Surgical treatment of adenocarcinoma of the rectum

OBJECTIVE: The authors' aim was to determine survival and recurrence rates in patients undergoing resection of rectal cancer achieved by abdominoperineal resection (APR), coloanal anastomosis (CAA), and anterior resection (AR) without adjuvant therapy. SUMMARY BACKGROUND DATA: The surgery of rectal cancer is controversial; so, too, is its adjuvant management. Questions such as preoperative versus postoperative radiation versus no radiation are key. An approach in which the entire mesorectum is excised has been proposed as yielding low recurrence rates. METHODS: Of 1423 patients with resected rectal cancers, 491 patients were excluded, leaving 932 with a primary adenocarcinoma of the rectum treated at Mayo. Eighty-six percent were resected for cure. Surgery plus adjuvant treatment was performed in 418, surgery alone in 514. These 514 patients are the subject of this review. Among the 514 patients who underwent surgery alone, APR was performed in 169, CAA in 19, AR in 272, and other procedures in 54. Eighty-seven percent of patients were operated on with curative intent. The mean follow-up was 5.6 years; follow-up was complete in 92%. APR and CAA were performed excising the envelope of rectal mesentery posteriorly and the supporting tissues laterally from the sacral promontory to the pelvic floor. AR was performed using an appropriately wide rectal mesentery resection technique if the tumor was high; if the tumor was in the middle or low rectum, all mesentery was resected. The mean distal margin achieved by AR was 3 +/- 2 cm. RESULTS: Mortality was 2% (12 of 514). Anastomotic leaks after AR occurred in 5% (16 of 291) and overall transient urinary retention in 15%. Eleven percent of patients had a wound infection (abdominal and perineal wound, 30-day, purulence, or cellulitis). The local recurrence and 5-year disease-free survival rates were 7% and 78%, respectively, after AR; 6% and 83%, respectively, after CAA; and 4% and 80%, respectively, after APR. Patients with stage III disease, had a 60% disease-free survival rate. CONCLUSIONS: Complete resection of the envelope of supporting tissues about the rectum during APR, CAA, and AR when tumors were low in the rectum is associated with low mortality, low morbidity, low local recurrence, and good 5-year survival rates. Appropriate "tumor-specific" mesorectal excision during AR when the tumor is high in the rectum is likewise consistent with a low rate of local recurrence and good long-term survival. However, the overall failure rate of 40% in stage III disease (which is independent of surgical technique) means that surgical approaches alone are not sufficient to achieve better long-term survival rates.     

Blood-flow sensing by anionic biopolymers

The purpose of this study was to compare local recurrence, distant metastases, and survival rate in 350 patients with cancer of the middle and low rectum who underwent a radical abdominoperineal resection (APER) or a sphincter-saving resection (SSR) in our Institute. There were 257 APER patients and 93 SSR patients, with a median follow-up of 77 months. At 5 years, the estimates in APER and SSR patients were respectively 11% and 30% for the incidence of pelvic recurrence, 18% and 8% for the incidence of distant metastases, and 64% and 73% for overall survival. In the multivariate analysis it was found that Dukes' stage significantly affected pelvic recurrences, distant metastases rate and overall survival; histologic type affected only the pelvic recurrence rate. However, the final outcome of patients following APER or SSR was similar, suggesting that local failure per se does not affect long-term survival.     

Pancreatic duct antibodies and subclinical insufficiency of the exocrine pancreas in Sj?gren''s syndrome]

AIM: To investigate prognostic factors and complications after radical hysterectomy followed by postoperative radiotherapy for carcinoma of the uterine cervix. PATIENTS AND METHODS: One hundred twenty-eight patients with T1b-2b carcinoma of the uterine cervix following radical hysterectomy with bilateral pelvic lymphadenectomy and postoperative radiation therapy were reviewed. Pathologic and treatment variables were assessed by multivariate analysis for local recurrence, distant metastases and cause specific survival. RESULTS: The number of positive nodes (PN) in the pelvis was the strongest predictor of pelvic recurrence and distant metastases. These 2 failure patterns independently affect the cause specific survival. The 5-year cumulative local and distant failure were PN(0): 2% and 12%, PN(1-2): 23% and 25%, PN(2 <): 32% and 57%, respectively (p = 0.0029 and p = 0.0051). The 5-year cause specific survival rates were PN(0): 90%, PN(1-2): 59% and PN(2 <): 42% (p = 0.0001). The most common complication was lymphedema of the foot experienced by one-half of the patients (5-year: 42%, 10-year: 49%). CONCLUSION: These results suggest that patients with pathologic T1b-T2b cervix cancer with pelvic lymph node metastases are at high risk of recurrence or metastases after radical hysterectomy with pelvic lymphadenectomy and postoperative irradiation.     

Viruses and atherosclerosis: do they play a pathogenic role?

PURPOSE: To evaluate the results of interstitial radiotherapy of anorectal tumors. PATIENTS AND METHODS: From 1972 to 1993, one of the authors treated 45 patients by an interstitial implant for anorectal tumors. Of these, 33 patients suffered from primary tumors, 19 from squamous carcinoma, 2 from basaloid carcinoma of the anus and the other 12 from primary adenocarcinoma of the rectum. Of 12 patients treated for local recurrence, 10 had adenocarcinoma and 2 squamous cell carcinoma. Of the 33 patients with primary tumors, 27 received a course of external-beam radiotherapy before the implant. The median follow-up was 35 months. RESULTS: Local response depended on the tumor volume treated. All 21 anal tumors showed complete response, 5 patients developed local recurrence and 4 distant metastases: 3 died from their disease. Of 12 rectal adenocarcinomas, 9 responded completely, 4 patients developed local recurrence and 4 distant metastases; 6 died from active disease. In the last group of 12 patients who were treated for recurrent tumors, 7 responded completely. One patient developed local recurrence and 9 distant metastases, only 4 are alive. CONCLUSIONS: A combination of external-beam and interstitial radiotherapy is a relatively simple, non-mutilating, but well-tolerated and very effective method of treatment for early carcinoma of the lower rectum and anus.     

Adenocarcinoma in the middle third of the stomach--an evaluation for the prognostic significance of clinicopathological features

BACKGROUND/AIMS: The prognosis of patients with gastric adenocarcinoma varies with the location of the tumor. Adenocarcinoma in the middle third of the stomach has been claimed to have a better outcome than those in other locations. However, there is still very limited information specifically regarding the prognostic factors which influence the survival time of patients with adenocarcinoma in the middle third of the stomach. This retrospective study was designed with the aim to evaluate and uncover the possible significant clinicopathological parameters for adenocarcinoma in the middle third of the stomach. METHODOLOGY: Between 1986 and 1992, 363 patients underwent gastric resection for primary gastric adenocarcinoma at this hospital. Fifty-two (14.3%) of these patients were included in this study and they all met the following criteria: 1) tumor primarily located in the middle third of the stomach without distant metastases or peritoneal seeding, 2) undergoing curative resection and 3) undergoing R2 nodal dissection, at least. The clinicopathological findings were obtained by detailed review of the medical records and the histologic slides. All surviving patients were also contacted and their current conditions were recorded. RESULTS: The overall 5-year survival rate (Kaplan-Meier method) was 42.5%. In univariate survival analysis by Kaplan-Meier method and long-rank test, serosal invasion (p < 0.01), lymph node metastasis (p < 0.01) and lymphatic involvement (p < 0.01) had an individual prognostic significance. When a multivariate analysis using Cox proportional hazards regression was performed, serosal invasion (P < 0.01) and lymphatic involvement (p < 0.05) appeared as the only two independent prognostic factors regarding long-term survival. When these 52 patients were categorized into patients with early gastric cancer (n = 10) and patients with advanced gastric cancer (n = 42), there was a significant difference (p < 0.01) between the survival rates (90.0% vs. 29.1%). When these tumors were further categorized into early gastric cancer (n = 10), early simulating advanced gastric cancer (n = 14) and Borrmann type advanced gastric cancer (n = 28), there were significant differences (P < 0.01 and P < 0.01, respectively) in 5-year overall survival rates between early gastric cancer (90.0%) and Borrmann type advanced gastric cancer (18.9%), also between early simulating advanced gastric cancer (52.5%) and Borrmann type advanced gastric cancer (18.9%). UICC stage also had significant influence (P < 0.01) on the survival rates. CONCLUSIONS: Serosal invasion and lymphatic involvement are the significant, independent prognostic factors in predicting the survival rate of patients with adenocarcinoma in the middle third of the stomach. Since more advanced stage tumors usually carry a poorer prognosis, early detection is of extreme importance for improving the survival rate.     

Circumferential margin involvement after mesorectal excision of rectal cancer with curative intent. Predictor of survival but not local recurrence?

PURPOSE: This study examines the prognostic significance of circumferential margin involvement by tumor in resected specimens after potentially curative rectal cancer surgery. METHODS: During an eight-year period, all patients with rectal cancer were prospectively audited. For tumors of the middle and lower thirds of the rectum, a total mesorectal excision was performed; for tumor of the upper third, mesorectal excision proceeded at least 5 cm distal to the primary tumor. Resected specimens were subjected to careful histologic assessment, and patients undergoing curative procedures were entered into a surveillance program to detect both local and distant recurrence. RESULTS: Of 218 patients in the cohort, 9 had no resection, 14 underwent local excision, 1 had pre-operative radiotherapy, and 42 patients (20 percent) had palliative resections and were excluded from further analysis. This left 152 patients having a curative resection, of whom 20 (13 percent) had tumor within 1 mm of the circumferential margin. After follow-up until death or a median period of 41 months, recurrent disease was seen in 24 percent of patients with a negative margin and 50 percent with a positive margin. Both disease-free survival and mortality were significantly related to margin involvement (log-rank, P = 0.01 and P = 0.005, respectively). Local recurrence, however, was not significantly different in the two groups (11 and 15 percent, respectively; log-rank, P = 0.38). CONCLUSIONS: When mesorectal excision is performed, circumferential margin involvement is more an indicator of advance disease than inadequate local surgery. Patients with an involved margin may die from distant disease before local recurrence becomes apparent.     

Progression in and survival of patients with locally advanced prostate cancer (T3) treated with radical prostatectomy as monotherapy

PURPOSE: We determine the progression and survival rates in patients with locally advanced prostate cancer treated with radical prostatectomy without adjuvant treatment, and investigate subgroups of patients who may not benefit from this treatment. MATERIALS AND METHODS: Radical prostatectomy was performed in 83 patients with T3 prostate cancer. The patients were divided in subgroups with T3G1 to 2 and T3G3 tumors, which were evaluated for clinical progression, local recurrence, distant metastases, biochemical progression, and overall and cancer specific survival at 5 and 10 years by Kaplan-Meier curves. The results were compared to those of 190 patients with locally confined tumors. RESULTS: At 5 and 10 years overall survival was 75 and 60%, and cancer specific survival was 85 and 72%, respectively. At 5 and 10 years clinical progression was 41 and 69%, local recurrence 18 and 44%, and distant metastases 31 and 50%, respectively. Biochemical progression at 5 years was 71%. Patients with poorly differentiated tumors showed significantly lower survival and higher progression rates compared to those with well or moderately differentiated tumors. Progression and survival in patients with T3G1-2 tumor were not significantly different from those for patients with locally confined tumors. CONCLUSIONS: Radical prostatectomy as monotherapy in patients with locally advanced nonmetastatic prostate cancer (T3) produces acceptable results in those with well or moderately differentiated tumors. The results of progression and survival are not significantly different from those in patients with locally confined prostate cancer. However, patients with poorly differentiated tumors (T3G3) have early progression and need adjuvant treatment following surgery.     

A review of the principles of pulse oximetry and accuracy of pulse oximeter estimates during exercise

OBJECTIVE: The outcomes of patients with squamous cell carcinoma of the anal canal treated by either sphincter-preserving procedures or radical surgery were evaluated, with the goals of identifying factors predicting treatment failure and quantifying results of salvage therapy in patients with recurrent disease. BASIC PROCEDURES: A population-based study on all patients in all 159 hospitals of the Department of Veterans Affairs (VA) from 1987 to 1991 was carried out. Data were compiled from several national computerized VA data sets. Supplementary information from local tumor registrars also was obtained, including demographic information, discharge summaries, operative reports, pathology reports, and medical oncology and radiation oncology summaries. From these sources, information on tumor histology, tumor stage, tumor grade, presence of regional or distant metastases, surgical procedures, use of chemotherapy and radiation therapy (RT), toxicity of chemotherapy and RT, development of recurrent disease, treatment of recurrence, survival, and cause of death were obtained. MAIN FINDINGS: Four hundred five patients with anal cancer were identified by computer search, and 204 (51%) were evaluable; 164 of 204 (80%) had squamous cell carcinoma, 137 of whom (84%) were treated with sphincter-preserving procedures, and 27 of whom (16%) were treated by by radical surgery. One hundred fourteen of 138 (83%) were treated by multimodality therapy, which we defined as local excision followed by chemotherapy and RT. The mean dose of RT among patients treated by multimodality therapy was 4200 +/- 540 cGy and 82% of those treated with multimodality therapy received 5-FU/mitomycin C. Recurrent disease was diagnosed in 43 of all 149 patients (29%) with potentially curable disease. (stages I-III) Multivariate analysis revealed that stage at diagnosis (p = 0.04) and method of treatment (p = 0.03) were the sole predictors of recurrence. Fifty-three percent of patients who underwent salvage abdominoperineal resection (APR) are alive, whereas only 19% who underwent salvage chemotherapy with or without RT are alive. PRINCIPAL CONCLUSIONS: These data indicate that multimodality therapy currently is being employed in the majority of patients with squamous cell carcinoma of the anal canal in the VA system. Tumor stage and method of treatment appear to affect the likelihood of development of recurrent disease. Salvage APR has curative potential. Results with salvage chemotherapy and RT are disappointing.     

Local recurrences and distant metastases after breast-conserving surgery and radiation therapy for early breast cancer

PURPOSE: To identify predicting factors for local failure and increased risk of distant metastases by statistical analysis of the data after breast-conserving treatment for early breast cancer. METHODS AND MATERIALS: Between January 1976 and December 1993, 528 patients with nonmetastatic T1 (tumors < or = 1 cm [n = 197], >1 cm [n = 220]) or T2 (tumors < or = 3 cm [n = 111]) carcinoma of the breast underwent wide excision (n = 435) or quadrantectomy (n = 93) with axillary dissection (negative nodal status [n-]: 396; 1-3 involved nodes: 100; >3 involved nodes: 32). Radiotherapy consisted of 45 Gy to the entire breast via tangential fields. Patients with positive axillary lymph nodes received 45 Gy to the axillary and supraclavicular area. Patients with positive axillary nodes and/or inner or central tumor locations received 50 Gy to the internal mammary lymph node area. A boost dose was delivered to the primary site by iridium 192 Implant in 298 patients (mean total dose: 15.2+/-0.07 Gy, range: 15-25 Gy) or by electrons in 225 patients (mean total dose: 14.8+/-0.09 Gy, range: 5-20 Gy). The mean age was 52.5+/-0.5 years (range: 26-86 years) and 267 patient were postmenopausal. Histologic types were as follows: 463 infiltrating ductal carcinomas, 39 infiltrating lobular carcinomas, and 26 other histotypes. Grade distribution according to the Scarff, Bloom, and Richardson (SBR) classification was as follows: 149 grade 1, 271 grade 2, 73 grade 3, and 35 nonclassified. The mean tumor size was 1.6+/-0.3 cm (range: 0.3-3 cm). The intraductal component of the primary tumor was extensive (EIC = IC > or = 25%) in 39 patients. Tumors were microscopically bifocal in 33 cases. Margins were assessed in the majority of cases by inking of the resection margins and were classified as positive in 13 cases, close (< or = 2 mm) in 21, negative (>2 mm tumor-free margin) in 417, and indeterminate in 77. Peritumoral vascular invasion was observed in 40 patients. Tamoxifen was administered for at least 2 years in 176 patients. At least six cycles of adjuvant systemic chemotherapy were administered in 116 patients. The mean follow-up period from the beginning of the treatment was 84.5+/-1.7 months. RESULTS: First events included 44 isolated local recurrences, 8 isolated axillary node recurrences, 44 isolated distant metastases, 1 local recurrence with synchronous axillary node recurrence, 7 local recurrences with synchronous metastases, and 2 local recurrences with synchronous axillary node recurrences and distant metastases. Of 39 pathologically evaluable local recurrences, 33 were classified as true local recurrences and 6 as ipsilateral new primary carcinomas. Seventy patients died (47 of breast carcinoma, 4 of other neoplastic diseases, 10 of other diseases and 9 of unknown causes). The 5- and 10-year rates were, respectively: specific survival 93% and 86%, disease-free survival 85% and 75%, distant metastasis 8.5% and 14%, and local recurrence 7% and 14%. Mean intervals from the beginning of treatment for local recurrence or distant metastases were, respectively, 60+/-6 months (median: 47 months, range: 6-217 months) and 49.5+/-5.4 months (median: 33 months, range: 6-217 months). After local recurrence, salvage mastectomy was performed in 46 patients (85%) and systemic hormonal therapy and/or chemotherapy was administered to 43 patients. The 5-year specific survival rate after treatment for local recurrence was 78+/-8.2%. Multivariate analysis (multivariate generalization of the proportional hazards model) showed that the probability of local control was decreased by the following four independent factors: young age (< or = 40 yr vs. >40 yr; relative risk [RR]: 3.15, 95% confidence interval [CI]: 1.7-5.8, p = 0.0002), premenopausal status (pre vs. post; RR: 2.9, 95% CI: 1.4-6, p = 0.0048), bifocality (uni- vs. bifocal; RR: 2.7, 95% CI: 2.6-2.8,p = 0.018), and extensive intraductal component (IC <25% vs. IC > or = 25%; RR: 2.6, 95% CI: 13-5.2, p = 0     

Pharmacokinetics of oral glyburide in subjects with non-insulin-dependent diabetes mellitus and renal failure

There is considerable controversy about the distal clearance margin that needs to be maintained beyond the extent of a rectal tumor in order to reduce the risk of local recurrence. We investigated the rate of local recurrence, distant metastases and survival in 87 patients who had undergone radical restorative resection of the rectum for cancer and had been followed up for a median period of over 6 years, and we analyzed the statistical relation (log-rank test for trend) with the length of the distal margin. The distal margin length was divided into three categories: 1 cm, 2 cm, and > or = 3 cm. No significant correlation was found between the length of the distal clearance margin and the oncologic outcome. Taken together, our data suggest that if the resection line distally falls on healthy tissue, there is no need to resect additional rectum in order to achieve a better outcome.     

Operative risk and prognostic factors of typical bronchial carcinoid tumors

BACKGROUND: This study estimated operative risk and examined factors determining long-term survival after resection of typical carcinoid tumors. METHODS: From 1976 to 1996, 139 consecutive patients (66 male and 73 female patients with a mean age of 47 +/- 15 years) underwent thoracotomy for typical carcinoid tumor. The tumors were centrally located in 102 patients (73.4%). RESULTS: Radical resection was performed in 106 patients (7 pneumonectomies, 13 bilobectomies, and 86 lobectomies) and conservative resection in 33 (3 segmentectomies, 3 wedge resections, 20 sleeve lobectomies, and 7 sleeve bronchectomies). There were no postoperative deaths. Complications occurred in 19 patients (13.7%). The morbidity rate was not increased after bronchoplastic procedures (chi 2 = 0.033, not significant). Staging was pT1 in 107 patients (77.0%) and pT2 in 32 (23.0%); 13 patients (9.4%) had nodal metastases. Seventeen patients have died (12.2%), during follow-up, but only three deaths were related to the disease. The overall survival rate at 5, 10, and 15 years was estimated to be 92.4%, 88.3%, and 76.4%, respectively; estimated disease-free survival was 100% at 5 years and 91.4% at 10 and 15 years. Estimated survival of patients with lymph node metastasis was 100% at 5, 10, and 15 years. Univariate analysis failed to demonstrate any prognostic significance for sex, tumor size (T1 versus T2), tumor location (central versus peripheral), and type of resection. CONCLUSIONS: These data confirm an excellent prognosis after complete resection of typical carcinoid tumors, including those with lymph node metastases. Parenchyma-saving resections should be preferred.     

p53 nuclear protein overexpression in colorectal cancer: a dominant predictor of survival in patients with advanced hepatic metastases

PURPOSE: To determine whether p53 protein expression is similar within primary colorectal cancer (CRC) and synchronous regional and distant metastases and to assess whether p53 nuclear protein expression could predict outcome in patients with synchronous unresectable liver metastases treated by hepatic artery infusional (HAI) chemotherapy. MATERIALS AND METHODS: Paraffin sections from tumor and corresponding normal mucosa representative of 50 consecutive advanced CRC cases were examined for p53 nuclear protein expression by immunohistochemistry using the monoclonal antibody PAb 1801. Patterns of p53 nuclear expression were correlated with standard clinicopathologic variables and outcome, including response to HAI and survival. In a subset analysis, the pattern of nuclear p53 immunoreactivity was compared between primary CRC and lymph node and liver metastases. RESULTS: Positive nuclear immunoreactivity for p53 protein was found in 72% of cases. The pattern of p53 protein expression in lymph node and liver metastases was identical to that of the primary tumor. The median survival time was 21.0 months in patients with p53-positive tumors and 53.2 months in patients with p53-negative tumors (Wilcoxon test P = .038). Two-year survival rates were 41.7% and 78.6%, respectively (P < .01). No significant difference was found in the response rates to HAI chemotherapy between the two groups. By multivariate analysis, p53 protein status was the single best predictor of survival, with a relative risk of 6.312. CONCLUSION: Our results indicate that nuclear p53 protein status in primary CRC is similar to that in metastatic sites and may be the dominant predictor of survival in patients with advanced hepatic metastases.     

Resection of metastatic renal cell carcinoma

PURPOSE: Resection of solitary metastases from renal cell carcinoma (RCC) is associated with a 5-year survival rate of 35% to 50%. Selection criteria are not well defined. PATIENTS AND METHODS: We retrospectively analyzed our experience with 278 patients with recurrent RCC from 1980 to 1993. RESULTS: One hundred forty-one of 278 patients underwent a curative metastectomy for their first recurrence (44% 5-year overall survival [OS] rate), 70 patients underwent noncurative surgery (14% 5-year OS rate), and 67 patients were treated nonsurgically (11% 5-year OS rate). Favorable features for survival were a disease-free interval (DFI) greater than 12 months versus 12 months or less (55% v 9% 5-year OS rate; P < .0001), solitary versus multiple sites of metastases (54% v 29% 5-year OS rate; P < .001), and age younger than 60 years (49% v 35% 5-year OS rate; P < .05). Among 94 patients with a solitary metastasis, lung (n = 50; 54% 5-year OS rate) was more favorable than brain (n = 11; 18% 5-year OS rate; P < .05). Survival rates after curative resection of second and third metastases were not different compared with initial metastectomy (46% and 44%, respectively, v 43% 5-year OS rates; P = nonsignificant). Favorable predictors of survival by multivariate analysis included a single site of first recurrence, curative resection of first metastasis, a long DFI, a solitary site of first metastasis, and a metachronous presentation with recurrence. CONCLUSION: Selected patients with recurrent RCC who can undergo a curative resection of their disease have a good opportunity for long-term survival, particularly those with a single site of recurrence and/or a long DFI.     

Laser therapy of villous rectocolonic tumors. Evaluation of results by multivariate analysis

One hundred and twenty-four patients (mean age: 70 years) with a villous tumour of the rectum (n = 98) or the colon (n = 26) were treated by laser therapy from 1985 to 1991. Initial complete eradication was obtained in 93.5% of cases with a median time of 16 months. Using multivariate analysis, the tumor size (> 4 cm) only was predictive of eradication (P < 0.001). At 6 and 12 months, the actuarial eradication rates were 91 and 98% for small tumours versus 45 and 74% for larger tumours respectively. The actuarial recurrence rates were 10.5, 23, and 37% at 6, 12 and 24 months, and no longer increased after 3 years. No predictive factor of recurrence was isolated by multivariate analysis. Seven complications (5.6%) and 4 malignant transformations (3.4%) occurred. This study confirms the efficiency and low morbidity of laser therapy, especially in patients with small tumors, less than 4 cm in size.     

Relationship of tumor angiogenesis and nuclear p53 accumulation in invasive bladder cancer

The purpose of this investigation was to evaluate the relationship between tumor angiogenesis and nuclear p53 accumulation in invasive bladder cancer. We studied 161 patients with invasive transitional cell carcinoma of the bladder who had previously undergone radical cystectomy. Analysis was performed to determine the presence of p53 nuclear accumulation and extent of tumor-associated angiogenesis. p53 status identified a group of patients at high risk for tumor progression (p53-altered tumors), and microvessel density determinations added additional prognostic information by identifying a subset of aggressive tumors within the wild-type p53 subgroup. At 5 years, patients with tumors exhibiting no evidence of p53 alterations and low microvessel counts demonstrated 3% recurrence and 88% survival, compared to 43% recurrence and 59% overall survival for patients with intermediate vessel counts and 61% recurrence and 43% overall survival for patients with the highest vessel counts (P < 0.001 and P = 0.003, respectively). Angiogenesis also provides additional prognostic information to patients with tumors that demonstrate p53 alterations. An association between angiogenesis and p53 status did exist (P = 0. 05); however, 27% of the tumors that showed no evidence of p53 alterations exhibited high microvessel counts, and 26% of tumors with evidence of p53 alterations had low microvessel counts. Tumor-associated angiogenesis adds additional useful prognostic information to that which is obtained from p53 status in patients with invasive transitional cell carcinoma of the bladder. Although an association between p53 status and the degree of angiogenesis was identified, other factors appear to play a role in the regulation of tumor-induced neovasularization.     

Results of resection of gastric cancer with distant metastases

BACKGROUND/AIMS: The present study was carried out in order to examine the outcome of resection in cases of gastric cancer with distant metastases. METHODOLOGY: The survival rates of two hundred and eighty-one patients who had undergone resection for primary carcinomas of the stomach, and who had distant metastases according to the TNM classification, were studied. RESULTS: The 5-year survival rates for patients with metastasis to the peritoneum or group 3 nodes were 8.9% and 15.3% respectively and were significantly higher than the survival rates for patients with metastasis to the liver (0%), to group 4 nodes (2.2%) or to more than one site among the liver, lymph nodes and peritoneum (3.5%). Moreover, the 5-year survival rates for patients with metastasis to the peritoneum and N3 nodes increased significantly to 29.4% and 24.2%, respectively, when curative surgery was performed. CONCLUSIONS: The findings of the present study suggests that metastases to the adjacent peritoneum or group 3 nodes have a greater chance of being cured using radical surgery, and that gastrectomy with extended lymphadenectomy (D2-D3) may be used for advanced gastric cancer if there is no gross evidence of metastasis to the distant peritoneum, liver or group 4 nodes.     

Clinical study of incidentally diagnosed renal adenocarcinoma

OBJECTIVES: To determine the incidence of incidentally detected renal cell carcinoma and compare primary tumor size, clinical stage (TNM) and survival versus renal cell carcinoma with clinical manifestations. PATIENTS AND METHODS: 140 patients diagnosed as having renal cell carcinoma from 1986 to 1994 were retrospectively studied. Of these, 121 had undergone surgery. The statistical analyses were done using the ANOVA test and the Yates-adjusted chi 2 test for a significance value of p < 0.05. RESULTS/CONCLUSIONS: Incidentally detected renal cell carcinoma accounted for 40.7% of the cases. No differences were observed between both groups for age (p = 0.5), sex (p = 0.6), compromised side (p = 0.9), lymph node invasion (p = 0.1), distant metastasis (p = 0.01), multiple unsuspected tumors (p = 0.4) or survival (p = 0.8). The incidentally detected tumors, however, were smaller (p = 0.0002) and more frequently localized to the kidney (p = 0.0003).     

Differential spatio-temporal expression of the insulin-like growth factor genes in regenerating sciatic nerve

BACKGROUND: Prognosis following locoregional recurrence of breast cancer after mastectomy often is described as fatal. However, certain subgroups with better prognosis are supposed. We analysed established prognostic factors for their influence on post recurrence survival in order to discriminate favourable from unfavourable subgroups. PATIENTS AND METHODS: Between 1979 and 1989 163 patients with a local or regional recurrence of breast cancer following mastectomy were treated at the Department of Radiation Oncology of the University of Würzburg. One hundred and forty had an isolated recurrence, without evidence of distant disease at the time of recurrence. Median follow up for patients alive at the time of analysis was 102 months from diagnosis of recurrence. Thirteen prognostic factors were tested. RESULTS: Out of the 140 patients 94 (58%) developed distant metastases within the follow-up period. Metastatic-free rate was 42% at 5 years and 38% at 10 years following recurrence. Recurrences occurred in 50% of patients within the first 2 years from primary surgery, in 83% within 5 years. In univariate analysis statistically significant influence on survival rates was found for pT, pN-status, lymphatic vessel invasion, blood vessel invasion, tumor necrosis, hormonal receptor status, presence or development of distant metastases, time to recurrence and site and extension of recurrence. Two- and 5-year survival rates ranged from 64% to 81% and from 40% to 60%, respectively in the favourable subgroups compared to a survival rate ranging from 15% to 44% at 2 years and 0% to 29% at 5 years in the unfavourable subgroups. In patients with involved axillary lymph nodes, the absolute number of nodes did not prove to have significant influence on overall survival. Histopathological grading did not reach statistical significance levels although an influence on survival was observed. Preceding adjuvant radiotherapy did not influence post-recurrence survival rates. Also preceding adjuvant systemic therapy showed no significant impact on survival. Multivariate analysis demonstrated that primary axillary status correlated most strongly with overall survival (p < 0.001) followed by tumor necrosis (p < 0.01). CONCLUSIONS: The mentioned prognostic factors may be useful in determining the adequate (local and systemic) therapy and the best time for it. Our data support previous findings, that certain subgroups with favourable prognostic features exist and they might still have a chance for cure by an adequate local treatment, whereas subgroups of patients with unfavourable prognostic factors have to receive systemic therapy immediately following local therapy because of the forthcoming systemic progression.     

Autologous hapten-modified melanoma vaccine as postsurgical adjuvant treatment after resection of nodal metastases

PURPOSE: To determine whether treatment with an autologous whole-cell vaccine modified with the hapten dinitrophenyl (DNP vaccine) is an effective postsurgical adjuvant treatment for melanoma patients with clinically evident nodal metastases. PATIENTS AND METHODS: Eligible patients had regional nodal metastases that were large enough (> or = 3 cm diameter) to prepare vaccine. Following standard lymphadenectomy, patients were treated with DNP vaccine on a monthly or weekly schedule. RESULTS: Of 62 patients with metastasis in a single lymph node bed (stage III), 36 are alive after a median follow-up time of 55 months (range, 29 to 76); the projected 5-year relapse-free and overall survival rates are 45% and 58%, respectively. Of 15 patients with metastases in two nodal sites, five are alive with a median follow-up time of 73 months. An unexpected finding was the significantly better survival of older patients; the projected 5-year survival of patients greater than 50 versus < or = 50 years was 71% and 47%, respectively (P = .011, log-rank test). The development of a positive delayed-type hypersensitivity (DTH) response to unmodified autologous melanoma cells was associated with significantly longer 5-year survival (71% v 49%; P = .031). Finally, the median survival time from date of first recurrence was significantly longer for patients whose subcutaneous recurrence exhibited an inflammatory response (> 19.4 v 5.9 months; P < .001). CONCLUSION: Postsurgical adjuvant therapy with autologous DNP-modified vaccine appears to produce survival rates that are markedly higher than have been reported with surgery alone. Moreover, this approach has some intriguing immunobiologic features that might provide insights into the human tumor-host relationship.     

Adjuvant radiation therapy in resectable rectal cancer: should local recurrence rates affect the decision?

Adjuvant external beam pelvic radiotherapy (XRT) for resectable rectal cancer has been mandated by the National Cancer Institute because of reported 20 to 50 per cent reductions in local recurrence rates. However, these series' reported local recurrence rates are 18 to 39 per cent in the nonradiated patients, which seems extraordinarily high compared to the 3 to 5 per cent rates reported by surgeons advocating proctectomy with complete mesorectal excision. This fact, coupled with the high cost of XRT ($11,000-$14,000), the risk of radiation injury to small bowel and the neo-rectum, and the failure of XRT to provide any survival advantage, raises questions as to the precise role of XRT for rectal cancer. The purpose of this study was to perform a review of 212 consecutive patients undergoing curative resection via low anterior resection (LAR) or abdominoperineal resection (APR) for rectal cancer between 1989 and 1993, focusing on local and distant recurrence rates and survival. The choice of surgery alone (SUR), preoperative radiation (PRE) (45 Gy), or postoperative radiation (POST) (45-50 Gy) was at the surgeon's discretion. There were no significant differences in male:female ratio (SUR, 83:60; PRE, 14:8; POST, 34:13) or type of procedure (SUR-LAR, 112:APR, 31; PRE-LAR, 5:APR, 17; POST-LAR, 30:APR, 17) between the groups. There were no significant differences in age between the preoperative and postoperative radiation groups (PRE, 64.0 +/- 2.4; POST, 59.2 +/- 1.7); however, age was significantly different (P < 0.05) between the surgery-alone and the postoperative radiation groups (SUR, 68.5 +/- 0.8; POST, 59.2 +/- 1.7). With a median follow-up of 49 months, there were no significant differences in local recurrence (SUR, 4.2%; PRE, 4.5%; POST, 2.1%); however, there was a significantly longer survival for the SUR group compared to the other groups (SUR, 45.9 months; PRE, 36.4 months; POST, 39.3 months; P < 0.05 least significant difference). The PRE group also had shorter survival compared to the other groups when only Stage II and III lesions were studied (S, 40.0 months; PRE, 28.3 months; POST, 39.3 months). Local recurrences based on TNM stage were: T1N0 (S, 0 of 27; PRE, 0 of 3); T2N0 (S, 4 of 4S; PRE, 0 of 7); T2N1 (S, 0 of 9; POST, 1 of 5); T3,4N0 (S, 2 of 37; PRE, 1 of 9; POST, 0 of 10); and T3,4N1,2 (S, 0 of 21; PRE, 0 of 3; POST, 0 of 30). The results of this series support the contention that proctectomy with complete mesorectal excision yields a 4.2 per cent local recurrence rate without the need for adjuvant XRT. In this series, if all the patients had received adjuvant radiation, an additional $2.2 million would have been added to the costs of medical care. Therefore, the potential risks, costs, and benefits of adjuvant pelvic XRT for rectal cancer must be weighed against optimal benchmarks for local recurrence rate for surgery alone.