[Show abstract][Hide abstract] ABSTRACT: Goals:
Our aim was to determine whether the screening of family members of familial adenomatous polyposis (FAP) patients significantly influences survival, and to gauge the extent of FAP-related causes of death.
The screening of families with FAP has been shown to be profitable in reducing colorectal cancer-related mortality, but conclusions about the screening effect on overall survival has been controversial.
This is a nationwide population-based retrospective cohort study, and the primary outcome of interest was overall mortality and survival. A total of 154 families with at least 1 clinically diagnosed FAP patient between 1963 and 2015 were included. There were altogether 194 probands and 225 call-ups. During the follow-up period, 2639 person-years with 92 deaths among probands were observed and 3634 person-years and 30 deaths among call-ups. We report crude mortality rates and standardized mortality ratios together with descriptive statistics. We compared the survival of probands and call-ups to the population by relative survival method.
The crude mortality rate among probands was 34.9 per 1000 person-years and 8.3 among call-ups. The standardized mortality ratios for call-ups was 2.47 (confidence interval, 1.69-3.46) and for probands 4.07 (confidence interval, 3.29-4.96) (P=0.014). The relative survival of probands was significantly lower than call-ups (P=0.0018), and 20-year relative survival for call-ups was 94% (88% to 100%). Over two thirds of all deaths were FAP related.
Survival of screened family members of FAP patients is comparable to the general population within 20 years after diagnosis. Therefore, participation in surveillance should not be delayed when a family member with FAP has been detected.
No preview · Article · Oct 2015 · Journal of clinical gastroenterology
[Show abstract][Hide abstract] ABSTRACT: The adoption of the total mesorectum excision technique and circular stapler devices has enabled the performance of ultralow colorectal anastomosis in rectal cancer surgery. However, rupture of the anastomosis still usually leads to a permanent stoma. The aim of this study was to analyze the cumulative failure rate and risk factors associated with reversal of colorectal or coloanal anastomosis after sphincter-saving surgery for rectal cancer, using standardized surgical regimen with the routine use of covering stoma. Our secondary interest was the feasibilities of redo surgery after failure.
This was a retrospective study with 579 consecutive rectal cancer patients operated on at Helsinki University Hospital, Helsinki, Finland during 2005-2011. Data were collected from patient records. After exclusions, 273 consecutive patients treated with a low anterior resection with a protective stoma were included.
In total, 23 out of 271 (8.5 %) of the colorectal/coloanal anastomoses were converted to a permanent stoma. In five patients (1.8 %), the covering stoma was not closed. The permanent stoma rate was thus 28 out of 271 (10.3 %). The risk factors associated with failure were the tumor distance from the anal verge (p = 0.03), coloanal anastomosis (p = 0.003), early anastomotic complication (p < 0.001), anastomotic fistula (p < 0.001), anal incontinence (p = 0.05), and local recurrence (p < 0.001).
Our standardized surgical regimen with a covering stoma in low anterior resection for rectal cancer resulted in a minor anastomosis failure rate and a low risk of permanent stoma.
No preview · Article · Jun 2015 · International Journal of Colorectal Disease
[Show abstract][Hide abstract] ABSTRACT: Cohesin is present in almost all active enhancer regions, where it is associated with transcription factors. Cohesin frequently colocalizes with CTCF (CCCTC-binding factor), affecting genomic stability, expression and epigenetic homeostasis. Cohesin subunits are mutated in cancer, but CTCF/cohesin-binding sites (CBSs) in DNA have not been examined for mutations. Here we report frequent mutations at CBSs in cancers displaying a mutational signature where mutations in A•T base pairs predominate. Integration of whole-genome sequencing data from 213 colorectal cancer (CRC) samples and chromatin immunoprecipitation sequencing (ChIP-exo) data identified frequent point mutations at CBSs. In contrast, CRCs showing an ultramutator phenotype caused by defects in the exonuclease domain of DNA polymerase ɛ (POLE) displayed significantly fewer mutations at and adjacent to CBSs. Analysis of public data showed that multiple cancer types accumulate CBS mutations. CBSs are a major mutational hotspot in the noncoding cancer genome.
[Show abstract][Hide abstract] ABSTRACT: After curative rectal cancer surgery, local recurrences manifest in 2.4-10 % and distant metastases in 20-50 % of patients. The effectiveness of different surveillance regimens is not well established. We evaluated the pattern of recurrence and the utility of different surveillance instruments. Risk factors for recurrence were also recorded.
This retrospective study comprises 580 consecutive rectal cancer patients operated on at Helsinki University Central Hospital, Finland, during 2005-2011. Data were collected from patient records. After exclusions, 481 patients treated with curative intent remained. Patients were followed up according to an intensive surveillance program.
Rectal cancer recurrence was observed in 124 patients (25.8 %). Local recurrence manifested in 40 patients (8.3%) and distant metastases in 112 patients (23.3 %). Recurrences were observed a median of 1.3 years after surgery. Twelve patients had to be followed up to find one local recurrence and four patients to find one distant metastasis. Recurrences detected during regular follow-up visits were discovered on average earlier than those detected in additional visits arranged because of patient symptoms (p = 0.023 for local recurrence, p = 0.001 for distant metastases). All surveillance instruments were similarly useful in finding recurrence. Curative treatment was possible in 51 (41.1 %) of 124 patients with disease recurrence. Follow-up led to a 10.0 % chance of detecting recurrence that could be treated with curative intent.
Rectal cancer recurrences are detected earlier within a surveillance program than by symptoms alone. The most intensive follow-up should be focused on patients with known risk factors for recurrence.
No preview · Article · Mar 2015 · International Journal of Colorectal Disease
[Show abstract][Hide abstract] ABSTRACT: Prophylactic surgical options for familial adenomatous polyposis (FAP) are either colectomy and ileorectal anastomosis (IRA) or proctocolectomy and ileal pouch-anal anastomosis (IPAA). The aim of this study was to analyse the short-term and long-term outcomes of these two operative techniques. All patients with FAP in Finland have been prospectively recorded in a database since 1963 were retrospectively reviewed in this analysis. Altogether 140 (61 %) colectomies with IRA and 88 (39 %) proctocolectomies with IPAA have been performed. Complications occurred in 28 (21 %) patients after IRA and in 26 (30 %) patients after IPAA. There were 15 (11 %) severe complications for IRA and 5 (6 %) for IPAA. Twenty-one (15 %) patients of the IRA group ended up in conventional ileostomy whereas 3 (3.4 %) patients of the IPAA group had their ileal reservoir converted to an ileostomy (p = 0.01). Cumulative survival for IRA was lower than for the IPAA (p = 0.03), but if accounting only for operations made after the IPAA era had commenced, there was no significant difference. IPAA was associated with improved long-term survival without an increase in postoperative complications. The risk of death after colectomy and IRA seemed to be predominantly related to the remaining risk of rectal cancer. Therefore, we favour proctocolectomy with IPAA as the prophylactic surgical procedure for FAP with intermediate or severe polyposis.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Patients with pseudomyxoma peritonei (PMP) benefit from cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Reports on this modality usually have included only patients with successful HIPEC treatment, which can potentially cause biased results. We report the survival of a PMP population treated by CRS and HIPEC, including patients who were not eligible for HIPEC.
The outcome of the whole population of 87 patients with PMP treated by CRS and HIPEC in Helsinki University Central Hospital between 2008 and 2011 was evaluated. The results of treatment were compared with 33 patients treated by serial debulking in our unit between 1984 and 2008.
Of the 87 patients in the HIPEC-era group, 56 received HIPEC, 12 were treated non-radically in an attempt at HIPEC, 9 were debulked and 10 were referred back or transferred to palliative care without surgery. The 5-year overall survival for the debulking-era group and the HIPEC-era group were 67 and 69 %, respectively. The number of patients with no evidence of disease was higher in the HIPEC-era group (47/87) than that in the debulking-era group (8/33) at the end of the follow-up. Overall survival for patients who underwent successful CRS and HIPEC at 2 and 5 years was 95 and 93 %, respectively.
The improved survival from using the CRS and HIPEC was not apparent after 5-year follow-up, when the whole patient population was included in the analysis. Even so, patients successfully treated by CRS and HIPEC manage well.
No preview · Article · Jun 2014 · International Journal of Colorectal Disease
[Show abstract][Hide abstract] ABSTRACT: The aim of our retrospective study was to review the outcome of patients undergoing colectomy with ileorectal anastomosis (IRA) due to familial adenomatous polyposis (FAP) in Finland during the last 50 years.
The cumulative risk of rectal cancer and the rate of anus preservation were analyzed. A total of 140 FAP patients with previous colectomy combined with ileorectal anastomosis were included. Kaplan-Meier analysis was performed to evaluate cumulative risks.
Secondary proctectomy was performed for 39 (28 %) of 140 patients. The cumulative risk of secondary proctectomy was 53 % at 30 years after colectomy with IRA. A total of 17 (44 %) secondary proctectomies were performed due to cancer or suspicion of cancer, and another 17 (44 %) secondary proctectomies were performed due to uncontrollable rectal polyposis. During our study, the anus preservation rate in secondary proctectomies was 49 %. The cumulative risk of rectal cancer was 24 % at 30 years after colectomy with IRA. Therefore, the cumulative rectal cancer mortality 30 years after colectomy with IRA was 9 %.
Proctocolectomy and ileal pouch-anal anastomosis (IPAA) should be favored as a primary operation for patients not having technical or medical contraindications for it because colectomy with IRA carried a rectal cancer risk of 13 % with a mortality of 7 % during our study, and because IPAA is likely to succeed better at earlier phase of the disease. Patients with attenuated FAP had no rectal cancer in our study, and they may form a group where IRA should still be the first choice as an exception.
No preview · Article · Nov 2013 · International Journal of Colorectal Disease
[Show abstract][Hide abstract] ABSTRACT: We analyzed the feasibility of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with pseudomyxoma peritonei.
A prospective database comprised 90 consecutive patients with demonstrable pseudomyxoma peritonei collected during 48 months. These patients, referred to our unit for consideration for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, received both cytoreductive surgery and hyperthermic intraperitoneal chemotherapy if possible. We evaluated the factors associated with a successful procedure.
Hyperthermic intraperitoneal chemotherapy was successfully delivered to 56 of 90 patients (62%) with demonstrable pseudomyxoma peritonei. Tumor morphology of low grade (p = 0.013), age under 65 years (p = 0.004), and serum carcinoembryonic antigen level under 5.0 µg/L (p = 0.003) were associated with successful administration of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Mean peritoneal cancer index was lower (18.9 vs 32.6, p < 0.001) and age was younger (54.3 vs 61.6, p = 0.003) in patients who underwent hyperthermic intraperitoneal chemotherapy than in patients who did not. Four patients had complete cytoreductive surgery alone, and 20 patients underwent palliative debulking, but 10 were ineligible for this operation.
Although the combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is currently suggested the standard practice for pseudomyxoma peritonei, not all patients are eligible for this protocol. In this study, hyperthermic intraperitoneal chemotherapy was suitable for 62% of patients with pseudomyxoma peritonei of appendiceal origin.
Preview · Article · Sep 2013 · Scandinavian journal of surgery: SJS: official organ for the Finnish Surgical Society and the Scandinavian Surgical Society
[Show abstract][Hide abstract] ABSTRACT: Intestinal obstruction is a common complication in peritoneal cancers. Obstructions occur especially as the cancer advances, at a time when life expectancy is often only a few months. Characteristic symptoms include nausea, vomiting, constipation, lack of bowel function, colicky and persistent abdominal pains. Conservative treatment aims to secure intestinal transit by applying pharmacologic therapies in cases where surgical therapy in partial or functional obstruction is not possible or reasonable. Pharmacologic therapy consists of antisecretory and antiemetic drugs combined with opioids.
No preview · Article · Mar 2013 · Duodecim; lääketieteellinen aikakauskirja
[Show abstract][Hide abstract] ABSTRACT: Standardization of surgical techniques according to the TME (total mesorectal excision) principles is the most important single factor in improving treatment outcome in rectal cancer. In skilled hands surgical specimens are of equal quality both in open and laparoscopic surgery. In selected patient groups, cancer of the middle or low rectum can also be managed laparoscopically by an experienced surgeon and under good circumstances. Since both immediate and long-term results from large international randomized multicenter studies are lacking so far, open surgery should still be considered as the standard method for rectal cancer.
No preview · Article · Jun 2012 · Duodecim; lääketieteellinen aikakauskirja
[Show abstract][Hide abstract] ABSTRACT: Duodenal adenomatosis in familial adenomatous polyposis results in a cancer risk that increases with age. Endoscopic surveillance has been recommended, but the effect has not yet been documented. The aim of this study was to present the results of long-term duodenal surveillance and to evaluate the risk of cancer development.
Follow up of patients in a previous study with gastroduodenoscopy in 1990-2010. Statistical analysis included the χ(2) test, actuarial method and Kaplan-Meier analysis.
Among 304 patients, 261 (86%) had more than one endoscopy. The median follow up was 14 (interquartile range, 9-17) years. The cumulative lifetime risk of duodenal adenomatosis was 88% (95% CI, 84-93), and of Spigelman stage IV was 35% (95% CI, 25-45). The Spigelman stage improved in 32 (12%) patients, remained unchanged in 88 (34%) and worsened in 116 (44%). Twenty (7%) patients had duodenal cancer at a median age of 56 (range, 44-82) years. The cumulative cancer incidence was 18% at 75 years of age (95% CI, 8-28) and increased with increasing Spigelman stage at the index endoscopy to 33% in Spigelman stage IV (P < 0.0001). The median overall survival was 6.4 years (95% CI, 1.7 to not estimated): 8 years after a screen-detected cancer vs 0.8 years (95% CI, 0.03-1.7) after a symptomatic cancer (P < 0.0001). The location of the mutation in the APC gene did not influence the risk of developing Spigelman stage IV (P = 0.46) or duodenal cancer (P = 0.83).
The risk of duodenal cancer in familial adenomatous polyposis is considerable, and regular surveillance and cancer prophylactic surgery result in a significantly improved prognosis.
No preview · Article · Oct 2011 · Colorectal Disease
[Show abstract][Hide abstract] ABSTRACT: Self-expanding metal stents (SEMS) are used for colorectal obstruction preoperatively and palliatively. Limited data on the use of stents for obstruction caused by extracolonic malignancies exist, and the results are unclear. Our goal was to evaluate the efficacy and safety of SEMS for patients stented as a bridge to surgery and as palliation for colorectal cancer or extracolonic malignancies.
Between 1998 and 2009, a total of 101 patients underwent 108 stenting procedures for malignant colorectal obstruction. The results were studied retrospectively.
Of the study cohort, 11 patients were stented as a bridge to surgery. For palliatively stented patients, the etiology of obstruction was colorectal cancer in 66 patients and extracolonic malignancy in 24. Overall technical success was 99% and clinical success 88%. Complications occurred for 20 (20%) patients in 22 of 108 procedures. Complications included perforation (n = 6), recurrent obstruction (n = 8), and stent migration (n = 4). A median time to complication was 81.5 days. The overall stent placement-related mortality was 2/101 (2%). For patients stented as a bridge to surgery, a primary anastomosis in elective operations was achieved for 90% (9/10). In the palliation groups, patients with colorectal cancer had significantly higher clinical success rates than patients with extracolonic malignancies (94% vs. 65%, P = 0.0005). There was no difference in complications, operation, and stoma rates between the palliation groups.
SEMS is a safe and effective treatment for patients stented as a bridge to surgery or as palliation due to colorectal cancer. Stents are also useful in relieving obstruction due to extracolonic malignancies, but the clinical failure rate is higher than for colorectal cancer.
No preview · Article · Sep 2011 · Surgical Endoscopy
[Show abstract][Hide abstract] ABSTRACT: Self-expanding metal stents (SEMS) have been successfully used as a "bridge to surgery" or as palliation for acute malignant colorectal obstruction. Little data on the use of stents for benign obstruction exists and the results vary. The purpose of this study was to evaluate the efficacy and safety of SEMS in benign colorectal obstruction.
A total of 21 patients with 23 SEMS procedures between the years 1998 and 2008 were retrospectively studied. Eight patients had an obstruction in the surgical anastomosis. In addition, there were two patients with anastomotic strictures due to Crohn's disease. In 10 patients the obstruction was caused by diverticular disease and one patient had a stricture after radiation therapy.
Technical success was achieved for all the patients. Clinical success was achieved for 76% (16/21) of the patients. The anastomotic strictures were resolved with SEMS in 5 out of 8 cases (63%). Three patients with diverticular stricture (30%) were eventually resolved with SEMS. Nine (43%) patients in 10 out of 23 procedures (43%) had a complication, the majority being in patients with diverticular stricture.
SEMS is a good treatment option for patients with anastomotic stricture of the colon and for patients with benign colonic stricture who are unfit for surgery. SEMS can be used as a bridge to surgery in diverticular obstruction but there seems to be a considerable risk of complications. If a SEMS is placed into a diverticular stricture, the planned bowel resection should be performed within a month.
No preview · Article · Mar 2010 · Scandinavian Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: We analysed the clinical symptoms and signs of pseudomyxoma peritonei (PMP), a rare syndrome affecting one to two persons per million annually. Presumably, patients with PMP would benefit from early diagnosis. This study was conducted to further characterise the manifestations of PMP.
We performed a retrospective chart review of a consecutive series of 82 PMP cases at the Helsinki University Central Hospital from June 1984 to September 2009. We then analysed the patients' characteristics, clinical manifestations, indications for surgery and preoperative radiological investigations.
The study involved 53 women (65%) and 29 men (35%). The preponderance of women was statistically significant (p = 0.008). Abdominal pain was the most common chief complaint in the initial evaluation with 23% of the cases. The subsequent more common chief complaints were acute abdomen with 21%, increased abdominal girth with 17%, coincidental diagnosis with 13%, other reasons with 13% and newly onset hernia with 12% of the cases. Suspected ovarian tumour was the most common cause for surgery overall, with 26 of 82 initial operations (32%). Of the 82 initial operations, 23 (28%) were performed with a suspicion or diagnosis of PMP. Computed tomography had a sensitivity of 51% in recognising PMP.
While only 28% of patients underwent initial surgery for presumed PMP, the accuracy of preoperative diagnostics was modest. Diagnostics of PMP is challenging due to the mimicking nature of the disease. In case of indistinct intra-abdominal tumour, we recommend, careful patient examination prior to the initial surgery, when possible.
No preview · Article · Jan 2010 · Scandinavian journal of surgery: SJS: official organ for the Finnish Surgical Society and the Scandinavian Surgical Society
[Show abstract][Hide abstract] ABSTRACT: In pseudomyxoma peritonei a mucinous tumor of the appendix spreads into the abdominal cavity. Cytologic picture of the tumor may be benign, malignant or intermediary. The symptoms were previously relieved by repeated resections of the tumor mass, whereby even the most benign form of the disease progressed slowly. A method has now emerged in which radical-aimed surgery is combined with intraperitoneal lavage with a warmed solution of a cytotoxic agent. This treatment is associated with a morbidity of 33 to 56% and a mortality of 0 to 18%. Controlled studies have not been carried out on the novel treatment.
No preview · Article · Jan 2010 · Duodecim; lääketieteellinen aikakauskirja
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate the consequences of chronic pouchitis after restorative proctocolectomy for ulcerative colitis.
Forty-two patients with chronic pouchitis underwent pouch endoscopy with biopsies after a median of 8.3 years of postoperative follow up. The pouchitis disease activity index (PDAI) was calculated. Morphological changes were recorded. Immunohistochemical analyses for cyclooxygenase 2 (COX-2), Ki-67 and p53 were performed, as was DNA flow cytometry. Endoscopy was also carried out in 10 patients without pouchitis and in nine healthy subjects.
In patients with chronic pouchitis, the PDAI was 6 (standard error of the mean ± 4). Eighteen (43%) patients used continuous medication. The PDAI correlated positively with villous atrophy (P < 0.05). None of the pouch biopsies showed dysplasia. COX-2 immunostaining was detected in 35 (83.3%) patients with chronic pouchitis, in five (50%) without pouchitis, but in none of the normal controls. COX-2 expression correlated with mucosal atrophy (P < 0.01). In 15 (35.7%) of 42 patients with chronic pouchitis, Ki-67 immunostaining was increased, but no increase was observed in either control group (P < 0.002). No p53 immunopositivity was found, and DNA flow cytometry was normal in all pouches. One of the patients developed adenocarcinoma at the anal anastomosis.
No dysplastic changes were detected during the first decade after surgery. Routine follow up of patients with chronic pouchitis with a hand-sewn anastomosis may not be necessary, although a small risk of cancer seems to remain at the anal anastomosis. The follow up should be focused on at-risk groups.
No preview · Article · Oct 2009 · Colorectal Disease
[Show abstract][Hide abstract] ABSTRACT: Background
Malignant gastric outlet obstruction (GOO) leads to malnutrition and limits quality of life. Gastrojejunostomy has been the traditional treatment for GOO. Recently, the results of releasing duodenal obstruction with self-expandable metal stents (SEMS) have been encouraging.
After the exclusion of 13 patients with gastrojejunal or jejunal strictures and 1 patient with intraabdominal lymphoma, the authors palliated the malignant GOO in 104 patients with 130 SEMS at a single center during the years 1999–2007.
The GOO was caused by pancreatic (n = 51), gastric (n = 24), duodenal (n = 7), biliary (n = 5), and other (n = 17) malignancies. Of the 104 patients, 76 (73%) did well with only one enteral stent placement, 21 (20.2%) required two stent placements, 4 (3.8%) required three stent placements, and 1 required four stent placements. The median dysphagia score was 0 before stenting and 2 after treatment (p < 0.001). Immediate failure occurred after 10 procedures (7.7%). Among the 104 patients, 6 (5.8%) died of stent placement-related reasons. Complications occurred for 13 patients (12.5%). The median hospital stay was 3 days, and the overall survival time was 62 days (range, 1–933 days). Of 11 patients with concomitant biliary obstruction and GOO, 10 (91%) underwent successful enteral and biliary stent placement within the same session. Of 15 patients experiencing jaundice after enteral stent placement, 6 (40%) underwent endoscopic biliary drainage successfully.
Enteral stenting is a safe and effective way to treat GOO. Gastrojejunostomy should be preserved for cases in which endoscopic stenting is not successful or possible.
No preview · Article · Sep 2009 · Surgical Endoscopy