Histopathology reporting in large bowel cancer.

A review of histopathology reports on 2046 patients in the large bowel cancer project showed considerable observer variation in histological grading. Dukes staging, and lymph node harvest. These parameters have a well-established relationship to prognosis, but, if they are to be applied for both clinical and research purposes, they must be assessed consistently. A minimal level of information which should be recorded from a resection specimen is suggested, with a description of the methods by which this information can be obtained.

The association between melanoma, lymphoma, and other primary neoplasms.

BACKGROUND AND OBJECTIVE: Reports of multiple primary tumors are not new. However, we have noted a disproportionate number of patients with melanoma in whom lymphoma develops and wanted to define the incidence of this association. DESIGN: All 664 patients with melanoma treated at Yale-New Haven Hospital, Conn, during the 5-year period from 1986 to 1991 were reviewed. The incidence of all the associated malignant neoplasms among our patients with melanoma was compared with the incidence that would be expected in the normal population adjusted for age, race, and sex. RESULTS: Among the 664 patients, 54 (8.1%) had one or more additional malignant neoplasms. Of the 10 different malignant tumor types recorded, lymphomas were the most prevalent. This incidence of lymphoma among the melanoma patients was 12 of 664, resulting in an incidence of 548 per 100,000 population, 16 times higher (P < .0125) than the expected incidence (34 per 100,000) when adjusted for age, sex, and race. CONCLUSIONS: The incidence of a second malignant neoplasm in our patients with melanoma was 8.1%. Lymphoma was a particularly common type of second malignancy, showing an incidence more than 16-fold higher than that expected in the normal population. It is particularly important, from a clinical point of view, to be aware of this when clinically palpable lymph nodes develop in areas not normally the site of regional lymphatic drainage of the primary melanoma.

Survey of residents' attitudes toward reform of work hours.

Traditional work schedules of surgical residents have been cited as a factor that negatively influences residency education and the quality of patient care. As an adjunct to the formulation of recommendations for the development of the environment for general surgery training, the New England Association of Program Directors in Surgery set out to sample the attitudes of surgical residents in New England relative to their perceived need to reform work hours. Seventy-two percent of the residents thought there was a need for some level of resident work schedule change. The major variable that correlated with this opinion was the reported amount of sleep that a resident needed before returning to work after a 24-hour shift. The ultimate effect on education, patient care, and fiscal resources of these potentially sensitive changes remains to be determined.

Regional blood flow and water content of the obstructed small intestine.

The effects of small-bowel obstruction on the regional distribution of blood flow and water content were studied in a new chronic dog model. Nonstrangulative obstruction was induced 40 cm proximal to the canine ileocolic valve. Blood flow was measured with 15-micron microspheres and hemodynamic and respiratory values were recorded before (experimental phase I) and five days after (experimental phase II) the induction of the obstruction. Two separate control groups of dogs were studied: baseline controls and sham-operative groups (phases I and II). Hemodynamic and respiratory values were stable in both phases in all groups. A comparison of sham phase-II data with the experimental phase-II data in the 120-cm segment of bowel proximal to the site of obstruction showed an 85% increase in blood flow (range, 49% to 106%); for the 280 cm of bowel proximal to the site of obstruction, there was a 6% increase in water content (range, 5% to 9%), and a 39% decrease in dry bowel weight (range, 34% to 46%). These findings help illustrate the pathophysiologic characteristics of microvascular changes in bowel obstruction, which are likely to have particular clinical significance for patients with cardiopulmonary diseases.

Neuropeptide Y inhibition of vasoactive intestinal polypeptide-stimulated ion transport in the rabbit distal colon.

We have studied the effect of neuropeptide Y on basal and vasoactive intestinal polypeptide-stimulated changes in the short-circuit current of strips of colonic mucosa from New Zealand white rabbits mounted in Ussing chambers. When administered to the basolateral surface, neuropeptide Y is found to decrease basal short-circuit current. Neuropeptide Y inhibits vasoactive intestinal peptide-stimulated increases in short-circuit current in a concentration-dependent fashion by a tetrodotoxin-insensitive mechanism. Also, neuropeptide Y inhibited increases in short-circuit current produced by direct stimulation of adenylate cyclase with forskolin. Furthermore, neuropeptide Y prevents vasoactive intestinal peptide-stimulated increases in tissue cyclic adenosine monophosphate levels. These results indicate that neuropeptide Y administered to the basolateral membrane inhibits vasoactive intestinal peptide-stimulated short-circuit current changes by a tetrodotoxin-insensitive mechanism that decreases tissue levels of cyclic adenosine 3',5'-monophosphate.

Covering stoma for elective anterior resection of the rectum: an outmoded operation?

A prospective multicenter study of the management of large bowel cancer recorded the results in 4,500 patients in whom 2,056 have had an elective colorectal anastomoses. Of these patients, 15.8 percent had a synchronous covering stoma to protect the anastomoses. Although the anastomotic leak rate was high in patients with a stoma, no overall differences were observed in mortality between those patients who had a covering stoma and those patients who did not (7 percent and 6.1 percent, respectively). However, when surgical policies were analyzed, clinically large and statistically significant differences were found. Some surgeons frequently used a covering stoma for low anterior resection whereas others only rarely did so. The differences in anastomotic leak and mortality were 20 percent and 7.8 percent, and 8.4 percent and 3.6 percent, respectively. We conclude that all surgeons should know their own clinical and radiologic anastomotic leak rate. If and when this figure becomes low (less than 5 percent), the covering stomas will become necessary except for the very rare and difficult case.

Risks of surgery for upper gastrointestinal hemorrhage: 1972 versus 1982.

A retrospective comparison was undertaken to determine if the risks of undergoing surgery for nonvariceal upper gastrointestinal hemorrhage had changed between 1972 and 1982. In 1982, patients were on the average 9 years older, there was a significant decrease in bleeding from duodenal ulcers compared with 1972 data, gastric ulcer rates remained unchanged, and diffuse gastritis occurred more frequently in 1982. Mortality and morbidity rates showed no significant differences; however, the patient population did change with the emergence of older patients, in whom bleeding developed after hospitalization for other reasons. These patients comprised 30 percent of the 1982 study population. If further improvements in surgical treatment of upper gastrointestinal hemorrhage are to occur, these patients must be identified and aggressively managed.

Does vasoactive intestinal polypeptide mediate the pathophysiology of bowel obstruction?

We hypothesized that bioactive peptides might be released into the portal circulation and mediate pathophysiologic alterations accompanying small bowel obstruction. We studied this question in a subacute canine small bowel obstruction model using 50 percent diameter occlusion. Control animals underwent sham laparotomy. Vasoactive intestinal peptide (VIP), peptide YY, and gastrin were measured in portal and systemic plasma by specific radioimmunoassays at 24-hour intervals as the obstruction progressed to completion over 5 days. All peptides in both groups demonstrated portal and peripheral gradients. In control dogs, peptide concentrations did not change postoperatively but VIP increased markedly in obstructed dogs, demonstrating a median portal level of 95 pmol/liter at 96 hours compared with 31.5 pmol/liter in control animals. These portal VIP levels are known to cause hypersecretion and splanchnic vasodilation in experimental models. The release of vasoactive compounds such as VIP may mediate local pathophysiology in human small bowel obstruction. A similar explanation of the systemic effects is consistent with the known cardiopulmonary bioactivity of VIP.

College of American Pathologists Conference XXVI on clinical relevance of prognostic markers in solid tumors. Report of the Colorectal Cancer Working Group.

The College of American Pathologists Conference XXVI in June 1994 was devoted to a discussion of the clinical relevance of prognostic factors in three solid tumors (breast, prostate, and colorectal). The group considering prognostic factors for adenocarcinoma of the large gut consisted of 15 pathologists, investigators, and surgeons. The group concluded that only a few items are well supported in the existing literature and can be recommended for routine clinical use at this time (pathologic TNM information and stage, tumor type, tumor grade, extramural venous invasion, and preoperative serum carcinoembryonic antigen level). According to the classification system used at the conference, these markers warrant categorization as important prognostic factors (category I). A few factors should be considered as potentially useful after further study (category II). Furthermore, the group agreed that all other current measurements of so-called prognostic factors do not warrant the same recognition of importance, either because they have been studied insufficiently or studies have demonstrated that they do not contribute to prognostication. These additional items were placed in category III. It was also concluded that the statistical methods used to identify and validate prognostic markers, as well as their integration into single statements of prognosis need further national evaluation and standardization.

College of American Pathologists Conference XXXV: solid tumor prognostic factors-which, how and so what? Summary document and recommendations for implementation. Cancer Committee and Conference Participants.

The College of American Pathologists convened a prognostic factor conference in June 1999 to consider prognostic and predictive factors in breast, colon, and prostate cancer, and to stratify these factors into categories reflecting the strength of published evidence. Because so little progress in prognostic factor clinical utility has been made in the last 5 years, the conference participants focused their attention on decreasing variation in methods, interpretation, and reporting of these factors so that greater clarity of value could be achieved. The conference was organized to promote discussion, broad input, and future planning. An initial plenary session provided an overview of the status of tumor marker research, the impact of variation in medicine and pathology, and statistical issues related to prognostic factor research. In working group sessions for each cancer type, participants interactively evaluated and refined the documents created by the expert panels. A second plenary session dealt with issues common to all 3 groups, including the problem of micrometastases in lymph nodes in these sites; statistical issues that arose during the breakout discussions; and issues of variation in methods, interpretation, and reporting of immunohistochemical assays. A faculty session brainstormed strategies that could be used to implement the changes recommended. This session included invited representatives of the Food and Drug Administration, Health Care Financing Administration, Centers for Disease Control and Prevention, National Cancer Institute, American Joint Committee on Cancer, and International Union Against Cancer. Cancer site and general recommendations were presented and discussed during a final session to achieve consensus of the conference participants and to address feasibility of implementation of these recommendations. A final discussion focused on future initiatives that might lead to implementation of the changes proposed in the conference by the various organizations represented. This report summarizes the general conference recommendations, cancer working group recommendations, and plans for implementation of the recommendations.

Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999.

BACKGROUND: Under the auspices of the College of American Pathologists, the current state of knowledge regarding pathologic prognostic factors (factors linked to outcome) and predictive factors (factors predicting response to therapy) in colorectal carcinoma was evaluated. A multidisciplinary group of clinical (including the disciplines of medical oncology, surgical oncology, and radiation oncology), pathologic, and statistical experts in colorectal cancer reviewed all relevant medical literature and stratified the reported prognostic factors into categories that reflected the strength of the published evidence demonstrating their prognostic value. Accordingly, the following categories of prognostic factors were defined. Category I includes factors definitively proven to be of prognostic import based on evidence from multiple statistically robust published trials and generally used in patient management. Category IIA includes factors extensively studied biologically and/or clinically and repeatedly shown to have prognostic value for outcome and/or predictive value for therapy that is of sufficient import to be included in the pathology report but that remains to be validated in statistically robust studies. Category IIB includes factors shown to be promising in multiple studies but lacking sufficient data for inclusion in category I or IIA. Category III includes factors not yet sufficiently studied to determine their prognostic value. Category IV includes factors well studied and shown to have no prognostic significance. MATERIALS AND METHODS: The medical literature was critically reviewed, and the analysis revealed specific points of variability in approach that prevented direct comparisons among published studies and compromised the quality of the collective data. Categories of variability recognized included the following: (1) methods of analysis, (2) interpretation of findings, (3) reporting of data, and (4) statistical evaluation. Additional points of variability within these categories were defined from the collective experience of the group. Reasons for the assignment of an individual prognostic factor to category I, II, III, or IV (categories defined by the level of scientific validation) were outlined with reference to the specific types of variability associated with the supportive data. For each factor and category of variability related to that factor, detailed recommendations for improvement were made. The recommendations were based on the following aims: (1) to increase the uniformity and completeness of pathologic evaluation of tumor specimens, (2) to enhance the quality of the data needed for definitive evaluation of the prognostic value of individual prognostic factors, and (3) ultimately, to improve patient care. RESULTS AND CONCLUSIONS: Factors that were determined to merit inclusion in category I were as follows: the local extent of tumor assessed pathologically (the pT category of the TNM staging system of the American Joint Committee on Cancer and the Union Internationale Contre le Cancer [AJCC/UICC]); regional lymph node metastasis (the pN category of the TNM staging system); blood or lymphatic vessel invasion; residual tumor following surgery with curative intent (the R classification of the AJCC/UICC staging system), especially as it relates to positive surgical margins; and preoperative elevation of carcinoembryonic antigen elevation (a factor established by laboratory medicine methods rather than anatomic pathology). Factors in category IIA included the following: tumor grade, radial margin status (for resection specimens with nonperitonealized surfaces), and residual tumor in the resection specimen following neoadjuvant therapy (the ypTNM category of the TNM staging system of the AJCC/UICC). (ABSTRACT TRUNCATED)

Large bowel cancer: the effect of perioperative blood transfusion on outcome.

Perioperative blood transfusion has been reported to adversely affect survival in cancer patients, but the evidence is inconclusive and may be an epiphenomenon. From the Large Bowel Cancer Project, 961 patients who underwent curative resection and left hospital alive have been reviewed to compare the effect of perioperative blood transfusion on outcome; 591 patients (61%) had been given a blood transfusion while 370 (39%) had not been transfused. Some clinical variables were equally distributed between the two groups; ie age, sex, obstruction, perforation, tumour differentiation. Three other variables known to influence patient prognosis were not equally distributed, ie tumour site, Dukes' stage and tumour mobility. Patients with tumours of the rectum and rectosigmoid, with Dukes' stage C lesions and with some degree of tumour fixation were more likely to have received blood transfusions. Using the logrank method of multivariate analysis to allow for differences in distribution of all those variables known to affect prognosis, there was no survival disadvantage for those patients who had received perioperative blood transfusion. Furthermore, there were no overall differences between the two groups of patients in their risk of developing local tumour recurrence or distant metastases. The distribution of metastases differed: in the 'transfused' group only 37% of distant metastases were found in the liver, while 71% were found in this site in the 'not transfused' group (chi 2 = 18.46, d.f. = 1, P less than 0.001). By contrast, there was a larger proportion of patients with lung metastases in the transfused group (27% vs 11%) (chi 2 = 5.59, d.f. = 1, P less than 0.05). Therefore, these data do not support the concept of an overall deleterious effect of blood transfusion on patient survival, but suggest that blood given in the perioperative period may change the biology of the metastatic process.

Low back injury in industry: the value of a recovery program.

Low back pain is the most frequent chronic disabling condition in the United States in patients younger than 45 years, and it is the second largest cause of employee absenteeism. In this retrospective study involving extreme working conditions at an industrial plant, we found that 20% of all employees incurred a back injury (occupational and nonoccupational) during the 12-month study period, costing more than 5,000 days of work lost, and approximately $920,000. Based on these findings a three-phased program of education/prevention, physical therapy, and an on-site rehabilitation workshop was implemented. After the first operational year, the net saving to the corporation was $255,000, and all employees who participated in the program returned to work within 60 days. We conclude that good job design, employee education on back injury prevention, and immediate on-site rehabilitation for injuries incurred can reduce employee disability and lost work time thus benefiting the employer and employee alike.

Acute perforated diverticulitis: primary resection and anastomosis?

Surgical management of patients with acute colonic diverticulitis is evolving from multiple towards single operations. The patterns of presentation and treatment of 146 patients with acute perforated diverticulitis have been reviewed (1983-1988) using the Hinchey classification system (Stages I-IV). This paper focuses on the six patients who presented with fecal peritonitis (Stage IV disease), half of whom were treated by primary resection and anastomosis and the remainder by a Hartmann procedure. The mean length of stay was 18.7 +/- 7.9 days and 12.7 +/- 4.8 days with a mortality of zero and one, respectively. These data suggest that in selected patients who present with perforated diverticular disease, primary resection with anastomosis offers a possible alternative to other operative management. The presence of fecal peritonitis should no longer be considered an absolute contraindication to immediate bowel reconstruction. Furthermore, we suggest that this decision be based on the relative absence of concomitant disease, a satisfactory response to preoperative resuscitation, the availability of a surgeon experienced in colonic surgery, and attention to postoperative management.