVE: The reduction in tumour stage induced by full course radiotherapy plus chemotherapy is apparent from histological changes. The purpose of this study was to determine the rate of complete pathological response and to evaluate the prognostic value for disease free survival (DFS) and disease specific survival (DSS) of the response. The relation between pretreatment variables (age, gender, stage, tumour height and [carcinoembryogenic antigen (CEA)] and postsurgical variables was compared to the pathological response. METHOD: A total of 119 patients with stage II or III rectal cancer underwent surgery 6 weeks after neoadjuvant treatment. Group A included patients with a complete or good pathological response (Mandard grade I-II) and group B patients with a poor response (Mandard grade III-IV-V). The pretreatment endo-rectal ultrasound scan stage was compared with histopathology stage of the resected specimen. DFS and DSS were compared using the log-rank test. RESULTS: All 119 patients (mean age 67.9 years, 83 males) underwent resection. The tumour was located in the upper, middle and lower third of the rectum in 11, 51 and 57 patients. 88 patients had a low anterior resection, 28 patients abdomino-perineal resection and three a Hartmann's operation. There was no postoperative death. The circumferential margin (CM) was involved in 10%. A complete pathological response was observed in 17 (14.2%) patients. Thirty-six (30.2%) patients had a group A and 83 a group B response. Group A showed DFS to be significantly higher than group B (log rank: P = 0.007). The DSS rate was not significantly different between the two groups (log rank P = 0.113). Down-staging was not related with DFS. No relation was found between pretreatment variables and response. A good pathological response was related to a lower rate of permanent colostomy but not with CM involvement or the number of lymph nodes. CONCLUSION: Tumour regression of grades I or II was a good indicator of DFS in locally advanced rectal cancer, treated by neoadjuvant chemotherapy and radiotherapy. Patients with a high regression grade were associated with a lower incidence of definitive stoma formation. The regression grade was shown to be a better prognostic factor than down-staging.

Exposure to non-arsenic pesticides is associated with lymphoma among farmers in Spain.

OBJECTIVES: To estimate the risk of lymphoma among farmers in Spain. METHODS: This is a multicentre case control study conducted in Spain. Cases were subjects diagnosed with lymphoma according to the World Health Organization (WHO) classification in four hospitals between 1998-2002. Hospital controls were frequency matched to the cases by sex, age, and centre. All subjects were interviewed about jobs ever held in lifetime for at least one year and the exposures in those jobs were recorded. The risk of lymphomas among subjects ever having had a job as a farmer was compared with all other occupations. Farmers were analysed according to the type of farming job performed: crop farming, animal farming, and general farming. Occupational exposure was summarised into 15 main categories: organic dust, radiation, contact with animals, PAH, non-arsenic pesticides (carbamates, organophosphates, chlorinated hydrocarbons, triazines and triazoles, phenoxy herbicides, chlorophenols, dibenzodioxin, and dibenzofuran), arsenic pesticides, contact with meat, contact with children, solvents, asbestos, soldering fumes, organic colourants, polychlorinated biphenyls, ethylene oxide, and hair dyes. RESULTS: Although farmers were not at an increased risk of lymphoma as compared with all other occupations, farmers exposed to non-arsenic pesticides were found to be at increased risk of lymphoma (OR = 1.8, 95% CI 1.1 to 2). This increased risk was observed among farmers working exclusively either as crop farmers or as animal farmers (OR = 2.8, 95% CI 1.3 to 5.8). Risk was highest for exposure to non-arsenic pesticides for over nine years (OR = 2.4, 95% CI 1.2 to 2.8). CONCLUSIONS: Long term exposure to non-arsenic pesticides may induce lymphomagenesis among farmers.

[Laparoscopic surgery in colorectal diseases]. / Cirugía laparoscópica en las enfermedades colorrectales.

The present state of laparoscopic surgery in colorectal diseases is presented, showing results that are superior to open surgery during the hospital stay, infection of the wound and quality of life in the first postoperative month. It is technically possible to carry out all of the techniques of colorectal resection with assisted laparoscopic surgery. The counter-indications depend above all on the state of the patient and his disease: emergency laparoscopy of the colon and rectum barely have a place in the therapeutic arsenal. However, elective surgery contributes a great number of cases, as well as colon cancer, whose laparoscopic approach is only contraindicated if the neighbouring organs are affected or if surgery by laparoscopy is not radical and oncological, due to the case itself or if the surgical team lacks the technique, given that the results for curing cancer are identical to open surgery, with level I scientific evidence. The results of cure and survival from laparoscopic surgery of cancer of the rectum are being studied. A description is given of the details of the surgical technique of right and left colectomies, laparoscopic resections of the rectum and of total colectomy.

[The role of laparoscopy in emergency abdominal surgery]. / El papel de la laparoscopia en la cirugía abdominal urgente.

Abdominal emergencies can also be operated on through the laparoscopic approach: the approach can be diagnostic laparoscopy, surgery assisted by laparoscopy or laparotomy directed according to the findings of the laparoscopy. The general contraindications refer above all to the state of haemodynamic instability of the patient and to seriously ill patients (ASA IV). In the absence of any specific counter-indications for the specific laparoscopic procedure to be carried out, many abdominal diseases requiring emergency surgery can be performed with the laparoscopic approach. The most frequent indications are appendicitis, acute colecistitis, gastroduodenal perforation, occlusion of the small intestine, and some abdominal traumas. With a correct selection of patients and the appropriate experience of the surgeon, the results are excellent and better than open surgery (less infection of the wound, complications, hospital stay and postoperative pain). A detailed explanation is given of the basic aspects of the surgical technique in the most frequent procedures of emergency laparoscopy.

Giant jejunoileal duplication: prenatal diagnosis and complete excision without intestinal resection.

A 7-week-old child presented to the pediatrician after persistent vomiting and abdominal distension developed. Intestinal dilatation had been detected in utero. Emergency ultrasonography showed only small bowel dilatation. There were no signs of intestinal obstruction; however, complete intestinal malrotation was demonstrated by an upper gastrointestinal series and barium enema. Intestinal duplication was also suspected, and emergency laparotomy was performed. A 70-cm-long jejunoileal duplication was found and successfully dissected free from the normal small bowel and excised without intestinal resection-anastomosis. The authors describe this unique case and the surgical technique for the treatment of small bowel duplications.

[Somatostatin prophylaxis following cephalic duodenopancreatectomy]. / Profilaxis con Somatostatina tras duodenopancreatectomía cefálica.

This study was aimed at assessing the value of prophylactic somatostatin after cephalic duodenopancreatectomy. A randomized prospective study was undertaken using two groups of patients, one with prophylactic somatostatin (4.5 mg daily in continuous perfusion for 7 days postoperatively), known as group I, and group II, which did not receive somatostatin. During a five-year period, from April 1989 to April 1994, we performed 35 duodenopancreatectomies, of which 21 belonged to group I and 14 to group II. We found a lower incidence of pancreatic anastomosis fistulae in group I (9.5% vs 35.7%; p < 0.05). We did not find any correlation between prophylaxis with somatostatin and the appearance of other complications or postoperative mortality. The mean time of fistula closure in group I was 5 days while that of group II was 19.2 days. In conclusion, the administration of prophylactic somatostatin after cephalic duodenopancreatectomy reduces the incidence and duration of pancreatic fistula.

[Resection of hepatic metastases of colo-rectal carcinoma. Indications and initial results]. / Resección de metástasis hepáticas de carcinoma colo-rectal. Indicaciones y resultados iniciales.

We report our initial experience in the resection of metastases from colo-rectal cancer confined to the liver. Seventeen hepatic resections were performed in sixteen patients over a thirty-eight months period. Median age was 58 years (45-75). The extent of liver involvement was assessed by computerized tomographic portography and magnetic resonance. In fourteen cases there was a solitary lesion. Mean interval time between colo-rectal resection and hepatic resection was 18 months (0-69). Twelve major hepatic resections and five wedge resections were performed. There was not operative mortality. Seven patients received complementary chemotherapy. Mean follow-up was 14.8 months (2-34). One patient died from carcinoma of the lung, five patients (31.25%) are alive with recurrence of some sort (three recurrences being in the liver) and ten patients (62.5%) are free of disease. Indications for resection, methods used for identification of candidates, prognostic determinants and indications for complementary chemotherapy are discussed.

[Malignant fibrous histiocytoma of the pancreas]. / Histiocitomas fibrosos malignos de páncreas.

Malignant fibrous histiocytoma (MFH), a frequent sarcoma in retroperitoneal mesenchimal tissues, has also been reported, although in a few cases, in digestive viscera. We present a case of a primary MFH of the pancreas in a 37-year-old male, treated with a 90% distal pancreatectomy, plus external and intraoperative radiotherapy over the tumoral bed, and polychemotherapy. Response to treatment was poor, with early local recurrence, liver and bone metastases and a survival of 7 months. Only 4 other cases of MFH of the pancreas have been reported. We analyze these 5 cases: they have been usually diagnosed in young adults, with vague symptoms and large tumoral masses without jaundice. Local recurrence seems to be frequent; they develop liver metastases rather than lung metastases. Even when they are resectable, the anatomical relations of the pancreas with vital vascular structures make broad resection difficult, and local recurrences frequent. Analysis of these five reported cases of MFH of the pancreas, allows to expect a local recurrence rate higher than 50% and a 5-year-survival rate lower than 30% due to distant metastases. Only radiotherapy seems to play a role as an adjuvant treatment after surgery for pancreas and other retroperitoneal sarcoma as it significantly increases survival.

[Cancer of the esophagus (II): the results of surgery, anatomicopathological study and patient survival]. / Cáncer de esófago (II): resultados de la cirugía, estudio anatomopatológico, y supervivencia de los pacientes.

We present a retrospective study of 68 esophageal cancer patients treated with surgery between 1975 and 1991. Results showed a resectability of 73.5% with the most frequent surgical approach being a Lewis esophagectomy. The mean hospitalization time was 24.7 days with a postoperative mortality of 7.3%. Other complications included anastomotic leakage, wound infection, sepsis and pulmonary disorders. Over-all survival at 3 years was 17.3%, reaching 24% in resected patients. Survival according to lymph node involvement was 13.4% for lymph node positive patients and 34.5% for node negative patients. According to histopathologic stage, survival rates were 34.6% and 8.59% for early and advanced tumor respectively, the difference being statistically significant using the Mantel-Haenszel test.

[Spontaneous rupture of a hepatic adenoma associated with hepatic peliosis]. / Rotura espontánea de un adenoma hepático asociado a peliosis hepática.

Benign hepatic tumors, although rare, are each time encountered more frequently, occasionally posing diagnostic and therapeutic problems. Within this group of tumors, hepatic adenomas are the least common, although its increasing incidence could be attributed to the use of contraceptives or to the availability of newer diagnostic methods. A hepatic adenoma presenting with spontaneous rupture at diagnosis is associated with a mortality of 20%, for which emergency hepatectomy is indicated and usually carried out under unstable hemodynamic conditions. In this report, we present the case of a 30 year old female with three previous pregnancies carried to term, without any history of intake of contraceptive or hepatotoxic drugs, who presented with spontaneous rupture of a large hepatic adenoma associated with hepatic peliosis.

[Utilisation of organs proceeding from donors with heart failure: review of the pathogenesis of organic damage and the possible mechanisms of prevention]. / Utilización de órganos procedentes de donantes en parada cardíaca: revisión de la patogenia del daño orgánico y los posibles mecanismos de prevención.

There is an evident imbalance between the number of patients awaiting a kidney transplant and the availability of organs proceeding from donors with brain death. A high number of patients die each day from heart failure, whose organs could be used for transplants if specific care is employed. Although centres do exist where these methods of extraction are established, the problems of organic damage have yet to be resolved, since one third of the organs are still lost, besides the increase in the need for early dialysis, and the number of dysfunctioning grafts two years after the transplant, when this type or organ is employed. There is increasingly detailed knowledge of the pathogenesis of organic damage following heart failure and reanimation, as well as of the damage following the conservation and reimplantation of the kidney. Knowledge of the maximum time of hot ischemic that an organ can withstand is of crucial importance if organs are not to be unduly discarded. Besides, the increasing understanding of the physiopathology of oxidative stress could make it possible for us, through the use of antioxidants, to attempt to improve the utilisation of the organs and diminish the incidence of dysfunctions and rejections.

[Present state of the surgical treatment of hepatic metastasis of colorectal origin: a practical view]. / Estado actual del tratamiento quirúrgico de las metástasis hepáticas de origen colorrectal: una visión práctica.

Hepatic resection is the only real possibility of cure for a selected group of patients with hepatic metastasis of colorectal cancer. Survival obtained in these patients is of some 30-40% after 5 years and some 20-25% after ten years following surgery; no other treatment approaches these results. The key for obtaining these results is the treatment of these patients by a multidisciplinary team, a team that must include the participation of surgeons specially trained in the techniques of hepatic resection. The present review describes: the pre-operational staging of hepatic metastasis of colorectal origin by diagnostic imaging techniques, the selection criteria for surgery, the standards of the surgical technique and the adjuvant treatment that forms part of the Protocol of the Hepatobiliary Surgery Section of the Hospital of Navarra, based on our experience in 150 hepatectomies and on the best scientifically available evidence.

[Acute cholecystitis: analysis of the different therapeutic approaches in a General Surgery Service during the years 1994-1996]. / Colecistitis aguda: análisis de las distintas actitudes terapeúticas en un servicio de cirugía general durante los años 1994-1996.

INTRODUCTION: The commonly accepted approach in the treatment of acute cholecystitis is urgent cholecystectomy. Laparoscopy has renewed interest in the option of "cooling" the inflammatory process, in order to subsequently carry out a programmed cholecystectomy through the technique mentioned. We present an analysis of the data collected on hospital stay and medico-surgical complications in both therapeutic options. The aim of this work is to reflect on the results obtained in the treatment of acute cholecystitis and to evaluate the results of the application of laparoscopic cholecystectomy in the emergency area. MATERIAL AND METHODS: 152 patients diagnosed with acute cholecystitis are studied. They are distributed in 3 groups, analysing the simple and accumulated hospital stay, the index of medical and surgical complications and mortality. RESULTS: Of the 152 patients with a diagnosis of acute cholecystitis, 91 (59.8%) were operated on in their first admission, 47 (30.9%) were treated using "cooling" of the process to be operated on in a second admission and 14 (9.3%) by means of percutaneous cholecystostomy. A total of 29 patients were readmitted, 4 for relapse of acute cholecystitis and 25 for programmed operations. Urgent conventional cholecystectomy shows a greater rate of infections. The cholecystectomy on second admission supposes a moderate increase of the accumulated average stay. 17% of these patients were operated on using open surgery. CONCLUSIONS: Urgent surgery seems the most suitable approach in acute cholecystitis. The employment of laparoscopic surgery in these cases probably reduces the rate of the medical and surgical complications due to laparotomy in infectious acute pathology, and increases the comfort of the patient

[Technique and function of an experimental multiorgan transplant model in pigs]. / Técnica y función de un modelo experimental de trasplante multivisceral en el cerdo.

En bloc transplantation of the liver, duodenum and pancreas has been successful in humans for the treatment of tumors requiring exenteration of the upper abdomen. We have developed an experimental model in 40 pigs of en bloc transplantation of the liver, duodenum and pancreas. The surgical technique for organ harvesting and preservation has been correct as the early graft function was excellent. We describe in detail the surgical technique in the recipient animal, the anesthetic model and the autopsy findings. Liver function was excellent and endocrine pancreatic function was normal within 8 hours after transplantation. Absorption and insulin-secreting response was normal in a few animals studied with an oral glucose overdose and with the intravenous glucagon test.