A MLH1 polymorphism that increases cancer risk is associated with better outcome in sporadic colorectal cancer.

Germline mutations or the malfunctioning of postreplicative mismatch repair genes (MMR) are responsible of hereditary nonpolyposis colorectal cancer (HNPCC), and are also implied in some sporadic colorectal cancer (CRC) forms without any familial history of this disease. Besides germinal mutations and methylation, single-nucleotide polymorphisms (SNP) can predispose to nonfamilial CRC with low to moderate penetrance. In this case-control study, we analyzed three MLH1 single-nucleotide polymorphisms (exon 5: 415G-->C, rs28930073; exon 8: 655A-->G, rs1799977 and exon 16: 1852-1853AA-->GC) in 140 sporadic colorectal cancer cases and 125 healthy individuals to evaluate the relationship among CRC risk and clinicopathologic and genetic characteristics of the tumors. In our study, no 415G-->C variant carrier was found among all analyzed samples. The 1852-1853AA-->GC is a rare variant detected in heterozygoses in five controls and one case. In relation to the more frequent 655A-->G polymorphism, association analyses revealed that G carriers (AG or GG genotype) displayed a higher risk of CRC compared with AA homozygous [odds ratio (OR) AG=2.55, 95% confidence interval (CI)=1.48-4.39; P=0.01 and OR GG=2.48, 95% CI=1.20-5.11; P=0.01, respectively]. G-carrier males showed high CRC risk compared with homozygous AA wild-type individuals (OR: AG=3.05; 95% CI=1.49-6.26, P=0.002; OR: GG=3.60; 95% CI=1.29-10.03). Nevertheless, patients carrying the G allele displayed a better outcome than wild-type genotype carriers (log rank=7.26; P=0.007) and did not present vascular invasion (P=0.03), distant metastasis (P=0.004), or recurrence (P=0.01). MLH1 655A-->G change is associated with an increased risk, although it seems to have a favorable effect on patients, providing a better outcome. Moreover, our results suggest that for genomic profiling to predict the clinical outcome of patients with colorectal cancer, gender must also be considered.

Usefulness of laboratory data in the management of right iliac fossa pain in adults.

PURPOSE: This study examined the usefulness of inflammatory markers in the management of patients with right iliac fossa pain. PATIENTS AND METHODS: A single site, prospective observational study was conducted from October 2001 to April 2003. Patients with right iliac fossa pain referred to the surgeon were included. Blood samples were obtained for C-reactive protein, leukocyte, and granulocyte analysis. Clinical, surgical, and histopathologic data were collected. Analysis of inflammatory parameters was performed with logistic regression and areas under the receiver operating characteristic curve were compared. RESULTS: C-reactive protein increased with the severity of appendicitis and predicted accurately perforation (r(2) = 0.613; P < 0.0005), showing the highest accuracy among inflammatory markers (areas under the receiver operating characteristics curve were 0.846, 0.753, and 0.685 for C-reactive protein, leukocyte and granulocytes, respectively; P < 0.001). Accuracy improved when C-reactive protein and leukocytes were combined; positive and negative predictive values were 93.2 percent and 92.3 percent, respectively. CONCLUSIONS: C-reactive protein is a helpful marker in the management of patients with right iliac fossa pain; the predictive value improves when combined with leukocyte count. A patient with normal C-reactive protein and leukocytes has a very low probability of appendicitis and should not undergo surgery.

Postoperative Analgesic THerapy Observational Survey (PATHOS): a practice pattern study in 7 central/southern European countries.

Surveys evaluating pain in hospitals keep on showing that postoperative pain (POP) remains undertreated. At the time when guidelines are edited and organisational changes are implemented, more recent data are necessary to check the impact of these measures on daily practice and needs for improvement. This prospective, cross-sectional, observational, multi-centre practice survey was performed in 2004-2005 in 7 European countries. It was conducted in surgical wards of a randomised sample of hospitals. Data on POP management practices following surgery in adult in-patients were collected anonymously via a standardised multiple choice questionnaire. Among 1558 questionnaires received from 746 European hospitals, 59% were provided by anaesthetists and 41% by surgeons. There are no regular on-site staff training programmes on POP management in the institution for 34% of the respondents, patients are systematically provided with POP information before surgery for 48% of respondents; balanced analgesia following major surgery and regular administration of analgesics are largely used; 25% of respondents have specific written POP management protocols for all patients in their ward; 34% of respondents say that pain is not assessed and 44% say that pain scores are documented in the patient's chart. This largest ever performed survey confirms the extensive body of evidence that current POP management remains suboptimal and identifies needs for improvement on European surgical wards. However, the wide use of balanced analgesia and the regular administration of analgesics are indicators of ongoing change.

Do MSI-L sporadic colorectal tumors develop through "mild mutator pathway"?

BACKGROUND: The mutator pathway implied in the development of colorectal cancer (CRC) is characterized by microsatellite instability (MSI). MSI tumors can be subdivided according to the level of instability: MSI-H (high), MSI-L (low) or stable MSS. MSI-H CRC displays a well described distinct phenotype, but the true biologic significance of MSI-L is still uncertain. The objective of this study was to further clarify if the MSI-L phenotype could reflect a distinct pathway of tumor development with a different clinical behavior. METHODS: We analyzed the clinicopathological and genetic variables of 156 patients with sporadic CRC in relation with the level of MSI of the tumors. RESULTS: We have found that MSI-L tumors are someway in the middle of MSI-H and MSS CRC, as they share some features with each of the other 2 subgroups: left side location, lower incidence of LOH at MSH2 as MSS and Dukes B (stage II TNM) like MSI-H. Moreover, MSI-L tumors show higher incidence of KRAS mutations. CONCLUSION: We believe that MSI-L tumors could be considered a distinct phenotype that develops through a "mild mutator pathway."

Genetic alterations and MSI status in primary, synchronous, and metachronous tumors in a family with hereditary nonpolyposis colorectal cancer (HNPCC).

In colorectal cancer, different levels of microsatellite instability (MSI) have been described: high-frequency MSI, low-frequency MSI, and stable microsatellites. MSI-H characterizes a unique clinical and pathologic phenotype known as hereditary nonpolyposis colorectal cancer syndrome (HNPCC). In this case, an increased incidence of synchronous and metachronous tumors has been reported, but there are few reports with standardized criteria of MSI in HNPCC-associated tumors. The authors attempted to establish whether tumors of the HNPCC spectrum with different levels of MSI could predict the development of metachronous carcinomas. We have examined the levels of MSI at loci frequently affected in colorectal cancers in primary, synchronous, and metachronous tumors in a family that fulfils the Amsterdam criteria for HNPCC. This family presents colorectal cancers, HNPCC-extracolonic tumors (endometrial and ureter), and tumors (breast and bladder) not described in the HNPCC spectrum. The tumors exhibited MSI-H, irrespective of their location and regardless whether they were primary, synchronous, or metachronous, with the only exception of both endometrial tumors that showed low-frequency MSI tumors (MSI-L). Our results suggest that not only colorectal tumors with MSI-H result in a potential marker for the determination of high-risk individuals for metachronous and synchronous tumors, but also MSI-L endometrial tumors might be considered as indicative of high-risk individuals.

Supervivencia del cáncer de mama diagnosticado como lesión mamaria no palpable / Survival in nonpalpable breast cancer diagnosed as nonpalpable breast lesions

Introducción. El carcinoma de mama no palpable supone alrededor del 30 por ciento de todos los cánceres de mama debido al uso generalizado de la mamografía. El objetivo de este trabajo es determinar la supervivencia de las pacientes con cáncer de mama diagnosticado como lesión mamaria no palpable. Material y métodos. Se analizó de manera retrospectiva el historial clínico de 110 pacientes con lesiones mamarias no palpables. La lesión mamográfica se clasificó como microcalcificaciones, nódulo y distorsiones o asimetría. En las pacientes con carcinoma se realizó cirugía conservadora si cumplían los siguientes criterios: estadios 0, I o II, proporción volumen mamario/tumoral aceptable, lesión solitaria, microcalcificaciones focales y paciente conforme con el tratamiento. Resultados. En el estudio histológico 64 lesiones (57,6 por ciento) fueron carcinomas. En la clasificación TNM patológica el 32,7 por ciento pertenecían al estadio 0, el 43,6 por ciento al I y el 23 por ciento al II. Se realizó cirugía conservadora en 108 pacientes (98 por ciento). La supervivencia global ha sido del 100 por ciento y la supervivencia libre de enfermedad del 95 por ciento, con una recidiva local del 5 por ciento. Conclusiones. El estudio de las lesiones mamarias no palpables permite diagnosticar a un mayor número de pacientes con cáncer de mama en estadio temprano, realizar cirugía conservadora en un mayor número de pacientes e incrementar la supervivencia libre de enfermedad y la supervivencia global (AU)

Self-expandable stent before elective surgery vs. emergency surgery for the treatment of malignant colorectal obstructions: comparison of primary anastomosis and morbidity rates.

PURPOSE: At present there are not enough studies that demonstrate the usefulness of self-expandable stents in patients with left-sided malignant colon and rectal obstruction. We evaluated primary anastomosis and morbidity rates obtained with this method in comparison with the results of the emergency surgical treatment. METHODS: From February 1994 to November 1999, 72 consecutive patients with left-sided malignant colorectal obstruction were enrolled. Forty-three patients were assigned to the study group (preoperative stent and elective surgical treatment or palliative stent, depending on the assessment of the stage of the tumor) and 29 to the control group (emergency surgical treatment). The resection was not indicated in 18 cases in the study group (after preoperative staging in 17 and intraoperative staging in 1) and in 3 cases in the control group. RESULTS: In the study group, the obstruction was relieved in 41 cases (95 percent) after the stent placement. Of 26 patients who underwent surgical treatment, a primary anastomosis was possible in 22 (84.6 vs. 41.4 percent in the control group, P = 0.0025), with lower need for a colostomy (15.4 vs. 58.6 percent in the control group). The anastomotic failure rate was similar and the reintervention rate was lower (0 vs. 17 percent, P = 0.014). The total stay (14.23 vs. 18.52 days; P = 0.047), the intensive care unit stay (0.3 vs. 2.9 days; P = 0.015), and the number of patients with severe complications (11.6 vs. 41.2 percent; P = 0.008) were significantly lower in the study group. CONCLUSIONS: In our patients with left-sided malignant colon and rectal obstruction, placement of a preoperative stent prevented 17 (94 percent) of 18 of unnecessary operations and a large number of colostomies after elective surgery. These results were obtained with a lower severe complication rate as well as a shorter hospital stay.

Empleo de los documentos de consentimiento informado por los servicios de cirugía españoles / Use of informed consent documents by spanish surgery departments

Objetivo. Conocer la opinión de los cirujanos sobre el uso de los documentos de consentimiento informado (CI) y la utilización e implantación de los documentos editados por la Asociación Española de Cirujanos (AEC).Método. Se envió una encuesta a los jefes de servicio de cirugía (anexo I) y se realizó un análisis descriptivo de los resultados Resultado. Un total de 91 encuestas. Usan documento de CI el 98,9 por ciento, siendo específico en el 75,82 por ciento. Un total de 23 (27,27 por ciento) hospitales son de nivel I, 35 (38,46 por ciento) de nivel II y 30 (32,96 por ciento) de nivel III. El número medio (media [DE]) de consentimientos es mayor en los hospitales de nivel I (28,78 [14,15]), que en los de nivel II (27,36 [13,9]) y en los de nivel III (26,78 [15,72]). El 92 por ciento conoce los documentos de CI de la AEC. El 69,23 por ciento los usa. La puntuación media (DE) de los documentos de CI de la AEC es 7,84 (1,35).Conclusiones. Está muy extendido el uso de documentos de CI en los hospitales españoles, sobre todo en los hospitales de menor nivel. Donde se usan documentos específicos el número de procedimientos que tiene documento de CI es muy alto. La aceptación de los documentos realizados por la asociación ha sido muy buena y su uso muy extendido (AU)