New insights in the neuroanatomy of the human adult superior hypogastric plexus and hypogastric nerves.

BACKGROUND: The superior hypogastric plexus (SHP) is an autonomic plexus, located ventrally to the abdominal aorta and its bifurcation, innervating pelvic viscera. It is classically described as being composed of merely sympathetic fibres. However, post-operative complications after surgery damaging the peri-aortic retroperitoneal compartment suggest the existence of parasympathetic fibres. This immunohistochemical study describes the neuroanatomical composition of the human mature SHP. MATERIAL AND METHODS: Eight pre-determined retroperitoneal localizations including the lumbar splanchnic nerves, the SHP and the HN were studied in four human cadavers. Control tissues (white rami, grey rami, vagus nerve, splanchnic nerves, sympathetic ganglia, sympathetic chain and spinal nerve) were collected to verify the results. All tissues were stained with haematoxylin and eosin and antibodies S100, tyrosine hydroxylase (TH), vasoactive intestinal peptide (VIP) and myelin basic protein (MBP) to identify pre- and postganglionic parasympathetic and sympathetic nerve fibres. RESULTS: All tissues comprising the SHP and hypogastric nerves (HN) showed isolated expression of TH, VIP and MBP, revealing the presence of three types of fibres: postganglionic adrenergic sympathetic fibres marked by TH, unmyelinated VIP-positive fibres and myelinated preganglionic fibres marked by MBP. Analysis of control tissues confirmed that TH, VIP and MBP were well usable to interpret the neurochemical composition of the SHP and HN. CONCLUSION: The human SHP and HN contain sympathetic and most likely postganglionic parasympathetic fibres. The origin of these fibres is still to be elucidated, however surgical damage in the peri-aortic retroperitoneal compartment may cause pelvic organ dysfunction related to both parasympathetic and sympathetic denervation.

Tumour response to preoperative anthracycline-based chemotherapy in operable breast cancer: the predictive role of p53 expression.

The aim of this retrospective study was to identify markers capable of predicting pathological complete (pCR) and overall clinical tumour response to preoperative anthracycline-based chemotherapy and clinical outcome in women with operable breast cancer. Therefore, we used the pre-treatment core biopsies from 107 patients who were enrolled in the EORTC trial 10902 to analyse tumour characteristics and the oncogenic markers Bcl-2, p53, ER, PgR, HER2, and p21. Median follow-up was 7 years (95% confidence interval [CI], 6.89-7.45). pCR was seen in seven patients (6.5%) and was associated with improved overall survival (hazards ratio, 0.39; 95% CI, 0.05-2.56; P = 0.30). In multivariate logistic regression analysis, pCR was independently predicted by p53 overexpression estimated by immunohistochemistry (odds ratio [OR], 16.83; 95% CI, 1.78-159.33; P = 0.01). Fifty-eight patients showed clinical tumour response (>50% decrease in tumour size), however responders experienced no benefit in clinical outcome. Clinical tumour response was independently predicted by p53 overexpression (OR, 5.57; 95% CI, 1.58-19.65; P = 0.008) and small clinical tumour size (OR, 10.26; 95% CI, 2.01-52.48; P = 0.005). In multivariate Cox regression analysis, negative pathological lymph node status, low tumour grade and use of tamoxifen showed improved overall survival. In conclusion, our data suggest p53 expression is of predictive significance in anthracycline-containing chemotherapeutic regimens.

Low rectal cancer: a call for a change of approach in abdominoperineal resection.

PURPOSE: Despite the major improvements that have been made due to total mesorectal excision (TME), low rectal cancer still remains a challenge. METHODS: By investigating a prospective randomized rectal cancer trial in which surgeons had undergone training in TME the factors responsible for the poor outcome were determined and a new method for assessing the quality of surgery was tested. RESULTS: Survival differed greatly between abdominoperineal resection (APR) and anterior resection (AR; 38.5% v 57.6%, P = .008). Low rectal carcinomas have a higher frequency of circumferential margin involvement (26.5% v 12.6%, P < .001). More positive margins were present in the patients operated with APR (30.4%) compared to AR (10.7%, P = .002). Furthermore, more perforations were present in these specimens (13.7% v 2.5%, P < .001). The plane of resection lies within the sphincteric muscle, the submucosa or lumen in more than 1/3 of the APR cases, and in the remainder lay on the sphincteric muscles. CONCLUSION: We systematically described and investigated the pathologic properties of low rectal cancer in general, and APR in particular, in a prospective randomized trial including surgeons who had been trained in TME. The poor prognosis of the patients with an APR is ascribed to the resection plane of the operation leading to a high frequency of margin involvement by tumor and perforation with this current surgical technique. The clinical results of this operation could be greatly improved by adopting different surgical techniques and possibly greater use of radiochemotherapy.

Bcl-2 overexpression does not prevent but retards adriamycin toxicity in CC531 colon carcinoma cells.

BACKGROUND: The Bcl-2 protein is a critical regulator of susceptibility towards cell death induced by antineoplastic drugs. Reduced growth activity and increased glutathione (GSH) levels protect against adriamycin toxicity. We recently demonstrated statistically significantly reduced growth activity and elevated cellular GSH levels in exponentially growing rat CC531 colon carcinoma cells overexpressing the full-length human Bcl-2 protein (CCbcl2#A3). METHODS: To assess the importance of reduced growth activity or increased GSH levels, we determined the mitochondrial function, 24 h after adriamycin treatment, in CCbcl2#A3 cells, parental CC531 cells and cells overexpressing the Bcl-2 protein lacking the N-terminal BH4 domain (CC Delta BH4): these latter cells contained elevated cellular GSH levels but were not reduced in growth activity. RESULTS: CCbcl2#A3, but not CC Delta BH4, cells were 3-fold less susceptible than parental cells suggestive of a protective role for reduced growth but not for increased GSH levels in BCL-2 transfectants. This was confirmed in several growth-inhibited CC531 transfectants and in slowly proliferating (ca. 100% confluent) cell populations compared to exponentially growing (ca. 50% confluent) cell populations. Reduced growth activity might delay the onset of cell death. Therefore, we tested the effect of adriamycin five days after treatment. In this long-term assay we found no differences between the various cells. CONCLUSION: Reduction of growth activity, for instance by an overexpression of the Bcl-2 protein, only transiently reduced the susceptibility towards adriamycin treatment.

Will we need lymph node dissection at all in the future?

Traditionally in the treatment of primary breast cancer, axillary lymph node dissection (ALND) plays an important role. However, a substantial and increasing percentage of patients appear to have no nodal involvement and have been subjected to ALND unnecessarily. The first reason to perform an ALND is axillary nodal staging. After reviewing the literature, it can be concluded that in clinically node-negative patients an adequately conducted lymphatic mapping by sentinel node procedure is equal to ALND for this purpose. The second reason to perform an ALND is to establish the extent of nodal involvement, which might have an impact on adjuvant treatment recommendations. However, there is no evidence available that patients with extensive nodal involvement (= 4 positive nodes) benefit more from adjuvant systemic treatment (either standard or high dose) in terms of reduction of odds of recurrence and mortality compared to patients with limited nodal involvement and optimally administered so-called standard adjuvant treatment. The third reason to perform an ALND is to ensure axillary tumor control. Reviewing the different treatment options, it can be concluded that in clinically node-negative patients axillary control after axillary radiotherapy appears to be similar to axillary control after ALND. In clinically overt axillary involvement, ALND (with or without adjuvant radiotherapy) may result in an improved regional control. In the near future, ALND will not be the standard of care but will be reserved for those patients with proven axillary lymph node involvement. In microscopic disease, radiotherapy may be an alternative with equal control and less morbidity.