Is MSI-H of value in predicting the development of metachronous colorectal cancer?

Nearly 10% of patients with colorectal cancer (CRC) develop a metachronous cancer after curative resection of their primary malignancy, however identifying these patients is problematic. Although microsatellite instability (MSI) is associated with the development of multiple CRC, this is predominantly seen in those with hereditary non-polyposis colon cancer (HNPCC). This study has examined the value of MSI analysis in identifying patients at risk of developing metachronous cancer from the general population. MSI analysis was performed at the Bat25, Bat26, Bat40, D2S123, D5S346 and D17S250 loci using polymerase chain reaction and single-stranded conformational polymorphism on DNA extracted from 62 specimens taken from 49 patients with metachronous CRC, and from 71 primary single CRCs. MSI status was classified into MSI-H, MSI-L and MSS. MSI-H was more prevalent in metachronous cancers, 34/62 compared to 8/71 single cancers (P < 0.0001). The incidence of MSI-H from proximal colon cancers in index metachronous group, 4/22 was similar to single cancer group, 7/71 (P = 0.28), however MSI-H was more commonly identified in index metachronous cancers located distal to the splenic flexure 9/22 than single cancers 1/71 (P < 0.0001). Patients presenting with MSI-H colorectal cancers distal to the splenic flexure are more likely to develop a metachronous cancer and will benefit from surveillance.     

Predictive validity of five comorbidity indices in prostate carcinoma patients treated with curative intent

BACKGROUND: Comorbidity is important to consider in clinical research on curative prostate carcinoma because of the role of competing risks. Five chart-based comorbidity indices were assessed for their ability to predict survival. METHODS: This was a case-cohort study of prostate carcinoma patient cohort treated with curative intent in Toronto and Southeast Cancer Care Ontario regions between 1990 and 1996; the subcohort was drawn from these men, whereas cases were cohort members who died from causes other than prostate carcinoma. Comorbidity data were obtained from medical charts (269 subjects). Vital status, age, area of residence, and socioeconomic status information were available. Predictive validity was quantified by the percent variance explained (PVE) over and above age using proportional hazards modeling. RESULTS: The Chronic Disease Score (CDS) (PVE = 11.3%; 95% confidence interval [95% CI], 3.5-22.8%), Index of Coexistent Disease (ICED) (PVE = 9.0%; 95% CI, 2.9-17.9%), Cumulative Illness Rating Scale (CIRS) (PVE = 7.2%; 95% CI, 1.4-17.1%), Kaplan-Feinstein Index (PVE = 4.9%; 95% CI, 0.6-12.8%), and Charlson Index (PVE = 3.8%; 95% CI, 0.3-10.9%) each explained some outcome variability beyond age. PVE differences among indices were not statistically significant. A comorbidity identified at the time of cancer diagnosis was the cause of death in 59.2% of cases (75% for cardiac or vascular causes). CONCLUSIONS: The better-performing, more comprehensive indices (CDS, ICED, and CIRS) would be useful in measuring and controlling for comorbidity in this setting. The CDS was easiest to apply and explained the most outcome variability.     

The management of deep sternal wound infections using vacuum assisted closure (V.A.C.) therapy

A group of international experts met in May 2006 to develop clinical guidelines on the practical application of vacuum assisted closure (V.A.C.)+ therapy in deep sternal wound infections. Group discussion and an anonymous interactive voting system were used to develop content. The recommendations are based on current evidence or, where this was not available, the majority consensus of the international group. The principles of treatment for deep sternal wound infections include early recognition and treatment of infection. V.A.C. therapy should be instigated early, following thorough wound irrigation and surgical debridement. V.A.C. therapy in deep sternal wound infections requires specialist surgical supervision and should only be undertaken by clinicians with adequate experience and training in the use of the technique.     

Cimetidine and the gastric surgeon

A study of the effects of cimetidine has been made in patients referred to a surgical clinic. Cimetidine is undoubtedly useful in aiding the healing of acute duodenal ulcers, but once treatment is stopped, the majority recur. After healing, maintenance treatment is useful in preventing ulcer recurrence, but once the drug is stopped, recurrence soon follows. At present the evidence suggests that treatment with cimetidine may have to be life-long. Most surgeons would not accept this as an alternative to surgery in the treatment of chronic duodenal ulcer. However, in the treatment of recurrent ulceration after surgery, and where symptoms are relieved by cimetidine, the patient may prefer drugs to further operation.

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Résumé Nous avons étudié les effets de la cimétidine chez un groupe de malades admis dans un service de chirurgie. La cimétidine est sans aucun doute utile pour la cicatrisation des ulcères duodénaux aigus; mais la majorité des lésions récidivent lorsque le traitement est arrêté. Après cicatrisation, le traitement d'entretien prévient la récidive ulcéreuse; mais celle-ci survient vite lorsqu'on arrête l'administration du médicament. A l'heure actuelle, il apparait que le traitment à la cimétidine doit peutêtre être maintenu ad vitam. La plupart des chirurgiens n'accepteront pas ce type de thérapeutique comme une alternative à la chirurgie pour l'ulcère duodénal chronique. Cependant, en cas de récidive après chirurgie gastrique et lorsque les symptomes sont amendés par la cimétidine, le malade peut préférer la drogue à la réintervention.

     

Insulin- and histamine-stimulated secretion in relation to recurrence of duodenal ulceration after vagotomy

Gastric secretion after vagotomy for duodenal ulcer in response to a single injection of insulin and in response to a histamine infusion has been compared in 25 patients with and 56 patients without recurrent duodenal ulceration proven by endoscopy. The lower 95 per cent tolerance limits of the pre-operative ranges of secretion to either insulin or histamine stimulation measured in 81 unoperated patients provided thresholds that separated postvagotomy patients with recurrent ulceration and those without. Neither the ratios, nor the regression line, between secretion in response to each secretagogue provided similar discrimination. In a group of 43 patients who had gastric secretion studies before and after vagotomy the reductions in secretion to below the established 95 per cent tolerance limits of secretion were respectively 60 and 80 per cent of their pre-operative insulin- and histamine-stimulated secretion. The percentage reductions however failed to differentiate asymptomatic patients from patients with recurrent ulceration. It appears therefore that, irrespective of the pre-operative level or of the magnitude of the reduction of secretion, a vagotomy to be adequate must achieve a reduction of secretion to below a threshold level.     

Resection and reconstruction of the carotid artery in metastatic squamous cell carcinoma

Although it is uncommon to consider resection of the common and internal carotid arteries for involvement by carcinoma, nevertheless, if this is the only significant finding precluding an adequate ablative procedure, this operation is worthy of consideration. Ten procedures were performed in nine such patients; the carotid bifurcation was resected and continuity reestablished using Teflon or autogenous saphenous vein grafts. In attempting to predict the efficiency of the collateral cerebral cross-flow, arteriography, oculopneumoplethysmography and intraoperative measurement of carotid stump pressure were used in some patients. There was no operative mortality. The postoperative mortality rate was 20 percent and cerebrovascular complications occurred in 20 percent of the cases. Seven patients survived 9 months to $\text{4}\text{1}\text{4}$ years. Teflon grafts appeared to have a higher patency rate than saphenous vein autogenous grafts. Although this series is very small, it is an evaluation of a procedure of last resort which appears worthwhile in carefully selected patients.