Chemotherapy reduces long-term quality of life in recurrence-free colon cancer survivors (LaTE study)-a nationwide inverse probability of treatment-weighted registry-based cohort study and survey.

AIM: Stage III colon cancer is routinely treated with adjuvant chemotherapy, which causes significant short-term morbidity. Its effect on long-term quality of life (QoL) is poorly investigated. The aim of this study was to investigate long-term QoL after curative treatment for colon cancer and explore the impact of chemotherapy on general and disease-specific QoL. METHOD: All patients aged under 75 years operated on for colon cancer between 30 September 2007 and 1 October 2019 were identified by the Cancer Registry of Norway. Exclusion criteria were distant metastasis, recurrence, dementia and rectal/rectosigmoid cancer operation. The primary outcome measure was Gastrointestinal Quality of Life Index (GIQLI). Secondary outcome measures included the Short Form Health Survey (SF-36). To achieve balanced groups when assessing differences in outcome measures the analyses were weighted by inverse probability weights based on a multiple logistic regression model with prechosen confounders. RESULTS: A total of 8627 patients were invited and 3109 responded (36% response rate). After exclusions 3025 patients were included, of whom 1148 (38%) had received adjuvant chemotherapy and 1877 (62%) had surgery alone, with mean follow-up of 75.5 versus 74.5 months, respectively. The GIQLI differed significantly between the groups [mean 111.0 (SD 18.4) vs. 115.6 (SD 17.8), respectively; mean difference: -4.6 (95% CI -5.9; -3.2); p < 0.001]. Those with the highest neurotoxicity exhibited the lowest GIQLI. The adjuvant chemotherapy group scored significantly lower in six of eight SF-36 domains compared with the surgery alone group. The main differences were found in social, physical and emotional function. CONCLUSION: Long-term QoL was significantly lower in patients who received adjuvant chemotherapy than in patients who did not. Neurotoxicity was closely related to reduced QoL in these patients. The low response rate limits the generalizability of the results.

Determinants of optimal bowel function in ileal pouch-anal anastomosis - physiological differences contributing to pouch function.

BACKGROUND: Variability in functional outcome after ileal-pouch anal anastomosis (IPAA) is to a large extent unexplained. The aim of this study was to perform multiple physiological and biochemical tests including an endoscopic examination with histology on IPAA patients with well and poorly functioning pouches to determine factors, or combinations thereof, contributing to functional outcome. METHODS: All patients with ulcerative colitis undergoing restorative proctocolectomy between 2000 and 2013 (N = 108) were interviewed using a pouch functioning score. The best and worst functioning quartiles were invited to undergo examination with a barostat measuring pouch volume at preset variable distension pressures, and a pouch endoscopy. RESULTS: Forty five of 58 eligible patients agreed to participate. The most significant physiological parameter differing between the well and poorly functioning pouches was pouch volume at first sensation, urge and discomfort (p value <.001). Urge volumes were 213 (CI 171-256) ml for poorly and 352 (CI 305-401) ml for well functioning pouches. Pouchitis episodes were negatively correlated to function. The poorly functioning patients had a higher prevalence of histological signs of inflammation and hand-sewn anastomosis, and a longer remaining rectal cuff, however, nonsignificant. The pouch pressure at sensation thresholds did not differ between the groups. CONCLUSIONS: Pouch volume is the most dominant predictor of pouch function in this study. The present comprehensive study of a multitude of different factors that possibly could be contributing to functional outcome, failed to shed much further light on the functional variability among pouch patients. The pouch physiology remains to a large extent unexplained.

The Norwegian dietary guidelines and colorectal cancer survival (CRC-NORDIET) study: a food-based multicentre randomized controlled trial.

BACKGROUND: Colorectal cancer survivors are not only at risk for recurrent disease but also at increased risk of comorbidities such as other cancers, cardiovascular disease, diabetes, hypertension and functional decline. In this trial, we aim at investigating whether a diet in accordance with the Norwegian food-based dietary guidelines and focusing at dampening inflammation and oxidative stress will improve long-term disease outcomes and survival in colorectal cancer patients. METHODS/DESIGN: This paper presents the study protocol of the Norwegian Dietary Guidelines and Colorectal Cancer Survival study. Men and women aged 50-80 years diagnosed with primary invasive colorectal cancer (Stage I-III) are invited to this randomized controlled, parallel two-arm trial 2-9 months after curative surgery. The intervention group (n = 250) receives an intensive dietary intervention lasting for 12 months and a subsequent maintenance intervention for 14 years. The control group (n = 250) receives no dietary intervention other than standard clinical care. Both groups are offered equal general advice of physical activity. Patients are followed-up at 6 months and 1, 3, 5, 7, 10 and 15 years after baseline. The study center is located at the Department of Nutrition, University of Oslo, and patients are recruited from two hospitals within the South-Eastern Norway Regional Health Authority. Primary outcomes are disease-free survival and overall survival. Secondary outcomes are time to recurrence, cardiovascular disease-free survival, compliance to the dietary recommendations and the effects of the intervention on new comorbidities, intermediate biomarkers, nutrition status, physical activity, physical function and quality of life. DISCUSSION: The current study is designed to gain a better understanding of the role of a healthy diet aimed at dampening inflammation and oxidative stress on long-term disease outcomes and survival in colorectal cancer patients. Since previous research on the role of diet for colorectal cancer survivors is limited, the study may be of great importance for this cancer population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01570010 .

Correlation between pouch function and sexual function in patients with IPAA.

OBJECTIVE: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the treatment of choice for ulcerative colitis refractory to medical treatment and familial adenomatous polyposis. The objective of this study was to study the impact of postoperative pouch function on sexual function. Sexual function after IPAA surgery has also been compared to sexual function in the average Norwegian population. MATERIAL AND METHODS: All patients having undergone IPAA from 2000 to June 2013 were identified from the hospital medical record files and sent validated questionnaires regarding their sexual function. Pouch function was scored according to Oresland score through a phone interview. Patients operated on or before June 2012 were asked to answer the same questionnaires twice with an interval of one year to see how stable sexual function is over time. RESULTS: Sixty-eight out of 100 consecutive patients answered the questionnaire regarding both sexual function and pouch function (44 men, 24 women). There was no significant relationship between pouch and sexual function in men (p-value 0.158, corr. coefficient - 0.216). In women there was a significant relationship (p-value - 0.01, corr. coefficient 0.517). There was no significant shift in sexual function during the study period. CONCLUSION: We found no significant correlation between sexual function and pouch function in men. In women, we found a significant correlation between poor pouch function and impaired sexual function. As similar studies have found, sexual function remains good after IPAA surgery. This is an important information for patients and physicians, both to inform patients correctly prior to surgery, and in the postoperative follow-up.

Surgery in the age of biological treatment.

Surgery for IBD is in constant evolution; it does not appear that the introduction of biologicals has had a major effect on the chance of a patient being operated on or not. Pouch surgery had its heydays in the 80s and 90s and has since then become less frequent, but the number of patients undergoing surgery still seem about the same from one year to the other. Likewise, there is no substantial evidence that surgery for Crohn's disease is diminishing. There have been fears that patients on biological treatment have an increased risk of postoperative complications. The issue is not completely settled but it is likely that patients on biological treatment who come to surgery are those who do not benefit from biologicals. Thus, they are compromised in that they have an ongoing inflammation, are in bad nutritional state, and might have several other known risk factors for a complicated postoperative course. These factors and perhaps not the biologicals per se is what surgeons should consider. During the recent years, we have seen several new developments in IBD surgery; the ileorectal anastomosis is being used for ulcerative colitis and laparoscopic surgery usually resulting in a shorter hospital stay, less pain, and better cosmetics. We have also seen the introduction of robotic surgery, single incision minimal invasive surgery, transanal minimal invasive surgery, and other approaches to minimize surgical trauma. Time will show which of these innovations patients will benefit from.

Nationwide improvement of rectal cancer treatment outcomes in Norway, 1993-2010.

BACKGROUND: The Norwegian Rectal Cancer Project was initated in 1993 with the aims of improving surgery, decreasing local recurrence rates, improving survival, and establishing a national rectal cancer registry. Here we present results from the Norwegian Colorectal Cancer Registry (NCCR) from 1993 to 2010. MATERIAL AND METHODS: A total of 15 193 patients were diagnosed with rectal cancer in Norway 1993-2010, and were registered with clinical data regarding diagnosis, treatment, locoregional recurrences and distant metastases. Of these, 10 796 with non-metastatic disease underwent tumour resection. The results were stratified into five time periods, and the treatment outcomes were compared. Recurrence rates are presented for the 9785 patients who underwent curative major resection (R0/R1). RESULTS: Among all 15 193 patients, relative five-year survival increased from 54.1% in 1993-1997 to 63.4% in 2007-2010 (p < 0.001). Among the 10 796 patients with stage I-III disease who underwent tumour resection, from 1993-1997 to 2007-2010, relative five-year survival improved from 71.2% to 80.6% (p < 0.001). An increasing proportion of these patients underwent surgery at large-volume hospitals; and 30- and 100-day mortality rates, respectively, decreased from 3.0% to 1.4% (p < 0.001) and from 5.1% to 3.0% (p < 0.011). Use of preoperative chemoradiotherapy increased from 6.5% in 1993 to 39.0% in 2010 (p < 0.001). Estimated local recurrence rate after major resection (R0/R1) decreased from 14.5% in 1993-1997 to 5.0% in 2007-2009 (p < 0.001), and distant recurrence rate decreased from 26.0% to 20.2% (p < 0.001). CONCLUSION: Long-term outcomes from a national population-based rectal cancer registry are presented. Improvements in rectal cancer treatment have led to decreased recurrence rates of 5% and increased survival on a national level.

Imaging the tumour microenvironment in rectal cancer: Decline in tumour blood flow during radiotherapy predicts good outcome.

Background and purpose: Measuring rectal tumour response to radiation is pivotal to restaging patients and for possibly stratification to a watch-and-wait strategy. Recognizing the importance of the tumour microenvironment, we investigated a less explored quantitative imaging marker assessing tumour blood flow (BF) for its potential to predict overall survival (OS). Materials and methods: 24 rectal cancer patients given curative-intent neoadjuvant radiotherapy underwent a multi-echo dynamic magnetic resonance imaging (MRI) sequence with gadolinium contrast for quantification of tumour BF before either 25x2 Gy (n = 18) with concomitant chemotherapy or 5x5 Gy (n = 6). CD34 staining of excised tumour tissue was performed and baseline blood samples were analysed for lactate dehydrogenase (LDH) and angiopoietin-2 (ANGPT-2). Tumour volumes were measured before and after treatment. After subsequent surgery, ypTN scoring assessed tumour response. Cox regression for 5-year OS analysis and t-test for group comparisons were performed. Results: The change in tumour BF (ΔBF) during neoadjuvant radiotherapy was a significant marker of OS, whereas tumour stage and volume were not related to OS. All patients with >20 % decline in BF were long-term survivors. Separating cases in two groups based on ΔBF revealed that patients with increase or a low decrease had higher baseline LDH (p = 0.032) and ANGPT-2 (p = 0.028) levels. Conclusion: MRI-assessed tumour ΔBF during neoadjuvant treatment is a significant predictor of OS in rectal cancer patients, making ΔBF a potential quantitative imaging biomarker for treatment stratification. Blood LDH and ANGPT-2 indicate that non-responding tumours may have a hypoxic microenvironment resistant to radiotherapy.

Lymph node micrometastases and isolated tumor cells influence survival in stage I and II colon cancer.

PURPOSE: Lymph-node status is considered the most important prognostic factor in colorectal cancer. The aim of the present prospective study was to evaluate the influence of micrometastases and isolated tumor cells on recurrence and disease-free survival in colon cancer. METHODS: A total of 193 patients with colon cancer, operated on between 2000 and 2005, were enrolled in the study. All lymph nodes were examined by routine microscopy in hematoxylin and eosin-stained sections. If no metastases were identified in any node, all nodes were examined immunohistochemically with monoclonal antibody CAM 5.2. RESULTS: Ordinary metastases were found in 67 patients, leaving 126 patients in stage I/II. Immunohistochemistry showed that 5% (6/126) of these had micrometastases and 26% (33/126) had isolated tumor cells. A median of 5 years of follow-up revealed local or distant recurrence in 23% (9/39) of stage I/II patients with micrometastases or isolated tumor cells, compared with 7% (6/87) without micrometastases or isolated tumor cells (P = .010). Five-year disease-free survival for patients with and without micrometastases or isolated tumor cells was 75% and 93%, respectively (P = .012). When analyzed separately, patients with isolated tumor cells (excluding micrometastases) had also lower survival than node-negative patients (P = .012). CONCLUSION: The presence of micrometastases and isolated tumor cells was found to be a prognostic factor for recurrence and disease-free survival. This may have implications for future treatment of stage I/II colon cancer.

Sentinel node mapping does not improve staging of lymph node metastasis in colonic cancer.

PURPOSE: This study was designed to evaluate the reliability of the sentinel node concept in colonic cancer. METHODS: Patent blue was used as tracer. The four blue nodes closest to the tumor were defined as the sentinel node(s) by the pathologist. All nodes were examined by routine microscopy (hematoxylin-eosin staining). If no metastases were detected, all lymph nodes were examined immunohistochemically with antibody to cytokeratin. RESULTS: Two hundred colon specimens were examined. Sentinel node(s) were identified in 93 percent. Sixty contained metastases in hematoxylin-eosin sections. In 32 these were found in sentinel nodes (sensitivity 53 percent). Twenty-eight patients had metastases in nonsentinel nodes only, giving a false-negative rate of 47 percent. Immunostaining revealed 39 (30 percent) micrometastases or submicrometastases in 131 TNM Stages I and II patients, and in 17 of these patients metastases were found in nonsentinel nodes only (false-negative rate 44 percent). CONCLUSIONS: Sentinel lymph node mapping shows low sensitivity for detection of ordinary metastases, micrometastases, and submicrometastases. If only the sentinel nodes had been examined, approximately half of the metastases would have been lost after routine staining, as well as half of the micrometastases and submicrometastases when immunohistochemical examination was added.

[Transanal endoscopic microsurgery for tumours in rectum]. / Transanal endoskopisk mikrokirurgi ved svulster i rectum.

BACKGROUND: Rectal tumors up to 25 cm from the anal verge may be resected by transanal endoscopic microsurgery (TEM). TEM is suitable for resection of benign adenomas, but can also be used for selected malignant tumours. MATERIAL AND METHODS: Based on review of the literature and our own experience with 150 procedures, we present a review of the method and indications for TEM. RESULTS: TEM is a safe and suitable method for resection of rectal adenomas that cannot be radically removed by endoscopic methods. TEM offers lower recurrence rates and less morbidity than traditional treatment. Large tumours and involvement of the microscopical resection margin disposes for recurrence. Selected malignant tumours (like small carcinoid tumours and early stage [Tis, T1] adencarcinomas) with higer moderate differentiation may be resected by TEM with the same oncological result as open surgery. INTERPRETATION: Tumours can be resected in the entire rectum with TEM. TEM is especially suitable to resect benign adenomas, and may also have a place as primary treatment of selected malignant tumours in Norway. Depending on selection criteria and combination with radiotherapy, the method may be suitable for 30 - 110 patients/year with rectal cancer in Norway.

Biofeedback vs. electrostimulation in the treatment of postdelivery anal incontinence: a randomized, clinical trial.

PURPOSE: This study was designed to evaluate the effect of biofeedback and electrostimulation in a randomized, clinical trial for the treatment of patients with postdelivery anal incontinence. METHODS: Forty-nine females who sustained third-degree or fourth-degree perineal rupture with a mean age of 36 (range, 22-44) years were included in the study. The females were randomized to biofeedback or electrostimulation treatment. Forty females completed the study: 19 in the biofeedback and 21 in the electrostimulation group. Biofeedback or electrostimulation sessions were performed two times daily for eight weeks in each group. Wexner incontinence score, fecal incontinence quality of life scores, and reduced quality of life on visual analog scale were registered before and after treatment. Patients' self-rating of treatment effect also was registered in both groups. The primary outcome measure was the Wexner incontinence score. RESULTS: There were no differences in treatment effect between groups. Comparing pretreatment status to posttreatment in each group showed no improvement in Wexner score, reduced quality of life, or any of the fecal incontinence quality of life scores. Patients' self-rating of the treatment effect, however, showed a subjective improvement of symptoms both in the biofeedback and in the electrostimulation group (median, 7 vs. 5.) CONCLUSIONS: This study shows that there was no difference in effect between biofeedback and electrostimulation. Neither biofeedback nor electrostimulation treatments improved Wexner incontinence score, reduced quality of life, or fecal incontinence quality of life scores. Both treatments resulted in improvement of patients' subjective perception of incontinence control.

Total mesorectal excision for rectal cancer: difference in outcome for low and high rectal cancer.

PURPOSE: This prospective study was designed to assess the outcome through the first five years after the introduction of total mesorectal excision in 1993 in a Norwegian central hospital, with special regard to the difference between low (< or =6 cm from anal verge) and high (>6 cm) rectal cancers. METHODS: A total of 140 patients (81 males; median age, 64 (range, 29-87) years) underwent surgery for rectal cancer under curative intention. RESULTS: Local recurrence rates were 8 of 44 (18 percent) for the low cancers and 5 of 96 (5 percent) for the high, a statistically significant difference (P = 0.0014). Corresponding numbers when the R1 resections are excluded were 5 of 36 (13 percent) for the low and 4 of 92 (4 percent) for the high cancers (P = 0.002). The five-year survival after R0 resections of cancers <6 cm was significantly reduced compared with those >6 cm. The five-year overall survival for the whole material was 72 percent. CONCLUSIONS: Surgery alone for rectal cancer can achieve overall good results, with five-year overall survival of 72 percent. The prognosis of the cancers of the lower rectum seems to be inherently different from the tumors of the higher level, both concerning local recurrence and five-year survival, suggesting different biologic behavior of the two cancers.