Considering Value in Rectal Cancer Surgery: An Analysis of Costs and Outcomes Based on the Open, Laparoscopic, and Robotic Approach for Proctectomy.

OBJECTIVE: The aim of the study was to compare value (outcomes/costs) of proctectomy in patients with rectal cancer by 3 approaches: open, laparoscopic, and robotic. BACKGROUND: The role of minimally invasive proctectomy in rectal cancer is controversial. In the era of value-based medicine, costs must be considered along with outcomes. METHODS: Primary rectal cancer patients undergoing curative intent proctectomy at our institution between 2010 and 2014 were included. Patients were grouped by approach [open surgery, laparoscopic surgery, and robotic surgery (RS)] on an intent-to-treat basis. Groups were compared by direct costs of hospitalization for the primary resection, 30-day readmissions, and ileostomy closure and for short-term outcomes. RESULTS: A total of 488 patients were evaluated; 327 were men (67%), median age was 59 (27-93) years, and restorative procedures were performed in 333 (68.2%). Groups were similar in demographics, tumor characteristics, and treatment details. Significant outcome differences between groups were found in operative and anesthesia times (longer in the RS group), and in estimated blood loss, intraoperative transfusion, length of stay, and postoperative complications (all higher in the open surgery group). No significant differences were found in short-term oncologic outcomes. Direct cost of the hospitalization for primary resection and total direct cost (including readmission/ileostomy closure hospitalizations) were significantly greater in the RS group. CONCLUSIONS: The laparoscopic and open approaches to proctectomy in patients with rectal cancer provide similar value. If robotic proctectomy is to be widely applied in the future, the costs of the procedure must be reduced.

Factors associated with the location of local rectal cancer recurrence and predictors of survival.

PURPOSE: The location of locally recurrent rectal cancer (LRRC) may influence survival. This study examines factors affecting the location of LRRC, the effect of LRRC location on survival, and predictive factors for survival in patients with LRRC. METHODS: Patients undergoing initial proctectomy and subsequent management of LRRC at the Cleveland Clinic (1980-2011) were included. Data regarding index surgery, LRRC, and survival were obtained from a prospectively maintained database. RESULTS: One hundred and fifty-seven patients were identified with a mean follow-up 59.8 ± 50.1 months and time to LRRC of 31.7 ± 30.1 months. Sixty patients underwent surgery with curative intent. Anastomotic leak and retrieving less than 12 lymph nodes at index proctectomy were associated with posterior (P = 0.019) and lateral (P = 0.036) recurrences, respectively. Having an axial relative to an anterior, posterior, or lateral recurrence was associated with improved overall survival (P = 0.001). On multivariable analysis, undergoing primarily palliative treatment (OR, 5.2; 95 % confidence interval (CI), 3.2-8.4; P < 0.001), age at LRRC >60 years (OR, 1.9; 95 % CI, 1.3-2.7, P < 0.001), advanced primary tumour stage (OR, 1.5; 95 % CI, 1.1-2.1; P = 0.021), and anastomotic leak at index surgery (OR, 1.8; 95 % CI, 1.2-2.7; P = 0.008) were associated with reduced LRRC 5-year survival. CONCLUSIONS: The current study suggests that features of the primary tumour and technical factors at the time of index proctectomy influence both the location of LRRC and survival.

Risk and location of cancer in patients with preoperative colitis-associated dysplasia undergoing proctocolectomy.

OBJECTIVE: To evaluate the influence of preoperative dysplasia grade, appearance, and site on risk and location of cancer in patients with colitis. BACKGROUND: The ability to predict the presence and location of cancer in colitis patients with dysplasia is essential to facilitate recommendations regarding the necessity and type of surgery. METHODS: Ulcerative and indeterminate colitis patients who underwent proctocolectomy for dysplasia were retrospectively selected. Patient characteristics and findings at colonoscopic surveillance were associated with findings on the surgical specimen by regression analysis. RESULTS: From 1984 to 2007, 348 proctocolectomy specimens with preoperative dysplasia showed cancer in 51 (15%) and dysplasia in 172 (49%) cases. Patients with preoperative high-grade dysplasia (HGD) had cancer in 29% compared with 3% in low-grade dysplasia (LGD) (P < 0.001). Patients with preoperative dysplasia-associated lesion/mass (DALM) had cancer in 25% compared with 8% in flat dysplasia (P < 0.001). In LGD with DALM, the risk of cancer was not significantly higher than in flat LGD (7% vs 2%, P = 0.3), but risk of cancer or HGD was higher with a threefold increase (29% vs 9%, P = 0.015). On multivariate analysis, HGD, DALM, and disease duration were independent risk factors for postoperative cancer. In patients with isolated colonic dysplasia above the sigmoid level, postoperative rectal involvement was limited. CONCLUSIONS: Risk of cancer for patients with HGD or DALM is substantial. Despite low risk of cancer in patients with flat LGD, threshold for surgery should be low given the high prevalence of postoperative pathologic findings. Only in selected cases, colonoscopic surveillance after discussion of associated risks may be acceptable, provided high patient compliance can be assured. Surgery should be considered in all other cases, because it is the only modality that can eliminate the risk of cancer. The location of preoperative dysplasia may allow for the clarification of the need for proctectomy especially in the poor risk surgical patient.

Less than 12 nodes in the surgical specimen after total mesorectal excision following neoadjuvant chemoradiation: it means more than you think!

BACKGROUND: A minimum of 12 examined lymph nodes (LN) is recommended to ensure adequate staging and oncologic resection of patients undergoing proctectomy for rectal adenocarcinoma. However, a decreased number of LN is not unusual in patients receiving neoadjuvant chemoradiation. PURPOSE: We hypothesized that a decreased number of LN in the proctectomy specimen of these patients may be an indicator of tumor response and be associated with improved prognosis. METHODS: A single-center colorectal cancer database was queried for c-stage II-III rectal cancer patients undergoing neoadjuvant chemoradiation followed by proctectomy between 1997 and 2007. Patients were categorized into two groups according to the number of LN retrieved from the proctectomy specimen: <12 LN versus ≥12 LN. Groups were compared with respect to demographics, tumor and treatment characteristics, and the following oncologic outcomes: overall-survival (OS), cancer-specific-mortality (CSM), cancer-free-survival (CFS), distant (DR), and local recurrences (LR). RESULTS: The query returned 237 patients. There were 173 (73 %) males, and the median age was 57 years [interquartile range (IQR) 49-66 years]. The median number of LN retrieved was 15 (IQR 10-23) and 70 (30 %) patients had less than 12 nodes examined. The <12 nodes group was older [60 (IQR 51-71 years) vs. 55 (IQR 48-65 years), p = 0.009] and had more pathologic complete responders (36 vs. 19 %, p = 0.01). No <12 nodes patient experienced a LR, whereas the 5-year LR rate was 11 % in the ≥12 nodes group (p = 0.004). Other oncologic outcomes were not significantly different. CONCLUSIONS: Retrieval of less than 12 nodes in the proctectomy specimen of rectal cancer patients treated with neoadjuvant chemoradiation does not affect OS, CSM, CFS, or DR and may be a marker of higher tumor response and, consequently, decreased LR rate.

Impact of obesity on operation performed, complications, and long-term outcomes in terms of restoration of intestinal continuity for patients with mid and low rectal cancer.

BACKGROUND: The impact of obesity per se on the surgical strategy, ie, sphincter sacrifice (abdominoperineal resection) vs sphincter-preserving resection, outcomes, and long-term maintenance of intestinal continuity has been poorly studied in patients with mid and low rectal cancer. OBJECTIVE: The aim of this study is to compare the outcomes and long-term maintenance of intestinal continuity for obese and nonobese patients treated surgically for mid and low rectal cancers. DESIGN: This is a retrospective cohort study from a prospectively collected database. SETTING: The investigation took place in a high-volume specialized colorectal surgery department. PATIENTS: All patients who underwent curative surgery for mid or low rectal adenocarcinoma at a single institution from 1976 to 2011 were identified. MAIN OUTCOME MEASURES: Obese (BMI ≥ 30 kg/m) and nonobese patients were matched 1:2 for age, sex, ASA class, location, and stage of tumor. Demographics, use of neoadjuvant chemoradiotherapy, operative and perioperative outcomes, pathology, long-term outcomes including oncologic outcomes, and whether restoration of intestinal continuity was obtained were compared. RESULTS: One hundred fifty-seven obese patients and 314 nonobese patients were included in the study. The groups were similar for matched characteristics. The use of neoadjuvant chemoradiotherapy (p = 0.048) and anastomotic leak (p = 0.0003) rates were higher in obese patients. A similar proportion of nonobese and obese patients underwent sphincter-preserving resection (p > 0.99), and postoperative hospital stay (p = 0.23), 30-day postoperative reoperation (p = 0.83), mortality (p > 0.99), and readmissions (p = 0. 13) were similar. The obese and nonobese groups had similar overall (p = 0.61) and disease-free survival (p = 0.74) at a mean follow-up of 5 years for both groups. LIMITATIONS: This study was limited by its retrospective and nonrandomized nature. CONCLUSION: At a high-volume specialized colorectal unit, proctectomy can be performed in obese patients with similar long-term oncologic outcomes and ability to restore intestinal continuity in comparison with nonobese patients. Proctectomy in obese patients, however, is associated with an increased risk of anastomotic leak in comparison with nonobese patients.

Endorectal ultrasound does not reliably identify patients with uT3 rectal cancer who can avoid neoadjuvant chemoradiotherapy.

PURPOSE: Neoadjuvant chemoradiation (NCRT) may be avoided in some patients with T3-staged rectal cancer undergoing radical resection. We aimed to evaluate the accuracy of endorectal ultrasound (ERUS) in the nodal staging of uT3 tumors and hence the decision for administration of NCRT. METHODS: Patients with uT3-staged rectal cancer who underwent proctectomy were retrospectively identified. The accuracy of ERUS for detecting nodal involvement was determined for patients who did not undergo NCRT. In order to evaluate the impact of use of NCRT, oncologic outcomes, functional outcomes, and quality of life (QOL) were compared for patients who received NCRT (group A) and those who did not (group B). RESULTS: For 384 patients who were included, ERUS overstaging rate for nodal involvement was 6.3% while understaging rate was 23.2%. For the 289 patients in group A and 95 in group B, Kaplan-Meier analysis showed similar 5-year local recurrence rates (3.5%), overall survival (76.9 vs 75.6%), and disease-free survival (87.9 vs 88.1%). Node positivity on final pathology was however associated with worse 5-year local recurrence (9.3 vs 4.3%). For patients undergoing restorative resection, NCRT was associated with worse functional outcomes but QOL was similar. CONCLUSIONS: ERUS identification of nodal involvement used as a criterion for NCRT carries a greater risk for undertreatment than overtreatment. Undertreatment adversely affects oncologic outcomes. While there is functional impairment related to NCRT, its effect on QOL is non-significant. The decision for omitting neoadjuvant chemoradiation for uT3 rectal cancer should hence not be based on ERUS nodal staging alone.

Dysplasia associated with Crohn's colitis: segmental colectomy or more extended resection?

BACKGROUND AND OBJECTIVE: There is limited data on the appropriate management of dysplasia in Crohn's colitis. An evidence-based surgical strategy is provided. METHODS: Patients with a pathologic diagnosis of dysplasia in Crohn's colitis from 1987 to 2009 were identified. Patients were classified by dysplasia grade (low grade or LGD, high grade or HGD). Clinical, endoscopic, operative, and pathologic data were retrieved. Factors associated with a final cancer diagnosis were analyzed. Survival data on patients undergoing limited versus radical resection for cancer and HGD was compared. RESULTS: From 1987 to 2009, 50 patients underwent a colectomy for Crohn's colitis-associated dysplasia. The predictive value of HGD for a final HGD or cancer diagnosis was 73%. The predictive value of LGD on biopsy for HGD in the colectomy was 36%. Sixteen patients (44%) who underwent a total proctocolectomy (TPC) or subtotal colectomy (STC) had multifocal dysplasia. Four of 10 (40%) cancer patients had evidence of dysplasia remote from cancer site on pathologic examination. During follow-up, there were 3 cancer-related deaths. One patient died of metachronous cancer after STC. CONCLUSIONS: The findings confirm the risk of cancer in patients with CD dysplasia. Because of the multifocal nature of dysplasia in Crohn's colitis, TPC is recommended in good-risk patients. In specific circumstances, such as poor-risk patients especially in the setting of LGD, close endoscopic surveillance or alternatively segmental or STC with close postoperative endoscopic surveillance, depending upon the individual circumstance, may be discussed.

Is adjuvant chemotherapy really needed after curative surgery for rectal cancer patients who are node-negative after neoadjuvant chemoradiotherapy?

PURPOSE: Adjuvant chemotherapy is currently offered, as standard, after curative resection for patients with rectal cancer who receive neoadjuvant chemoradiation (NCRT). We postulate that adjuvant chemotherapy adds minimal oncologic benefit for patients who undergo total mesorectal excision who are node-negative after neoadjuvant chemoradiation. METHODS: From a prospective, institutional cancer database, rectal cancer patients who completed neoadjuvant chemoradiation and curative surgery (2000-2008) and were node-negative on final pathology were identified. Patient, tumor, treatment characteristics, and oncologic outcomes were compared for patients who completed intended adjuvant chemotherapy (group chemo) or did not receive any chemotherapy (group no-chemo). RESULTS: Chemo (n=58) and no-chemo (n=70) patients had similar age (P=0.13), gender (P=0.67), body mass index (P=0.46), American Society of Anesthesiologists class (P=0.67), preoperative tumor stage (P=0.16), type of surgery (P=0.76), and postoperative complications. The no-chemo group had greater complete pathologic response (n=34, 48.6% vs. n=14, 24.1%). After prolonged follow-up, local recurrence (P=1), disease-free survival (P=0.41), and overall survival (P=0.52) were similar. Oncologic benefits of adjuvant chemotherapy were especially questionable for patients with complete pathologic response (chemo vs. no-chemo, local recurrence at 5 years: 0 vs. 2.9%, P>0.99), disease-free (79.1% vs. 88%, P=0.51), and overall survival (90.9% vs. 95.2%, P=0.41). CONCLUSIONS: These results question the routine use of adjuvant chemotherapy for patients with rectal cancer who undergo curative surgery who have been rendered node-negative by neoadjuvant chemoradiation.

Effects of chronic immunosuppression on long-term oncologic outcomes for colorectal cancer patients undergoing surgery.

INTRODUCTION: The effects of chronic immunosuppressive therapy (CIST) on long-term oncologic outcomes for patients who undergo surgery for colorectal cancer are not known. We investigate whether CIST affects these outcomes. METHODS: From a prospective colorectal cancer database, patients undergoing colorectal resection for cancer between 1996 and 2005 and on CIST (steroids and/or cyclosporine, azathioprine, 6-mercaptopurine, FK-506, methotrexate) were identified and compared with a control group matched for age(±5 year), gender, type, and year (±2 year) of operation; American Society of Anesthesiology score; cancer stage; differentiation; vascular invasion; blood transfusion; and postoperative adjuvant therapy. The groups were compared for early and long-term outcomes. Cox models produced hazard ratios and Wald P values to assess associations between survival and the presence of immunosuppressive treatment. RESULTS: Fifty-five (20 female and 35 male) patients were on CIST for inflammatory disease, transplantation, chronic obstructive lung disease, other cancers, and hypopituitarism. Both groups were comparable for the matched characteristics. Chronic immunosuppressive therapy and control groups had similar overall postoperative morbidity (36.4% vs 27.3%, P = 0.3) and wound infection rates (14.5% vs 5.5%, P = 0.13). Chronic immunosuppressive therapy group had significantly lower 3- and 5-year overall (49.1% vs 76.3%, and 45.1% vs 66.2%, respectively, P = 0.003) and disease-free survival (45.5% vs 69.1%, and 41.7% vs 63.3%, respectively, P = 0.005) than the control group. Local recurrence was similar between groups. CONCLUSION: Patients on chronic immunosuppression tolerate colorectal cancer resection but have significantly worse long-term oncologic outcomes.These findings need careful consideration when evaluating the relative roles of the various treatment modalities for this group of patients presenting with colorectal cancer.

Preoperative colorectal neoplasia increases risk for pouch neoplasia in patients with restorative proctocolectomy.

BACKGROUND & AIMS: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has substantially reduced the risk for ulcerative colitis (UC)-associated dysplasia or cancer (neoplasia). We characterized features, risk factors, and outcomes of pouch neoplasia in patients with inflammatory bowel disease in a historical cohort study. METHODS: A total of 3203 patients with a preoperative diagnosis of inflammatory bowel disease underwent restorative proctocolectomy with IPAA from 1984 to 2009 at the Cleveland Clinic. Demographic, clinical, and endoscopic data were reviewed and samples were examined by histological analyses. Univariable and Cox regression analyses were performed. RESULTS: Cumulative incidences for pouch neoplasia at 5, 10, 15, 20, and 25 years were 0.9%, 1.3%, 1.9%, 4.2%, and 5.1%, respectively. Thirty-eight patients (1.19%) had pouch neoplasia, including 11 (0.36%) with adenocarcinoma of the pouch and/or the anal-transitional zone (ATZ), 1 (0.03%) with pouch lymphoma, 3 with squamous cell cancer of the ATZ, and 23 with dysplasia (0.72%). In the Cox model, the risk factor associated with pouch neoplasia was a preoperative diagnosis of UC-associated cancer or dysplasia, with adjusted hazard ratios of 13.43 (95% confidence interval: 3.96-45.53; P < .001) and 3.62 (95% confidence interval: 1.59-8.23; P = .002), respectively. Mucosectomy did not protect against pouch neoplasia. CONCLUSIONS: Risk for neoplasia in patients with UC and IPAA is small and not eliminated by colectomy or mucosectomy. A preoperative diagnosis of dysplasia or cancer of colon or rectum is a risk factor for pouch dysplasia or adenocarcinoma.

Pathologic complete response after neoadjuvant treatment for rectal cancer decreases distant recurrence and could eradicate local recurrence.

BACKGROUND: The aim of this study was to evaluate the clinical implications of pathologic complete response (pCR) (i.e., T0N0M0) after neoadjuvant chemoradiation and radical surgery in patients with locally advanced rectal cancer. MATERIALS AND METHODS: A single-center, prospectively maintained colorectal cancer database was queried for patients with primary cII and cIII rectal cancer staged by CT and ERUS/MRI undergoing long-course neoadjuvant chemoradiation followed by proctectomy with curative intent between 1997 and 2007. Patients were stratified into pCR and no-pCR groups and compared with respect to demographics, tumor and treatment characteristics, and oncologic outcomes. Outcomes evaluated were 5-year overall survival, disease-free survival, disease-specific mortality, local recurrence, and distant recurrence. RESULTS: The query returned 238 patients (73% male), with a median age of 57 years and median follow-up of 54 months. Of these, 58 patients achieved pCR. Patients with pCR vs no-pCR were statistically comparable with respect to demographics, chemoradiation regimens, tumor distance from anal verge, clinical stage, surgical procedures performed, and follow-up time. No patient with pCR had local recurrence. Overall survival and distant recurrence were also significantly improved for patients achieving pCR. CONCLUSIONS: Achievement of pCR after neoadjuvant chemoradiation is associated with greatly improved cancer outcomes in locally advanced rectal cancer. Future studies should evaluate the relationship between increases in pCR rates and improvements in cancer outcomes in this population.

Does a subcentimeter distal resection margin adversely influence oncologic outcomes in patients with rectal cancer undergoing restorative proctectomy?

BACKGROUND: A 1-cm distal clearance margin is recommended for mid/low rectal cancers. OBJECTIVE: We evaluate whether shorter distal margins after restorative rectal resection affect oncologic outcomes for patients with a clear circumferential margin. DESIGN: From a prospective cancer database, patients undergoing restorative proctectomy for mid/lower third rectal cancer from 1991 to 2006 with a distal margin of ≤ 1 cm (group A) were compared with those with >1-cm distal margin (group B) for demographics, tumor, treatment, and outcomes. The impact of a distal margin ≤ 0.5 cm was also similarly assessed. RESULTS: Of 784 patients, distal resection margin was ≤ 1 cm in 198 and >1 cm in 586. Local recurrence occurred in 26 patients (3.3%). Mean distal resection margin was 2.3 ± 1.6 cm. Group A was associated with a lower level of tumor (1.3, 0.1-9 cm vs 2, 0.1-9 cm; P < .001), a higher rate of handsewn anastomosis (29.5% vs 12.9%, P < .001), and fewer T3/T4 tumors (28.2% vs 39.1%, P = .06). The 5-year local recurrence rate was 4.4% in group A and 4.3% in group B, and was 6.4% in patients with a distal margin <5 mm and 4.1% in those with a distal margin >5 mm. On multivariable analysis, local recurrence or disease-free survival was not associated with distal margin irrespective of whether this was <1 or <0.5 cm, adjusting for age, sex, use of adjuvant therapy, T stage, and differentiation. CONCLUSIONS: A distal resection margin of <1 cm for patients undergoing restorative radical resection for low-lying rectal cancer does not adversely influence oncologic outcomes when other factors are carefully considered and a multimodality approach is used. This factor, when carefully considered, will help avoid a permanent stoma in some circumstances.

Prone or lithotomy positioning during an abdominoperineal resection for rectal cancer results in comparable oncologic outcomes.

BACKGROUND: There is debate whether performing the perineal part of the abdominoperineal resection in a prone position in comparison with a lithotomy position optimizes circumferential resection margins and, subsequently, cancer outcomes. OBJECTIVE: The aim of this study was to compare outcomes of patients undergoing abdominoperineal in a prone vs a lithotomy position. DESIGN: A single-center, prospectively maintained colorectal cancer database was queried for patients with stages I to III rectal cancer undergoing abdominoperineal resection in a prone vs a lithotomy position from 1997 to 2007. Patients were compared with respect to demographics, tumor and treatment characteristics, perioperative morbidity, and oncologic outcomes. Oncologic outcomes were adjusted for age, ASA class, tumor stage, and use of adjuvant treatments. χ², Fisher exact probability test, Wilcoxon rank-sum test, Kaplan-Meier estimates, log-rank sum test, and Cox regression models were used for the analysis. P < .05 was considered significant. RESULTS: The query returned 168 patients (81 prone and 87 lithotomy), with a median age of 63 (interquartile range, 52-74) years and a median follow-up of 42 (interquartile range, 23-69) months. Prone and lithotomy patients were not statistically different regarding demographics, tumor stage, rates of R0 resection, number of harvested nodes, perioperative morbidity, follow-up time, and oncologic outcomes. CONCLUSIONS: Surgical positioning during the perineal part of the abdominoperineal resection does not affect perioperative morbidity or oncologic outcomes and should be left to the surgeon's discretion.

Colorectal cancer complicating inflammatory bowel disease: similarities and differences between Crohn's and ulcerative colitis based on three decades of experience.

INTRODUCTION: The aim of this study was to evaluate patient- and tumor-related characteristics for patients undergoing surgery for cancer complicating inflammatory bowel disease (IBD), and to assess differences between patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Data on all IBD patients with colon and rectal cancer (CRC) undergoing surgery between 1980 and 2007 were evaluated from prospectively maintained CRC and IBD databases. Clinical presentation, tumor stage, presence of associated dysplasia, and short- and long-term outcomes after surgery were investigated. Outcomes for IBD patients were compared with a matched group of patients with sporadic cancer. RESULTS: A total of 240 IBD patients (64 CD and 176 UC) with CRC were identified. At the time of CRC diagnosis, 68% UC and 26% CD patients had pancolitis. About 92% of the patients who underwent preoperative colonoscopy were noted to have suspicious lesions. Although 92.5% of the patients had a preoperative histopathologic diagnosis of cancer or dysplasia, incidental diagnosis of cancer in the resection specimen was made in 3%. Examination of the resection specimen revealed synchronous dysplasia in 48% of the patients and synchronous cancer in 12% patients. Tumor location was rectum in 36%, right colon in 28%, sigmoid colon in 17%, transverse colon 10%, and left colon in 9% of patients. CD patients were diagnosed at a more advanced cancer stage than UC. Local recurrence and overall 5-year survival rates were comparable (5.6% vs. 6.7%, P = 0.78 and 77% vs. 72%, P = 0.5, respectively) for patients with IBD and sporadic cancer. CONCLUSIONS: Most IBD cancer can be diagnosed or suspected on the basis of endoscopic findings, biopsy of areas of active colitis, and an incidental finding of malignancy after colorectal resection for other indications is rare. CD patients present with a more advanced cancer stage. Optimal endoscopic surveillance may identify most patients with IBD cancer.

Downstaging without complete pathologic response after neoadjuvant treatment improves cancer outcomes for cIII but not cII rectal cancers.

BACKGROUND: The aim of this study was to evaluate whether downstaging impacts prognosis in patients with cII versus cIII rectal cancer. MATERIALS AND METHODS: We identified from our colorectal cancer database 295 patients with primary cII and cIII rectal cancer staged by CT and ERUS/MRI who received 5-FU-based chemoradiation followed by R0 surgery after a median interval of 7 weeks during 1997-2007. The median radiotherapy dose was 5040 cGy. We excluded 58 patients with pathologic complete response (pCR) and compared among the remaining 162 patients pathologic downstaging (cII to ypI, cIII to ypII or ypI) versus no pathologic downstaging (c stage < or = yp stage). Outcomes evaluated were 5-year overall survival, 3-year cancer-specific survival, disease-free survival, overall recurrence, local recurrence, and distant recurrence. RESULTS: The median age was 58 years and median follow-up was 48 months. Patients with downstaging versus no downstaging were statistically comparable with respect to demographics, chemoradiation regimen, interval time between neoadjuvant chemoradiation and surgery, tumor distance from anal verge, surgical procedures performed, and follow-up time. With the exception of local recurrence rates, downstaging resulted in significantly improved cancer outcomes for cIII but not cII. CONCLUSIONS: Downstaging without pCR is a significant prognostic factor for patients with stage cIII rectal cancer. Tumor response to neoadjuvant chemoradiation should be taken into account when defining the optimal adjuvant chemotherapy regimen for patients with cIII rectal cancer.

Downstaging after chemoradiotherapy for locally advanced rectal cancer: is there more (tumor) than meets the eye?

PURPOSE: Preoperative chemoradiotherapy can lead to pathologic complete response of rectal cancer. This study was designed to determine the relationship between postchemoradiotherapy pathologic T stage (ypT stage) and nodal metastases and to evaluate whether pathologic complete response of the primary tumor results in sterilization of mesorectal lymph nodes. METHODS: Clinicopathological data from 1997 to 2007 of a prospectively maintained colorectal cancer database were examined. Inclusion criteria were patients with extraperitoneal rectal cancer who underwent preoperative chemoradiotherapy and subsequent radical resection. Statistical analysis was performed by use of Kruskall-Wallis and Wilcoxon rank-sum tests. RESULTS: Two hundred forty-two patients were identified (73.1% male, median age, 57 y (range, 36-85 y)). Data regarding preoperative chemoradiotherapy were available for 177 patients (73.1%). The median dose of radiotherapy was 5040 cGy (3060-6100 cGy). The mean preoperative radiotherapy dose and interval between chemoradiotherapy and surgery are similar when stratified by ypT stage (P = .55 and P = .72, respectively). Low anterior resection was performed in 174 patients (71.6%), and the remainder underwent abdominoperineal resection. A mural pathologic complete response was achieved in 62 patients (25.6%). In this pathologic complete-response group, positive lymph nodes were found in 2 patients (3.2%). The rate of metastatic lymph nodes increased as ypT stage increased (ypT1 = 11.1%, ypT2 = 29.2%, ypT3 = 37.3%). CONCLUSION: Patients with a mural pathologic complete response have a low rate of positive lymph nodes. These findings may have implications for the management strategies of these patients, including the use of local resection or a watch-and-wait policy. When the response to chemoradiotherapy is not complete, radical surgery should remain the treatment based on high rates of lymph node involvement.

How to evaluate risk and identify stage II patients requiring referral to a medical oncologist: a surgeon's perspective.

The surgical oncologist's ability to identify which patients with stage II colon cancer should be referred to a medical oncologist is subjective and qualitative. It includes assessment of the qualitative aspects of the pathology reports, the patient's suitability to receive potentially toxic medication, and their personal preference. The prognosis of colorectal cancer varies greatly in accordance with disease stage and tumor site. Patients with stage II colon cancer are cured with surgery alone in 75% to 80% of cases. This means that if all patients with stage II tumors are referred to a medical oncologist, a large number will receive treatment that is not necessary and potentially toxic. If none are referred, some will be undertreated. The question is how to identify those who should appropriately be considered for adjuvant therapy. In this article, we will discuss the strengths and limitations of the factors that must be considered when making the decision to refer to a medical oncologist or not.

Do preoperative factors predict subsequent diagnosis of Crohn's disease after ileal pouch-anal anastomosis for ulcerative or indeterminate colitis?

AIM: The aim of this study was to determine preoperative clinical factors associated with subsequent diagnosis revision to Crohn's disease (CD) following total proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) or indeterminate colitis (IC) patients. METHOD: Presumed UC and IC patients undergoing IPAA from a large single-institution prospective database with change of diagnosis to CD were identified and compared with patients without diagnosis change. RESULTS: A total of 2814 patients (47% male, median age 37 years) with presumed UC (85%) or IC (15%) underwent primary IPAA. At a median follow up of 9.6 years, 184 (7%) had the diagnosis revised to CD from histopathological examination of the colectomy specimen immediately in 97 (53%) or at a median interval of 36 months in 87 (47%). CD and UC/IC patients had had a similar operative technique, length of stay and 30-day morbidity. The postoperative CD diagnosis was associated with a preoperative diagnosis of IC (P < 0.0001) and perianal fistula (P = 0.002). Patients with a delayed diagnosis of CD were associated with a 3-stage procedure (P < 0.0001, OR = 2.8) (95% CI = 1.8-4.4), colonic stricture (P = 0.04, OR = 2.9 [95% CI = 1.1-7.4]), perianal fistula (P = 0.02, OR = 2.9 [95% CI = 1.2-7.2]), oral ulceration (P = 0.009, OR = 3.8 [95% CI = 1.2-9.6]) and younger age (P < 0.0001, OR = 0.048 [95% CI = 0.011-0.19]). CONCLUSION: A few patients having IPAA for presumed UC/IC were subsequently diagnosed to have CD which was associated with perianal fistula and the diagnosis of postoperative preoperative IC. The delayed diagnosis of CD was associated with a three-stage procedure, colorectal stricture, anal fissure, mouth ulceration and younger age.

Predictive factors of pathologic complete response after neoadjuvant chemoradiation for rectal cancer.

OBJECTIVE: This study evaluates factors associated with a pathologic complete response (pCR) after neoadjuvant chemoradiation for rectal cancer. SUMMARY BACKGROUND DATA: Approximately 20% of rectal cancer patients undergoing neoadjuvant chemoradiation achieve pCR, which has been associated with decreased local recurrence and improved recurrence-free survival. Means of predicting pCR remain incompletely defined. METHODS: A total of 306 consecutive patients with stage II or stage III rectal cancer who underwent neoadjuvant chemoradiation then surgery between 1997 and 2007 were identified from a single-institution. Sixty-four patients with concurrent inflammatory bowel disease, hereditary colorectal cancer, other malignancy, urgent surgery, incomplete chemoradiation, or insufficient data were excluded. All patients received neoadjuvant 5-FU-based chemotherapy and external beam radiation. Histologic response was categorized as pCR or not-pCR, which defined the 2 study cohorts. Variables were analyzed by univariate and multivariate analysis with pCR as the dependent variable. Fisher exact test, chi2, Wilcoxon rank-sum, and logistic regression were used for analysis. P < 0.05 was considered statistically significant. RESULTS: Of the total patients, 242 were studied, including 58 (24%) that achieved pCR. The 2 groups were statistically similar in terms of age, gender, body mass index, tumor differentiation, radiation dose, and pretreatment stage. On multivariate analysis, an interval ≥ 8 weeks between treatment completion and surgical resection was significantly associated with a higher rate of pCR, which correlated with decreased local recurrence and improved overall survival. CONCLUSION: Despite traditional beliefs that certain patient and tumor factors influence pCR, an extended interval between completion of neoadjuvant therapy and surgery was the single most important determinant in achieving a pCR.

Association between immune-associated disorders and adverse outcomes of ileal pouch-anal anastomosis.

OBJECTIVES: Autoimmune disorders (ADs) frequently coexist with inflammatory bowel disease. The aim of the study was to determine whether coexisting AD in patients with ileal pouches increases the risk for chronic antibiotic-refractory pouchitis (CARP) and other inflammatory conditions of the pouch. METHODS: A total of 622 patients seen in our Pouchitis Clinic were enrolled. We compared the prevalence of adverse outcomes of the pouch (including CARP, Crohn's disease of the pouch, and pouch failure) in patients with or without concurrent AD and assessed the factors for these adverse outcomes. RESULTS: There were seven pouch disease categories: normal (N=60), irritable pouch syndrome (N=112), active pouchitis (N=131), CARP (N=67), Crohn's disease (N=131), cuffitis (N=83), surgical complications (N=36), and anismus (N=2). The prevalence of AD in these pouch disease categories was 4.5%, 12.5%, 9.2%, 13.4%, 10.7%, 3.8%, 1.5%, and 0%, respectively. The presence of at least one AD at time of pouch surgery was shown to be associated with a twofold increase in the risk for CARP (hazard ratio=2.29; 95% CI: 1.52, 3.46; P<0.001) and for pouch-associated hospitalization (hazard ratio=2.39; 95% CI: 1.59, 3.58; P<0.001). The presence of AD was not associated with increased risk for irritable pouch syndrome, active pouchitis, Crohn's disease, cuffitis, surgical complications, or pouch failure. Patients with Crohn's disease of the pouch had a 2.42 times higher risk for pouch failure (P=0.042) than these without. Active smoking or a history of smoking was shown to be associated with an increased risk for pouch-associated hospitalization and pouch failure. CONCLUSIONS: AD appears to be associated with an increased risk for CARP, and the presence of the association between these AD and pouch disorders may stimulate further research on the link of these organ systems on an immunological basis.