Centralized repeated resectability assessment of patients with colorectal liver metastases during first-line treatment: prospective study.

BACKGROUND: Metastasectomy is probably underused in metastatic colorectal cancer. The aim of this study was to investigate the effect of centralized repeated assessment on resectability rate of liver metastases. METHODS: The prospective RAXO study was a nationwide study in Finland. Patients with treatable metastatic colorectal cancer at any site were eligible. This planned substudy included patients with baseline liver metastases between 2012 and 2018. Resectability was reassessed by the multidisciplinary team at Helsinki tertiary referral centre upfront and twice during first-line systemic therapy. Outcomes were resectability rates, management changes, and survival. RESULTS: Of 812 patients included, 301 (37.1 per cent) had liver-only metastases. Of these, tumours were categorized as upfront resectable in 161 (53.5 per cent), and became amenable to surgery during systemic treatment in 63 (20.9 per cent). Some 207 patients (68.7 per cent) eventually underwent liver resection or ablation. At baseline, a discrepancy in resectability between central and local judgement was noted for 102 patients (33.9 per cent). Median disease-free survival (DFS) after first resection was 20 months and overall survival (OS) 79 months. Median OS after diagnosis of metastatic colorectal cancer was 80, 32, and 21 months in R0-1 resection, R2/ablation, and non-resected groups, and 5-year OS rates were 68, 37, and 9 per cent, respectively. Liver and extrahepatic metastases were present in 511 patients. Of these, tumours in 72 patients (14.1 per cent) were categorized as upfront resectable, and 53 patients (10.4 per cent) became eligible for surgery. Eventually 110 patients (21.5 per cent) underwent liver resection or ablation. At baseline, a discrepancy between local and central resectability was noted for 116 patients (22.7 per cent). Median DFS from first resection was 7 months and median OS 55 months. Median OS after diagnosis of metastatic colorectal cancer was 79, 42, and 17 months in R0-1 resection, R2/ablation, and non-resected groups, with 5-year OS rates of 65, 39, and 2 per cent, respectively. CONCLUSION: Repeated centralized resectability assessment in patients with colorectal liver metastases improved resection and survival rates.

Combination of microsatellite instability and BRAF mutation status for subtyping colorectal cancer.

BACKGROUND: The objective of the study was to examine the role of microsatellite instability (MSI) and BRAF(V600E)mutation in colorectal cancer (CRC) by categorising patients into more detailed subtypes based on tumour characteristics. METHODS: Tumour samples from 762 population-based patients with sporadic CRC were analysed for MSI and BRAF(V600E) by immunohistochemistry. Patient survival was followed-up for a median of 5.2 years. RESULTS: Compared with microsatellite stable (MSS) CRC, MSI was prognostic for better disease-free survival (DFS; 5 years: 85.8% vs 75.3%, 10 years: 85.8% vs 72.9%, P=0.027; HR 0.49, CI 0.30-0.80, P=0.005) and disease-specific survival (DSS; 5 years: 83.2% vs 70.5%; 10 years: 83.2 vs 65.0%, P=0.004). Compared with BRAF wild type, BRAF(V600E) was a risk for poor survival (overall survival; 5 years: 62.3% vs 51.6%, P=0.014; HR 1.43, CI 1.07-1.90, P=0.009), especially in rectal cancer (for DSS, HR: 10.60, CI: 3.04-36.92, P<0.001). The MSS/BRAF(V600E) subtype was a risk for poor DSS (HR: 1.88, CI: 1.06-3.31, P=0.030), but MSI/BRAF(V600E) was a prognostic factor for DFS (HR: 0.42, CI: 0.18-0.96, P=0.039). Among stage I-II patients, the MSS/BRAF(V600E) subtype was independently associated with poor DSS (HR: 5.32, CI: 1.74-16.31, P=0.003). CONCLUSIONS: Microsatellite instable tumours were associated with better prognosis compared with MSS. BRAF(V600E) was associated with poor prognosis unless it occurred together with MSI. The MSI/BRAF(V600E) subtype was a favourable prognostic factor compared with the MSS/BRAF wild-type subtype. BRAF(V600E) rectal tumours showed particularly poor prognosis. The MSS/BRAF(V600E) subtype was associated with increased disease-specific mortality even in stage I-II CRC.

Remission of membranous glomerulonephritis after pancreatectomy for pancreatic neuroendocrine neoplasm - a rare coincidence.

The concomitant existence of a non-malignant neuroendocrine tumor (NET) and membranous glomerulonephritis (MGN) is rare. We report a subject with kidney biopsy proven MGN and nephrotic syndrome in which a computerized scan tomography (CT) examination was performed revealing a pancreatic tumor. A pancreatectomy was performed and the tumor was shown to be a non-malignant NET with a malignant potential. Although treatment with corticosteroids was initiated remission of MGN was observed within the next month after pancreatectomy. The rapid remission observed shortly after pancreatectomy pointed to that tumor removal contributed to, and that neither spontaneous nor corticosteroid treatment alone did induce the rapid remission of the MGN. The coexistence of the two disorders NET and MGN is very rare, however. This is the first report on remission of MGN after pancreatectomy for a NET.

Incidence and management of patients with colorectal cancer and synchronous and metachronous colorectal metastases: a population-based study.

BACKGROUND: This population-based study aimed to examine the incidence, patterns and results of multimodal management of metastatic colorectal cancer. METHODS: A retrospective population-based study was conducted on patients with metastatic colorectal cancer in Central Finland in 2000-2015. Clinical and histopathological data were retrieved and descriptive analysis was conducted to determine the pattern of metastatic disease, defined as synchronous, early metachronous (within 12 months of diagnosis of primary disease) and late metachronous (more than 12 months after diagnosis). Subgroups were compared for resection and overall survival (OS) rates. RESULTS: Of 1671 patients, 296 (17·7 per cent) had synchronous metastases, and 255 (19·6 per cent) of 1302 patients with resected stage I-III tumours developed metachronous metastases (94 early and 161 late metastases). Liver, pulmonary and intraperitoneal metastases were the most common sites. The commonest metastatic patterns were a combination of liver and lung metastases. The overall metastasectomy rate for patients with synchronous metastases was 16·2 per cent; in this subgroup, 3- and 5-year OS rates after any resection were 63 and 44 per cent respectively, compared with 7·1 and 3·3 per cent following no resection (P < 0·001). The resection rate was higher for late than for early metachronous disease (28·0 versus 17 per cent respectively; P = 0·048). Three- and 5-year OS rates after any resection of metachronous metastases were 78 and 62 per cent respectively versus 42·1 and 18·2 per cent with no metastasectomy (P < 0·001). Similarly, 3- and 5-year OS rates after any metastasectomy for early metachronous metastases were 57 and 50 per cent versus 84 and 66 per cent for late metachronous metastases (P = 0·293). CONCLUSION: The proportion of patients with metastatic colorectal cancer was consistent with that in earlier population-based studies, as were resection rates for liver and lung metastases and survival after resection. Differentiation between synchronous, early and late metachronous metastases can improve assessment of resectability and survival.

ANTECEDENTES: El objetivo de este estudio de base poblacional fue analizar la incidencia, la forma de presentación y los resultados del tratamiento multimodal del cáncer colorrectal metastásico (metastatic colorectal cancer, mCRC). MÉTODOS: Se realizó un estudio retrospectivo de base poblacional en pacientes con mCRC en la región central de Finlandia entre 2000 a 2015. Se recuperaron los datos clínicos e histopatológicos y se realizó un análisis descriptivo con el objetivo de analizar la forma de presentación de la enfermedad metastásica. La enfermedad metastásica se definió como sincrónica, metacrónica precoz (< 12 meses) y metacrónica tardía (> 12 meses después del diagnóstico de la enfermedad primaria) y se compararon las tasas de resección y de supervivencia global (overall survival, OS) en estos subgrupos. RESULTADOS: De los 1.671 pacientes revisados, 296 (17,7%) presentaron metástasis sincrónicas, mientras que de los 1.302 pacientes resecados en estadios I-III, 255 (19,6%) tuvieron metástasis metacrónicas: 94 precoces y 161 tardías. La localización metastásica más frecuente fue el hígado, los pulmones y el peritoneo. La combinación más frecuente fue la de metástasis hepáticas y pulmonares. La tasa de resección para pacientes con metástasis sincrónicas fue del 16,2%; en este subgrupo, la OS a 3 y 5 años después de cualquier tipo de resección fue del 62,6% y 44,2% versus 7,1% y 3,3% en los pacientes sin resección, respectivamente (P < 0,001). La tasa de resección fue mayor en la enfermedad metacrónica tardía que en la enfermedad metacrónica precoz (28% versus 17%, P = 0,048). Las tasas de OS a 3 y 5 años después de cualquier resección en los casos de metástasis metacrónicas fueron del 77,8% y 61,9% versus 42,1% y 18,2% en los pacientes sin metastasectomía, P < 0,001. Las tasas de OS a 3 y 5 años después de cualquier metastasectomía en los casos de metástasis metacrónicas precoces fueron del 57,4% y 50,3%, versus 84,3% y 65,6% en las tardías (P = 0,29) CONCLUSIÓN: La proporción de pacientes con mCRC fue similar a la de estudios anteriores de base poblacional, así como las tasas de resección para metástasis hepáticas y pulmonares y la supervivencia después de la resección. Diferenciar entre metástasis sincrónicas, metacrónicas precoces y tardías puede mejorar la posibilidad de resecabilidad y la supervivencia.

Differences in lectin reactivities of cellular glycoconjugates between primary human colorectal carcinomas and their metastases.

Recent studies have demonstrated that colonic carcinomas consist of heterogeneous populations of cells endowed with different abilities to metastasize. Increasing evidence suggests that cell surface carbohydrates may play an important role in cancer invasion and metastasis. Therefore the binding of five fluorescein isothiocyanate-conjugated lectins to cellular glycoconjugates was analyzed immunohistochemically in paraffin-embedded tissue sections obtained from 16 colorectal carcinomas and their 25 metastases. In positive cases peanut agglutinin (galactose beta 1----3N-acetylgalactosamine), Ulex europeus' agglutinin 1 (alpha-L-fucose), Griffonia simplicifolia agglutinin 1 (galactose), Vicia villosa agglutinin (N-acetylgalactosamine), and G. simplicifolia agglutinin 2 (N-acetylglucosamine) stained apical cell membranes in carcinomatous glands and intraluminal secretions. Nine of 16 primary colorectal carcinomas showed intratumoral heterogeneous cell populations with regard to the lectin binding which resulted in areas of fluorescence-positive and fluorescence-negative carcinomatous glands. Only one liver metastasis showed this intralesional heterogeneity in lectin binding. Nineteen of 25 metastatic tumors produced cellular glycoconjugates which differed in their lectin binding profiles from those made by the majority of the cells in the respective primary colorectal carcinomas. The findings of the present work suggest that many primary colorectal carcinomas consist of phenotypically distinct subpopulations of carcinomatous cells. Most metastatic tumors appeared to result from a selective emergence of carcinoma cells producing glycoconjugates which differed in their lectin-binding profiles from those in their respective primary colorectal carcinomas.

Exclusion of PTEN and 10q22-24 as the susceptibility locus for juvenile polyposis syndrome.

Juvenile polyposis syndrome (JPS; MIM 174900) is an autosomal dominant condition with incomplete penetrance characterized by hamartomatous polyps of the gastrointestinal tract and a risk of gastrointestinal cancer. Gastrointestinal hamartomatous polyps are also present in Cowden syndrome (CS; MIM 158350) and Bannayan-Zonana syndrome (BZS; also called Ruvalcaba-Myhre-Smith syndrome; MIM 153480). The susceptibility locus for both CS and BZS has recently been identified as the novel tumor suppressor gene PTEN, encoding a dual specificity phosphatase, located at 10q23.3. A putative JPS locus, JP1, which most likely functions as a tumor suppressor, had previously been mapped to 10q22-24 in both familial and sporadic juvenile polyps. Given the shared clinical features of gastrointestinal hamartomatous polyps among the three syndromes and the coincident mapping of JP1 to the region of PTEN, we sought to determine whether JPS was allelic to CS and BZS by mutation analysis of PTEN and linkage approaches. Microsatellite markers spanning the CS/BZS locus (D10S219, D10S551, D10S579, and D10S541) were used to compute multipoint lod scores in eight informative families with JPS. Lod scores of < -2.0 were generated for the entire region, thus excluding PTEN and any genes within the flanking 20-cM interval as candidate loci for familial JPS under our statistical models. In addition, analysis of PTEN using a combination of denaturing gradient gel electrophoresis and direct sequencing was unable to identify a germline mutation in 14 families with JPS and 11 sporadic cases. Therefore, at least a proportion of JPS cases are not caused by germline PTEN alteration or by an alternative locus at 10q22-24.

Laparoscopic Wide Mesocolic Excision and Central Vascular Ligation for Carcinoma of the Colon.

BACKGROUND AND AIMS: The principle of complete mesocolic excision for colon cancer has been introduced to improve oncologic outcome. However, this approach is scantily discussed for laparoscopic surgery and there is a lack of randomized trials. This study examined oncologic and clinical outcome after laparoscopic wide mesocolic excision and central vascular ligation for colon cancer. MATERIAL AND METHODS: This is a review of prospectively gathered data from a single-institution colorectal cancer database. This study was conducted in the Central Hospital of Central Finland. From January 2003 to December 2011, 222 patients underwent laparoscopic colonic resections with wide mesocolic excision and central vascular ligation in the multimodal setting. The main measures of outcome were cancer recurrence and survival, with early recovery, 30d-mortality and morbidity, reoperation, readmission, and late complications as secondary outcomes. RESULTS: The median follow-up was 5.5 (interquartile range (IQR) = 3.7-8.0) years. The 5-year overall survival for all 222 patients was 80.2% and disease-specific survival was 87.5%, and for those 210 R0-patients with stage I-III disease, 83.9% and 91.3%, respectively. The 5-year disease-free survival was 85.8%: stage I was 94.7%, stage II was 90.8%, and stage III was 75.6% ( p = 0.004). Increasing lymph node ratio significantly decreased the 5-year disease-free survival. Conversion rate to open surgery was 12.2%. Thirty-day mortality was 1.3% and morbidity, 19.7%. Median postoperative hospital stay was 5 (IQR = 3-7) days. CONCLUSION: Laparoscopic wide mesocolic excision and central vascular ligation for colon cancer resulted in good long-term oncologic outcome. Randomized trials are needed to show that laparoscopic complete mesocolic excision technique would become the standard of care for the carcinoma of the colon.

Epidemiologic aspects of complete rectal prolapse.

BACKGROUND AND AIMS: This study was undertaken to find out the incidence of rectal prolapse. MATERIAL AND METHODS: Ninety-nine patients operated on for rectal prolapse at Jyväskylä Central Hospital were studied. Patients operated between 1988 and 1998 were studied retrospectively from hospital records using chart review and thirty-five patients operated on between 1999 and 2002 were studied prospectively using our proctologic database. RESULTS: The annual incidence of diagnosed complete rectal prolapse in the district of Central Finland was mean 2.5 (range, 0.79-6.08) per 100 000 population. There were ten men (10 percent) and 89 women (90 percent). Median age of the patients was 69 (range, 21-91) years. Forty-eight percent of the patients had concomitant cardiovascular disease and 15 percent psychiatric illness. Anal incontinence affecting quality of life was seen in 64 percent and constipation in 72 percent of patients. Constipation tended to be more attributed to difficult evacuation (72 percent) than to impaired bowel action (18 percent). CONCLUSION: The annual incidence of rectal prolapse is 2.5 per 100 000 population. Rectal prolapse is associated with anal incontinence and constipation in majority of patients.

Comparison of laparoscopic and open colonic resection within fast-track and traditional perioperative care pathways: Clinical outcomes and in-hospital costs.

BACKGROUND: This study examined short-term clinical outcomes and in-hospital costs of laparoscopic and open colonic resection within fast-track and traditional care pathways. MATERIAL AND METHODS: A case-control study was performed. From 2007 to 2009, 116 patients underwent laparoscopic or open colonic resection for benign or malignant disease within fast-track care pathway. The control group consisted of 116 age-, sex-, comorbidity-, type of surgery-, and diagnosis-matched patients who received a traditional perioperative care from 2000 to 2007. The main measures of outcome were postoperative hospital stay and in-hospital costs, with 30-day mortality, morbidity, reoperation, and readmission rates as secondary outcomes. RESULTS: The study groups were well balanced for baseline characteristics. Postoperative hospital stay was shorter in the fast-track than in the control group: laparoscopic resection median 3 versus 5 days (p < 0.001) and open resection 4 versus 7 days (p < 0.001). In multivariate analysis fast-track care, laparoscopic surgery and complications were independent determinants affecting the length of hospital stay. Overall, there was a trend toward lower in-hospital costs in the fast-track group compared with the traditional care group, but the difference was not statistically significant. Open surgery within fast-track care was the least costly option compared to laparoscopic or open surgery within traditional care but not significantly so when compared with laparoscopy within fast-track care. Intake of solid food and bowel function recovered 1 day earlier in the fast-track group than in the control group (p < 0.001). Complications were more frequent after open surgery than after laparoscopic surgery (23.3% vs 11.0%, p = 0.012). Reoperation and readmission rates were similar between the study groups. CONCLUSION: Laparoscopy improves the efficiency of fast-track perioperative care without significantly increasing in-hospital costs.

The true extent of ulcerative colitis? A radiological, endoscopic and histological study.

Twenty-six radiological, endoscopic and histological examinations of the large bowel were performed in 25 patients with ulcerative colitis. Extensive colitis was observed in 42% of the radiological, in 38% of the endoscopic, and in 27% of the histological examinations. Agreement as to the extent of the colitis between all three examination methods was reached in 53% of the cases. The endoscopic extent of colitis varied between left-sided and extensive in 41% of the patients during a 7-year median follow-up. The frequent change in the extent of ulcerative colitis and the considerable disagreement between radiography, colonoscopy and histology in evaluating the extent of colitis justify the question, "Does a true, unambiguous extent of colitis really exist?" It is more likely that the extent of colitis is just a function of time and the examination method used.

HLA antigens in ulcerative colitis and primary sclerosing cholangitis.

The aims of this study were to find out whether the alleles of the HLA class I or II region are associated with susceptibility to ulcerative colitis, and to show whether there is a difference or similarity in HLA associations between primary sclerosing cholangitis and ulcerative colitis. HLA-A, B, C and DR antigens were studied using the standard lymphocyte microcytotoxicity test in 24 Finnish patients with primary sclerosing cholangitis, 77 patients with ulcerative colitis, and 106 controls. HLA-B8 (54%) and DR3 (60%) were associated with primary sclerosing cholangitis. HLA-DR1 (46%) and DR6 (20%) seemed more common in ulcerative colitis than in controls. A positive association with Cw7 was common to both ulcerative colitis (25%) and primary sclerosing cholangitis (33%). Our results indicate that ulcerative colitis is more heterogeneous than primary sclerosing cholangitis in its HLA-DR associations.

Functional outcome after laparoscopic or open Nissen fundoplication: a follow-up study.

OBJECTIVE: To compare the results of open and laparoscopic fundoplication. DESIGN: Nonrandomized controlled study with a 3-year follow-up. PATIENTS AND METHODS: Fifty-seven consecutive patients with erosive reflux esophagitis underwent laparoscopic (30 patients) or open (27 patients) fundoplication. INTERVENTIONS: Interview by an independent person. In addition, 52 patients (91%) underwent postoperative endoscopy, and 38 patients (67%) underwent esophageal 24-hour pH recording. RESULTS: Temporary dysphagia was reported by 20 patients (67%) after laparoscopic and by 11 (41%) after open fundoplication (P = .05). There were no differences between groups concerning incidence of persistent dysphagia (20% vs 18%, respectively) and mild to no reflux symptoms (97% vs 100%, respectively). In addition, bloating (50% vs 63%, respectively) and increased flatus (77% vs 78%, respectively) were equally common. Visual analog scale scores for dysphagia, bloating, and increased flatus were 0.6, 2.4, and 4.3, respectively, in the laparoscopic and 0.6, 3.5, and 3.4, respectively, in the open groups. Normal belching ability was reported by 12 patients (40%) after laparoscopic and by 20 (74%) after open fundoplication (P = .01). Visick grade 1 or 2 was reported by 21 patients (70%) after laparoscopic and by 24 (89%) after open fundoplication (P = .08). Defective fundic wrap was detected in 4 patients (13%) in the laparoscopic and in none in the open group. In addition, abnormal results of 24-hour pH recording were found in 4 patients (22%) after laparoscopic and in 2 (10.5%) after open fundoplication. CONCLUSION: From a functional point of view, both techniques were equally effective except concerning belching ability and temporary dysphagia.

The role of biofeedback therapy in functional proctologic disorders.

BACKGROUND AND AIMS: The question which patients with functional proctologic disorders truly benefit from the biofeedback has not been equivocally resolved. The aim of this study was to assess our results of biofeedback therapy in patients with anal incontinence or constipation. MATERIAL AND METHODS: Fifty-two consecutive patients who were treated with biofeedback therapy between January 1998 and March 2002 were studied. Data was collected from our proctologic database. RESULTS: Of the twenty-two patients with anal incontinence who underwent biofeedback therapy during the study period, twenty patients had incontinence affecting quality of life. Twelve patients (60 percent) benefited from biofeedback as judged by improvement of incontinence symptoms affecting quality of life; all four patients with partial sphincter defects, three out of four patients after secondary repair, three out of five patients with persistent incontinence after rectal prolapse surgery and two out of seven patients having idiopathic incontinence. Of the thirty patients who underwent biofeedback therapy for constipation, twenty-five had intractable symptoms of constipation. Constipation resolved in sixteen patients (64 percent); in thirteen out of nineteen (68 percent) of those with pelvic floor dysfunction (PFD) and in three out of six (50 percent) having combined PFD and slow transit constipation. In patients with PFD constipation was resolved in ten out of thirteen patients (77 percent) with anismus but in only three out of six (50 percent) having other causes. CONCLUSIONS: Biofeedback therapy improves incontinence after sphincter repairs and in patients with partial external sphincter defects, but does not improve idiopathic incontinence. Biofeedback is also effective in patients with constipation, especially when anismus is the only cause for symptoms of constipation and difficult evacuation.

Evaluation of a fast-track protocol for patients undergoing colorectal surgery.

BACKGROUND AND AIMS: Fast-track protocols have been used to optimize the perioperative care and to enhance postoperative recovery. This study examined short-term clinical outcomes and determinants affecting the length of postoperative hospital stay. MATERIAL AND METHODS: From 2007 to 2009, 180 patients underwent laparoscopic or open bowel resection (N = 138) or sacrocolporectopexy (N = 42) in the Central Hospital of Central Finland for various colorectal diseases in the fast-track setting. The main measures of outcome were time to functional recovery, 30-day morbidity, and readmission rates, with hospital stay and patient satisfaction as secondary outcomes. RESULTS: There were no deaths. Time to functional recovery was median 2 (interquartile range 2-3) days. The overall 30-day postoperative morbidity was 14.5% after bowel resection and 0% after sacrocolporectopexy. Relaparotomy rate was 3.6% and 30-day readmission rate 7.2%. Postoperative hospital stay was median 3 days after small bowel and ileo-colic resection, 4 days after segmental colectomy, and 6 days after rectal resection and subtotal colectomy. Patient's body mass index > 30 kg/m2, malignant disease, complexity of surgery, recovery of bowel function later than 2 days after surgery, time to functional recovery > 2 days and postoperative morbidity were patient- and treatment-related determinants increasing postoperative hospital stay. Protocol compliance-related determinants increasing postoperative hospital stay were intake of normal food and mobilization ≥ 6 h/day later than 2 days after surgery and removal of urinary catheter later than 1 day after surgery. CONCLUSION: Postoperative functional recovery was fast, morbidity and readmission rates were low, and postoperative hospital stay short indicating that fast-track care should form the mainstay of elective colorectal surgery.