Lauren Kosinski

Shifting concepts in rectal cancer management: a review of contemporary primary rectal cancer treatment strategies.

The management of rectal cancer has transformed over the last 3 decades and continues to evolve. Some of these changes parallel progress made with other cancers: refinement of surgical technique to improve organ preservation, selective use of neoadjuvant (and adjuvant) therapy, and emergence of criteria suggesting a role for individually tailored therapy. Other changes are driven by fairly unique issues including functional considerations, rectal anatomic features, and surgical technical issues. Further complexity is due to the variety of staging modalities (each with its own limitations), neoadjuvant treatment alternatives, and competing strategies for sequencing multimodal treatment even for nonmetastatic disease. Importantly, observations of tumor response made in the era of neoadjuvant therapy are reshaping some traditionally held concepts about tumor behavior. Frameworks for prioritizing and integrating complex data can help to formulate treatment plans for patients. CA Cancer J Clin 2012;.

Effects of autonomic nerve stimulation on colorectal motility in rats

Background  Several disease processes of the colon and rectum, including constipation and incontinence, have been associated with abnormalities of the autonomic nervous system. However, the autonomic innervation to the colon and rectum are not fully understood. The aims of this study were to investigate the effect of stimulation of vagus nerves, pelvic nerves (PN) and hypogastric nerves (HGN) on colorectal motility in rats.

Angiogenesis, proliferation, and apoptosis in anal high-grade squamous intraepithelial lesions

PURPOSE: Management of anal high-grade squamous intraepithelial lesions is controversial. Anal and cervical high-grade squamous intraepithelial lesions are similar in that they occur in transitional squamous epithelium, are associated with human papilloma virus infection, and have increased incidence in the immunocompromised population. Ablation of cervical high-grade squamous intraepithelial lesions is preferred, but similar ablation or excision of anal high-grade squamous intraepithelial lesions may compromise bowel control; thus, there is a need to define the malignant potential of anal high-grade squamous intraepithelial lesions. METHODS: We analyzed 50 paraffin sections of normal anoderm, anal low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and anal squamous-cell carcinoma. Microvessels were detected immunohistochemically with von Willebrand factor and counted manually along the epithelial-stromal junction. Proliferation and apoptosis were determined in the epithelial cells with MIB-1 antibody immunostaining and the terminal deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labeling, respectively. RESULTS: Microvascular density was significantly greater in anal high-grade squamous intraepithelial lesions (mean, 0.50 vessels/cm)vs. normal anoderm (mean, 0.21 vessels/cm;P=0.0017, Mann-WhitneyU test). The proliferative percentages were greater in low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and squamous-cell carcinoma (mean, 20.4, 21.8, and 23.6 percent)vs. normal anoderm (mean, 14.4 percent), although not significantly (P=0.06, Kruskal-Wallis statistic). Although the mean proliferative proportions were similar in low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions, the apoptotic proportion was lower for high-grade squamous intraepithelial lesions than low-grade squamous intraepithelial lesions (10.13vs. 19.96 percent, respectively;P=NS, Mann-WhitneyU test). CONCLUSIONS: Angiogenesis, increased proliferation, and decreased apoptosis occur in anal high-grade squamous intraepithelial lesions as they do in the cervix before the development of malignancy. These biologic markers support the importance of anal high-grade squamous intraepithelial lesions as a potential premalignant lesion warranting surgical intervention.

The impact of stage, grade, and mucinous histology on the efficacy of systemic chemotherapy in adenocarcinomas of the appendix: Analysis of the National Cancer Data Base

Adenocarcinomas of the appendix represent a heterogeneous disease depending on the presence of mucinous histology, histologic grade, and stage. In the current study, the authors sought to explore the interplay of these factors with systemic chemotherapy in a large population data set.

Obesity and Colorectal Cancer

Obesity is a risk factor for colorectal cancer based on its molecular and metabolic effects on insulin and IGF-1, leptin, adipocytokines, and sex hormones. Obese men have a higher risk of colorectal cancer compared with normal weight men, but the association between obesity and rectal cancer is weaker than with colon cancer. There is a weaker association between obesity and colon cancer in women than in men, and no appreciable association between obesity and rectal cancer in women. Although obesity does not seem to have an effect on the number of lymph nodes harvested with resection, obesity does seem to be associated with more-aggressive colorectal cancers in a handful of studies. Survival and local recurrence studies are contradictory with no conclusive evidence that obesity predisposes to worse overall survival or increased recurrence in colon and rectal cancers. The literature is not definitive as far as overall morbidity and mortality rates in the obese are concerned, though obese rectal cancer patients seem to incur proportionally more morbidity and mortality. Preexisting steatosis or steatohepatitis in obese colorectal cancer patients or chemotherapy-induced liver dysfunction may lead to an increased mortality in obese patients with colorectal liver metastases. Diabetes may cause poorer response to neoadjuvant therapy in rectal cancer and contribute to higher mortality and recurrence in colon cancer.

Fragmented pattern of tumor regression and lateral intramural spread may influence margin appropriateness after TEM for rectal cancer following neoadjuvant CRT

The main tenets of local excision of rectal cancer following neoadjuvant chemoradiation (CRT) are that the mucosal scar represents the main focus of residual disease and a solid conglomerate around this rather than being scattered (fragmented) through the bowel wall.

The Role of 5-HT3 and 5-HT4 Receptors in the Adaptive Mechanism of Colonic Transit Following the Parasympathetic Denervation in Rats

BACKGROUND Clinical studies show that disturbed colonic motility induced by extrinsic nerves damage is restored over time. We studied whether 5-HT3 and 5HT4 receptors are involved in mediating the adaptive mechanisms following parasympathetic denervation. METHODS Parasympathetic denervation of the entire colon was achieved by bilateral pelvic nerve transection and truncal vagotomy in rats. Colonic transit was measured by calculating the geometric center (GC) of 51Cr distribution. Expression of 5-HT3 and 5HT4 receptor mRNA was determined by real time RT-PCR. RESULTS Parasympathetic denervation caused a significant delay in colonic transit (GC=4.36) at postoperative day (POD) 1, compared with sham operation (GC=6.31). Delayed transit was gradually restored by POD 7 (GC=5.99) after the denervation. Restored colonic transit was antagonized by the administration of 5-HT3 and 5HT4 receptors antagonists at POD 7. 5-HT3 and 5HT4 receptors mRNA expression were significantly increased in the mucosal/submucosal layer at POD 3 or POD 7, whereas no significant difference was observed in the longitudinal muscle layers adherent with the myenteric plexus (LMMP). CONCLUSIONS It is suggested that up-regulation of 5-HT3 and 5-HT4 receptors expression in the mucosal/submucosal layer is involved to restore the delayed transit after the parasympathetic denervation in rats.

Recovery of colonic transit following extrinsic nerve damage in rats

Abstract Introduction. Injury to pelvic sympathetic and parasympathetic nerves from surgical and obstetrical trauma has long been cited as a cause for abnormal colorectal motility in humans. Using a rat model, acute transaction of these extrinsic nerves has been shown to effect colorectal motility. The aim of this study is to determine in a rat model how transection of these extrinsic nerves affects colonic transit over time. Methods. Eighty-two Sprague–Dawley rats underwent placement of a tunneled catheter into the proximal colon. Bilateral hypogastric, pelvic nerves (HGN and PN) or both were transected in 66 rats. The remaining 16 rats received a sham operation. Colonic transit was evaluated at postoperative days (PODs) 1, 3, and 7 by injecting and calculating the geometric center (GC) of the distribution of 51Cr after 3 h of propagation. Results. At POD 1, transection of PNs significantly delayed colonic transit (GC = 4.9, p < 0.05), while transection of HGNs (GC = 8.5, p < 0.05) or transection of both nerves (GC = 7.8, p < 0.05) significantly accelerated colonic transit, when compared with sham operation (GC = 6.0). A significant trend toward recovery was noted in both the HGN and PN transection groups at POD 7. Conclusions. Damage to the extrinsic sympathetic and/or parasympathetic PNs affects colonic transit acutely. These changes in large bowel motor function normalize over time implicating a compensatory mechanism within the bowel itself.

Upregulation of mucosal 5‐HT3 receptors is involved in restoration of colonic transit after pelvic nerve transection

Background  Colonic dysfunction occurs after pelvic autonomic nerve damage. The enteric nervous system can compensate. We investigated the role of mucosal serotonin receptors, 5‐HT3 and 5‐HT4, in the colonic motility restoration over 2 weeks after parasympathetic pelvic nerve transection in a rat model.

Is splenic flexure mobilization necessary in laparoscopic anterior resection? Another view.

DISEASES OF THE COLON & RECTUM VOLUME 55: 11 (2012) Change of approach certainly provides the opportunity to rethink dogma and critically appraise key steps of a procedure. However, this should be undertaken rationally, there should be an accounting of how the proposed change impacts the technical feasibility of other steps of an operation and the overall goals of the procedure, and, on some level, the proposed change must pass the “common sense test.” A successful example of this kind of revision engendered by the transition from open to laparoscopic colectomy is the move away from closure of mesenteric defects. Eliminating closure of the defect presents no difficulty completing other steps of a bowel resection, and there are few reports of internal hernias after laparoscopic colectomy. Those reports that do exist suggest that internal hernias may be underreported, but the numbers are small and larger studies have failed to show an increased incidence of small-bowel obstruction following laparoscopic in comparison with open colectomy. In fact, the burden of proof of the laparoscopist’s departure from dogma rests with the laparoscopist, keeping in mind that skepticism about the risk of compromising a procedure in terms of intraand postoperative complications for the sake of enabling a laparoscopic approach still exists. The proposed revision of mandatory splenic flexure mobilization (SFM) for low anterior resection (LAR) challenged our “common sense test.” In the spirit of academic curiosity, we tried to set aside our bias (always mobilize the splenic flexure) and consider how we would incorporate this suggestion into our practice. What would the operation look like? What else would have to change to make it feasible to eliminate SFM from a LAR? We asked some of our experienced rectal cancer surgical colleagues to consider this as well, and we were all stumped. This prompted us to look more deeply into the literature cited to support the proposal and to articulate what we see as problematic.