Changes in the multidisciplinary management of rectal cancer from 2009 to 2015 and associated improvements in short-term outcomes.

AIM: Significant recent changes in management of locally advanced rectal cancer (LARC) include preoperative staging, use of extended neoadjuvant therapies and minimally invasive surgery (MIS). This study was aimed at characterizing these changes and associated short-term outcomes. METHOD: We retrospectively analysed treatment and outcome data from patients with T3/4 or N+ LARC ≤ 15 cm from the anal verge who were evaluated at a comprehensive cancer centre in 2009-2015. RESULTS: In total, 798 patients were identified and grouped into five cohorts based on treatment year: 2009-2010, 2011, 2012, 2013 and 2014-2015. Temporal changes included increased reliance on MRI staging, from 57% in 2009-2010 to 98% in 2014-2015 (P < 0.001); increased use of total neoadjuvant therapy, from 17% to 76% (P < 0.001); and increased use of MIS, from 33% to 70% (P < 0.001). Concurrently, median hospital stay decreased (from 7 to 5 days; P < 0.001), as did the rates of Grade III-V complications (from 13% to 7%; P < 0.05), surgical site infections (from 24% to 8%; P < 0.001), anastomotic leak (from 11% to 3%; P < 0.05) and positive circumferential resection margin (from 9% to 4%; P < 0.05). TNM downstaging increased from 62% to 74% (P = 0.002). CONCLUSION: Shifts toward MRI-based staging, total neoadjuvant therapy and MIS occurred between 2009 and 2015. Over the same period, treatment responses improved, and lengths of stay and the incidence of complications decreased.

Effectiveness of a multidisciplinary patient care bundle for reducing surgical-site infections.

BACKGROUND: Surgical-site infection (SSI) is associated with significant healthcare costs. To reduce the high rate of SSI among patients undergoing colorectal surgery at a cancer centre, a comprehensive care bundle was implemented and its efficacy tested. METHODS: A pragmatic study involving three phases (baseline, implementation and sustainability) was conducted on patients treated consecutively between 2013 and 2016. The intervention included 13 components related to: bowel preparation; oral and intravenous antibiotic selection and administration; skin preparation, disinfection and hygiene; maintenance of normothermia during surgery; and use of clean instruments for closure. SSI risk was evaluated by means of a preoperative calculator, and effectiveness was assessed using interrupted time-series regression. RESULTS: In a population with a mean BMI of 30 kg/m2 , diabetes mellitus in 17·5 per cent, and smoking history in 49·3 per cent, SSI rates declined from 11·0 to 4·1 per cent following implementation of the intervention bundle (P = 0·001). The greatest reductions in SSI rates occurred in patients at intermediate or high risk of SSI: from 10·3 to 4·7 per cent (P = 0·006) and from 19 to 2 per cent (P < 0·001) respectively. Wound care modifications were very different in the implementation phase (43·2 versus 24·9 per cent baseline), including use of an overlying surface vacuum dressing (17·2 from 1·4 per cent baseline) or leaving wounds partially open (13·2 from 6·7 per cent baseline). As a result, the biggest difference was in wound-related rather than organ-space SSI. The median length of hospital stay decreased from 7 (i.q.r. 5-10) to 6 (5-9) days (P = 0·002). The greatest reduction in hospital stay was seen in patients at high risk of SSI: from 8 to 6 days (P < 0·001). SSI rates remained low (4·5 per cent) in the sustainability phase. CONCLUSION: Meaningful reductions in SSI can be achieved by implementing a multidisciplinary care bundle at a hospital-wide level.

Prognostic aspects of DCE-MRI in recurrent rectal cancer.

OBJECTIVE: To explore whether pre-reoperative dynamic contrast-enhanced (DCE)-MRI findings correlate with clinical outcome in patients who undergo surgical treatment for recurrent rectal carcinoma. METHODS: A retrospective study of DCE-MRI in patients with recurrent rectal cancer was performed after obtaining an IRB waiver. We queried our PACS from 1998 to 2012 for examinations performed for recurrent disease. Two radiologists in consensus outlined tumour regions of interest on perfusion images. We explored the correlation between K(trans), Kep, Ve, AUC90 and AUC180 with time to re-recurrence of tumour, overall survival and resection margin status. Univariate Cox PH models were used for survival, while univariate logistic regression was used for margin status. RESULTS: Among 58 patients with pre-treatment DCE-MRI who underwent resection, 36 went directly to surgery and 18 had positive margins. K(trans) (0.55, P = 0.012) and Kep (0.93, P = 0.04) were inversely correlated with positive margins. No significant correlations were noted between K(trans), Kep, Ve, AUC90 and AUC180 and overall survival or time to re-recurrence of tumour. CONCLUSION: K(trans) and Kep were significantly associated with clear resection margins; however overall survival and time to re-recurrence were not predicted. Such information might be helpful for treatment individualisation and deserves further investigation.

Multivisceral resections for rectal cancer.

BACKGROUND: En bloc resection of adjacent pelvic organ(s) may be needed to achieve clear surgical margins in rectal cancer surgery. An institutional experience is reported with perioperative morbidity and oncological outcomes. METHODS: Patients were identified retrospectively from a prospectively collected institutional database (1992-2010). Outcomes, and clinical and pathological factors were determined from medical records. Estimated overall survival, overall recurrence and local recurrence were compared using the log rank method and Cox regression analysis. RESULTS: Among 1831 patients with rectal cancer, 124 (6·8 per cent) underwent en bloc resection of part or all of an adjacent organ (vagina/uterus/ovary 90, prostate/seminal vesicle 23, bladder/ureter 15, small bowel/appendix 7). Five-year overall survival and local recurrence rates were 53·3 and 18·8 per cent respectively. There was one postoperative death, from multiple organ failure in a patient with liver cirrhosis. Fifty-two patients underwent sphincter-preserving surgery and three (6 per cent) developed an anastomotic leak. On univariable analysis, the only factor associated with local recurrence was completeness of resection (local recurrence rate 15 per cent versus 69 per cent for R0 versus R1 resection; P < 0·001). On multivariable analysis, factors associated with overall survival were sphincter-preserving surgery, absence of metastatic disease and R0 resection. CONCLUSION: Multiple organ resection for locally advanced primary rectal cancer had good oncological outcomes when clear resection margins were achieved.

Risk-reducing surgery in FAP: role for surgeons beyond the incision.

BACKGROUND: Although primary therapy in familial adenomatous polyposis (FAP) is surgical, little is known about patients' surgical decision-making experience. The objective was to explore the decision-making process surrounding risk-reducing surgery in FAP using qualitative methodology. METHODS: In-depth, semi-structured interviews with 14 FAP patients and 11 healthcare providers with experience caring for FAP patients were conducted. Using grounded theory, line-by-line content analysis identified categories from which themes describing patients' experiences emerged; analysis continued until data saturation. RESULTS: Median age at surgery was 23 (7-37) years; at interview 41 (19-74) years. Two patients underwent surgery secondary to cancer, the remainder for risk-reduction. Content experts included colorectal surgeons (3), geneticists (2), gastroenterologists (3), nurses (3).Three themes emerged: Information: Family was the primary information source, and patients' level of information varied. The importance of up-front information was emphasized. Influences on decision-making: Influential factors included family experiences, youth, emotional state, support, and decision-making role. Although patients often sought opinions, most (12/14) wanted an active/shared role in decision-making. Life after surgery: Patients described surgery as the "easy part," emphasizing the need for long-term relationships with care providers. CONCLUSIONS: Decisions surrounding risk-reducing surgery in FAP are unique. A decision support tool may facilitate decision-making, better preparing patients for life after surgery.

Production of diacylglycerol, an activator of protein kinase C, by human intestinal microflora.

Although dietary lipids have been implicated in colon cancer causation, the underlying mechanisms are not known. This paper indicates that when bacteria obtained from normal human feces are incubated with 14C-labeled phosphatidylcholine there is appreciable production of diacylglycerol (DAG), monoacylglycerol, and free fatty acid. Curiously, the production of DAG and monoacylglycerol, but not fatty acid, is strictly dependent on addition of certain bile acids to the incubation system. Among the bile acids tested deoxycholic acid is the most active. Assays of fecal specimens from 10 normal individuals demonstrate a 27-fold interindividual variation in the production of DAG in the in vitro assay system, and also in the absolute levels of DAG present in the same fecal samples. On the other hand, both parameters of DAG are quite constant in repeated fecal samples obtained from the same individual over a period of about 4 months. DAG is a normal physiological activator of protein kinase C, an enzyme that plays a key role in growth control and tumor promotion. We speculate, therefore, that DAG produced by the intestinal microflora might stimulate growth of colonic epithelial cells. Thus an interaction between dietary lipids, bile acids, and specific bacteria in the intestinal lumen could contribute to the risk of colon cancer development in humans.

Decreased levels of 1,2-sn-diacylglycerol in human colon tumors.

We have found that in 15 of 15 primary human colon tumors there was a significant decrease (by about 40%) in the levels of diacylglycerol when compared to paired adjacent normal mucosa samples. Assays on the same samples indicated that this decrease was seen both in tumors that did and did not display mutations in codon 12 of c-K-ras. These results, taken together with previous studies on protein kinase C, suggest that the protein kinase C signal transduction pathway is suppressed in human colon cancer.

Altered levels of protein kinase C and Ca2+-dependent protein kinases in human colon carcinomas.

Protein kinase C (PKC) is a Ca2+- and phospholipid-dependent protein kinase which is implicated in tumor promotion, since it has been demonstrated to be a high affinity receptor for tumor promoters such as 12-O-tetradecanoylphorbol-13-acetate. Colon carcinogenesis appears to proceed through distinct stages of initiation and promotion. The present studies show that PKC and calcium-dependent protein kinase specific activities are reduced in human colon carcinomas when compared to their normal adjacent colon mucosa. There were significantly higher Ca2+-dependent protein kinase and PKC specific activities observed in both the cytosolic and particulate fractions of the normal mucosa relative to the corresponding values obtained with the carcinoma fractions. The average specific activity ratios were 5.1 (normal cytosolic/carcinoma cytosolic) and 3.7 (normal particulate/carcinoma particulate) for PKC. PKC activity was reduced in the carcinoma tissues with respect to both protein and tissue weight. The percentage of Ca2+-dependent protein kinase and PKC activities that were present in the particulate fraction of each of the samples varied considerably among tissues, and in general there was no systematic difference between the carcinoma and normal mucosa samples. However, in the carcinoma samples that contained an extensive admixture of benign adenomatous tissue, the particulate fractions consistently contained greater than 60% of the total Ca2+-dependent protein kinase and PKC activities. The present studies indicate that colon carcinogenesis is associated with alterations in cellular levels of protein kinase activities.

Changes in expression of oncogenes and endogenous retroviral-like sequences during colon carcinogenesis.

The possible roles in experimental colon carcinogenesis of two protooncogenes (c-myc and c-H-ras), two endogenous retrovirus-related DNA sequences [rat leukemia virus (RaLV) and the 30S sequence], and two cell cycle related genes (beta-actin and ornithine decarboxylase) were studied by analyzing the levels of their corresponding RNAs during the course of azoxymethane induced and high fat promoted colon carcinogenesis. F-344 male rats received three s.c. injections of azoxymethane (15 mg/kg) or normal saline and were then subdivided into high or low fat diet groups. During subsequent serial sacrifices normal colon mucosa, adenomas, and carcinomas were harvested for histology and RNA extraction. Seventy-one RNA samples were analyzed by the Northern blot hybridization procedure using the appropriate 32P-labeled DNA probes. A marked increase in the abundance of c-myc, RaLV, and 30S RNAs were seen in all of the colon tumors, including adenomas and invasive carcinomas. No or a very low level of expression of RaLV and c-myc RNA was found in the flat grossly normal mucosa adjacent to the tumors and in the mucosa of the control rats. Some of the colon tumors also displayed increased levels of c-H-ras, ornithine decarboxylase and beta-actin RNAs but these findings were less striking and more variable than those seen with c-myc, RaLV, and 30S RNAs. These results suggest that increased expression of the c-myc protooncogene and of the endogenous retrovirus-like sequences (RaLV) and 30S are hallmarks of colon carcinogenesis in this model system.

Incisional hernias after laparoscopic and robotic right colectomy.

PURPOSE: Incisional hernia (IH) is a common complication after colectomy, with impacts on both health care utilization and quality of life. The true incidence of IH after minimally invasive colectomy is not well described. The purpose of this study was to examine IH incidence after minimally invasive right colectomies (RC) and to compare the IH rates after laparoscopic (L-RC) and robotic (R-RC) colectomies. METHODS: This is a retrospective review of patients undergoing minimally invasive RC at a single institution from 2009 to 2014. Only patients undergoing RC for colonic neoplasia were included. Patients with previous colectomy or intraperitoneal chemotherapy were excluded. Three L-RC patients were included for each R-RC patient. The primary outcome was IH rate based on clinical examination or computed tomography (CT). Univariate and multivariate time-to-event analyses were used to assess predictors of IH. RESULTS: 276 patients where included, of which 69 had undergone R-RC and 207 L-RC. Patient and tumor characteristics were similar between the groups, except for higher tumor stage in L-RC patients. Both the median time to diagnosis (9.2 months) and the overall IH rate were similar between the groups (17.4 % for R-RC and 22.2 % for L-RC), as were all other postoperative complications. In multivariable analyses, the only significant predictor of IH was former or current tobacco use (hazard raio 3.0, p = 0.03). CONCLUSIONS: This study suggests that the incidence of IH is high after minimally invasive colectomy and that this rate is equivalent after R-RC and L-RC. Reducing the IH rate represents an important opportunity for improving quality of life and reducing health care utilization after minimally invasive colectomy.

Rapid detection of ras oncogenes in human tumors: applications to colon, esophageal, and gastric cancer.

We have developed a rapid, nonradioactive large scale method for the detection of ras oncogenes in human tumors. DNA is amplified by the polymerase chain reaction (PCR), and then digested with specific restriction enzymes to detect either endogenous or primer-mediated Restriction Fragment Length Polymorphisms (RFLPs). We report here that three of 15 colon tumors tested contain K-ras codon 12 aspartic acid mutations and one, along with the HCT 116 colon carcinoma cell line, contains a K-ras codon 13 aspartic acid mutation. On the other hand, we did not detect H- or K-ras codon 12 mutations or the K-ras codon 13 aspartic acid mutation in 25 esophageal and 27 gastric cardia tumors isolated from patients in Lin-xing County, China. By incorporating nucleotide substitutions in PCR primers, this method can be applied towards the rapid, non-radioactive screening of virtually any genetic disease caused by known point mutations.

Prediction of colorectal cancer relapse and survival via tissue RNA levels of matrix metalloproteinase-9.

PURPOSE: In this study, we investigated the association between matrix metalloproteinase (MMP)-9 RNA expression in primary colorectal cancer (CRC) and standard clinicopathologic variables and determined whether levels of MMP-9 RNA predict relapse and survival. PATIENTS AND METHODS: Tumor and paired normal mucosa specimens from 71 primary CRC patients following resections were assessed. RNA levels were determined via Northern blot hybridization and quantitated with laser densitometry. Results were expressed as tumor/normal mucosa (T/N) fold-increase calculated after normalizing for RNA loading using 28S expression. Statistical analysis was performed using the SAS statistical package procedure. Kaplan-Meier survival curves were compared with the two-sided log-rank test. RESULTS: The mean T/N MMP-9 RNA fold-increase was 9.4 +/- 1.0 (mean +/- SE) (P < .001). Overexpression of MMP-9 RNA correlated significantly with status of synchronous distant metastases (M stage) (P = .004) and Dukes' stage (P = .008). A T/N fold-increase of 5.0 was used to discriminate between high (> 5.0) and low (< or = 5.0) T/N MMP-9 expression. High T/N MMP-9 RNA expression was associated with a significantly shorter disease-free (P = .0001) and overall (P = .0002) survival duration. In univariate and multivariate analyses, T/N MMP-9 RNA level was found to be an independent prognostic factor for disease-free survival. CONCLUSION: This report provides the first evidence that increased MMP-9 RNA production in primary human CRC may be a powerful, independent predictor of recurrence and outcome.

p53 nuclear protein overexpression in colorectal cancer: a dominant predictor of survival in patients with advanced hepatic metastases.

PURPOSE: To determine whether p53 protein expression is similar within primary colorectal cancer (CRC) and synchronous regional and distant metastases and to assess whether p53 nuclear protein expression could predict outcome in patients with synchronous unresectable liver metastases treated by hepatic artery infusional (HAI) chemotherapy. MATERIALS AND METHODS: Paraffin sections from tumor and corresponding normal mucosa representative of 50 consecutive advanced CRC cases were examined for p53 nuclear protein expression by immunohistochemistry using the monoclonal antibody PAb 1801. Patterns of p53 nuclear expression were correlated with standard clinicopathologic variables and outcome, including response to HAI and survival. In a subset analysis, the pattern of nuclear p53 immunoreactivity was compared between primary CRC and lymph node and liver metastases. RESULTS: Positive nuclear immunoreactivity for p53 protein was found in 72% of cases. The pattern of p53 protein expression in lymph node and liver metastases was identical to that of the primary tumor. The median survival time was 21.0 months in patients with p53-positive tumors and 53.2 months in patients with p53-negative tumors (Wilcoxon test P = .038). Two-year survival rates were 41.7% and 78.6%, respectively (P < .01). No significant difference was found in the response rates to HAI chemotherapy between the two groups. By multivariate analysis, p53 protein status was the single best predictor of survival, with a relative risk of 6.312. CONCLUSION: Our results indicate that nuclear p53 protein status in primary CRC is similar to that in metastatic sites and may be the dominant predictor of survival in patients with advanced hepatic metastases.

p53 nuclear overexpression: an independent predictor of survival in lymph node--positive colorectal cancer patients.

PURPOSE: This study was performed to determine the prognostic significance of p53 gene overexpression in a homogeneous group of node-positive colorectal cancer patients. MATERIALS AND METHODS: Paraffin sections from the primary tumors in 107 colorectal cancer patients who had preoperative serum carcinoembryonic antigen (CEA) levels less than five were examined for the expression of p53 nuclear protein by immunohistochemical staining using the monoclonal antibody PAb 1801. The nuclear p53 overexpression was compared with clinicopathologic variables and follow-up data. RESULTS: Positive staining was not observed in normal colorectal mucosal cells. Specific p53 nuclear staining was detected in primary tumor from 50 patients (46.7%). p53 nuclear overexpression was not significantly correlated with patients' sex, age, tumor location, differentiation, T stage, N stage, and lymphatic and/or vascular vessel invasion. With a median follow-up of 61.7 months, 60% of the p53-positive patients have had disease recurrence, versus only 35% of the p53-negative group (P = .02). Forty-two percent of the p53-positive patients died of colorectal cancer compared with 21.1% of the p53-negative patients (P = .03). By multivariate analysis, p53 overexpression was found to be an independent predictor for disease-free and disease-specific survival. CONCLUSION: In node-positive colorectal cancer patients with low preoperative CEA levels, nuclear p53 overexpression as determined by immunohistochemistry on archived tissue is an independent predictor for prognosis.

Elevated tissue inhibitor of metalloproteinase 1 RNA in colorectal cancer stroma correlates with lymph node and distant metastases.

Tissue inhibitor of metalloproteinase (TIMP) inhibits the proteolytic activity of several matrix metalloproteinases centrally involved in tumor invasion and metastases. The purpose of this study was to determine the origin of TIMP-1 mRNA production in both human colorectal cancer (CRC) and metastatic liver lesions as well as define the relationships between TIMP-1 RNA expression and standard clinicopathological variables of CRC. Total cellular RNA, extracted from 56 CRC and 10 liver metastases, were examined by Northern blot hybridization. The mean/normal mucosa fold increase of TIMP-1 RNA was significantly elevated in both CRC (12.1 +/- 1.7) and liver metastases (10.0 +/- 3.6). No relationship was noted between TIMP-1 expression and tumor size, location nor differentiation. Based on lymph node metastases status, significantly higher TIMP-1 RNA levels were found in CRC with metastases than in those without metastases (15.6 +/- 3.3 versus 7.9 +/- 1.3) (P = 0.04). Similarly, TIMP-1 RNA levels were higher in primary CRC with distant metastases than those without distant metastases (17.6 +/- 4.1 versus 9.3 +/- 1.9) (P = 0. 04). In situ hybridization localized TIMP-1 mRNA predominantly in tumor stroma within spindle fibroblast-like cells rather than in cancer cells themselves. The correlation between the increased TIMP-1 mRNA level and advanced CRC stage noted in this study reflects a possible growth-promoting function for TIMP-1 in human CRC.

Metastatic colorectal cancer cells induce matrix metalloproteinase release by human monocytes.

Matrix metalloproteinases-2 (MMP-2) and -9 (MMP-9) facilitate tumor invasion and metastasis via basement membrane degradation. In colorectal cancer (CRC) specimens, MMP production is largely stromal in origin, implicating monocytes (M phi s) and fibroblasts. We hypothesize that CRC cells induce stromal cell MMP production. This study examines the differential effect of metastatic and non-metastatic CRC cells on M phi MMP production. The human M phi line THP-1 was co-cultured with either a non-metastatic human CRC cell line (SW620-P) or a metastatic clone (SW620-S5) established by serial cecal transplantation of SW620-P in nude mice. Conditioned medium MMP activity and cellular MMP mRNA expression were assessed by gelatinase zymography and Northern blot analysis, respectively. Neither CRC line released MMP-2 or MMP-9. Isolated THP-1 M phi s produced basal levels of both MMP-2 and MMP-9. The level of MMP-9 activity was increased moderately by co-culture of M phi s with the metastatic SW620-S5 clone, but decreased by the non-metastatic SW620-P cells. MMP-2 activity was greatly augmented by co-culturing M phi s with SW620-S5 cells, but was not affected by SW620-P cells. The stimulatory effect of SW620-S5 cells on MMP-2 secretion was confirmed by Western blot analysis. Both isolated and co-cultured M phi s expressed MMP-2 mRNA while SW620-S5 cells under similar conditions did not, implicating M phi s as the source of increased MMP-2 activity. Since the induction of MMP-2 activity was not associated with a parallel increase in M phi MMP-2 mRNA, the modulation of M phi MMP-2 release appears to be post-transcriptionally regulated. Metastatic CRC cells are distinct from non-metastatic cells in their ability to induce M phi MMP release. This observation emphasizes the role of M phi-derived MMPs in facilitating CRC invasion and metastasis and suggests modulation of stromal cell MMP production by CRC cells in a paracrine fashion.

Metastatic and non-metastatic colorectal cancer (CRC) cells induce host metalloproteinase production in vivo.

Numerous studies have demonstrated the persistent localization of matrix metalloproteinase (MMP) expression to the interface between invading human colorectal cancer (CRC) cells and surrounding stroma supporting a role for MMPs in CRC invasion and metastasis. The present study sought to determine whether CRC cells of varying metastatic potential would have differential effects on host MMP release. Subcutaneous CRC tumors were generated in BALB/c nude mice using three CRC cell lines: SW480, SW620, and the highly metastatic SW620S5 clone. Representative samples from the subcutaneous CRC were then orthotopically implanted on the cecum of recipient nude mice. Subcutaneous and cecal tumors were analyzed for MMP expression via zymography, western blot, and RT-PCR. In vitro, none of the three cell lines expressed MMP-2 nor MMP-9. In contradistinction, the subcutaneous tumors expressed limited amounts of MMP-2 and MMP-9 while the cecal tumors expressed significant amounts of MMP-2 and MMP-9 as well as other smaller members of the MMP family. MMP-9 mRNA and protein was confirmed as host in origin by RT-PCR with mouse specific primers and a mouse MMP-9 molecular weight of 105 kDa as determined by zymography and western blot analysis. In situ hybridization also localized the mRNA for MMP-9 to the host stromal cells. In conclusion, CRC cells appear incapable of producing MMP-2 and MMP-9 in vitro but are capable of up-regulating host MMP production in vivo. Enhanced host MMP-9 production in metastatic CRC cell-derived subcutaneous and cecal tumors suggests that metastatic colon cells may acquire the expression of important MMP regulating factor(s) in vivo.

Current issues in colorectal cancer surgery.

Increased understanding of the pathology and natural history of colorectal cancer has led to significant advances in the management of this disease. Surgical management of rectal cancer currently includes a spectrum of operative procedures ranging from radical operations to innovative sphincter-preserving techniques. At one end of the spectrum, 5% to 10% of patients present with small, superficially invasive rectal cancers amenable to a curative local excision. At the other end, a subset of patients present with locally advanced rectal cancers that require multimodality therapy, including sharp pelvic dissection with en-bloc resection of involved organs. However, the majority of rectal cancer patients present with nonfixed, yet deeply invasive, lesions requiring either a low anterior resection (LAR) or an abdominal perineal resection (APR). This report will address the controversies in the surgical management of colorectal cancer.

Sphincter preservation in rectal cancer with preoperative radiation therapy and coloanal anastomosis: long term follow-up.

BACKGROUND: To determine if preoperative radiation therapy allows sphincter preservation in the treatment of rectal cancer. METHODS: Thirty six patients with the diagnosis of invasive, resectable, primary adenocarcinoma of the rectum limited to the pelvis were enrolled on a Phase I/II trial of preoperative radiation therapy plus low anterior resection/coloanal anastomosis. By preoperative assessment, all patients had invasive tumors (5,T2; 31,T3) involving the distal half of the rectum and clinically required an abdominoperineal resection. The median tumor size was 3.8 cm [range: 1.5-7 cm] and the median distance from the anal verge was 4 cm [range: 3-7 cm]. The whole pelvis received 46.80 Gy followed by a 3.60 Gy boost to the primary tumor bed. The median follow-up was 56 months [range: 4-121 months]. RESULTS: Of the 35 patients who underwent resection, 5 (14%) had a complete pathologic response and 27 (77%) were able to successfully undergo a low anterior resection/coloanal anastomosis. The incidence of local failure was crude: 17% and 5-year actuarial: 21%. The 5-year actuarial survival was 64%. Analysis of sphincter function using a previously published scale was performed at the time of last follow-up in the 27 patients who underwent a low anterior resection/coloanal anastomosis. Function was good or excellent in 85%. The median number of bowel movements/day was 2 (range: 0-8). CONCLUSIONS: Our data suggest that preoperative radiation therapy allows sphincter preservation in 77% of selected patients who would otherwise require an abdominoperineal resection, and 85% have good to excellent sphincter function. Given the moderate local failure rate, we now routinely use preoperative combined modality therapy plus postoperative chemotherapy for patients with clinical T3 disease.

Conservative management of rectal cancer with local excision and postoperative adjuvant therapy.

BACKGROUND: To determine the local control, survival, and functional outcome of local excision plus postoperative therapy for patients with rectal cancer. METHODS: A total of 39 patients underwent a local excision (2 with snare excision of a T1 polyp and 37 with full-thickness local excision) followed by postoperative radiation therapy +/- 5-FU-based chemotherapy. The median follow-up was 41 months, and 11 patients had positive margins. RESULTS: The 5-year actuarial colostomy-free survival was 87% and overall survival was 70%. Crude local failure increased with T stage: 0% T1, 24% T2, and 25% T3. Of the 8 patients (21%) who developed local failure, 5 underwent salvage APR and were locally controlled. Actuarial local failure at 5 years was 31% for T2 disease and 27% for the total patient group. In the 32 patients with an intact sphincter, 94% had good to excellent sphincter function. CONCLUSION: Although local failure in patients with T2 tumors has increased since our prior report, the survival, sphincter function, and local salvage rates are acceptable. Local excision and postoperative therapy remains a reasonable alternative to APR in selected patients.