Predictors of recurrence after local excision and postoperative chemoradiation therapy of adenocarcinoma of the rectum.

BACKGROUND: Local excision of rectal cancer preserves anal continence, bladder function, and normal sexual function. However, local recurrence after excision remains a significant problem. To further define the indications for local excision, we analyzed possible factors predictive of recurrence after local excision of rectal cancer. METHODS: The charts of all patients undergoing local excision of adenocarcinoma of the rectum between 1985 and 1995 at a single institution were reviewed. Patients with metastatic disease at the time of excision and patients treated preoperatively with chemoradiation therapy were excluded. All available slides were reviewed by a single pathologist, who assessed the depth of invasion; the presence or absence of vascular invasion, lymphatic invasion, perineural invasion, and lymphocytic infiltrate; the mucinous status; and the degree of differentiation. Using the log-rank test and Cox proportional hazards model, univariate and multivariate analyses were performed to identify predictors of recurrence. RESULTS: Ninety patients underwent local excision, 46 transanally and 44 using a Kraske approach. The breakdown of patients by tumor stage was as follows: Tis, 13%; T1, 41%; T2, 30%; T3, 15%; and Tx, 1%. Sixty-eight percent of patients with T1 tumors were treated with postoperative radiotherapy; all patients with T2 or T3 tumors were treated postoperatively with or without 5-fluorouracil. The median duration of follow-up was 51 months. The median tumor diameter was 2.5 cm (range, 0.4 to 7 cm), and the median distance of the tumor from the anal verge was 4.5 cm (range, 1 to 10 cm). The 4-year actuarial local disease-free survival rate broken down by tumor stage was as follows: Tis, 100%; T1, 95%; T2, 80%; and T3, 73%. The median time to local recurrence was 23 months (range, 7 to 61 months). Multivariate analysis showed that only tumor stage and margin status were predictors of local recurrence. CONCLUSIONS: Local excision and postoperative radiotherapy result in adequate local control of early stage (Tis and T1) adenocarcinoma of the rectum. Higher rates of recurrence were seen in patients with T2 and T3 tumors, especially in those with positive margins.

Clinical, pathologic, and economic parameters of laparoscopic colon resection for cancer.

BACKGROUND: The appropriateness of laparoscopic colon resection (LCR) as treatment for malignancy has been questioned. METHODS: From 1992 to 1997, 91 patients were entered into a prospective study of LCR for cancer. Clinical, pathologic, and economic parameters of LCR were compared in a cohort of patients matched for age, tumor stage, and type of colectomy who underwent open colon resection (OCR) during the same time period. RESULTS: With a median follow-up of 26 months, there were no significant differences in survival rate for patients in the LCR, converted colon resection, and OCR groups. There were no port-site recurrences and the number of lymph nodes harvested was similar among the procedures. Hospital stay was significantly shorter if laparoscopic resection was successful. Total hospital costs were similar for LCR and OCR; however, the costs were significantly higher for converted colon resection. CONCLUSIONS: LCR is a sound oncologic procedure that can be performed with costs similar to OCR.

Pelvic exenteration for locally advanced rectal carcinoma: factors predicting improved survival.

BACKGROUND: The purpose of this retrospective review was to determine whether a number of clinicopathologic factors (age, gender, type of exenteration, tumor extent, adjuvant therapy, tumor DNA ploidy, and S-phase fraction) that could be determined before operation were useful in predicting survival in patients undergoing pelvic exenteration for rectal cancer. METHODS: Between 1983 and 1992, 40 patients (15 male and 25 female) at our institution underwent pelvic exenteration for rectal adenocarcinoma in which tumor-free pathologic margins were obtained. Twenty-nine patients presented with primary tumors; 11 had recurrent disease. A total exenteration was performed in 20 patients, posterior exenteration in 18 patients, and an anterior exenteration in 2 patients. RESULTS: By multivariate (Cox proportional hazards regression) analysis, age, preoperative chemoradiation therapy, and an S phase of 10% or greater were found to be significant predictors of survival. Age older than 55 years was associated with a relative risk for cancer-related death (RR) of 0.13 (p = 0.02), and chemoradiation had an RR of 0.05 (p = 0.01), indicating their beneficial effect. An S-phase fraction of 10% or greater had an RR of 16.97 (p = 0.03), indicating a poor survival. The clinicopathologic factors listed above were used to derive a prognostic index (PI). A PI of less than 1.37 was associated with a 5-year survival rate of 65% (low risk), whereas patients with a PI of 1.37 or greater had a 5-year survival rate of 20% (high risk) (p = 0.005). CONCLUSIONS: These results indicate that adjuvant chemoradiation may significantly improve survival in patients who require pelvic exenteration for resection of locally advanced rectal carcinoma. An S-phase fraction of 10% or greater is also predictive of a poor outcome. Use of these factors allowed the generation of a PI that identifies high- and low-risk patients. Consideration of the ability to deliver chemoradiation and the determinates of the tumor S-phase fraction in patients requiring pelvic exenteration for rectal cancer may be helpful in predicting outcome and planning therapy.

Carcinoid tumors of the rectum: effect of size, histopathology, and surgical treatment on metastasis free survival.

BACKGROUND: The purpose of this study was to determine the clinical course, effects of specific tumor histopathologic characteristics, and extent of surgical treatment on the metastatic rate in patients with rectal carcinoids. METHODS: Medical records of 44 patients who presented with rectal carcinoids were retrospectively reviewed. Primary tumors were classified by size (< 1 cm, 1-2 cm, and > 2 cm), and tumor histopathologic features (atypical or typical). Extensive surgery was defined as abdominoperineal or low anterior resection of the rectum or laparotomy with intent of curative resection. RESULTS: Median follow-up for patients who presented without metastasis was 84 months. Thirteen of the 44 patients (30%) presented with metastatic disease. The 5-year metastasis free survival rates for those patients presenting without metastatic disease were 100% for patients with tumors < 1 cm (n = 16), 73% for those with tumors 1-2 cm (n = 8), and 25% for those with tumors > 2 cm (n = 4) (P = 0.04 comparing < 1 cm with 1-2 cm and P = 0.05 comparing 1-2 cm with > 2 cm); tumor size data were not available for 3 patients. The 5-year metastasis free survival rate for patients presenting without metastatic disease with typical histology (n = 20), regardless of size, was 100%, compared with 50% for patients with tumors with atypical histology (n = 11) (P = 0.001). Nine patients underwent extensive surgery for rectal carcinoid tumors but no survival benefit was demonstrated. CONCLUSIONS: Atypical histopathologic features and a tumor size > 1 cm are associated with aggressive behavior of rectal carcinoid tumors. Extensive surgery offers no survival advantage over local excision for patients with rectal carcinoid tumors.

p53 immunohistochemical staining predicts residual disease after chemoradiation in patients with high-risk rectal cancer.

This study was conducted to investigate the value of p53 immunohistochemical staining of pretreatment biopsy specimens in predicting the response of rectal cancer to chemoradiation. The study group comprised 42 patients with high-risk rectal cancer treated between July 1990 and July 1995 with a preoperative chemoradiation regimen of 45 Gy of external-beam irradiation and continuous-infusion 5-fluorouracil followed by surgical resection. p53 immunohistochemical staining was performed on pretreatment biopsy specimens. p53 immunohistochemical staining pattern and standard clinical and pathological parameters were correlated with extent of residual cancer in the surgical specimen. Twenty tumors were positive for p53 on immunohistochemical staining, 19 were negative, and 3 were focally positive. Thirteen patients experienced a complete response to chemoradiation. Aberrant p53 protein accumulation, as measured by immunohistochemical staining, correlated inversely with a complete pathological response to chemoradiation (P = 0.005; correlation coefficient = -0.43) and directly with an increased likelihood of residual cancer in the lymph nodes of surgical specimens (P = 0.02; correlation coefficient = 0.39). p53 immunohistochemical staining of pretreatment biopsy specimens correlates with the extent of residual disease after chemoradiation in patients with high-risk rectal cancer.

Survival factors in 186 patients younger than 40 years old with colorectal adenocarcinoma.

BACKGROUND: We sought to determine the clinical factors and tumor characteristics associated with the reported poor prognosis in young patients with carcinoma of the colon and rectum. STUDY DESIGN: A retrospective review was performed of 186 patients younger than 40 years of age who were treated for primary colorectal adenocarcinoma. The median age was 34.3 years, and the median follow-up period was 9.4 years. Clinical and tumor histopathologic parameters were analyzed. RESULTS: Regional lymph node metastases, distant metastases, or both, were seen at first examination in 65.6 percent of young patients. Histopathologic indicators of more aggressive tumor biology were present at a significantly higher frequency in young patients compared with patients older than 40 years (p < 0.001). Poorly differentiated tumor grade was present in 41.0 percent, signet-ring cell tumors were found in 11.1 percent, and infiltrating tumor leading edges were present in 69.0 percent of young patients. Among young patients with stage II disease, vascular invasion was a significant negative prognostic variable (p < 0.05). CONCLUSIONS: We have demonstrated an increased incidence of three biological indicators of aggressive and potentially metastatic tumor biology in 186 young patients with carcinoma of the colon and rectum: signet-ring cell carcinoma, infiltrating tumor edges, and aggressive histologic grade in the primary adenocarcinoma. The increased incidence of these three histologic measures of more aggressive carcinoma of the colon and rectum in part accounts for the higher rate of advanced disease at presentation in patients younger than 40.

The prognostic implications of location for scalp melanoma.

The clinical and pathologic records of 95 patients with primary cutaneous melanoma isolated to the scalp and regional lymph nodes treated at the MD Anderson Cancer Center between 1976 and 1985 were reviewed to assess the effect of lesion location on the prognosis of scalp melanoma. The scalp was defined as an area bounded by the supraorbital ridges, superior nuchal line, zygoma, and mastoid, thereby including a large non-hair-bearing area. Patients were grouped according to lesion location: hair-bearing or non-hair-bearing; anterior or posterior to the mid-tragal line; and parietal versus frontal, temporal, or occipital. There was a similar distribution of prognostic factors between the anatomic subsites. Analysis by univariate and multivariate methods demonstrated that, in a hair-bearing area, in an area posterior to the mid-tragal line, or in the parietal region, lesion location was highly predictive of the patient's survival. For example, the 5-year, melanoma-specific survival rate was 65% overall, 86% for patients with lesions located in non-hair-bearing regions and 47% for those with lesions in hair-bearing regions (p = 0.0019).

Typical and atypical bronchopulmonary carcinoids. A clinicopathologic and flow cytometric study.

The clinicopathologic and flow cytometric characteristics of 47 bronchopulmonary carcinoids were assessed, relative to patient survival. Aneuploidy was associated more often with tumor size of greater than or equal to 3.0 cm (P less than 0.004) and lymph node (P less than 0.013) or vascular involvement (P less than 0.004). Also, an aneuploid DNA content was seen significantly more often in histologically atypical (79%) than in typical carcinoid neoplasms (18%) (P less than 0.0001). Cox proportional hazard model analysis revealed that the histologic category (typical vs. atypical) and ploidy pattern were important prognostic indicators. Size of the primary tumor and the presence of vascular involvement were also significant predictors of outcome. Histologically atypical carcinoids with diploid DNA content pursued a less aggressive course than did their aneuploid counterparts.

The prognosis of Hodgkin's disease in older adults.

This investigation was undertaken to assess the apparent poor survival of older patients with Hodgkin's disease. The clinical course of Hodgkin's disease in 136 patients, 60 to 79 years of age, was compared with that of 223 patients, 40 to 59 years of age. The patients registered from November 1977 through December 1983 had not been previously treated, and were treated at eight cancer centers. When the prognosis of all patients was examined by age, a definite change in the pattern of survival first appeared in the 60- to 69-year-old cohort. The entire older group (60 to 79 years) experienced twice the risk of dying from Hodgkin's disease and four times the risk of dying from other causes than did the younger group. In both groups, stage of disease was the strongest factor in predicting adjusted survival. Delay in treatment and advanced stage at presentation were not characteristic of Hodgkin's disease in older patients as has been postulated. Older patients responded to therapy with a similar complete remission rate (84% v 88% in the younger group, P = .24). From this study, we conclude that (1) Hodgkin's disease in the older adult does not have a different natural history, its major risk factors are similar to those known in other age groups, and thus should be amenable to existing therapeutic approaches; and (2) the prognosis of older patients with Hodgkin's disease has been obscured in previous studies by the inclusion of deaths due to other causes in survival estimates.

Ectopic expression of mucins in colorectal cancer metastasis.

Cancer metastasis is an ectopic growth of malignant cells. In human colorectal cancer, it is hypothesized that, during the progression of the disease to an advanced stage, highly malignant and metastatic tumor cells arise within primary tumors and become predominant. Based on this hypothesis, molecules associated with metastatic cells have been sought by the comparison of surgical specimens from patients at various clinical stages. Colorectal carcinomas with increased metastatic potential and with poor prognosis have been characterized by a loss of an organ-specific mucin determinant (sulfomucin), by an increased expression of non-intestinal sialomucins, and by an ectopic expression of adhesion ligands (sialyl-dimeric Lex antigens) on mucins.

Renal cell carcinoma. A clinicopathologic and DNA flow cytometric analysis of 103 cases.

Renal cell carcinoma is unpredictable in outcome, although the best predictor is tumor stage, followed by histologic grade. The authors retrospectively assessed the clinicopathologic features and DNA ploidy of 103 cases of renal cell carcinoma, the latter determined by flow cytometry of formalin-fixed, paraffin-embedded tissue. The study group comprised 63 men and 40 women (age, 28-80 years; mean, 57 years). Robson stage at diagnosis was Stage I in 52 patients, Stage II in 21, and Stage III in 30. Statistically significant variables in predicting outcome were Robson stage (P less than 0.0001), DNA ploidy (P = 0.0008), mitotic rate (MR, P less than 0.0001), worst nuclear grade (WNG, P = 0.00009), predominant nuclear grade (P = 0.019), and sex (P = 0.044). Tumor size, cell type, and architectural pattern were also assessed but did not prove to be significant. Statistically significant associations occurred between DNA ploidy and WNG (P less than 0.0001), stage (P = 0.0037), and MR (P = 0.015); between WNG and MR (P less than 0.0001) and stage (P = 0.0007); and between stage and MR (P = 0.002). Cox proportional hazards regression analysis of all significant variables showed Robson stage, tumor ploidy, and MR to be independent, significant predictors of outcome. If ploidy data had not been available, WNG would have been independently significant. The authors conclude that DNA ploidy analysis provides significant predictive information on renal cell carcinoma.

Role of nuclear grading in stage I renal cell carcinoma.

Through a retrospective histologic analysis of 55 cases of Stage I renal cell carcinoma, we evaluated the usefulness of the nuclear grading system (Fuhrman, Lasky, Limas) in identifying those tumors that will eventually metastasize and kill the patient. The difference in five-year survival rates between patients with combined nuclear grade 1-3 tumors (n = 50, 91%) and grade 4 tumors (n = 5, 9%) was significant (P less than 0.0046). Other predictors of death due to renal cell carcinoma included: tumor size greater than 8 cm (P less than 0.001) and mitoses greater than one per 10 high-power field (P less than 0.01). Within Stage I tumors, therefore, nuclear grade is an important morphologic variable for predicting long-term survival. Identification of nuclear grade 4 neoplasms may become prognostically indispensable to determine the metastatic potential of early-stage tumors and thereby to institute appropriate systemic therapy.

DNA flow cytometry as a predictor of outcome of stage I renal cell carcinoma.

The features most frequently used in predicting the outcome of renal cell carcinoma are stage at presentation and nuclear grade. Recently DNA ploidy pattern, as detected by DNA flow cytometry has also been shown to be predictive. In this study DNA flow cytometry was performed on formalin-fixed paraffin-embedded tissue from 50 patients with Stage I renal cell carcinoma for whom long-term follow-up data were available. Two were eliminated for technical reasons. Of the 48 evaluable tumors, 25 (52%) were diploid, 19 (40%) were nondiploid, and in four, (8%) the ploidy was uncertain. The ploidy pattern was statistically significantly associated with nuclear grade (P less than 0.02), and primary tumor size (P less than 0.05) but did not correlate with cell type, microscopic growth pattern, or the presence or absence of mitotic activity. In the group as a whole, ten patients (21%) died of renal cell carcinoma, seven of 19 (37%) with nondiploid tumor patterns, and two of 25 (8%) with a diploid pattern (P less than 0.03). One of four patients (25%) with tumors of uncertain ploidy also died. However, only two factors, nuclear grade and primary tumor size, were independent predictors of outcome. For Stage I renal cell carcinoma, ploidy can significantly predict patient outcome and correlates with nuclear grade and tumor size, but is not an independent predictive variable.

Effect of donation time on platelet concentrates and fresh-frozen plasma. An in vitro study.

To investigate the effect of donation time on the quality of blood components, we measured the platelet count and pH on platelet concentrates, and the factor V and VIII:C levels and fibrinopeptide A concentration on fresh-frozen plasma by duration of donation time. Platelet concentrates and fresh-frozen plasma were classified into three groups according to donation time: group 1, less than 10 min; group 2, 10-15 min, and group 3, longer than 15 min. Mean platelet counts of platelet concentrate were: group 1, 8.6 +/- 2.5 (in x 10(10], group 2, 8.1 +/- 2.6, and group 3, 6.5 +/- 3.2 (p less than 0.05). The same pH was maintained in all three groups. The fibrinopeptide A concentrations in groups 1 and 2 were 24 +/- 53 and 169 +/- 64 ng/ml, respectively, while in group 3 all were greater than 200 ng/ml, indicating correlation of a higher fibrinopeptide A level with longer donation time. Although a higher fibrinopeptide A level indicated a greater degree of thrombin generation, assays of factors V and VII:C did not show decreased activity in groups 2 and 3.

Prognosis in node-negative breast cancer.

In a selected group of 207 breast cancer patients with tumor-free axillary nodes, clinical and pathological features were evaluated as to their relationship to long-term disease-free survival. No clinical feature was found to be prognostically useful. Of pathologic features studied, four appear to have significance. These are the volume of the primary mass, the histologic or nuclear grade, the presence of invasive lobular carcinoma in the primary mass, and possibly the presence of neoplastic cells in intramammary lymphatic vessels. When two or more of these four features are present, prognosis is less favorable than when there is only one, but the influences are not arithmetically additive.

The incidence of herpes zoster in patients with Hodgkin's disease. An analysis of prognostic factors.

The incidence of zoster in 717 patients with Hodgkin's disease was determined by a retrospective chart review. All patients had been treated and followed in one of six cancer centers. Prognostic factors that might predict the subsequent incidence of zoster were examined by univariate and multivariate analytic techniques. Intensity of treatment was a key factor in the incidence of zoster. Thirty-six months after initiation of treatment, patients receiving chemotherapy-radiation-chemotherapy had twice the attack rate (27.3%) of those receiving radiation alone (11.5%). The pediatric age group had a significantly higher attack rate (26.6%) than did adults (18.7%). Stage, histology, and laparotomy did not influence the incidence of zoster.

Epidermoid cancer of the anorectum.

The optimal treatment for squamous and cloacogenic tumors of the anorectum is controversial. Radical surgery, limited surgery, and radiotherapy (XRT) are all potentially curative. This study was undertaken to determine which patients are candidates for each type of treatment and which would benefit from combined treatment. The records of 192 patients treated at this institution between 1954 and 1979 with the diagnosis of squamous or cloacogenic carcinoma of the anorectum were retrospectively reviewed. A subgroup of 132 patients undergoing abdominal perineal resection (APR) was analyzed to determine prognostic factors for these tumors. No survival difference was observed between the two histologic types (P = 0.51). Prognostic variables significant at P = 0.05 or better were sex, size, nodal status, and level of invasion. A new staging system is proposed that utilizes tumor size, invasion, grade, and nodal status. Actuarial 10-year survival was 100%, 76%, 29%, and 0% for Stages A, B, C and D, respectively (P values 0.22, 0.0007, and 0.01, respectively). Twelve patients undergoing APR received postoperative XRT; when compared by stage with APR alone no survival difference can be shown, although there is a trend towards fewer local recurrences. Of 26 patients (14 Stage B, 12 Stage C) receiving preoperative XRT (average 4000 R) before APR, 10 had inoperable tumors prior to XRT. All became operable. Eight patients had negative surgical margins and survival was equivalent stage for stage to the operable group (Stage B 78%, 5-year survival; Stage C 43%, 5-year survival). Eleven patients had no demonstrable primary tumor after XRT, although three had nodal metastasis. Five-year survival was 83% for this group. Thirty-one local recurrences were retreated for cure by surgery, XRT, or combination. Actuarial 5-year survival after retreatment was 38%. Thirty metachronous inguinal metastases were seen, 20 were retreated for cure, 18 by inguinal lymphadenectomy. Actuarial 5-year survival was 42%. Using a new staging system based on analysis of prognostic parameters for this disease, the outcome of combined surgery and XRT is compared. The efficacy of preoperative XRT for inoperable tumors is demonstrated. An appreciable salvage rate for local or inguinal recurrence was observed.

Palliative total gastrectomy and esophagogastrectomy. A reevaluation.

In the interval from 1941-1981 when 1887 patients with gastric cancer were seen at The University of Texas System Cancer Center M.D. Anderson Hospital and Tumor Institute, 151 curative and 45 palliative total gastrectomies or esophagogastrectomies were performed. Over the same interval, 21 patients with extent of primary and metastatic tumor roughly comparable to that seen in the palliative resection group were treated by exploration only or, infrequently, by attempted bypass. In individual patients subtle differences in extent of disease as well as differences in philosophy of the operating surgeon regarding the value of palliative resection undoubtedly contributed to the procedure selected. Survival after curative resection was greater than after palliative resection which in turn was greater than survival after exploration bypass (P less than or equal to .0006). Operative mortality fell significantly in CR patients in the interval 1970-1981 compared to 1941-1969 and was significantly lower than in the PR group in the interval 1970-1981 (P less than or equal to 0.01). Five-year survival increased significantly (P less than or equal to 0.03) in the CR group when results in the two time intervals were compared but not in other groups.