Health-Related Quality of Life, Cachexia and Overall Survival After Major Upper Abdominal Surgery: A Prospective Cohort Study.

BACKGROUND AND AIMS: Major upper abdominal surgery is often associated with reduced health-related quality of life and reduced survival. Patients with upper abdominal malignancies often suffer from cachexia, represented by preoperative weight loss and sarcopenia (low skeletal muscle mass) and this might affect both health-related quality of life and survival. We aimed to investigate how health-related quality of life is affected by cachexia and how health-related quality of life relates to long-term survival after major upper abdominal surgery. MATERIALS AND METHODS: From 2001 to 2006, 447 patients were included in a Norwegian multicenter randomized controlled trial in major upper abdominal surgery. In this study, six years later, these patients were analyzed as a single prospective cohort and survival data were retrieved from the National Population Registry. Cachexia was derived from patient-reported preoperative weight loss and sarcopenia as assessed from computed tomography images taken within three months preoperatively. In the original trial, self-reported health-related quality of life was assessed preoperatively at trial enrollment and eight weeks postoperatively with the health-related quality of life questionnaire Short Form 36. RESULTS: A majority of the patients experienced improved mental health-related quality of life and, to a lesser extent, deteriorated physical health-related quality of life following surgery. There was a significant association between preoperative weight loss and reduced physical health-related quality of life. No association between sarcopenia and health-related quality of life was observed. Overall survival was significantly associated with physical health-related quality of life both pre- and postoperatively, and with postoperative mental health-related quality of life. The association between health-related quality of life and survival was particularly strong for postoperative physical health-related quality of life. CONCLUSION: Postoperative physical health-related quality of life strongly correlates with overall survival after major upper abdominal surgery.

The outcome and the frequency of pathological complete response after neoadjuvant radiotherapy in curative resections for advanced rectal cancer: a population-based study.

AIM: Pathological complete response (ypCR) after neoadjuvant treatment for rectal cancer is associated with favourable survival and a low rate of local recurrence. The aim of the study was to assess the incidence of ypCR among patients with advanced rectal cancer treated with neoadjuvant chemoradiotherapy and curative resection and to explore factors associated with survival. METHOD: From 2000 to 2009, 1384 patients enrolled in the national population- based colorectal cancer registry of Norway with advanced T3 and T4 rectal cancer with N0-2, M0 received neoadjuvant long-course (chemo)radiation. The duration of follow-up was a median of 5 years. RESULTS: ypCR was achieved in 147 (10.6%) patients. The estimated 5-year overall survival rate was 87% (confidence interval ± 5.4) among ypCR and 67% among non-ypCR (confidence interval ± 2.7) (P < 0.0001). Distant metastasis developed in 12 (8%) of 147 and 328 (26.5%) of 1237 patients respectively (P < 0.001). In a Cox proportional hazards ratio model the effect of ypCR on survival was adjusted for age [hazard ratio (HR) 1.056, P = 0.0001], metachronous metastasis (HR 4.7, P = 0.0001), local recurrence (HR 4.3, P = 0.0001) and surgical procedure (HR 1.48, P = 0.0001). The independent effect of ypCR (HR 0.65, P = 0.041) on survival almost disappeared compared with the univariate analysis. CONCLUSION: The rate of ypCR in advanced rectal cancer was about 10%. This phenomenon seems to occur in tumours with a low risk of metastasizing. The contribution of neoadjuvant therapy to ypCR on survival was small or absent.

Risk factors, complications and survival after upper abdominal surgery: a prospective cohort study.

BACKGROUND: Preoperative weight loss and abnormal serum-albumin have traditionally been associated with reduced survival. More recently, a correlation between postoperative complications and reduced long-term survival has been reported and the significance of the relative proportion of skeletal muscle, visceral and subcutaneous adipose tissue has been examined with conflicting results. We investigated how preoperative body composition and major non-fatal complications related to overall survival and compared this to established predictors in a large cohort undergoing upper abdominal surgery. METHODS: From 2001 to 2006, 447 patients were included in a Norwegian multicenter randomized controlled trial in major upper abdominal surgery. Patients were now, six years later, analyzed as a single prospective cohort and overall survival was retrieved from the National Population Registry. Body composition indices were calculated from CT images taken within three months preoperatively. RESULTS: Preoperative serum-albumin <35 g/l (HR = 1.52, p = 0 .014) and weight loss >5 % (HR = 1.38, p = 0.023) were independently associated with reduced survival. There was no association between any of the preoperative body composition indices and reduced survival. Major postoperative complications were independently associated with reduced survival but only as long as patients who died within 90 days were included in the analysis. CONCLUSIONS: Our study has confirmed the robust significance of the traditional indicators, preoperative serum-albumin and weight loss. The body composition indices did not prove beneficial as global indicators of poor prognosis in upper abdominal surgery. We found no association between non-fatal postoperative complications and long-term survival.

Identification of serum microRNA profiles in colon cancer.

BACKGROUND: microRNAs (miRNAs) exist in blood in an apparently stable form. We have explored whether serum miRNAs can be used as non-invasive early biomarkers of colon cancer. METHODS: Serum samples from 30 patients with colon cancer stage IV and 10 healthy controls were examined for the expression of 375 cancer-relevant miRNAs. Based on the miRNA profile in this study, 34 selected miRNAs were measured in serum from 40 patients with stage I-II colon cancer and from 10 additional controls. RESULTS: Twenty miRNAs were differentially expressed in serum from stage IV patients compared with controls (P<0.01). Unsupervised clustering revealed four subgroups; one corresponding mostly to the control group and the three others to the patient groups. Of the 34 miRNAs measured in the follow-up study of stage I-II patients, 21 showed concordant expression between stage IV and stage I-II patient. Based on the profiles of these 21 miRNAs, a supervised linear regression analysis (Partial Least Squares Regression) was performed. Using this model we correctly assigned stage I-II colon cancer patients based on miRNA profiles of stage IV patients. CONCLUSION: Serum miRNA expression profiling may be utilised in early detection of colon cancer.

Long-term function after ileal pouch-anal anastomosis - function does not deteriorate with time.

AIM: There are conflicting reports regarding long term function after ileal pouch-anal anastomosis (IPAA). The aim of the present prospective study was to investigate the influence of duration as an independent factor on long-term function results. METHOD: Between 1984 and 2007, 315 patients underwent IPAA and were followed by a standardised interview and endoscopy protocol. There were 1802 interviews. Two hundred and thirty-five patients had three or more visits and these data were analysed by Time-Series-Cross-Section multivariate regression analysis. The mean time follow up was 12 years and the mean interval between visits was 34.5 months. RESULTS: Mean frequency of defecation was 5.2 in the day and 0.55 at night. This did not change with time. Daytime and night incontinence occurred in 13% and 21%. There was no change in incontinence, urgency, soiling or perineal excoriation with time. After 24 years the cumulative incidence of pouchitis was 43.5%. Twenty patients had chronic pouchitis (6.3%). CONCLUSION: The interval from IPAA did not influence the long-term functional outcome.

Performance of clinical guidelines compared with molecular tumour screening methods in identifying possible Lynch syndrome among colorectal cancer patients: a Norwegian population-based study.

BACKGROUND: The aim of this study was to assess the performance of the Revised Bethesda Guidelines (RBG) and the accuracy of the Amsterdam II criteria (AM II) in identifying possible Lynch syndrome (LS) compared with the results of molecular tumour testing. METHODS: Tumours from 336 unselected colorectal cancer patients were analysed by three molecular tests (namely microsatellite instability (MSI), BRAF mutation and methylation of mismatch-repair genes), and patients were classified according to the RBG and AM II criteria. RESULTS: A total of 87 (25.9%) patients fulfilled the RBG for molecular tumour analyses (MSI and/or immunohistochemistry), and the AM II identified 8 (2.4%) patients as having possible LS. Molecular tests identified 12 tumours (3.6%) as probable LS. The RBG identified 6 of the 12 patients (sensitivity 50%), whereas 5 of the 8 patients who fulfilled the AM II criteria were not likely to be LS, based on molecular tests (predictive value of positive test, 38%). INTERPRETATION: Assuming a fairly high accuracy of molecular testing, the performance of the RBG in identifying patients with possible LS was poor, and the AM II criteria falsely identified a large proportion as having possible LS. This favours the use of molecular testing in the diagnosis of possible LS.

Failed pelvic pouch substituted by continent ileostomy.

OBJECTIVE: The long-term failure rate of ileal pouch-anal anastomosis (IPAA) is 10-15%. When salvage surgery is unsuccessful, most surgeons prefer pouch excision with conventional ileostomy, thus sacrificing 40-50 cm of ileum. Conversion of a pelvic pouch to a continent ileostomy (CI, Kock pouch) is an alternative that preserves both the ileal surface and pouch properties. The aim of the study was to evaluate clinical outcome after the construction of a CI following a failed IPAA. METHOD: During 1984-2007, 317 patients were operated with IPAA at St Olavs Hospital and evaluated for failure, treatment and outcome. Seven patients with IPAA failure had CI. Four patients with IPAA failure referred from other hospitals underwent conversion to CI and are included in the final analysis. RESULTS: Seven patients had a CI constructed from the transposing pelvic pouch and four had the pelvic pouch removed and a new continent pouch constructed from the distal ileum. Median follow up after conversion to CI was 7 years (0-17 years). Two CI had to be removed due to fistulae. One patient needed a revision of the nipple valve due to pouch loosening. At the end of follow-up, 8 of the 11 patients were fully continent. One patient with Crohn's disease had minor leakage. CONCLUSION: In patients with pelvic pouch failure, the possibility of conversion to CI should be presented to the patient as an alternative to pouch excision and permanent ileostomy. The advantage is the continence and possibly a better body image. Construction of a CI on a new ileal segment may be considered, but the consequences of additional small bowel loss and risk of malnutrition if the Kock pouch fails should be appraised.

Long-term surgical load in patients with ileal pouch-anal anastomosis.

AIM: To evaluate surgical workload and complications in patients who had undergone restorative proctocolectomy, through long-term follow-up in one single institution. METHOD: From 1984 to 2006, 304 consecutive patients underwent Ileal Pouch-Anal Anastomosis (IPAA). There were 182 stapled and 122 hand-sewn anastomoses. A protective loop ileostomy was established in 256 patients (84%), whereas 48 patients (16%) were without a covering stoma. RESULTS: Twenty-nine patients (10%) suffered from early anastomotic leakage. A protective stoma did not prevent early anastomotic dehiscence (P = 0.11) or the number of pelvic abscesses (P = 0.09). Early complications required 20 laparotomies with creation of a diverting stoma in nine patients. There were 16 (6%) complications related to closure of the loop ileostomy. Sixty-six patients needed an additional re-operation related to the IPAA procedure. There were 20 removals of pouches and three permanent diverting stomas. The estimated removal rate at 20 years of a functioning pouch was 11% (CI +/- 6). Altogether 100 (33%) patients had one or more surgical procedures, excluding dilations of anastomotic strictures and closing of a loop ileostomy. These 100 patients underwent 187 surgical procedures. The estimated rate of a first re-operation due to complications was 52% (CI +/- 16) in 20 years. Hand-sewn anastomoses had similar complications and failure rates as stapled anastomoses. CONCLUSIONS: More than half of patients operated with restorative proctocolectomy will need surgical intervention within 20 years and the failure rate is more than 10%. The high risk of complications and failure inherent in the procedure should not be ignored.

Awareness of heredity in colorectal cancer patients is insufficient among clinicians: a Norwegian population-based study.

OBJECTIVE: The assessment of family history and medical data is crucial in identifying families with Lynch syndrome (LS). Among consecutive colorectal cancer (CRC) patients, we aimed at identifying all patients with a hereditary predisposition, and to study a possible discrepancy with assessments made by the responsible clinicians. METHOD: All consecutively diagnosed patients with CRC from two Norwegian hospitals were included, and information on family history was collected in a detailed interview. We assessed information in medical records, and tumours were examined for LS-associated histopathological features. RESULTS: Among 562 patients, there was no documentation of family history in 388 (69.0%) medical records, and in 174 (31.0%) patients, there was no clinical assessment of the information that was collected on family history. Based on detailed interviews and extended pathological examination, we found that 137 (24.4%) of the 562 patients could be classified as possible LS according to the Revised Bethesda Guidelines (RBG); and that 46 (33.6%) of these patients could be identified by family history alone. CONCLUSION: Family history and relevant information in patient records can identify patients with possible LS. However, clinicians often fail to include information on hereditary factors and to assess relevant data in medical records. Familial CRC is therefore not acknowledged, and genetic counselling is not offered.

Surgical load and long-term outcome for patients with Kock continent ileostomy.

OBJECTIVE: The aim of the study was to evaluate the results of Kock continent ileostomy (CI) during the same period when ileal pouch-anal anastomosis was the preferred operation for patients with ulcerative colitis (UC) or familial adenomatous polyposis (FAP). METHOD: During the period 1983-2002, 50 patients underwent CI. The surgical technique was unchanged during the period. Follow-up included all patients. Forty-eight patients had UC, two of these had the diagnosis later changed to Crohn's disease and two had FAP. RESULTS: Twenty-two patients had 38 reoperations, four (8%) of whom had the pouch removed. The main causes for reoperation included leakage and difficulty in intubation due to sliding of the nipple valve (42%), fistula formation (29%) and stenosis (21%). Seventeen (45%) underwent a revision of the nipple valve and the pouch and nine (24%) a local procedure. The reoperation rate was higher among patients having a conventional ileostomy converted to CI than among those having CI. As a primary procedure (P = 0.016). The risk of a second reoperation was higher for those reoperated within the first year after having a CI, than for those reoperated later (P = 0.007). CONCLUSIONS: The reoperation rate of patients with CI is high but the removal rate of the pouch is low and is not associated with a high rate of revision. CI is a good alternative to conventional ileostomy in patients not suitable for restorative proctocolectomy or where this procedure has failed.