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.

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

Se presenta el estado actual de la cirugía laparoscópica en las enfermedades colorrectales, que muestra resultados superiores a la cirugía abierta en estancia hospitalaria, infección de herida y calidad de vida en el primer mes postoperatorio. Las indicaciones son cualquier enfermedad colorrectal. Todas las técnicas de resección colorrectal son técnicamente realizables con cirugía laparoscópica asistida. Las contraindicaciones son dependientes sobre todo del estado del paciente y de su enfermedad: la laparoscopia urgente de colon y recto apenas tiene sitio en el armamentario terapéutico. Sin embargo, la cirugía programada aporta una gran cantidad de casos, incluyendo también el cáncer de colon, cuyo abordaje laparoscópico se contraindica sólo si hay afectación de órganos vecinos o si la cirugía por laparoscopia no es radical y oncológica, por razones del caso o de falta de técnica del equipo quirúrgico, dado que los resultados de curación de cáncer son idénticos a la cirugía abierta, con nivel I de evidencia científica. Están en estudio los resultados de curación y supervivencia de la cirugía laparoscópica del cáncer de recto. Se describen los detalles de técnica quirúrgica de las colectomías derecha e izquierda, de las resecciones laparoscópicas del recto y de la colectomía total

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

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

La urgencia abdominal también puede ser intervenida mediante abordaje laparoscópico: el planteamiento puede ser de laparoscopia diagnóstica, cirugía asistida por laparoscopia o laparotomía dirigida según los hallazgos de la laparoscopia. Las contraindicaciones generales se refieren sobre todo al estado de inestabilidad hemodinámica del paciente y a pacientes graves (ASA IV). En ausencia de contraindicación específica para el procedimiento laparoscópico concreto a realizar, muchas enfermedades abdominales que requieren cirugía urgente pueden realizarse con abordaje laparoscópico. Las indicaciones más frecuentes son la apendicitis, la colecistitis aguda, la perforación gastroduodenal, la oclusión de intestino delgado, y algunos traumas abdominales. Con una correcta selección de pacientes y la oportuna experiencia del cirujano, los resultados son excelentes, y mejoran la cirugía abierta (menos infección de herida, complicaciones, estancia hospitalaria y dolor postoperatorio). Se explican con detalle los aspectos básicos de la técnica quirúrgica en los procedimientos más frecuentes de laparoscopia de urgencia

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

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

La resección hepática constituye la única posibilidad real de curación para un grupo seleccionado de pacientes con metástasis hepáticas de cáncer colorrectal. La supervivencia obtenida en estos pacientes es de un 30-40 por ciento a los 5 años y un 20-25 por ciento a los 10 años de la cirugía; ningún otro tratamiento se acerca a estos resultados. La clave para conseguir estos resultados es el tratamiento de estos pacientes por un equipo multidisciplinar, equipo que debe contar con la participación de cirujanos especialmente entrenados en las técnicas de resección hepática. En la presente revisión se describen: la estadificación preoperatoria de las metástasis hepáticas de origen colorrectal por técnicas de imagen, los criterios de selección para la cirugía, los estándares de la técnica quirúrgica y el tratamiento adyuvante que forman parte del Protocolo de la Sección de Cirugía Hepatobiliar del Hospital de Navarra, basados en nuestra experiencia en 150 hepatectomías y en la mejor evidencia científica disponible. (AU)

[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.

[The behavioral determinants for health centers in health districts of urban Africa: results of a survey of households in Kinshasa, Congo]. / Les déterminants du comportement de recours au centre de santé en milieu urbain africain: résultats d'une enquête de ménage menée à Kinshasa, Congo.

This study analyses the choice determinants of the population for health centres through a survey of the behaviour of families in a representative sample of 1,000 households in the health districts of Kinshasa, Congo in 1997. For the most recent episode of illness, the respondents turned to seven types of care: the health centre (37%), private dispensaries (26.5%), self-medication through a pharmacy (23.9%), traditional practitioner (21%), traditional self-medication (16.9%), private outpatients' clinic (16.7%) and a reference hospital (10.4%). Past logistics have shown that patients resort to a health centre rather than another type of care structure (P = 0.05) when looking for quality care, reasonable prices and the availability of varied services. On the other hand, concern about the geographical proximity in relation to the family's residence calls for using the private dispensary. When looking for a doctor or the existence of a 'convention', families are more inclined to choose a private officially recognized outpatients' clinic. Those who had been looking for a solution to a special type of illness opted primarily for a traditional practitioner. In conclusion, the results of this study show that if people choose the care offered by health centres, it is because they judge it to be of good quality. The integrated care offered by the same technician, with a required training, is a major asset in the acceptability of the first line of primary health care in Kinshasa. This study suggests that it would no doubt be beneficial to integrate non-official private care structures into the primary health care system, as far as it is possible for them to achieve a level of quality comparable to that of the health centres. In order that the traditional practitioner might play an important complementary role in the realization of primary health care, even in urban areas, the possibility of promoting sites of communication should be studied. Moreover, considering the weak buying power of the city's inhabitants and the previous existence of tontines out of solidarity, the 'conventions' providing relief of health care costs, under the leadership of the local communities, should be integrated into the organization of the urban health system.

Linfadenectomía axilar en 594 pacientes con tumores infiltrantes de mama / Axillary lymphadenectomy in 594 patients with infiltrating breast tumors

Presentamos un estudio de 594 pacientes con carcinoma infiltrante de mama a las que se les realizó linfadenectomía axilar completa en los últimos 8 años.Se analizan diversos parámetros clínicos, radiológicos y anatomopatológicos en relación con la afectación ganglionar. Destaca la existencia de significación estadística al correlacionar el tamaño tumoral con la afectación ganglionar. Ello nos permite concluir que la linfadenectomía axilar sigue siendo necesaria en pacientes con tumores grandes. Resta por dilucidar si debe o puede ser sustituida por el estudio del ganglio centinela en tumores de menos de 1 cm. (AU)

Tratamiento quirúrgico de la obstrucción intestinal aguda por cáncer colorrectal. experiencia reciente en 1994-1998 / Surgical treatment of acute intestinal obstruction due to colorectal cancer: recent experience occurring between 1994 and 1998

Introducción. Estudiamos prospectivamente la morbimortalidad de la cirugía urgente por obstrucción intestinal secundaria a cáncer colorrectal en 5 años (1994-1998).Pacientes y método. Incluimos a todos los pacientes tratados en este período, seleccionando la técnica de acuerdo con el riesgo del paciente y el estado del colon. Resultados. Fueron intervenidos de urgencia por obstrucción completa 60 pacientes (un 17 por ciento de todos los cánceres colorrectales intervenidos en el servicio) de los que 12 fueron de colon derecho, 45 de colon transverso e izquierdo y tres de recto. Se realizaron 50 resecciones de colon: 44 con anastomosis primaria (colectomía derecha, izquierda, segmentaria, resección anterior de recto, y colectomía subtotal) y 6 intervenciones de Hartmann, así como 9 colostomías de descarga o derivación ileocólica y una tumorectomía. Se realizó lavado anterógrado del colon en 11 de 25 pacientes candidatos a ello por resección de tumores de colon izquierdo sin colostomía. La mortalidad operatoria fue de 3 pacientes (5 por ciento) y la morbilidad del 45 por ciento, con una estancia media de 17 días. Se produjeron 2 fístulas anastomóticas que no precisaron reintervención. Conclusiones. Seleccionando la técnica quirúrgica según el estado del paciente se pueden obtener buenos resultados de morbimortalidad en estos enfermos, a pesar de realizar resección y anastomosis, sin colostomía, en la mayoría de los casos (AU)

Repair of ventral hernias with expanded polytetrafluoroethylene patch.

BACKGROUND: Operations for large and recurrent abdominal hernias have a high associated recurrence rate, although it is lower when prosthetic material is used. Expanded polytetrafluoroethylene (ePTFE) seems to be the best tolerated prosthetic material in surgery. METHODS: A series of 45 ventral hernias repaired using ePTFE for closure or reinforcement of the herniorrhaphy has been evaluated prospectively. Thirty-six were midline incisional hernias and nine were transverse or pararectal ventral hernias. There were 13 recurrent ventral hernias and three defects were operated as an emergency procedure. The patch was sutured to the anterior aponeurosis with a running non-absorbable suture. Some other kind of intra-abdominal procedure was undertaken in 12 cases. RESULTS: ePTFE was well tolerated. Complications occurred in five patients. Major complications were found in three patients: cutaneous necrosis requiring a myocutaneous flap; and infection of the prosthesis (primary, and secondary to enterocutaneous fistula due to diverticulitis, both requiring removal of the patch). Mean follow-up was 39 months and hernia recurrence occurred in only one patient. CONCLUSION: This clinical experience shows that ePTFE is a very reliable prosthetic material for the repair of abdominal wall hernias.