Effects of omeprazole or anti-reflux surgery on lower oesophageal sphincter characteristics and oesophageal acid exposure over 10 years.

OBJECTIVE: To compare the effect of anti-reflux surgery (ARS) versus proton pump inhibitor therapy on lower oesophageal sphincter (LOS) function and oesophageal acid exposure in patients with chronic gastro-oesophageal reflux disease (GORD) over a decade of follow-up. MATERIAL AND METHODS: In this randomised, prospective, multicentre study we compared LOS pressure profiles, as well as oesophageal exposure to acid, at baseline and at 1 and 10 years after randomisation to either open ARS (n = 137) or long-term treatment with omeprazole (OME) 20-60 mg daily (n = 108). RESULTS: Median LOS resting pressure and abdominal length increased significantly and remained elevated in patients operated on with ARS, as opposed to those on OME. The proportion of total time (%) with oesophageal pH <4.0 decreased significantly in both the surgical and medical groups, and was significantly lower after 1 year in patients treated with ARS versus OME. After 10 years, oesophageal acid exposure was normalised in both groups, with no significant differences, and bilirubin exposure was within normal limits. After 10 years, patients with or without Barrett's oesophagus did not differ in acid reflux control between the two treatment options. CONCLUSIONS: Open ARS and OME were both effective in normalising acid reflux into the oesophagus even when studied over a period of 10 years. Anatomically and functionally the LOS was repaired durably by surgery, with increased resting pressure and abdominal length.

Reduced neurons in the ileum of proctocolectomized rat models.

Ileal pouch-anal anastomosis (IPAA) is the operation of choice following proctocolectomy for patients who suffer from ulcerative colitis and familial adenomatous polyposis. The aim of this study was to morphologically examine the neurons, endocrine cells and mast cells in the ileum of rats subjected to proctocolectomy followed by three different types of ileoanal anastomosis. Rats were subjected to either sham operation or proctocolectomy followed by ileoanal anastomosis end-to-end, side-to-end or IPAA (J-pouch). In comparison to sham-operated rats, the body weight was reduced in rats that underwent proctocolectomy with end-to-end or side-to-end, but not IPAA procedure. In all three models of ileoanal anastomosis, the ileum displayed crypt hyperplasia with a chronic inflammatory infiltrate located in the interstitium, hyperplasia of goblet cells, but reduced protein gene product 9.5 (PGP 9.5)-immunoreactive neurons in the mucosa as well as submucosa. Numbers of endocrine cells in the mucosa (chromogranin A immunostaining) and mast cells in the mucosa and submucosa (Astra blue staining) were unchanged after proctocolectomy. In conclusion, neurons, but neither endocrine cells nor mast cells, were reduced in the ileum of proctocolectomized rats followed by either of three different types of ileoanal anastomosis.

Adenoma formation and malignancy after restorative proctocolectomy with or without mucosectomy in patients with familial adenomatous polyposis.

BACKGROUND: There is controversy concerning whether or not to perform mucosectomy after IPAA in patients with familial adenomatous polyposis. Although more frequent adenoma formation at the anastomotic site in patients without a mucosectomy is documented, the interpretation of the theoretical reflections and empirical findings are ambiguous. OBJECTIVE: The aim of this study was to assess the differences in adenoma formation at the anastomotic site and in the ileal pouch among patients with familial adenomatous polyposis after IPAA with or without mucosectomy. DESIGN: Data were gathered from The Norwegian Polyposis Registry and The Cancer Registry of Norway. PATIENTS: Sixty-one patients with familial adenomatous polyposis who had IPAA were included in the Norwegian Polyposis Registry. MAIN OUTCOME MEASURES: The frequency of adenoma development in the pouch or at the anastomotic site was measured. RESULTS: Thirty-nine patients had a pelvic pouch performed with mucosectomy and 22 patients without. The observational time was 15.5 and 13.7 years. Adenoma formation at the anastomotic site was 4 in 39 and 14 in 22, and the estimated rate was 17% vs 75% (p = 0.0001). One patient without mucosectomy had a cancer (Dukes A) at the anastomotic site. There was no estimated long-term difference in adenoma formation in the ileal pouches between the 2 surgical procedures (38%) (p = 0.10). LIMITATIONS: The study is retrospective, in part, and relies on data from registries. There is a limited number of cases, and selection bias because of surgeon preference may exist. CONCLUSION: In patients with familial adenomatous polyposis who undergo IPAA, adenoma formation at the anastomotic site is significantly reduced after mucosectomy. Mucosectomy may be the preferable procedure to prevent adenomas at the anastomotic site.

Primary sclerosing cholangitis and extraintestinal manifestations in patients with ulcerative colitis and ileal pouch-anal anastomosis.

OBJECTIVE: The aim of this study was to assess complications and functional outcomes in patients having ileal pouch-anal anastomosis for ulcerative colitis with or without primary sclerosing cholangitis or extraintestinal manifestations and to assess if primary sclerosing cholangitis is a risk factor for pouchitis. MATERIALS AND METHODS: From 1984 to 2007, 289 patients underwent proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. Mean follow-up time was 12 years and data was recorded prospectively. Eleven patients had primary sclerosing cholangitis, six had pyoderma gangrenosum, and 12 had arthritis or ankylosing spondylitis. RESULTS: Early complications were similar for patients with or without extraintestinal manifestations. Functional outcomes were similar, but more incontinence among patients with sclerosing cholangitis was found. These patients had more frequent pouchitis, 5.25 vs. 2.72 average episodes of pouchitis (p = 0.048), and more chronic pouchitis, 4/11 vs. 17/260 (p < 0.001) compared to patients without adjunct disease. Neoplasm of the colon was more frequent in patients with primary sclerosing cholangitis, 4/11 vs. 4/260 in ulcerative colitis patients (p < 0.001). CONCLUSION: An association between primary sclerosing cholangitis and chronic/severe pouchitis was found, but not with other extraintestinal manifestations. Functional results were good and alike in patients with and without primary sclerosing cholangitis. Primary sclerosing cholangitis is a risk factor for chronic pouchitis and is associated with neoplasia.

Durability of ileal pouch-anal anastomosis and continent ileostomy.

PURPOSE: This study was designed to evaluate pouch durability and salvage in patients undergoing continent ileostomy and ileal pouch-anal anastomosis. METHODS: Three hundred seventeen patients undergoing ileal pouch-anal anastomosis and 63 undergoing continent ileostomy were evaluated in a prospective observational study. Median observation time was 10.6 (range, 1-23) years for patients who underwent ileal pouch-anal anastomosis and 14 (1-24) years for those who underwent continent ileostomy. RESULTS: Twenty-three pelvic pouches failed (8%), and six continent ileostomies (10%) were excised (difference not significant). Estimated failure rates at 20 years were 11.4% (CI, +/-4.8) for ileal pouch-anal anastomosis and 11.6% (CI, +/-8,2) for continent ileostomy (P = 0.8). Sixty-five patients who had received an ileal pouch-anal anastomosis (21%) and 21 of those who had a continent ileostomy (30%) had one or more salvage procedures. Estimated salvage rates at 20 years were 31% vs. 38%, respectively (P = 0.06). The crude success rates of functioning ileal pouch-anal anastomosis and continent ileostomy were 92.8% and 90.5%, respectively. CONCLUSION: Success rates after ileal pouch-anal anastomosis and continent ileostomy are high. Their rates of failure are similar. Salvage procedures are substantial with both procedures. Complications and failure after continent ileostomy are not inferior to those after ileal pouch-anal anastomosis. Continent ileostomy remains an option in patients for whom ileal pouch-anal anastomosis is unsuitable.

Comparison of outcomes twelve years after antireflux surgery or omeprazole maintenance therapy for reflux esophagitis.

BACKGROUND & AIMS: It is important to evaluate the long-term effects of therapies for gastroesophageal reflux disease (GERD). In a 12-year study, we compared the effects of therapy with omeprazole with those of antireflux surgery. METHODS: This open, parallel group study included 310 patients with esophagitis enrolled from outpatient clinics in Nordic countries. Of the 155 patients randomly assigned to each arm of the study, 154 received omeprazole (1 withdrew before therapy began), and 144 received surgery (11 withdrew before surgery). In patients who remained in remission after treatment, post-fundoplication complaints, other symptoms, and safety variables were assessed. RESULTS: Of the patients enrolled in the study, 71 who were given omeprazole (46%) and 53 treated with surgery (37%) were followed for a 12-year follow-up period. At this time point, 53% of patients who underwent surgery remained in continuous remission, compared with 45% of patients given omeprazole with a dose adjustment (P = .022) and 40% without dose adjustment (P = .002). In addition, 38% of surgical patients required a change in therapeutic strategy (eg, to medical therapy or another operation), compared with 15% of those on omeprazole. Heartburn and regurgitation were significantly more common in patients given omeprazole, whereas dysphagia, rectal flatulence, and the inability to belch or vomit were significantly more common in surgical patients. The therapies were otherwise well-tolerated. CONCLUSIONS: As long-term therapeutic strategies for chronic GERD, surgery and omeprazole are effective and well-tolerated. Antireflux surgery is superior to omeprazole in controlling overall disease manifestations, but post-fundoplication complaints continue after surgery.

Final results of a randomised phase III study on adjuvant chemotherapy with 5 FU and levamisol in colon and rectum cancer stage II and III by the Norwegian Gastrointestinal Cancer Group.

BACKGROUND: The recommendation of adjuvant chemotherapy for colon cancer with lymph node metastases, based on two studies from USA, was reluctantly accepted by Norwegian medical doctors. It was therefore decided to assess the role of adjuvant therapy with 5fluorouracil (5-FU) combined with levamisole (Lev) in a confirmatory randomised study. MATERIAL AND METHODS: Four hundred and twenty five patients with operable colon and rectum cancer, Stage II and III (Dukes' stage B and C), were from January 1993 to October 1996, included in a randomised multicentre trial in Norway. The age limits were 18-75 years. Therapy started with a loading course of bolus i.v. 5-FU (450 mg/m(2)) daily for 5 days and p.o. doses of Lev (50 mg x 3) for 3 days. From day 28 a weekly i.v. 5-FU dose (450 mg/m(2)) were administered for 48 weeks. From day 28 also p.o. doses of Lev (50 mg x 3) for 3 days were given every 14 days. In total 214 patients were randomised to 5FU/Lev and 211 were included in the control group with surgery alone. Some did not comply with the inclusion and exclusion criteria, thus leaving 206 evaluable patients in each group. RESULTS: There was no significant survival difference between the two groups at 5 years: Disease-free survival (DFS) was 73% after chemotherapy, 68% (p=0.24) in the control group, and corresponding cancer specific survival (CSS) 75% and 71%, respectively (p=0.69). There was no difference between the two groups when analysed for colon and rectum separately. However, the subgroup of colon cancer with stage III exhibited a statistically significant difference both for DFS, 58% vs. 37% (p=0.012) and CSS, 65% vs. 47% (p=0.032) in favour of adjuvant chemotherapy. The benefit was further statistically significant for women but not for men. Toxicity was generally mild and acceptable with no drug related fatalities. CONCLUSIONS: Colon cancer patients with lymph node metastases benefit from adjuvant chemotherapy with 5-FU/Lev with acceptable toxicity. In a subgroup analysis females did better than males. Rectal cancer does not benefit from this regimen.

A homozygote splice site PMS2 mutation as cause of Turcot syndrome gives rise to two different abnormal transcripts.

Turcot syndrome is a rare, inherited disease predisposing of tumours in the central nerve system and in the colorectal system. This report describes a Turcot patient with an extraordinary clinical history. The patient is still alive at the age of 43. She was operated at the age of 10 by brain tumour and at the age of 16 by colorectal cancer. She has since then been treated for multiple cancers (gastrointestinal, endometrial, basal cell carcinomas), and removal of adenomatous polyps at several occasions. The aim of this work was to investigate if there was any specific genotype that explains her remarkable clinical history. Microsatellite instability and immunohistochemistry analysis for four DNA mismatch repair proteins were performed. DNA mutation analysis was done for genes involved in polyposis and mismatch repair by denaturing high performance liquid chromatography and sequencing. cDNA analysis was carried out for the mismatch repair gene PMS2. The patients genotype was found to be a homozygous splice site mutation in the PMS2 gene, c.989-1G

Anal carcinoma in mid-Norway 1970-2000.

The treatment of anal carcinoma changed from surgery to chemoradiotherapy 20-25 years ago. The aim of this observational study was to compare surgery with chemoradiotherapy with regard to side effects, local recurrence and survival during and after the implementation of a new treatment policy for anal carcinoma. The study includes all 111 patients with anal carcinoma diagnosed between 1970 and 2000 in mid-Norway. One hundred patients were treated with the intention to cure, and 11 patients received palliative treatment. Thirty-four patients were treated with surgery alone, and 57 patients with chemoradiotherapy. Among patients treated for cure, 17 patients (17%) developed local recurrence; ten patients (33%) in the surgically treated group and 4 (7%) in the chemoradiotherapy group (p = 0.15). Five year overall survival was 48% after surgery, compared to 78% after chemoradiotherapy (p = 0.004). Stage, age and treatment were all significant indicators of survival in uni- and multivariable analysis. Late side effects were moderate after combined therapy; only one patient preferred getting a stoma due to radiation damage of the anal sphincter. The change of strategy for anal cancer treatment from surgery to combined therapy has probably reduced local recurrence and improved survival. Side effects in this series of patients were minor after chemoradiotherapy compared to a permanent stoma after surgery.

Rectal cancer in the young patient.

PURPOSE: The purpose of this national study was to evaluate the results of treatment for young rectal cancer patients. METHODS: This prospective study from the Norwegian Rectal Cancer Project includes all 2,283 patients younger than aged 70 years with adenocarcinoma of the rectum from November 1993 to December 1999. Patients younger than aged 40 years (n = 45), 40 to 44 years (n = 87), 45 to 49 years (n = 153), and 50 to 69 years (n = 1998) were compared for patient and tumor characteristics and five-year overall survival. Patients treated for cure (n = 1,354) were evaluated for local recurrence, distant metastasis, and disease-free survival. RESULTS: Patients younger than aged 40 years had significantly higher frequencies of poorly differentiated tumors (27 vs. 12-16 percent; P = 0.014), N2-stage (37 vs. 13-18 percent; P = 0.001), and distant metastases (38 vs. 19-24 percent; P = 0.019) compared with older patients. Among those treated for cure, 56 percent of the patients younger than aged 40 years developed distant metastases compared with 20 to 26 percent of the older patients (P = 0.003). Overall five-year survival was 54 percent for patients younger than aged 40 years compared with 71 to 88 percent for the older patients (P = 0.029). Age younger than 40 years was a significant independent prognostic factor and increased the risk for metastasis and death. CONCLUSIONS: Patients younger than aged 40 years had a more advanced stage at the time of diagnosis and poor prognosis compared with older patients. Young patients treated for cure more often developed distant metastases and had inferior survival.

Long-term outcome of surgically and medically treated patients with gastroesophageal reflux disease: a matched-pair follow-up study.

OBJECTIVE: A recent randomized study has shown that the long-term effects of continuous medical treatment of gastroesophageal reflux disease (GERD) with a proton-pump inhibitor are comparable to those of open fundoplication. We compared the long-term effects of anti-reflux surgery with those of medical care according to clinical practice. MATERIAL AND METHODS: This is a questionnaire-based 3-10 years follow-up study of 373 patients with GERD operated on in two hospitals with either open or laparoscopic fundoplication, and pair-matched non-operated controls treated medically according to clinical practice. The controls were matched for hospital, age, sex, follow-up time, degree of esophagitis, presence of hiatus hernia and Barrett's esophagus. The questionnaires used for symptoms and health-related quality of life (QoL) were the Gastrointestinal Symptoms Rating Scale and the Psychological General Well-Being Index, respectively. RESULTS: Response rates were about 80%, and 179 pairs of operated patients and controls remained for analysis (102 based on laparoscopic and 77 on open fundoplication). Independently of the surgical technique, the operated patients suffered at the follow-up from significantly (p <0.001) fewer reflux symptoms than the non-operated controls, the mean scores being 1.34 and 2.51, respectively. The operated patients suffered from slightly more symptoms of indigestion (p <0.05). No consistent significant differences between the groups were found for QoL. Significant differences in QoL in favor of the operated patients were found when dealing only with the 43 pairs with no concurrent disease. CONCLUSION: The study shows that in our area anti-reflux surgery is more effective in relieving reflux symptoms than medical care according to clinical practice.

Transanal excision vs. major surgery for T1 rectal cancer.

PURPOSE: The purpose of this national study was to examine the long-term results of transanal excision compared with major surgery of T1 rectal cancer. METHODS: This prospective study from the Norwegian Rectal Cancer Project included all 291 patients with a T1M0 tumor within 15 cm from the anal verge treated by anterior resection, abdominoperineal resection, Hartmann's procedure, or transanal excision in the period from November 1993 to December 1999. RESULTS: Two hundred fifty-six patients were treated by major surgery and 35 patients by transanal excision. None of the patients had neoadjuvant therapy. Macroscopic tumor remnants (R2) occurred in 17 percent (6/35) of the transanal excisions, while major surgery obtained 100 percent R0 resections. Eleven percent of the patients treated with major surgery had glandular involvement. There were no significant differences according to tumor localization, size, or differentiation between Stage I and Stage III tumors. Patients treated with transanal excision were older than patients having major surgery (mean age, 77 vs. 68 years, P < 0.001). After curative resection (R0, R1, Rx) the five-year rate of local recurrence was 12 percent (95 percent confidence interval, 0-24) in the transanal excision group compared with 6 percent (95 percent confidence interval, 2-10) after major surgery (P = 0.010). The overall five-year survival was 70 percent (95 percent confidence interval, 52-88) in the transanal excision group compared with 80 percent (95 percent confidence interval, 74-85) in the major surgery group (P = 0.04) and the five-year disease-free survival was 64 percent (95 percent confidence interval, 46-82) in the transanal excision group compared with 77 percent (95 percent confidence interval, 71-83) in the major surgery group (P = 0.01). CONCLUSIONS: The main problem of transanal excision for early rectal cancer in the present study was the inability to remove all the malignancy. Patients treated with transanal excision had significantly higher rates of local recurrence compared with patients who underwent major surgery. Patients who had transanal excision had inferior survival, but they were older than those who had major surgery.

Endoanal ultrasound is of little value in follow-up of anal carcinomas.

PURPOSE: The treatment of anal carcinoma has a vigorous follow-up regimen, and several authors have stated that endoanal ultrasound is a useful and necessary part of this regimen. This study was designed to evaluate the value of endoanal ultrasound in follow-up of anal carcinoma. METHODS: In this retrospective study, 82 patients were treated between 1983 and 1999. Main outcome measures were five-year survival and local recurrence rates, and in particular, it was focused on how local recurrences have been detected. RESULTS: Overall five-year survival was 68 percent. Fourteen patients (17 percent) developed local recurrence. Despite an estimated number of 780 scheduled endoanal ultrasound examinations, all the local recurrences were detected by digital and visual examination before the ultrasound procedures. CONCLUSIONS: In this study, all the local recurrences of anal carcinoma were detected by digital and visual examination. Thus, the addition of endoanal ultrasound was costly and unnecessary.

Oncological outcomes after total mesorectal excision for cure for cancer of the lower rectum: anterior vs. abdominoperineal resection.

PURPOSE: This study was designed to examine the outcome of cancer of the lower rectum, particularly the rates of local recurrence and survival for tumors located in this area that have been treated by anterior or abdominoperineal resections. METHODS: A prospective, observational, national, cohort study which is part of the Norwegian Rectal Cancer Project. The present cohort includes all patients undergoing total mesorectal excision in 47 hospitals during the period November 1993 to December 1999. A total of 2,136 patients with rectal cancer within 12 cm of the anal verge were analyzed; there were 1,315 (62 percent) anterior resections and 821 (38 percent) abdominoperineal resections. The lower edge of the tumor was located 0 to 5 cm from the anal verge in 791 patients, 6 to 8 cm in 558 patients, and 9 to 12 cm in 787 patients. According to the TNM classification, there were 33 percent Stage I, 35 percent Stage II, and 32 percent Stage III. RESULTS: Univariate analyses: The five-year local recurrence rate was 15 percent in the lower level, 13 percent in the intermediate level, and 9 percent in the upper level (P=0.014). It was 10 percent local recurrence after anterior resection and 15 percent after abdominoperineal resection (P=0.008). The five-year survival rate was 59 percent in the lower level, 62 percent in the intermediate level, and 69 percent in the upper level (P<0.001), respectively, and it was 68 percent in the anterior-resection group and 55 percent in the abdominoperineal-resection group (P<0.001). Multivariate analyses: The level of the tumor influenced the risk of local recurrence (hazard ratio, 1.8; 95 percent confidence interval, 1.1-2.3), but the operative procedure, anterior resection vs. abdominoperineal resection, did not (hazard ratio, 1.2; 95 percent confidence interval, 0.7-1.8). On the contrary, operative procedure influenced survival (hazard ratio, 1.3; 95 percent confidence interval, 1-1.6), but tumor level did not (hazard ratio, 1.1; 95 percent confidence interval, 0.9-1.5). In addition to patient and tumor characteristics (T4 tumors), intraoperative bowel perforation and tumor involvement of the circumferential margin were identified as significant prognostic factors, which were more common in the lower rectum, explaining the inferior prognosis for tumors in this region. CONCLUSIONS: T4 tumors, R1 resections, and/or intraoperative perforation of the tumor or bowel wall are main features of low rectal cancers, causing inferior oncologic outcomes for tumors in this area. If surgery is optimized, preventing intraoperative perforation and involvement of the circumferential resection margin, the prognosis for cancers of the lower rectum seems not to be inherently different from that for tumors at higher levels. In that case, the level of the tumor or the type of resection will not be indicators for selecting patients for radiotherapy.

A national strategic change in treatment policy for rectal cancer--implementation of total mesorectal excision as routine treatment in Norway. A national audit.

INTRODUCTION: Rectal cancer surgery has been characterized by a high incidence of local recurrence, an occurrence which influences survival negatively. In Norway there was a growing recognition that local recurrence rates were related to surgeon performance and that surgeons applying a standardized surgical technique in the form of total mesorectal excision could achieve better results. This contrasts with the prevailing argument voiced by many opinion leaders that local recurrence rates and possibly survival rates can only be improved by adjuvant or neoadjuvant treatment strategies. The Norwegian Rectal Cancer Project-initiated in 1993-aimed at improving the outcome of patients with rectal cancer by implementing total mesorectal excision as the standard rectal resection technique. METHODS: This observational national cohort study covers all new patients (3,319) with rectal cancer from a population of 4.5 million treated between November 1993 and August 1997. The main outcome measures were local recurrence, survival, and postoperative mortality and morbidity rates. The technique of total mesorectal excision was compared with conventional surgery. RESULTS: The proportion of patients undergoing total mesorectal excision was 78 percent in 1994, increasing to 92 percent in 1997. The observed local recurrence rate for patients undergoing a curative resection was 6 percent in the group treated by total mesorectal excision and 12 percent in the conventional surgery group. Four-year survival rate was 73 percent after total mesorectal excision and 60 percent after conventional surgery. Postoperative mortality rate was 3 percent and the anastomotic dehiscence rate was 10 percent. Radiotherapy was given to 5 percent and chemotherapy to 3 percent of the patients in the curative resection group. CONCLUSION: A refinement of the surgical resection technique for rectal cancer can be achieved on a national level, the technique of total mesorectal excision can be widely distributed, and surgery alone can give good results.

[Laparoscopic surgery in Norway]. / Laparoskopisk kirurgi i Norge.

BACKGROUND: Laparoscopic procedures in gastrointestinal surgery have increasingly been used over the last ten years. This study explores the use of various common laparoscopic procedures in Norway. METHODS: A questionnaire was sent to all 59 public hospitals in Norway in January 1999, of which all but one responded. Laparoscopic surgery was performed in 54 out of 58 hospitals. RESULTS: Most hospitals perform between 11 and 20% of all gastrointestinal operations with laparoscopic technique. Laparoscopic cholecystectomies and anti-reflux surgery have generally replaced open procedures in all hospitals. Appendectomy by the laparoscopic technique accounts for approximately 10% of cases and has become the preferred technique in only one of ten hospitals. Laparoscopic hernia repairs are done in less than 10% of cases. Overall, surgeons' satisfaction with laparoscopy is good and seems slightly higher in district and central hospitals than in university hospitals. Half of all surgical departments plan to use more laparoscopic procedures. INTERPRETATION: Laparoscopic procedures have replaced conventional open surgical procedures for some procedures but is less used than expected ten years ago. A slow and gradual increase may be expected in the years ahead.