Matthew Morgan

P53, deleted in colorectal cancer gene, and thymidylate synthase as predictors of histopathologic response and survival in low, locally advanced rectal cancer treated with preoperative adjuvant therapy

AbstractPURPOSE: Adjuvant therapy, either preoperatively or postoperatively, and modifications of surgery have been used to try to improve outcome of surgery for rectal cancer in regard to both local recurrence and survival. Assessment of prognosis in patients after resection is currently primarily based on clinicopathologic factors. These predict the subsequent behavior of the tumor only imperfectly. The aim of this study was to evaluate three potential molecular genetic markers of prognosis (p53, deleted in colorectal cancer gene, and thymidylate synthase) in Dukes Stage B and C low rectal tumors treated with adjuvant therapy and to determine whether they correlate with survival, local recurrence, or the pathologic response to adjuvant therapy (assessed by extent of tumor regression and tumor down-staging). METHODS: Sixty locally advanced low rectal tumors resected after preoperative chemoradiotherapy or radiotherapy alone were studied by immunohistochemical staining for p53, deleted in colorectal cancer gene, and thymidylate synthase. In addition, p53 gene mutations were sought by polymerase chain reaction–single-strand conformation polymorphism analysis. These results were correlated with survival, local recurrence, and pathologic response to adjuvant therapy. RESULTS: Lack of thymidylate synthase staining by immunohistochemistry was associated with tumor down-staging after preoperative chemoradiotherapy but not after radiotherapy or for these two combined groups. There was no correlation between p53, deleted in colorectal cancer gene, or thymidylate synthase immunohistochemical staining or between p53 polymerase chain reaction–single-strand conformation polymorphism and local recurrence or survival in locally advanced low rectal cancers treated with preoperative adjuvant therapies. CONCLUSION: Prediction of prognosis in patients with locally advanced low rectal cancers treated with preoperative adjuvant therapies continues to be problematic. Thymidylate synthase immunohistochemistry appears to be the most promising factor of those assessed in predicting tumor down-staging after preoperative chemoradiotherapy for locally advanced low rectal cancers.

Tumor pathology and long-term survival in emergency colorectal cancer.

PURPOSEPatients who have an emergency operation for colorectal cancer have poorer long-term survival outcomes compared with elective patients. This study was designed to define the role of tumor pathology as a basis for the differences in survival outcomes.METHODSThere were 1,537 elective and 286 emergency patients who had an operation for bowel cancer from 1997 to 2003. Tumor pathology and survival data collected prospectively for these patients were compared by modes of presentation.RESULTSExcluding 30-day mortality, emergency patients as a whole had a five-year all-cause survival rate of 39.2 percent compared with 64.7 percent for elective patients P < 0.0001 they also had more advanced Dukes C and D tumors (P < 0.0001). The rates of early T1 and T2 cancers were 4.7 percent for the emergency and 25 percent for the elective group. Emergency cases had more lymph node-positive patients and N2 patients (57.1 vs. 41.8 percent and 26.6 vs. 15.9 percent, respectively; P < 0.0001). Curatively resected emergency colon patients again had more advanced Dukes staged tumors (P < 0.0001) with a five-year survival rate of 51.6 percent compared with 75.6 percent for elective patients P < 0.0001. On stage-for-stage analysis, the survival rates for curatively resected Dukes B and C colon cancers remained worse for emergency patients (P = 0.003 and P = 0.0002, respectively). Both emergency Dukes B and C groups had more T4 cases (21.5 vs. 10.6 percent; P = 0.017 and 26.4 vs. 15 percent; P = 0.016, respectively).CONCLUSIONAdvanced tumor pathology is a basis for poor long-term survival in emergency colorectal cancers.

Improved short-term outcomes of laparoscopic versus open resection for colon and rectal cancer in an area health service: a multicenter study.

BACKGROUND: Evidence demonstrates short-term benefits of laparoscopic surgery for colon cancer. The situation for rectal cancer is less clear. OBJECTIVES: This review assessed the use and short-term outcomes of elective open and laparoscopic colon and rectal cancer resections within an area health service. DESIGN: This was a multicenter, retrospective review of a prospective database. SETTINGS: All elective colon and rectal cancer resections in the western zone of Sydney South West Area Health Service from 2001 until 2008 were included. PATIENTS: Included were 1721 patients who underwent either a laparoscopic colon (n = 434) or rectal (n = 157) resection or an open colon (n = 742) or rectal (n = 388) resection. MAIN OUTCOME MEASURES: Outcome measures included operating time, blood loss, adequacy of resection, conversion rate, intensive care unit admission, length of stay, and 26 acute postoperative complications. RESULTS: Patients were matched for age, sex, ASA, BMI, and tumor stage. Laparoscopic surgery increased in frequency. Fewer patients experienced a complication in both the laparoscopic colon (28.8 vs 54.4%; p < 0.0001) and rectal (41.4 vs 60.3%; p < 0.0001) group irrespective of age. Laparoscopic operating time for colon and rectal cancer was 24.1 minutes (p < 0.0001) and 25.8 minutes (p < 0.0001) longer, with a low conversion-to-open rate (6.5% and 8.3%; p = 0.44). Laparoscopic surgery resulted in fewer transfusions (0.4 vs 0.7units; p = 0.0028) and length of stay (7 vs 10 days; p = 0.0011) for colon cancers, and reduced intraoperative hemoglobin drop (20.5 vs 24.8; p = 0.029) and intensive care unit admissions (26.8 vs 36.3%; p = 0.032) for rectal cancers. LIMITATIONS: This was a nonrandomized study with rectal cancers more often resected with the open technique (71.2 vs 28.8%; p < 0.001). CONCLUSIONS: Within an area health service, elective laparoscopic resection for colon and rectal cancer had improved short-term outcomes in comparison with open surgery.

Histological tumour response to pre-operative combined modality therapy in locally advanced rectal cancer

Pre‐operative combined modality therapy (CMT) is used in locally advanced rectal cancer. Its use affects the clinicopathological staging based on the resected specimen. Assessment of the tumour response in the resected specimen may provide prognostic information. This study was undertaken to determine the histological response to pre‐operative chemoradiation and to assess the interobserver reliability of a newly developed tumour response grading system for rectal cancer.

Fertility and pain outcomes following laparoscopic segmental bowel resection for colorectal endometriosis: A review

Intestinal involvement in endometriosis is thought to occur in up to 12% of all endometriosis cases. While colorectal resection is being increasingly advocated as a feasible management option in patients with severe disease, there still remains significant resistance towards this surgery. This article aims to review the current literature to determine the pain and fertility outcomes following segmental bowel resection for colorectal endometriosis.

Bowel resection for severe endometriosis: An Australian series of 177 cases

Background: Colorectal resection for severe endometriosis has been increasingly described in the literature over the last 20 years.

Surgical management of colorectal cancer in south-western Sydney 1997−2001: a prospective series of 1293 unselected cases from six public hospitals

Background:  The aim of the present study is to provide local data for the management of colorectal cancers in the south‐western Sydney health area from 1997 to 2001.

Laparoscopic versus open reversal of Hartmann's procedure: a retrospective review

Restoration of bowel continuity following Hartmanns procedure may be performed using a laparoscopic or open technique. This study is the first of its kind comparing laparoscopic with open reversal of Hartmanns procedure in Australasia.

Direct tumor invasion in colon cancer: correlation with tumor spread and survival.

PurposeThis study examined the correlation between depth of local invasion in colon cancer and tumor spread and patient survival.MethodsA cohort of 796 patients with a complete set of TNM staging information following an elective resection for colon cancer was selected. The rates of lymph node and distant metastasis, tumor differentiation, and extramural venous invasion for different tumor (T) categories were compared. The effects of initial tumor (T) category on overall patient survival were studied.ResultsThe depth of local tumor invasion correlated strongly with nodal involvement (P = 0.0001), rates of extramural venous invasion (P = 0.0002), poor differentiation (P = 0.0001), and distant metastasis (P = 0.0001). Fifty-seven percent of the patients remained lymph node-negative and distant metastasis-negative irrespective of their depth of tumor invasion had no impact on overall survival (P = 0.49). For patients with lymph node or distant metastasis (43 percent), depth of tumor invasion had significant impact on overall survival (P = 0.001). Thirteen percent of T3N1, 33 percent of T3N2, 40 percent of T4N1, and 68.percent of T4N2 cases had distant metastasis at presentation.ConclusionTwo types of colon cancer were observed: locally active and tendency to metastasize. For the latter, overall mortality and the risk of metastasis increased with depth of tumor invasion.

Positron emission tomography and colorectal cancer

Colorectal cancer (CRC) is a major cause of cancer-related morbidity and mortality. Molecular imaging using positron emission tomography (PET) is now an integral part of multidisciplinary cancer care. In this review, we discuss the role of PET in CRC including well established indications in the assessment of recurrent disease and emerging applications such as initial staging, monitoring therapy efficacy and using PET for radiotherapy planning. With rapid advancement in imaging technology, we also discuss the future potential of combining PET and magnetic resonance imaging and the use of novel radiotracers.