Roger Vander Zwaag

From dukes through jass: Pathological prognostic indicators in rectal cancer

In the recently described Jass staging system for resected adenocarcinoma of the rectum, peritumoral lymphocytic infiltration and tumor growth pattern are introduced as significant indicators of prognosis in conjunction with depth of tumor invasion and lymph node metastasis. The authors of this study have tested the applicability of the Jass system by reviewing 348 resected rectal cancers for 12 pathological variables, including two newly recognized features, namely the Crohns-like lymphoid reaction and metastatic tumor nodules in pericolic fat. By univariate analysis improved 5-year survival rate was associated with tubular-type adenocarcinoma, low tumor grade, retention of tubule configuration and nuclear polarity, expanding tumor growth pattern, prominent peritumoral lymphocytic infiltration, absence of extramural vein invasion by tumor, all levels of intramural and extramural invasion short of widespread local tumor dissemination, a Crohns-like lymphoid reaction pattern, and absence of both nodal metastasis and tumor nodules in perirectal fat. By Cox stepwise proportional hazards analysis, depth of tumor invasion, lymph node metastasis, Crohns-like lymphoid reaction, and extramural venous invasion retained independent prognostic significance. Peritumoral lymphocytic infiltration and tumor growth pattern of the Jass staging system failed to compete successfully with other variables in the proportional hazards model, in part because of their correlation with the models selected variables. Both intramural and extramural extent of tumor invasion coupled with lymph node metastasis form the cornerstones of rectal cancer staging. However, other factors do refine prognostication. From this study the Crohns-like lymphoid reaction emerges as a significant new independent indicator of prognosis for survival from rectal cancer. Although the Crohns-like lymphoid reaction and extramural vein invasion took precedence as staging variables in this study, a complex interrelationship with other parameters was observed.

Left ventricular hypertrophy: Effect on survival

OBJECTIVESnThe aim of the study was to determine whether left ventricular hypertrophy has an independent adverse effect on survival.nnnBACKGROUNDnLeft ventricular hypertrophy is considered to be a significant risk factor for coronary heart disease mortality; however, the impact of coexisting coronary artery stenosis on survival statistics is not clear.nnnMETHODSnThe relations among electrocardiographic (ECG) left ventricular hypertrophy, ST-T segment abnormality, coronary artery disease and survival were examined in 18,969 patients undergoing coronary arteriography between 1972 and 1985. Patients were excluded if they underwent coronary revascularization or had unstable angina, rheumatic or congenital heart disease, cardiomyopathy, pericardial disease or ECG changes other than left ventricular hypertrophy or repolarization abnormalities, leaving 4,824 patients for analysis.nnnRESULTSnLeft ventricular hypertrophy was present in 249 patients, whereas 4,575 were free of left ventricular hypertrophy. Five-year survival was 90.2% in the group without left ventricular hypertrophy and was significantly lower (81.9%, p < 0.001) in the group with left ventricular hypertrophy. Five-year survival was significantly lower in patients with left ventricular hypertrophy, regardless of whether coronary artery disease was present: 84.4% versus 94.5% (p = 0.016) in the absence of coronary artery disease and 81.0% versus 87.7% (p < 0.001) in the presence of coronary artery disease. The presence of ST segment abnormalities was not associated with a significant reduction in survival in patients without coronary disease, although mortality was less in those without ST changes who had coronary disease (p = 0.012).nnnCONCLUSIONSnIt is concluded that ECG left ventricular hypertrophy has an adverse effect on survival, even in patients who are free of coronary artery disease.

Subtle appearance of pelvic endometriosis

This retrospective study demonstrates an increased documentation of subtle appearances of endometriosis. This documentation was associated with an increased emphasis on excising these lesions for histologic examination. Endometriosis was documented in pink, clear, red, white, and puckered black lesions in 106 (97%) of 109 patients. This included 22 (100%) of 22 patients undergoing laparotomy and 84 (97%) of 87 patients undergoing laparoscopy. Subtle lesions were documented at laparoscopy in 32% of patients in the first 5 months and in 72% of patients in the last 5 months of the study. The increased documentation of these subtle lesions appeared to be related to an increased awareness and anticipation of subtle lesions. The ability to detect such lesions increased with experience and was reinforced by histologic confirmation.

Prognostic Factors in Survival Free of Progression After Androgen Deprivation Therapy for Treatment of Prostate Cancer

We analyzed 110 patients with metastatic prostate cancer (stage D2) to determine the associations between interval until progression and the pretreatment testosterone level, extent of bone metastases, performance status, race, age and pretreatment level of prostatic acid phosphatase. The median followup was 21 months (4 to 89 months). All patients received androgen deprivation therapy when metastases were identified. This multivariate analysis demonstrated that the pretreatment serum testosterone was the most significant variable (p less than 0.01) associated with interval until progression and the extent of bone metastases observed on the bone scan was the second most important variable (p less than 0.05). Age, race and prostatic acid phosphatase were not significantly correlated with the interval free of progression. Performance status was significantly correlated but it was nonsignificant in the multivariate analysis if the model already included testosterone level and extent of metastasis. Patients with a pretreatment testosterone level of less than 300 ng. per 100 ml. and more than 6 areas of increased uptake on the bone scan had the most rapid progression. We conclude that serum testosterone and extent of bone metastases are the most important of the analyzed factors in terms of interval to progression in patients with prostate cancer following androgen deprivation.

Prognostic significance of changes in prostate-specific markers after endocrine treatment of stage D2 prostatic cancer

Background. The prognostic value was determined of prostate‐specific antigen (PSA) and prostatic acid phosphatase (PAP) measured before and after endocrine treatment in 57 patients with newly diagnosed Stage D2 prostatic cancer.

Impact of the Crohn's-like lymphoid reaction on staging of right-sided colon cancer: Results of multivariate analysis

The presence of lymphoid aggregates within the muscularis propria or pericolic fibroadipose tissue apposing invasive colorectal carcinoma, termed the Crohns-like lymphoid reaction, has been related to improved patient length of survival according to univariate statistical analysis. We tested the Crohns-like lymphoid reaction as an indicator of prognosis in a multivariate statistical analysis of 344 resected right-sided colonic cancers. Improved 5-year survival in univariate analysis was associated with low tumor grade, regular tubule configuration, expanding tumor growth pattern, prominent peritumoral lymphocytic infiltration, absence of tumoral invasion of extramural veins, all levels of intramural and extramural invasion short of widespread local tumor permeation, conspicuous Crohns-like lymphoid reaction, and absence of both nodal metastasis and nodal-independent tumor nodules in pericolic fat. By the Cox proportional hazard model using the stepwise method, depth of tumor invasion, lymph node metastasis, Crohns-like lymphoid reaction, and metastatic tumor nodules in pericolic fat retained independent prognostic significance. Combining the four variables to formulate pathological prognostic categories yielded a highly favorable prognostic group-92% 5-year survival and 95% confidence limits (88% to 96%)--encompassing 53% of the study population. It included all Dukes stage A carcinomas, 66% of Dukes stage B adenocarcinomas, and 11% of Dukes stage C cancers. Lymph node metastases coupled with intramural and extramural extent of tumor invasion are the cornerstones of colorectal cancer staging. Addition of other variables improves prognostication for the cecum and ascending colon. From this study the Crohns-like lymphoid reaction and metastatic tumor nodules in pericolic fat emerge as significant independent indicators of prognosis for right-sided colon cancer. Complex correlations of both indicators with nonselected variables were observed.

Adenocarcinoma of the stomach with invasion limited to the muscularis propria

Adenocarcinoma of the stomach having invasion limited to the muscularis propria with or without lymph node metastasis, termed PM (proper muscle) gastric cancer by Japanese investigators, has a prognosis superior to that of carcinoma extending to the serosa and approaching that of early gastric cancer in Japan. To evaluate the occurrence and significance of PM gastric cancer in the United States, we analyzed 272 gastric carcinomas resected at our institution between 1964 and 1983. Forty-two PM cancers (15%) were identified. Improved 5-year survival rate was noted for PM cancer when compared with survival rate for 215 neoplasms exhibiting serosal invasion (29% versus 7%, P less than 0.001). In univariate analysis, a survival advantage was also associated with absence of lymph node metastasis, intestinal-type histopathology of the Lauren classification, the expanding pattern of the Ming classification, and polypoid or fungating gross configuration of tumor. In multivariate analysis, depth of tumor invasion remained significantly associated with improved 5-year survival rate independently of other variables, including lymph node metastasis. Using continuous survival curves, the prognostic significance of PM cancer prevailed throughout the 5-year postgastrectomy interval. Our data indicate that PM gastric cancer occurs in the United States and need not be considered advanced gastric carcinoma; depth of tumor invasion should be recognized as a nodal metastasis-independent prognosticator of gastric cancer survival.

Eccentric and concentric muscle performance in patients with spastic paresis secondary to motor neuron disease. A preliminary report.

This study investigated the potential value of eccentric (ECC) and concentric (CONC) isokinetic testing for quantifying motor deficit in patients with spastic paresis secondary to motor neuron disease. We hypothesized that, at a moderately fast (120 degrees s-1) angular velocity, spastic patients would demonstrate different ECC-CONC torque relationships from healthy controls or patients with non-spastic neuromuscular disorders. Eleven patients with motor neuron disease having clinical evidence of spasticity, and 11 disease-control patients (with non-spastic disorders, e.g. lower motor neuron disease or myopathy) underwent isokinetic testing. One healthy subject was matched to each of the 22 patients. The average torque generated during maximal voluntary ECC and CONC knee flexion (KF) and extension (KE) was measured using an isokinetic dynamometer (Kin-Com). Reliability was established (all ICC > or = 0.97) for patient torque measurements. Relative strength (% of control subject torque) in spastic patients was significantly higher for ECC than for CONC actions in both KF and KE; conversely, in non-spastic disease-control patients relative strength was not affected by the type of muscle action. The ECC/CONC average torque ratios for KE and KF at 120 degrees s-1 were significantly greater in spastic patients than controls, but did not differ from controls in non-spastic patients. In spastic patients the ECC-CONC imbalances were related to ambulatory dysfunction. In four spastic patients followed with serial testing, the disproportion between ECC and CONC voluntary capacity persisted over time.(ABSTRACT TRUNCATED AT 250 WORDS)

Case-control study of coronary heart disease risk factors in the elderly.

We undertook a case-control study utilizing a large coronary arteriography database to determine if traditional cardiovascular risk factors are as predictive of the presence of angiographically-proven coronary artery disease (CAD) in elderly patients as in younger patients. Among the patients aged 65 years or more, there were 2120 cases and 193 controls, while for the patients aged 35-49 years there were 1493 cases and 707 controls. Odds ratios obtained from logistic regression indicated that age, male sex, diabetes, cigarette smoking, hypertension, total cholesterol and left ventricular hypertrophy were all significant risk factors for CAD in both age groups, although the odds ratios tended to be somewhat lower in the elderly. Logistic regression analysis for gender subgroups generally revealed similar findings when compared with the combined (males + females) age groups, although power was limited for the subgroup of elderly males which had few controls. We conclude that most of the traditional cardiovascular risk factors which have been described as correlated with the presence of CAD in younger populations are also correlated with angiographically-proven CAD in older patients.

Interactive effects of ST-T wave abnormalities on survival of patients with coronary artery disease

Previous studies have documented a reduced survival time in patients with an electrocardiographic (ECG) ST-T wave abnormality. This study was designed to determine the clinical, hemodynamic and angiographic correlates of this observation. Data from 9,731 patients undergoing cardiac catheterization from 1976 through 1986 were analyzed; 5,531 had severe (greater than 70%) obstruction of at least one major coronary artery, 1,706 had mild (10 to 69%) obstruction and 2,494 had no obstruction. Of the patients with severe obstruction, 2,536 were treated medically and 2,995 were treated by surgical revascularization. Patients with an ST-T abnormality had more clinical risk factors (including older age and greater prevalence of diabetes mellitus, hypertension and prior myocardial infarction) and greater left ventricular dysfunction (including higher end-diastolic pressure and ventricular volume, reduced ejection fraction and greater prevalence of contraction abnormality) than did those without this ECG pattern. Survival time was significantly (p less than 0.01) reduced in subsets of patients with an ST-T abnormality and with severe or mild coronary artery disease; in those without coronary disease, ST-T changes did not correlate with reduced survival. Stepwise regression analysis was applied to each group to determine the independent predictors of 5-year survival. In patients with severe disease or no disease, an ST-T abnormality was not chosen as an independent predictor of 5-year survival; in the group with mild disease, ST-T changes were an independent predictor of reduced survival. Thus, the independent impact of an ST-T abnormality on survival is dependent on the severity of underlying coronary artery disease.