The impact of pre- or postoperative radiochemotherapy on complication following anterior resection with en bloc excision of female genitalia for T4 rectal cancer.

OBJECTIVE: The aim of the study was to assess the mortality and morbidity following extended anterior resection with excision of internal female genitalia combined with pre- or postoperative chemoradiotherapy in women with extensive rectal cancer. METHOD: The study included a consecutive series of 21 women with T4 adenocarcinoma of the rectum infiltrating the reproductive organs treated with curative intent between 1997 and 2003. All patients had an extended anterior sphincter preserving resection of the rectum (total mesorectal excision) and hysterectomy with or without posterior vaginal wall excision. In all patients, surgery was combined with adjuvant radiochemotherapy. Ten patients received preoperative radiotherapy (50.4 Gy) concurrently with two courses of chemotherapy [fluorouracil with folinic acid (FA)] followed by surgery within 6-8 weeks and subsequently four courses of postoperative chemotherapy. Eleven received postoperative chemoradiotherapy (50.4 Gy plus fluorouracil with FA). RESULTS: There was no postoperative mortality. Postoperative complications were observed in 57% patients (early in 14% and late in 52%). These included: anterior resection syndrome with anorectal dysfunction in 52% (requiring proximal diversion in 5%), urinary complications in 24% (complete incontinence requiring a permanent catheter in 5%). In addition, postoperative acute bleeding requiring relaparotomy, delayed wound healing caused by superficial infection, anastomotic leakage, prolonged bowel paralysis, benign rectovaginal fistula and anastomotic stricture occurred (5% each). The risk of postoperative morbidity (52%) was similar for patients with or without preoperative radiochemotherapy. CONCLUSION: Despite this aggressive therapeutic approach, most postoperative complications were transient or could be treated. Preoperative radiochemotherapy did not increase the risk of morbidity.

Predictive value of lymphocytic infiltration and character of invasive margin following total mesorectal excision with sphincter preservation for the high-risk carcinoma of the rectum.

PURPOSE: To assess the prognostic significance of clinicopathological factors, especially histological parameters of new Jass classification, following sphincter-sparing total mesorectal excision (TME) for high-risk rectal cancer. MATERIAL AND METHODS: Forty-five consecutive patients treated with curative intent in 1998-1999 due to rectal cancer in Dukes stage B and C were studied prospectively. All of them underwent anterior resection with TME technique. Prognostic value was evaluated by the impact on five-year recurrence-free survival (RFS) in uni- and multivariate analysis. Only factors significant in univariate analysis entered the multivariate regression model. P value <0.05 was stated as a significance limit. RESULTS: Regarding traditional clinico-pathological factors patient age, tumor site, differentiation grade, mucinous histology and the extent of direct tumor penetration did not significantly affect survival rates. Only the lymph nodes status was associated with prognosis with statistical importance (negative vs positive, RFS: 53.8 +/- 10.0% vs 26.3 +/- 10.4%, respectively). Considering the additional parameters of Jass classification the character of invasive margin of the tumor did not reveal the important predictive value although the lymphocytic tumor infiltration was significantly related to patient outcome (presence vs absence, RFS: 63.6 +/- 15.2% vs 37.5 +/- 8.7%, respectively). In multivariate analysis the only one statistically important and independent predictive parameter was the lymph nodes status. CONCLUSIONS: Lymph nodes metastases remain the most important prognostic factor after anterior resection with TME for Dukes B and C rectal cancer. From variables included into Jass classification the absence of lymphocytic infiltration of the tumor can be helpful to identify patients with enhanced risk of oncological relapse.

Therapeutic results in low-rectal cancer patients treated with abdominosacral resection are similar to those obtained by means of anterior resection in mid- and upper-rectal cancer cases.

AIMS: To present the experiences of the Regional Comprehensive Cancer Center in Wroclaw with abdominosacral resection (ASR) carried out in low-rectal cancer patients. METHODS: Rectal cancer patients (n=294) were operated on by the same surgical team using the standardized TME technique between May 5, 1998 and February 23, 2001. Depending on the distance from the anal verge, the primary tumor was removed by means of standard abdominal resection (AR-mid- and upper-rectal cancers) or abdominosacral resection (ASR-low-rectal cancers). The patients who underwent the different operative procedures were comparable in terms of distributions of age, gender, tumor infiltration depth and regional lymph node involvement with no significant statistical difference between the groups. RESULTS: Ninety-seven cases were excluded from the analysis of survival based on exclusion criteria defined. Consequently, 197 cases were left for further analysis, including 154 patients operated on by AR and 43 who underwent ASR. AR and ASR patients did not differ significantly in terms of postoperative morbidity (11% and 14%, respectively), observed (57.1% vs. 60.4%) and relative 5-year survivals (74.3% vs. 73.2%) and the cumulative 5-year local recurrence rate (5.8% vs. 4.7%). CONCLUSION: The combined use of the modern TME technique and the "historical" abdominosacral excision of the rectum seems to give new, potentially attractive perspectives for successful surgical treatment of low-rectal cancers.

Multivariate analysis of oestrogen receptor alpha, pS2, metallothionein and CD24 expression in invasive breast cancers.

Determination of oestrogen receptor alpha (ER) represents at present the most important predictive factor in breast cancers. Data of ours and of other authors suggest that promising predictive/prognostic factors may also include pS2, metallothionein (MT) and CD24. Present study aimed at determining prognostic and predictive value of immunohistochemical determination of ER, pS2, MT, and CD24 expression in sections originating from 104 patients with breast cancer. An univariate and multivariate analysis was performed. Both univariate and multivariate analyses demonstrated that cytoplasmic-membranous expression of CD24 (CD24c-m) represents a strong unfavourable prognostic factor in the entire group and in most of the subgroups of patients. In several subgroups of the patients also a prognostic value was demonstrated of elevated expression of pS2 and of membranous expression of CD24. Our studies demonstrated that all patients with good prognostic factors (higher ER and pS2 expressions, lower MT expression, CD24c-m negativity) survived total period of observation (103 months). The study documented that cytoplasmic-membranous expression of CD24 represented an extremely strong unfavourable prognostic factor in breast cancer. Examination of the entire panel of the studied proteins permitted to select a group of patients of an exceptionally good prognosis.

Elevated metallothionein (MT) expression in invasive ductal breast cancers predicts tamoxifen resistance.

Elevated expression of the low molecular weight metallothionein (MT) proteins can be found typically in breast cancer cases with less favourable prognosis. The MT gene has been described to be potentially down-regulated by estrogen receptor alpha. The present study is aimed at examining the predictive value of MT expression for results of tamoxifen treatment in breast cancer in relation to steroid receptor status. Sixty patients with primary invasive ductal breast cancers with post-operative tamoxifen treatment were enrolled in the study. In paraffin sections of the studied tumours immmunohistochemical reactions were performed using antibodies directed against MT, estrogen receptors (ER) and progesterone receptors (PgR). Results of the immunohistochemical reactions and of clinical observations were analysed using multivariate progression analysis based on the Cox proportional hazard model. Elevated MT expression was demonstrated to be typical for cases with documented relapse of the disease (P<0.001) or terminated by death (P=0.03). Decreased ER expression was found to be typical for cases of a higher grade (P=0.02) and cases terminated by death (P=0.006). The multivariate analysis showed that elevated MT expression was characteristic for cases with shorter overall survival time (P=0.04). The data showed that MT carried an independent, and also independent from ER status, unfavourable predictive value as far as results of tamoxifen treatment were concerned.

Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomised trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy.

BACKGROUND AND PURPOSE: The aim was to verify whether preoperative conventionally fractionated chemoradiation offers an advantage in sphincter preservation in comparison with preoperative short-term irradiation. PATIENTS AND METHODS: Patients with resectable T3-4 rectal carcinoma without sphincters' infiltration and with a lesion accessible to digital rectal examination were randomised into: preoperative 5x5Gy short-term irradiation with subsequent total mesorectal excision (TME) performed within 7 days or chemoradiation to a total dose of 50.4Gy (1.8Gy per fraction) concomitantly with two courses of bolus 5-fluorouracil and leucovorin followed by TME after 4-6 weeks. Surgeons were obliged to base the type of operation on the tumour status at the time of surgery. RESULTS: Between 1999 and 2002, 316 patients from 19 institutions were enrolled. The sphincter preservation rate was 61% in the 5x5Gy arm and 58% in the radiochemotherapy arm, P = 0.57. The tumour was on average 1.9 cm smaller (P < 0.001) among patients treated with chemoradiation compared with short-term schedule. For patients who underwent sphincter-preserving procedure, the surgeons generally followed the rule of tailoring the resection according to tumour downsizing; the median distal bowel margin was identical (2 cm) for both randomised groups. However, in the chemoradiation group, five patients underwent abdominoperineal resection despite clinical complete response. CONCLUSIONS: Despite significant downsizing, chemoradiation did not result in increased sphincter preservation rate in comparison with short-term preoperative radiotherapy. The surgeons' decisions were subjective and based on pre-treatment tumour volume at least in clinical complete responders.