Cornelius J.H. van de Velde

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.

Evidence and research in rectal cancer

The main evidences of epidemiology, diagnostic imaging, pathology, surgery, radiotherapy, chemotherapy and follow-up are reviewed to optimize the routine treatment of rectal cancer according to a multidisciplinary approach. This paper reports on the knowledge shared between different specialists involved in the design and management of the multidisciplinary ESTRO Teaching Course on Rectal Cancer. The scenario of ongoing research is also addressed. In this time of changing treatments, it clearly appears that a common standard for large heterogeneous patient groups have to be substituted by more individualised therapies based on clinical-pathological features and very soon on molecular and genetic markers. Only trained multidisciplinary teams can face this new challenge and tailor the treatments according to the best scientific evidence for each patient.

Role of fine-needle aspiration biopsy and frozen section examination in determining the extent of thyroidectomy.

Abstract. Traditionally the extent of thyroidectomy in patients with nodular thyroid disease has been based on peroperative frozen section examination (FS). Fine-needle aspiration biopsy (FNAB) and FS were evaluated with regard to the reliability to determine whether an operation for cancer is necessary. Both methods were performed in 240 patients operated for nodular thyroid disease and compared with the final histology on paraffin sections. Altogether 72 (30%) patients were found to have a malignant lesion on final histology. Only a malignant FNAB diagnosis and a malignant FS diagnosis were considered positive results for determining the extent of thyroidectomy. The test characteristics were equal: the sensitivity of FNAB and FS was 67%, the specificity 99%, and the accuracy 89%. The positive predictive value was 96% for FNAB and 98% for FS; the negative predictive values were 88% and 87%, respectively. Further analysis of the results indicates that FS is not necessary for patients with a malignant FNAB result. These patients should undergo a therapeutic operation for malignancy. When the FNAB result is uncertain, patients should undergo diagnostic surgery, and definitive surgery should be based on the final histology. Routine use of FS can be omitted.

Surgically induced cytokinetic responses in experimental rat mammary tumor models.

The effect of surgical removal of “primary” tumors on the cytokinetics of local tumor remnants, secondary implants, and metastases was investigated in three different rat tumor models in the Wag/Rij rat: a slow‐growing (MCR83) and a fast‐growing (EMR86) hormone‐dependent mammary tumor and a rapidly, but autonomously growing carcinoma (MCR86). The latter two tumors had metastatic potential. Cell kinetic studies were done using in vivo labeling with 5′ ‐ bromodeoxyuridine (BrdUrd). Thirty‐three hours after removal of a subcutaneous MCR83 flank tumor, secondary implants showed a significant (P < 0.05) but transient increase in the BrdUrd labeling index (LI). A more rapid and prolonged increase, lasting for at least 7 days, was observed in EMR86 lymph node and lung metastases. In both models, no effect was observed after sham surgery (consisting of opening and closing of the skin under anesthesia). Removal of MCR86 tumors (growing in the hind leg muscle) also resulted in a rapid, transient LI increase in metastases. Continuous BrdUrd labeling experiments in this tumor model did not favor the hypothesis that the LI increase predominantly resulted from an increase in the growth fraction. Moreover, in this model, the effect was related to operation trauma. A similar increase in LI, although smaller than after tumor removal, was seen after major surgical trauma in MCR83 flank tumors. These results indicate that in the rat, tumor removal and/or major surgical trauma may modulate the cytokinetics of distant metastases significantly. A study of the systemic, possibly endocrine, factors involved in the growth‐stimulating effect of surgical trauma in these rat tumor models may help to assess the clinical relevance of these findings for patients with breast cancer.

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 (CCΔBH4): these latter cells contained elevated cellular GSH levels but were not reduced in growth activity. Results: CCbcl2#A3, but not CCΔBH4, 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.

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.

Will Extralevator Abdominoperineal Excision Become the New Gold Standard

The introduction of TME surgery led to the realization that the quality of surgery significantly influences the prognosis of rectal cancer patients and has resulted in a huge improvement in surgery and its outcome [1]. On a population-based level, an improved survival of more than 10% was realized in countries adopting TME as the standard surgical technique [2, 3].