Assessment of ideal ratio of mesh area to number of fixation tacks in laparoscopic ventral and incisional IPOM Plus hernia repair.

BACKGROUND: To clarify the optimum mesh-tack ratio MTR (mesh area in cm2 divided by the number of fixation tacks) in laparoscopic ventral and incisional hernia repair, we compared IPOM Plus procedures with more intensive mesh fixation to those with standard mesh fixation. METHODS: In a retrospective cohort study, 84 patients (mean hernia width 6.6 ± 4.4 cm) intraoperatively received an intensive mesh fixation I-IPOM Plus with MTR ≤ 4:1 (e.g. ,150 cm2 mesh fixed by 50 tacks) and 74 patients (mean hernia width 6.7 ± 3.4 cm) received a standard mesh fixation S-IPOM Plus with MTR > 4:1 (e.g., 150 cm2 mesh fixed by 30 tacks) at a community hospital between 2014 and 2017. Outcomes in recurrence rates, immediate and chronic postoperative pain, as well as long-term functionality of the abdominal wall were then evaluated. RESULTS: After a mean follow-up time of 34 months, a 2.3% recurrence rate in I-IPOM Plus patients and a 13.5% recurrence rate in S-IPOM Plus patients were recorded (p = 0.018). The recurrence was associated with large hernia > 10 cm (OR 3.7, 95% CI 1.3-5.4) and MTR > 5 (OR 2.4, 95% CI 1.1-3.8) in the multivariate analysis. There was a positive correlation between immediate postoperative pain intensity measured on day 7 and number of fixation tacks placed (I-IPOM Plus: mean 4.5 ± 2.5 VAS versus S-IPOM Plus: mean 2.7 ± 2.0 VAS, p = 0.001). However, there were no outcome differences in terms of length of immediate postoperative pain experience, sick leave duration, chronic pain rate and long-term abdominal wall functionality between these two groups. CONCLUSION: For ventral and incisional hernia patients with multiple recurrence risk factors, a mesh-tack ratio MTR ≤ 4:1 should be applied in laparoscopic IPOM Plus procedures.

Nonmetastatic pancreatic cancer : Improved survival with chemoradiotherapy > 40 Gy after systemic treatment.

PURPOSE: The role of radiotherapy (RT) for nonmetastatic pancreatic cancer is still a matter of debate since randomized control trials have shown inconsistent results. The current retrospective single-institution study includes both resected and unresected patients with nonmetastasized pancreatic cancer. The aim is to analyze overall survival (OS) after irradiation combined with induction chemotherapy. PATIENTS AND METHODS: Of the 73 patients with nonmetastatic pancreatic cancer eligible for the present analysis, 42 (58%) patients had adjuvant chemoradiotherapy (CRT), while 31 (42%) received CRT as primary treatment. In all, 65 (89%) had chemotherapy at any time before, during, or after RT, and 39 (53%) received concomitant CRT. The median total dose was 50 Gy (range 12-77 Gy), while 61 (84%) patients received >40 Gy. RESULTS: With a median follow-up of 22 months (range 1.2-179.8 months), 14 (19%) are still alive and 59 (81%) of the patients have died, whereby 51 (70%) were cancer-related deaths. Median OS and the 2­year survival rate were 22.9 months (1.2-179.8 months) and 44%, respectively. In addition, 61 (84%) patients treated with >40 Gy had a survival advantage (median OS 23.7 vs. 17.3 months, p = 0.026), as had patients with 4 months minimum of systemic treatment (median OS 27.5 vs. 14.3 months, p = 0.0004). CONCLUSION: CRT with total doses >40 Gy after induction chemotherapy leads to improved OS in patients with nonmetastatic pancreatic cancer.

The potential predictive value of tumor budding for neoadjuvant chemoradiotherapy response in locally advanced rectal cancer.

PURPOSE: This study was conducted to investigate the potential predictive value of tumor budding for neoadjuvant chemoradiotherapy response in locally advanced rectal cancer. PATIENTS AND METHODS: Surgical specimens of 128 ypUICC (Union for International Cancer Control) stage 0-III mid-to-low rectal cancer patients were identified from a prospectively maintained colorectal cancer database and classified into two groups using the 10 high-power field average method: none/mild tumor budding (BD-0) and moderate/severe tumor budding (BD-1). Overall survival, relapse-free survival (RFS), and recurrence estimates were calculated using the Kaplan-Meier method and compared with the log-rank test. For RFS, a multivariable Cox's proportional hazards regression analysis was performed. RESULTS: No (n = 20) or mild (n = 27) tumor budding (BD-0) was identified in 47 (37%) and moderate (n = 52) or severe (n = 29) tumor budding (BD-1) in 81 (63%) surgical specimens. Positive tumor budding (BD-1) was associated with significantly reduced T­level downstaging (P < 0.001) and tumor regression (P < 0.001). After a median follow-up time of 7 years (range 2.9-146.7 months), BD-0 patients had more favorable 5­year RFS (90 vs. 71%, P = 0.02) and distant recurrence (2 vs. 12%, P = 0.03) estimates. Multivariable analyses confirmed BD-1 as a negative predictive parameter for RFS (hazard ratio = 3.44, 95% confidence interval 1.23-9.63, P = 0.018). CONCLUSIONS: Our data confirm tumor budding as a strong prognostic factor and its potential predictive value for neoadjuvant chemoradiotherapy response in locally advanced rectal cancer patients. This provides the opportunity to modify and individualize neoadjuvant therapy regimens for non-responders.

Applicability of American Joint Committee on Cancer and College of American Pathologists Regression Grading System in Rectal Cancer.

BACKGROUND: Different tumor grading systems have been proposed to predict the association between tumor response and clinical outcome after preoperative chemoradiotherapy in patients with rectal cancer. The American Joint Committee on Cancer and College of American Pathologists regression grading system was recommended as the standard tumor regression grading system for rectal adenocarcinoma. OBJECTIVE: This study evaluated the clinical applicability of the American Joint Committee on Cancer and College of American Pathologists regression grading system in neoadjuvant-treated patients with rectal cancer. DESIGN: This is a retrospective cohort study based on clinical data from a prospectively maintained colorectal cancer database. SETTINGS: This study was performed at a single tertiary referral center. PATIENTS: A total of 144 patients with primary locally advanced mid-to-low rectal adenocarcinoma who underwent preoperative long-course chemoradiotherapy and total mesorectal excision between 2003 and 2012 were included. MAIN OUTCOMES MEASURES: The primary outcome measures were the 5-year overall survival rate, the relapse-free survival rate, the cancer-specific survival rate, and cumulative recurrence rates. RESULTS: Of the 144 patients, 16 (11%) were diagnosed as American Joint Committee on Cancer and College of American Pathologists regression grade 0, 43 patients (30%) as grade 1, 61 patients (42%) as grade 2, and 25 patients (17%) as grade 3.After a median follow-up time of 83 months (range, 3 to 147 mo), 5-year survival estimates for grades 0, 1, 2, and 3, were 93%, 77%, 81%, and 54% for overall survival (p = 0.006); 93%, 82%, 75%, and 55% for relapse-free survival (p = 0.03); and 100%, 86%, 89%, and 63% for cancer-specific survival (p = 0.006). The multivariate Cox regression analyses confirmed the American Joint Committee on Cancer and College of American Pathologists regression grading system as a prognostic factor for overall (p = 0.04), relapse-free (p = 0.02), and cancer-specific survival (p = 0.04). LIMITATIONS: This was a retrospective study. CONCLUSIONS: Our study findings confirm the clinical relevance and applicability of the American Joint Committee on Cancer and College of American Pathologists regression grade system as a predictive factor for patients with rectal cancer. See Video Abstract at http://links.lww.com/DCR/A320.

Dynamic magnetic resonance imaging evaluation of pelvic reconstruction with porcine dermal collagen mesh following extra-levator abdominoperineal excision for primary rectal cancer.

PURPOSE: Extra-levator abdominoperineal excision for rectal cancer includes resection of the levator ani muscle and therefore makes pelvic reconstruction advisable. The aim of our study was to evaluate morphologic and functional long-term results of pelvic floor augmentation with porcine dermal collagen mesh by dynamic magnetic resonance imaging and clinical examination. METHODS: Twenty consecutive patients underwent perineal reconstruction with porcine dermal collagen mesh following extra-levator abdominoperineal excision for primary rectal adenocarcinoma with curative intent between 2009 and 2012. Patient perioperative and postoperative data were collected prospectively. There were one cancer-related and two noncancer-related deaths in the follow-up period, and another three patients refused the dynamic magnetic resonance imaging. RESULTS: Fourteen patients were included in the study. The median time period from surgery to dynamic magnetic resonance imaging and clinical examination was 31 months (range 19-56). Wound infections were observed in 43% (6 of 14) of these patients in the postoperative period, but no mesh had to be removed. No focal mesh defect, no damage on the suture line, and no perineal hernia were detected on dynamic magnetic resonance imaging. Clinical examination revealed no pathological findings in any patient. CONCLUSIONS: The implantation of a porcine dermal collagen mesh is an effective and reliable option for pelvic floor reconstruction after extra-levator abdominoperineal excision. Despite a high incidence of primary wound infections, the healing rate was satisfactory, no mesh had to be removed, and long-term stability could be achieved.

Cumulative incidence of permanent stoma after sphincter preserving low anterior resection of mid and low rectal cancer.

BACKGROUND: Changes in the treatment of rectal cancer during the past decades have led to an increase in sphincter preservation with a consecutive decline in abdominoperineal resection rates. OBJECTIVE: The aim of this study was to analyze the cumulative incidence of permanent stoma in patients undergoing sphincter-preserving resection of mid and low rectal cancer. DESIGN: This study is a retrospective analysis of prospectively collected data. SETTINGS: This study was conducted at a tertiary referral cancer hospital. PATIENTS: From 2003 to 2010, 125 patients with primary mid and low rectal cancer who underwent sphincter-preserving low anterior resection were included. MAIN OUTCOME MEASURES: The occurrence of a permanent stoma over time was investigated by using a Cox proportional hazards regression model and competing-risk models, with death as a competing risk. The risk factors were assessed by computing HRs and a Cox proportional hazards regression. RESULTS: After a median follow-up time of 61 months (range, 22-113), 15 of 125 patients ended up with a permanent stoma, accounting for a 5-year cumulative incidence of 6% (95% CI, 4%-11%). The reasons for obtaining a permanent stoma were anastomotic leakage (60%, 9/15), intractable fecal incontinence (27%, 4/15), and local recurrence (13%, 2/15). The Cox proportional hazards regression identified anastomotic leakage (HR, 6.10; 95% CI, 2.23-16.71; p = 0.0004) and coloanal anastomosis (HR, 4.31; 95% CI, 1.49-12.47; p = 0.007) as statistically significant risk factors. LIMITATIONS: Because of the small number of events in this sample, further investigations with a larger number of patients are required. Fecal incontinence was assessed by patient self-reported data without the use of a validated score. CONCLUSION: The 5-year cumulative incidence of a permanent stoma was 6%. Anastomotic leakage and coloanal anastomosis were identified as risk factors. These details should be considered before sphincter-preserving surgery.

Impact of PD-L1 Scores and Changes on Clinical Outcome in Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiotherapy.

Reports on the prognostic role of programmed death-ligand 1 (PD-L1) expression in rectal cancer are controversial. We investigated expression patterns and changes of PD-L1 in rectal cancer patients undergoing neoadjuvant chemoradiotherapy (CRT). Seventy-two patients diagnosed with rectal cancer and/or treated with fluorouracil-based neoadjuvant CRT at the Department of Internal Medicine III of the Paracelsus Medical University Salzburg (Austria) between January 2003 and October 2012 were included. PD-L1 scoring was performed according to the tumor proportion score (TPS), combined positive score (CPS), and immune cell score (IC). PD-L1 TPS prior to neoadjuvant CRT had a statistically significant impact on survival (median: ≤1%: 95.4 months (95% CI: 51.8-not reached) vs. >1%: not reached, p = 0.03, log-rank). Patients with a PD-L1 TPS ≤1% prior to and after CRT showed an inferior survival compared to all other patients (median: 56.7 months (95% CI: 51.4-not reached) vs. not reached, p = 0.005, log-rank). In multivariate analysis, PD-L1 TPS prior to neoadjuvant CRT (>1% vs. ≤1%, hazard ratio: 0.29 (95% CI: 0.11-0.76), p = 0.01) remained independently associated with survival. In conclusion, low PD-L1 TPS was associated with inferior survival in rectal cancer patients undergoing neoadjuvant CRT. A prospective validation of the prognostic value of PD-L1 expression in rectal cancer patients within a clinical trial is necessitated.

Progressive Oncological Surgery Is Associated with Increased Curative Resection Rates and Improved Survival in Metastatic Colorectal Cancer.

BACKGROUND: Secondary resection rates in first-line chemotherapy trials for metastatic colorectal cancer (mCRC) remain below 15%, representing a clear contrast to reports by specialised surgical centres, where progressive liver, peritoneal-surface, and pulmonary surgery increased access to curative-intent treatment. We present a long-term evaluation of oncosurgical management in a single-centre, analysing the aggregate effect of gradual implementation of surgical subspecialties and systemic treatments on mCRC patients' resection rates and prognosis. METHODS: Patients with newly diagnosed mCRC from 2003 to 2014 were retrospectively categorised into palliative treatment (PAT) and curative intent surgery (CIS) and three time periods were analysed for treatment changes and factors associated with survival. RESULTS: Four hundred-twenty patients were treated (PAT:250/CIS:170). Over time periods, the number of presenting patients remained consistent, whereas curative resection rates increased from 29% to 55%, facilitated by an increment of patients undergoing hepatectomy (21 to 35%), pulmonary surgery (6 to 17%), and peritonectomy/intraoperative chemotherapy (0 to 8%). Also, recently, significantly more multi-line systemic treatments were applied. The median survival markedly improved from 21.9 months (2003⁻2006; 95% confidence interval (CI) 17.3⁻26.5) to 36.5 months (2011⁻2014; 95% CI 26.6⁻46.4; p = 0.018). PAT was a significant factor of poor survival and diagnosis of mCRC in the latest time period was independently associated with a distinctly lower risk for palliative treatment (odds ratio 0.15). CONCLUSIONS: In modern eras of medical oncology, achieving appropriate resection rates through utilization of state-of-the-art oncological surgery by dedicated experts represents a cornerstone for long-term survival in mCRC.

Primary tumour location affects survival after resection of colorectal liver metastases: A two-institutional cohort study with international validation, systematic meta-analysis and a clinical risk score.

BACKGROUND: Colorectal cancer (CRC) represents a major cause for cancer death and every third patient develops liver metastases (CRLM). Several factors including number and size of metastases and primary tumour lymph-node status have been linked to survival. The primary tumour location along the colo-rectum continuum (sidedness) was analysed in first-line chemotherapy trials, where right-sided CRCs showed decreased survival. This association has not yet been clearly established in patients undergoing resection for CRLM. METHODS: Clinicopathological differences in CRLM resections according to sidedness in two Austrian centres (2003-2016) are described and survival is compared through Kaplan-Meier and multivariable analysis. A risk-score is presented with time-dependent receiver operating curve analysis and international validation in two major hepatobiliary centres. Furthermore, a systematic meta-analysis of studies on primary tumour location and survival after CRLM resection was performed. RESULTS: 259 patients underwent hepatectomy. Right-sided CRC patients (n = 59) more often had positive primary tumour lymph-nodes (76.3%/61.3%;p = 0.043) and RAS-mutations (60%/34.9%;p = 0.036). The median overall and disease-free survival was 33.5 and 9.1 months in right-sided versus 55.5 (p = 0.051) and 12.1 months (p = 0.078) in left-sided patients. In multivariable analysis nodal-status (HR 1.52), right-sidedness (HR 1.53), extrahepatic disease (HR 1.71) and bilobar hepatic involvement (HR 1.41) were significantly associated with overall survival. Sidedness was not independently associated with disease-free survival (HR 1.33; p = 0.099). A clinical risk score including right-sidedness, nodal-positivity and extrahepatic involvement significantly predicted overall (p = 0.005) and disease-free survival (p = 0.027), which was confirmed by international validation in 527 patients (p = 0.001 and p = 0.011). Meta-analysis including 10 studies (n = 4312) showed a significant association of right-sidedness with overall survival after resection (HR 1.55;p<0.001). There was no significant association with disease-free survival (HR 1.22;p = 0.077), except when rectal-cancers were excluded (HR 1.39;p = 0.006). CONCLUSIONS: Patients with liver metastases from right-sided CRC experience worse survival after hepatic resection. Sidedness is a simple yet effective factor to predict outcome.

Comprehensive immunohistochemical analysis of histone deacetylases in pancreatic neuroendocrine tumors: HDAC5 as a predictor of poor clinical outcome.

Epigenetic factors contribute to carcinogenesis, tumor promotion, and chemoresistance. Histone deacetylases (HDACs) are epigenetic regulators that primarily cause chromatin compaction, leading to inaccessibility of promoter regions and eventually gene silencing. Many cancer entities feature overexpression of HDACs. Currently, the role of HDACs in pancreatic neuroendocrine tumors (pNETs) is unclear. We analyzed the expression patterns of all HDAC classes (classes I, IIA, IIB, III, and IV) in 5 human tissue microarrays representing 57 pNETs resected between 1997 and 2013 and corresponding control tissue. All pNET cases were characterized clinically and pathologically according to recent staging guidelines. The investigated cases included 32 (56.1%) female and 25 (43.9%) male pNET patients (total n=57, 47.4% immunohistochemically endocrine positive). Immunohistochemical profiling revealed a significant up-regulation of all HDAC classes in pNET versus control, with different levels of intensity and extensity ranging from 1.5- to >7-fold up-regulation. In addition, expression of several HDACs (HDAC1, HDAC2, HDAC5, HDAC11, and Sirt1) was significantly increased in G3 tumors. Correlation analysis showed a significant association between the protein expression of HDAC classes I, III, and IV and rate of the pHH3/Ki-67-associated mitotic and proliferation index. Furthermore, especially HDAC5 proved as a negative predictor of disease-free and overall survival in pNET patients. Overall, we demonstrate that specific members of all 4 HDAC classes are heterogeneously expressed in pNET. Moreover, expression of HDACs was associated with tumor grading, proliferation markers, and patient survival, therefore representing interesting new targets in pNET treatment.

Back to the start: Evaluation of prognostic markers in gastrointestinal stromal tumors.

The aim of this study was to provide a standardized risk stratification model for gastrointestinal stromal tumors (GISTs) based on tumor localization, tumor size, involved lymph nodes and metastases, as well as mitotic activity and other morphological and molecular markers, in order to improve the risk evaluation scheme for recurrence, metastatic spread and survival for patients with GIST. A total of 201 cases of patients with GIST were investigated according to standardized morphological markers, including nuclear pleomorphism, tumor cell necrosis, mucosal infiltration, ulceration, skeinoid fibers and growth pattern. In addition, all cases were immunohistochemically analyzed using a tissue microarray platform for various markers of differentiation (CD34, CD44, CD117, desmin, discovered on GIST 1, platelet-derived growth factor receptor α, S-100 and smooth muscle actin) and proliferation (B-cell lymphoma 2, P16, P53, phosphohistone H3 and Ki-67). These findings were correlated by uni- and multivariable analyses with clinicopathological characteristics, including recurrence, metastasis and survival. The general clinicopathological parameters of this GIST specimen cohort were comparable to previous studies. While several parameters exhibited clear associations to each other and to the defined clinical endpoints, the multivariate analysis reduced the number of relevant prognostic variables to localization, margin status, growth pattern and hematoxylin and eosin-based mitosis/Ki-67-based proliferation of GISTs. With the exception of CD34, none of the applied markers of differentiation and proliferation were found to be independent prognostic markers in GIST and the classical risk factors of GIST remain important prognostic factors. Additionally, growth pattern may predict the risk of recurrence and metastasis in GIST patients. Additional independent molecular prognostic markers remain to be identified and validated.

The association between late-onset fecal incontinence and obstetric anal sphincter defects.

HYPOTHESIS: Endoanal ultrasonographic results have demonstrated that clinically occult anal sphincter damage during vaginal delivery is common. This may or may not be associated with postpartum fecal incontinence (FI). Bayesian meta-analysis of the literature revealed that at least two thirds of obstetric sphincter disruptions are asymptomatic in the postpartum period. Women with postpartum asymptomatic sphincter damage may be at increased risk for FI with aging compared with those without sphincter injury. DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: After excluding patients with other possible causes of FI, the histories of 124 consecutive women with late-onset FI after vaginal delivery were analyzed. MAIN OUTCOME MEASURES: Endoanal ultrasonographic findings, pudendal nerve terminal motor latency assessment, and anal manometric results. RESULTS: Eighty-eight women (71%) with a median of 3 vaginal deliveries had sphincter defects on endoanal ultrasonographic results. The mean incontinence score, squeeze and resting pressures, median age at last delivery, and median duration of FI were not significantly different between patients with and without sphincter defects. Pudendal neuropathy was more frequent in patients without sphincter defects (10 [30.3%], left side; 12 [36.4%], right side) than in patients with sphincter defects (12 [14.3%] and 16 [19.3%], respectively), with the difference nearly reaching statistical significance (P =.054 and P =.059, respectively). The median age at onset of FI in patients with a sphincter defect was 61.5 years vs 68.0 years in those without a sphincter defect, which was not statistically significant (P =.08). CONCLUSION: Analysis of the current patient population revealed that 88 women (71%) with late-onset FI after vaginal delivery had an anatomical sphincter defect. Thus, FI related to anal sphincter defects is likely to occur even in an elderly population who had experienced vaginal deliveries earlier in life.

Intrathoracic major duodenal papilla with transhiatal herniation of the pancreas and duodenum: A case report and review of the literature.

Transhiatal herniation of the pancreas is an extremely rare condition. In the published literature we found only eleven cases reported in the period of 1958 to 2011. A coincidental hiatal herniation of the duodenum is described in two cases only. To our knowledge, we report the first case with a hiatal herniation of the complete duodenum and proximal pancreas presenting an intrathoracic major duodenal papilla with consecutive intrahepatic and extrahepatic cholestasis. A 72-year-old Caucasian woman was admitted to our department with a hiatal hernia grade IV for further evaluation. According to our recommendation of surgical hernia repair soon after the diagnosis of a transhiatal herniation of the proximal pancreas and entire duodenum, we had to respect the declared intention of the patient for a conservative procedure. So we were forced to wait for surgical repair within an emergency situation complicated by a myocardial infarction and reduced general condition. We discuss the therapeutic decision making process and a complete literature review of this rare entity.

Should ileoanal pouch surgery be staged for patients with mucosal ulcerative colitis on immunosuppressives?

INTRODUCTION AND OBJECTIVE: Much debate has revolved around whether patients with mucosal ulcerative colitis (MUC) receiving immunosuppression should be weaned off immunosuppressives before undergoing ileal pouch surgery. Therefore, the aim of this study was to assess the affect of immunosuppressive drugs on postoperative complications after ileoanal pouch surgery. MATERIALS AND METHODS: A retrospective medical record review of patients with MUC who underwent ileal pouch surgery while taking immunosuppressive drugs such as azathioprine, 6-mercaptopurine (6-MP), methotrexate, and cyclosporin A was performed. Postoperative complications in the study group were compared to three matched groups: patients with MUC who had ileoanal pouch surgery while taking systemic steroids, patients with MUC not receiving any immunosuppressive drugs, and patients with familial adenomatous polyposis. RESULTS: Twenty-two patients with MUC who underwent ileoanal pouch surgery while taking immunosuppressive drugs were identified from a prospectively entered database of patients who had this surgery between 1988 and 2005. All but two patients underwent temporary fecal diversion. Fifteen patients were taking 6-MP or azathioprine; six were on cyclosporine A, and one both on azathioprine and cyclosporine A. Fifteen patients were also taking steroids at the time of ileoanal pouch surgery. Early (within 30 days of surgery) and late complications occurred in 36 and 50% of the study group patients, respectively, but did not significantly differ from a matched group of patients with MUC who did not take immunosuppressive drugs. Patients with familial adenomatous polyposis had a significantly lower long-term complication rate. CONCLUSION: This retrospective case-matched study suggests that the use of immunosuppressive drugs and cyclosporine A may not be associated with an increased rate of complications after ileoanal pouch surgery.

Disseminated tumor cells in peripheral blood: a novel marker for therapy response in locally advanced rectal cancer patients undergoing preoperative chemoradiation.

PURPOSE: This study was designed to examine whether disseminated tumor cells in peripheral blood of locally advanced rectal cancer patients undergoing preoperative chemoradiation have the potential to serve as a marker for therapy response. Studies suggest that patients with advanced rectal cancer who respond to preoperative chemoradiation most likely benefit from this treatment. METHODS: From advanced rectal cancer patients undergoing preoperative chemoradiation, peripheral blood was obtained at defined times: before, during, and after chemoradiation and during surgery. Patients were divided into histopathologic responders (ypT0-T2) and nonresponders (ypT3-T4). Cytokeratin 20 and carcinoembryonic antigen reverse transcriptase-polymerase chain reaction were performed to detect disseminated tumor cells. A blood sample was deemed positive for disseminated tumor cells if both carcinoembryonic antigen and cytokeratin 20 were detected. RESULTS: The overall population (n = 26) showed a positivity rate of 32 percent for disseminated tumor cells before initiation of chemoradiation. Of the responders (n = 8), 63 percent were positive for disseminated tumor cells before chemoradiation, whereas only 18 percent of nonresponders (n = 18) were positive (P = 0.026). From initiation of chemoradiation to the end of surgery, a significant decrease was seen in tumor cell positivity in the blood of responders (P = 0.042). Moreover, the responders represented a trend toward a decrease in tumor cell positivity during chemoradiation (P = 0.079). In contrast, there were no noticeable alterations within the treatment course in nonresponders. CONCLUSIONS: This prospective proof of principle study demonstrates that locally advanced rectal cancer with preoperative chemoradiation shows different biologic behavior in terms of tumor cell dissemination in peripheral blood when therapy responders compared with nonresponders.

Outcome of patients with indeterminate colitis undergoing a double-stapled ileal pouch-anal anastomosis.

INTRODUCTION: The aim of this study was to assess the outcome of patients with indeterminate colitis undergoing double-stapled ileal pouch anal anastomosis. METHODS: A retrospective review of demographic, disease-related, and outcome variables of all patients undergoing double-stapled ileal pouch anal anastomosis from August 1988 to January 2000 was undertaken. All patients were evaluated using the validated American Society of Colon and Rectal Surgeons Fecal Incontinence Severity Index. Patients with familial adenomatous polyposis, those who had undergone pouch revision or had S-configured pouches, and patients with a follow-up of less than three months were excluded from analysis. RESULTS: Three hundred ninety-five patients underwent the double-stapled ileal pouch anal anastomosis; of these 303 patients were included for analysis. The mean duration of follow-up was 40 months. Fifty-six (18.1 percent) had a preoperative diagnosis of indeterminate colitis. Postoperatively, indeterminate colitis was diagnosed in 13 (4.3 percent), mucosal ulcerative colitis in 285 (94 percent), and Crohn's disease in 5 (1.6 percent). The overall complication rate was 37.7 percent, 60 percent, and (30.7) percent in patients with mucosal ulcerative colitis, Crohn's disease, and indeterminate colitis, respectively. Postoperative hemorrhage, abscess, and fistula occurred in 2.4 percent, 6.3 percent, and 3.9 percent, respectively, in patients with mucosal ulcerative colitis, and 0 percent, 15.3 percent, and 7.7 percent, respectively, in patients with indeterminate colitis. Small-bowel obstruction occurred in 8.5 percent, 20 percent, and 7.7 percent of patients with mucosal ulcerative colitis, Crohn's disease, and indeterminate colitis, respectively. Pouchitis occurred in 4.6 percent of patients with mucosal ulcerative colitis but in none of the patients with indeterminate colitis. Dysplasia of the anal transition zone was seen in one patient each with mucosal ulcerative colitis and indeterminate colitis. These patients had consistent follow-up and neither showed any sign of evolution to neoplastic disease. None of the patients with indeterminate colitis had a postoperative diagnosis of Crohn's disease during the follow-up period. Functional outcome was comparable in all three patient groups. CONCLUSION: The outcome of the double-stapled ileal pouch anal anastomosis in patients with indeterminate colitis is similar to that of patients with mucosal ulcerative colitis. Therefore, it is a safe option in patients with indeterminate colitis.