Search

Background Immune response against cancer has prognostic impact but its role in gastric cancer is poorly known. The aim of the study was to assess the prognostic significance of immune cell score (CD3+, CD8+), tumour immune escape (PD-L1, PD-1) and immune tolerance (Clever-1). Methods After exclusion of Epstein-Barr virus positive (n = 4) and microsatellite instable (n = 6) tumours, the study included 122 patients with GC undergoing D2 gastrectomy. CD3+ and CD8+ based ICS, PD-L1, PD-1 and Clever-1 expressions were evaluated. Differences in survival were examined using Cox regression adjusted for confounders. The primary outcome was 5-year survival. Results The 5-year overall survival rate was 43.4%. High ICS was associated with improved overall survival (adjusted HR 0.48 (95% CI 0.26–0.87)) compared to low ICS. In the high ICS group, patients with PD-L1 expression (5-year survival 69.2 vs. 53.1%, p = 0.317), high PD-1 (5-year survival 70.6 vs. 55.3% p = 0.312) and high Clever-1 (5-year survival 72.0% vs. 45.5% (p = 0.070) had poor prognosis. Conclusions High ICS was associated with improved survival. In the high ICS group, patients with high PD-L1, PD-1 and Clever-1 had poor prognosis highlighting the importance of immune escape and immune tolerance in GC.

Background Resection of colorectal cancer (CRC) metastases provides good survival but is probably underused in real-world practice. Methods A prospective Finnish nationwide study enrolled treatable metastatic CRC patients. The intervention was the assessment of resectability upfront and twice during first-line therapy by the multidisciplinary team (MDT) at Helsinki tertiary referral centre. The primary outcome was resection rates and survival. Findings In 2012–2018, 1086 patients were included. Median follow-up was 58 months. Multiple metastatic sites were present in 500 (46%) patients at baseline and in 820 (76%) during disease trajectory. In MDT assessments, 447 (41%) were classified as resectable, 310 (29%) upfront and 137 (18%) after conversion therapy. Six-hundred and ninety curative intent resections or local ablative therapies (LAT) were performed in 399 patients (89% of 447 resectable). Multiple metastasectomies for multisite or later developing metastases were performed in 148 (37%) patients. Overall, 414 liver, 112 lung, 57 peritoneal, and 107 other metastasectomies were performed. Median OS was 80•4 months in R0/1-resected (HR 0•15; CI95% 0•12–0•19), 39•1 months in R2-resected/LAT (0•39; 0•29–0•53) patients, and 20•8 months in patients treated with “systemic therapy alone” (reference), with 5-year OS rates of 66%, 40%, and 6%, respectively. Interpretation Repeated centralized MDT assessment in real-world metastatic CRC patients generates high resectability (41%) and resection rates (37%) with impressive survival, even when multisite metastases are present or develop later. Funding The funders had no role in the study design, analysis, and interpretation of the data or writing of this report. Tiivistelmä Tausta Kolorektaalisyövän etäpesäkkeiden leikkaushoitoa käytetään todennäköisesti liian vähän tosielämän hoidoissa. Menetelmät RAXO on maanlaajuinen suomalainen tosielämän prospektiivinen interventiotutkimus, joka rekrytoi lääkehoitokuntoisia, levinnyttä suolistosyöpää sairastavia potilaita. Tutkimuksessa arvioitiin keskitetysti etäpesäkkeiden leikattavuutta levinneen syövän toteamisvaiheessa ja kahdesti ensilinjan hoidon aikana Helsingin yliopistollisen sairaalan moniammatillisessa hoitokokouksessa. Tulokset Vuosina 2012-2018 tutkimukseen otettiin 1086 potilasta. Mediaaniseuranta-aika oli 58 kuukautta. Usean elimen etäpesäkkeet todettiin 500:lla (46 %) levinneen syövän toteamisvaiheessa ja 820:lla (76 %) seurannan aikana. Moniammatillisessa arvioinnissa 447 luokiteltiin leikattavaksi 310 (29%) toteamisvaiheessa ja 137 (18%) konversiohoidon jälkeen. Kuusisataayhdeksänkymmentä etäpesäkekirurgista ja/tai paikallishoitotoimenpidettä tehtiin 399 potilaalle (89 % 447:sta), joista parantavalla tavoitteella R0/1-resektio 326 potilaalle ja R2-resektio ja/tai paikallistoimenpide 73:lle. Useita toimenpiteitä tehtiin 148 (37%) potilaalle useamman elimen etäpesäkkeiden tai uusien etäpesäkekohtien ilmentymisen takia. Kaiken kaikkiaan tehtiin 414 maksa-, 112 keuhko-, 57 peritoneaalikarsinoosi- ja 107 muuta toimenpidettä. Mediaanielinaika oli 80,4 kuukautta R0/1-resekoiduilla potilailla (HR 0,15; 95 % luottamusväli 0,12–0,19), 39,1 kuukautta R2-resekoiduilla/paikallishoidetuilla (0,39; 0,29–0,53), ja 20,8 kuukautta vain lääkehoitoa saaneilla (referenssi), ja vastaavat viiden vuoden elossaololuvut olivat 66%, 40% ja 6%. Merkitys Keskitetyllä, toistetulla moniammatillisella toiminnalla saavutetaan korkea arvio etäpesäkkeiden leikattavuudesta (41%). Etäpesäkkeiden leikkaus- ja/tai paikallishoito toteutuu 37 prosentilla erinomaisin tuloksin silloinkin, kun syöpä on levinnyt useaan elimeen sairauden toteamisvaiheessa tai sen aikana Tuki Tutkimuksen tukijat eivät osallistuneet tutkimussuunnitelman kirjoittamiseen, datan analysointiin tai tulkintaan, eivätkä tämän raportin kirjoittamiseen. Abstrakt Bakgrund Resektion av kolorektalcancermetastaser ger god överlevnad, men används troligen suboptimalt i normal praktik. Metod RAXO-studien är en prospektiv finsk studie som inkluderade behandlingsbara patienter med spridd kolorektalcancer. Studiens intervention utvärderade möjligheten till metastasoperation vid centraliserad multidisciplinär konferens (MDK) på Helsingfors universitetssjukhus vid behandlingsinitiering och två gånger under första linjens behandling. Det primära syftet var att undersöka resekabilitet och resektioner, samt överlevnad. Fynd 1086 patienter inkluderades 2012-2018. Medianuppföljningstiden var 58 månader. Multipel metastasering sågs hos 500 (46%) av patienterna vid metastasdiagnostidpunkten och hos 820 (76%) under uppföljningen. I MDK-utvärderingen klassificerades 447 (41%) som operabla, varav 310 (29%) vid metastastasdiagnos och 137 (18%) efter konversionsbehandling. Sexhundranittio åtgärder gjordes hos 399 patienter (89% av de 447 operabla), med R0/1-resektion hos 326 och R2-resektion eller lokalbehandling hos 73. Flera åtgärder gjordes hos 148 (37%) patienter med multipla metastasorgan eller nya metastaslokaler under uppföljningen; totalt 414 lever-, 112 lung-, 57 peritoneal-, och 107 andra åtgärder. Medianöverlevnaden var 80,4 månader hos R0/1-opererade (HR 0,15; 95% konfidensintervall 0,12–0,19), 39,1 månader hos R2-opererade/lokalbehandlade (0,39; 0,29–0,53) och 20,8 månader hos ”enbart systembehandlade” (referens), och femårsöverlevnaden var 66%, 40% och 6% i respektive grupp. Betydelse Upprepad centraliserad MDK-utvärdering vid spridd kolorektalcancer visar att 41% av metastaserna någon gång bedöms som resekabla och att operation och/eller lokalbehandling är möjlig i 37% av fallen. Imponerande överlevnad ses även i fall med multipla metastaslokaler vid diagnostillfället eller under uppföljningen. Finansiering Finansiärerna hade ingen roll i utformningen av denna studie, i dataanalys, tolkning av data eller i skrivandet av denna forskningsrapport. publishedVersion

An immune cell score (ICS) was introduced for predicting survival in pancreatic ductal adenocarcinoma (PDAC). Few studies have compared different methods of evaluating immune infiltrate. This study compared ICSs determined in whole sections or tissue microarray-like hotspots for predicting survival after PDAC surgery. We included in 79 consecutive patients from a single geographical area that underwent surgery for PDAC (R0/R1, stages I–III). We performed digital image analyses to evaluate CD3 and CD8 staining. ICSs were classified as low, moderate, or high, based on the numbers of immune cells in the tumour core and invasive margin. We compared ICS groups determined with the hotspot and whole-section techniques. Associations between ICS and survival were analysed with Cox regression models, adjusted for sex, age, tumour stage, differentiation grade, perineural invasion, and resection radicality. In hotspot ICS analysis, 5-year overall survival rates for low, moderate, and high groups were 12.1%, 26.3%, and 26.8%, respectively (p = 0.193). In whole-section analyses, overall survival rates were 5.3%, 26.4%, and 43.8%, respectively (p = 0.030). In the adjusted Cox model, whole-section ICS groups were inversely associated with the overall mortality hazard ratio (HR): low, moderate, and high ICS groups had HRs of 1.00, 0.42 (95% CI 0.20–0.88), and 0.27 (95% CI 0.11–0.67), respectively. The number of immune cells per square millimetre in the tumour core and the invasive margin were significantly higher and had a wider range in hotspots than in whole-tissue sections. Accordingly, ICS could predict survival in patients with PDAC after surgery. Whole tissue section ICSs exhibited better prognostic value than hotspot ICSs.

Simple Summary Metastasis is the main cause for cancer mortality. The most common metastatic sites of colorectal cancer (CRC) are the liver and lungs. Tumour-infiltrating lymphocytes are recognized as beneficial prognostic factors both in primary and metastatic CRC, but less is known about their reciprocal differences. The aim of our study was to evaluate immune microenvironment and its prognostic value in a series of mismatch proficient (pMMR) CRC with matched liver and lung metastases. The proportion of tumours with high immune cell infiltration together with PD-L1-positivity almost doubled in metastases compared to primary tumours. Our study confirmed the prognostic value of high ICS in least immune-infiltrated metastases in pMMR CRC patients. Major differences observed in immune contexture between primary tumours and metastases may have significance for treatment strategies for patients with advanced CRC. Purpose: To evaluate immune cell infiltration, the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) expression and their prognostic value in a series of mismatch proficient (pMMR) CRC with matched liver and lung metastases. Methods: Formalin-fixed paraffin-embedded tissue sections stained for CD3, CD8, PD-L1 and PD-1 from 113 primary CRC tumours with 105 liver and 59 lung metastases were analyzed. The amount of CD3 and CD8 positive lymphocytes were combined as immune cell score (ICS). Comparative analyses on immune contexture were performed both between the primary tumour and matched metastases and between the metastatic sites. Results: In liver metastases, immune cell infiltration was increased in general compared to primary tumours but did not correlate case by case. On the contrary, ICS between lung metastases and primary tumours correlated well, but the expression of PD-1/PD-L1 was increased in lung metastases. The proportion of tumours with high ICS together with PD-L1-positivity almost doubled in metastases (39%) compared to primary tumours (20%). High ICS (compared to lowest) in patient's least immune-infiltrated metastasis was an independent prognostic marker for disease-specific (HR 9.14, 95%CI 2.81-29.68) and overall survival (HR 6.95, 95%CI 2.30-21.00). Conclusions: Our study confirms the prognostic value of high ICS in least immune-infiltrated metastases in pMMR CRC patients. Major differences observed in immune contexture between primary tumours and metastases may have significance for treatment strategies for patients with advanced CRC.

Immune suppressing molecule CD73 is overexpressed in various cancers and associated with poor survival. Little is so far known about the predictive value of CD73 in pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to investigate the prognostic significance of CD73 in PDAC. The study material consisted of 110 radically treated patients for PDAC. Tissue microarray blocks were constructed and stained immunohistochemically using CD73 antibody. Staining intensity and numbers of stained tumour cells, inflammatory cells, stroma, and blood vessels were assessed. High-level CD73 expression in tumour cells was positively associated with PD-L1 expression, perineural invasion, and histopathological grade. CD73 positivity in tumour-infiltrating lymphocytes was significantly associated with lymph node metastasis. Lymphocytic CD73 positivity was also associated with staining positivity in both stroma and vascular structures. In addition, CD73 positivity in vascular structures and stroma were associated with each other. There were no significant associations between CD73 positive tumour cells and CD73 positivity in any other cell types. PD-L1 expression was associated with CD73 staining positivity in stroma (p = 0.007) and also with histopathological grade (p = 0.033) and T class (p = 0.016) of the primary tumour. CD73 positivity in tumour cells was significantly associated with poor disease-specific (p = 0.021) and overall survival (p = 0.016). In multivariate analysis, CD73 positivity in tumour cells was an independent negative prognostic factor together with histopathological grade, TNM stage, and low immune cell score. In conclusion, high CD73 expression in tumour cells is associated with poor survival in PDAC independently of the number of tumour-infiltrating lymphocytes or TNM stage.

Hyaluronan (HA) accumulation has been associated with poor survival in various cancers, but the mechanisms for this phenomenon are still unclear. The aim of this study was to investigate the prognostic significance of stromal HA accumulation and its association with host immune response in pancreatic ductal adenocarcinoma (PDAC). The study material consisted of 101 radically treated patients for PDAC from a single geographical area. HA staining was evaluated using a HA-specific probe, and the patterns of CD3, CD8, CD73 and PD-L1 expression were evaluated using immunohistochemistry. HA staining intensity of tumour stromal areas was assessed digitally using QuPath. CD3- and CD8-based immune cell score (ICS) was determined. High-level stromal HA expression was significantly associated with poor disease-specific survival (p = 0.037) and overall survival (p = 0.013) In multivariate analysis, high-level stromal HA expression was an independent negative prognostic factor together with histopathological grade, TNM stage, CD73 positivity in tumour cells and low ICS. Moreover, high-level stromal HA expression was associated with low ICS (p = 0.017). In conclusion, stromal HA accumulation is associated with poor survival and low immune response in PDAC.

Purpose To compare laparoscopic non-CME colectomy with laparoscopic CME colectomy in two hospitals with similar experience in laparoscopic colorectal surgery. Methods Data was collected retrospectively from Päijät-Häme Central Hospital (PHCH, NCME group) and Central Finland Central Hospital (CFCH, CME group) records. Elective laparoscopic resections performed during 2007–2016 for UICC stage I–III adenocarcinoma were included to assess differences in short-term outcome and survival. Results There were 340 patients in the NCME group and 325 patients in the CME group. CME delivered longer specimens (p p p p = 0.528, NCME 93.2% vs CME 88.9%, p = 0.132, respectively). Thirty-day morbidity, mortality, and length of hospital stay were similar between the groups. Conversion to open surgery was associated with decreased survival. Discussion Complete mesocolic excision (CME) is reported to improve survival. Most previous studies have compared open CME with open non-CME (NCME) or open CME with laparoscopic CME. NCME populations have been historical or heterogeneous, potentially causing bias in the interpretation of results. Studies comparing laparoscopic CME with laparoscopic NCME are few and involve only small numbers of patients. In this study, diligently performed laparoscopic non-CME D2 resection delivered disease-free survival results comparable with laparoscopic CME but was not safer.

Background Hepatopancreatobiliary surgery is prone to complications. Methods are needed to monitor surgical outcomes and enable comparison between institutions. Methods Complications were collected prospectively and reviewed using the modified Accordion Severity Grading System (MASGS) and the Postoperative Morbidity Index (PMI). Results This study included 527 consecutive patients receiving either pancreatic or liver resection in 2000-2017 in Central Finland Central Hospital. The PMI was 0.177 for all patients, and 0.192, 0.094, 0.285, and 0.129 for patients receiving major pancreatic (n=218), minor pancreatic (n=93), major liver (n=73), and minor liver (n=143) resection, respectively. The rates of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomies (n=200) were 6.5% for grade B and 5.5% for grade C; rates for biliary leak were 1.0% (grade A), 2.5% (grade B), and 0.5% (grade C). Similarly, the rates for delayed gastric emptying (DGE) were 2.8% (grade A), 15.6% (grade B), and 3.7% (grade C). Postoperative hepatic dysfunction occurred in 2.3%, major surgical site bleeding in 2.3%, and biloma in 7.9% of patients after liver resection. Ninety-day mortality rates were 3.7% and 1.1% in major and minor pancreatic resections, and 8.2% and 0.7% in major and minor liver resections. Major complications occurred in 13.3% and 3.3% in pancreatic, and 19.2% and 6.3% in liver resections, respectively. Conclusions Major pancreatic and hepatic surgery are associated with significant morbidity and burden in our center, comparable with previous population-based studies. PMI is an informative way to monitor surgical outcomes and enable comparison between institutions.

Background Wait-and-see policy after endoscopic sphincterotomy (ES) for common bile duct (CBD) stones in patients with concomitant gallbladder stones may lead to recurrent biliary complications. The aim of this study was to assess the short and long-term results of wait-and-see policy in patients with intact gallbladder after endoscopic clearance of CBD stones. Materials and methods From January 1999 to December 2014 a total of 181 consecutive patients with intact gallbladder underwent ES for CBD stones. The main measures of outcome were long-term biliary complications, biliary related mortality, CBD stone recurrence and need for surgical interventions. Secondary outcomes were 30-day mortality and 30-day morbidity. Clinical data were retrospectively collected from hospital records and from the National Registry of Death. Results During the median follow-up of 3.9 years (IQR 1.6–6.6) late biliary complications were observed in 24 (13.8%) patients. Cumulative biliary related morbidity at 3 and 5 years was 7.6% and 10.8%, respectively. CBD stone recurrence was observed in 9 (5.2%) patients. On-demand cholecystectomy was performed in 6 (3.3%) patients. 30-day mortality was 3.9% and 30–day morbidity 9.4%. Overall cumulative mortality rate at 3 and 5 years after ES was 31.4% and 49.7%, respectively. Long-term biliary related mortality was 1.7%. No significant difference in long term complications or biliary mortality was observed between patients Conclusion Prophylactic cholecystectomy after ES has been shown to reduce mortality even in high-risk patients. In our series late biliary related mortality and morbidity were relatively low, because a considerable number of patients died from non-biliary related causes.However, most biliary-related events seem to occur evenly during the follow-up after ES. A prompt risk assesment and consideration of surgical treatment during index admission may prevent late biliary –related complications.

The aim of this study was to investigate immune response and its prognostic significance in colon carcinomas using the previously described Immunoscore (IS). A population-based series of 779 colorectal cancers, operated on between 2000 and 2010, were classified according to tumour, node, metastasis (TNM) status, mismatch repair (MMR), and BRAF mutation status. Rectal cancer cases (n = 203) were excluded as a high proportion of these patients received preoperative neoadjuvant chemoradiotherapy. Tissue microarray (TMA) samples collected from the tumour centre and invasive front were immunostained for CD3 and CD8. Lymphocytes were then digitally calculated to categorize IS from grade 0 to 4. Samples adequate for IS were available from 510 tumours. IS was significantly associated with AJCC/UICC stage, T stage, lymph node and distant metastases, perineural and lymphovascular invasion, MMR status, and BRAF mutation status. For IS0, IS1, IS2, IS3 and IS4, respectively, the 5-year disease-free survival (DFS) rates were 59, 68, 78, 83 and 94% (p

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, In a study of the incidence and management of metastatic colorectal cancer in a population‐based cohort, 17·7 per cent of 1671 patients with colorectal cancer had synchronous metastases, and 19·6 per cent of 1302 patients who had resection of stage I–III tumours developed metachronous metastases. In the whole population, the proportion of patients with any metastasis was 33·0 per cent. Metastasis from colorectal cancer

Prophylactic placement of a mesh has been suggested to prevent parastomal hernia, but evidence to support this approach is scarce.The aim of this study was to evaluate whether laparoscopic placement of a prophylactic, dual-component, intraperitoneal onlay mesh around a colostomy is safe and prevents parastomal hernia formation after laparoscopic abdominoperineal resection.This is a prospective, multicenter, randomized controlled clinical trial.This study was conducted at 2 university and 3 central Finnish hospitals.From 2010 to 2013, 83 patients undergoing laparoscopic abdominoperineal resection for rectal cancer were recruited. After withdrawals and exclusions, the outcome of 70 patients, 35 patients in each study group, could be examined.In the intervention group, an end colostomy was created with placement of a intraperitoneal, dual-component onlay mesh and compared with a group with a traditional stoma.The main outcome measures were the incidence of clinically and radiologically detected parastomal hernias and their extent 12 months after surgery. Stoma-related morbidity and the need for surgical repair of parastomal hernia were secondary outcome measures.Parastomal hernia was observed by clinical inspection in 5 intervention patients (14.3%) and in 12 control patients (32.3%; p = 0.049). Surgical repair of parastomal hernia was performed in 1 control patient (3.2%) and in none of the patients in the intervention group. CT detected parastomal hernia in 18 intervention patients (51.4%) and in 17 control patients (53.1%; p = 1.00). The extent of hernias was similar according to European Hernia Society classification (p = 0.41). Colostomy-related morbidity (32.3% vs 14.3%; p = 0.140) did not differ between the study groups.The study was limited by its small size and short follow-up time.Prophylactic laparoscopic placement of intraperitoneal onlay mesh does not significantly reduce the overall risk of radiologically detected parastomal hernia after laparoscopic abdominoperineal resection. However, prophylactic mesh repair was associated with significantly lower risk of clinically detected parastomal hernia.

Increasing evidence suggests that cancer progression is strongly influenced by host immune response, which is represented by immune cell infiltrates. T-lymphocyte-based immunoscore has proved to be a prognostic factor in colon cancer, but its significance in pancreatic cancer is poorly known. Total of 108 patients operated (R0/R1) for pancreatic ductal adenocarcinoma (PDAC) (TNM stage I–II) were included in the study. Immune cell score (IS) was determined by scoring the samples from grade 0 to 4 according to the number of immune cells (CD3+ and CD8+) in tumor core and invasion margin using tissue microarrays, immunohistochemistry, and digital analysis. Tumors with microsatellite instability were identified by MLH1 immunostaining. High IS and low histological grade were significantly associated with better disease-specific survival (DSS) and overall survival (OS). The 5-year DSS rate for low, moderate, and high IS groups were 5.0, 15.2, and 33.4%, respectively (p = 0.007). The 5-year OS rate for the low, moderate, and high IS groups were 4.2, 13.4, and 31.5%, respectively (p = 0.004). In addition, IS and prognosis varied within a single TNM stage. There was no association between IS and any of the clinicopathological variables. IS was shown to be an independent prognostic factor for better DSS and OS in multivariate analysis, together with the histological grade of the tumor and perineural invasion. Five MLH1-negative tumors (4.6%) were found showing no correlation with IS. IS could be a useful prognostic marker in patients with PDAC treated by primary surgery.

Helath-related quality of life (HRQoL) in patients with reflux disease is significantly impaired in comparison to the general population. The level of impairment and types of problems experienced by GERD patients relate to symptom severity, the type and effectiveness of the treatment, sideeffects of surgery, and non-disease related factors such as the presence of other medical conditions, sex or anxiety. Several randomized trials comparing PPI therapy with laparoscopic antireflux surgery have been conducted, particularly over short-medium terms. Based on available studies, it can be concluded that in the short-medium terms laparoscopic antireflux surgery effectively alleviates symptoms of GERD, cures erosive esophagitis and improves quality of life. Postoperative adverse effects are usually mild and patient satisfaction good. For the long term (>10 years), limited data indicate decreasing effectiveness of laparoscopic antireflux surgery. Some patients may revert to the use of PPI therapy, or need revision surgery to improve symptom control following recurrent symptoms. HRQoL of patients with long term treatment success seems to be similar to that of the general population . Failed antireflux surgery and symptom recurrence significantly worsens the QoL in most patients. GERD is prevalent worldwide, and the disease burden seems to be increasing. The range of GERD prevalence estimates are 18.1–27.8% in North America, 8.8–25.9% in Europe, 2.5–7.8% in East Asia, 8.7–33.1% in the Middle East, 11.6% in Australia and 23.0% in South America [1, 2]. Prior use of non-steroidal anti-inflammatory drugs, smoking, excess body weight and gastrointestinal and cardiac conditions are associated with an increased risk of gastro-oesophageal reflux disease [3].

Background One–stage laparoscopic common bile duct (CBD) stone clearance and laparoscopic cholecystectomy (LCBDE+LC) for cholecystocholedocholithiasis ( CCL) can be performed with similar short and long-term outcomes than two-stage endoscopic retrograde cholangiography followed by subsequent LC (ERCP+LC). This study examined retrospectively the outcome and hospital costs of one-stage versus two-stage treatment of CBD stones. Methods From January 1999 and December 2014, 217 consecutive, elective patients underwent one-stage (LCBDE + LC ) or two-stage (ERCP + subsequent LC ) treatment for CBD stones. The data from the one-stage management was collected prospectively, and from the two-stage management retrospectively. The main measure of outcome was hospital costs, with the success of one-stage versus two-stage management, postoperative morbidity and postoperative stay as secondary outcome measures. Results One-stage laparoscopic transcystic management was the least costly option compared to laparoscopic one-stage transductal approach (TC 5455€ versus TD 9364, p < 0.001) or two-stage management (6913 €, p = 0.02). Overall success rate of primary intervention (including conversions to open surgery) for CBD stone clearance was 96.9%, 97.0% and 98.3% after transcystic one-stage, transductal one-stage and two-stage approach, p = 0.79. Postoperative morbidity was 15.5% versus 7.5%, p = 0.64, and postoperative hospital stay median 2 days (IQR 2–5) versus 4.5 days ( IQR 3–7), p < 0.001 in the one-stage and two-stage management groups. Conclusions Our study shows that laparoscopic one-stage transcystic management of CCL results in high rate of CBD clearance, fewer procedures per patient, shorter hospital and lower costs than the two-stage management. Therefore the one-stage transcystic management seems to be an attractive strategy for the treatment of CCL depending on local resources and surgical expertise .

To audit short- and long-term outcomes after laparoscopic common bile duct exploration (LCBDE) and factors influencing the success of the laparoscopic treatment. From January 1999 to December 2011, 288 patients (93 males) underwent a single-stage laparoscopic cholecystectomy combined with LCBDE in two Finnish Hospitals. Short-term outcome data were collected prospectively. Long-term outcomes were examined retrospectively. The main measures of outcome were the success of laparoscopic CBD stone clearance and recurrence of CBD stones in the long-term, with 30-day mortality, morbidity, and the length of postoperative hospital stay as secondary outcome measures. CBD stones were successfully removed by one-stage laparoscopic procedure in 232 of the 279 patients (83.2 %) with verified CBD stones and after conversion to open surgery in additional 28 patients (93.2 %). Nineteen patients (6.8 %) having residual stones after surgery were successfully treated with postoperative ERCP. On multivariate analysis, the independent factors associated with a failed laparoscopic stone clearance were stone size over 7 mm [OR 3.51 (95 % CI 1.53–8.03), p = 0.003], difficult anatomy [OR 18.01 (5.03–64.49), p

3517 Background: Resection of oligometastatic mCRC is curable in up to half and is probably underused in real-life oncology practice. In 2011, a prospective nationwide centralized evaluation of resectability was initiated to assess upfront and conversion to resectability. Methods: The RAXO-study included 1086 mCRCs referred for oncological treatments at all 21 Finnish oncology units (40% of eligible mCRCs in Finland). The MDT at Helsinki tertiary referral center (TRC) assessed resectability of liver, lung and other metastases upfront and twice during first-line therapy. Resectability evaluation was provided online and resections were performed according to clinical praxis, with major resections at TRCs. Results: Median age was 66.5 (range 24-90) yrs, 60% males, ECOG was 0 in 295 (27%), 1 in 600 (55%) and 2-3 in 191 (18%). Tumor was right-sided in 310 (29%), left in 769 (72%) and multiple in 7 (.6%). In the MDT assessment, 435 (40%) were considered resectable, 28% upfront and 12% after conversion. Resections or local ablative therapy were performed in 396 (91% of resectable, R0-1 in 74% and R2 in 17%), with 368 liver-, 91 lung- and 96 other operations. One metastatic site (n = 407), 2 (n = 369) and 3-6 (n = 310) were or became resectable in 65, 33 and 15%, respectively, and R0-1 resected in 54, 30 and 6%, respectively (P < 0.001). In multivariate analysis age < 66.5 (OR 1.51), ECOG 0 (OR 2.40); left-sided primary (OR 1.55), metachronous metastases (OR 1.49), 1-2 metastatic sites (OR 1.86) increased R0-1 resection rates; whereas primary/relapse in situ (OR 0.49), metastases in lung (OR 0.22), peritoneum (OR 0.30) or lymph nodes (OR 0.23) decreased R0-1 rates (P < 0.05). In univariate analyses BRAF wt (OR 0.34), normal CEA (OR 0.31) or normal Ca19-9 (OR 0.45) associated with R0-1 rates. Median OS was 2.4 yrs (CI95% 2.3-2.6) in all, 6.7 yrs in R0-1 (HR 0.15; CI95% 0.11-0.19), 2.8 yrs in R2 (0.50; 0.36-0.68) and 1.7 yrs in non-resected (reference group). Median PFS was 1.1 yrs (1.0-1.1) in all patients, 2.4 yrs in R0-1 (0.24; 0.20-0.28), 1.4 yrs in R2 (0.55; 0.42-0.71) and 0.8 yrs in non-resected patients. P < 0.001 for all comparisons. Conclusions: Repeated centralized MDTs in real-life mCRC patients show high resectability (40%) and resection rates (36%), even if multiple metastatic sites are present. Curative resection associates with good survival. Clinical trial information: NCT01531621.

The aim of this study was to investigate immune response and its prognostic significance in colon carcinomas using the previously described Immunoscore (IS). A population‐based series of 779 colorectal cancers, operated on between 2000 and 2010, were classified according to tumour, node, metastasis (TNM) status, mismatch repair (MMR), and BRAF mutation status. Rectal cancer cases (n = 203) were excluded as a high proportion of these patients received preoperative neoadjuvant chemoradiotherapy. Tissue microarray (TMA) samples collected from the tumour centre and invasive front were immunostained for CD3 and CD8. Lymphocytes were then digitally calculated to categorize IS from grade 0 to 4. Samples adequate for IS were available from 510 tumours. IS was significantly associated with AJCC/UICC stage, T stage, lymph node and distant metastases, perineural and lymphovascular invasion, MMR status, and BRAF mutation status. For IS0, IS1, IS2, IS3 and IS4, respectively, the 5‐year disease‐free survival (DFS) rates were 59, 68, 78, 83 and 94% (p

Introduction Gastro-oesophageal reflux disease (GORD) is suggested to cause or aggravate several respiratory conditions. Studies with proton pump inhibitors have resulted in only minor improvements in pulmonary outcomes in patients with GORD. It has been speculated that operative treatment of GORD might be more efficient as it also diminishes non-acidic reflux. Objectives To compare the effects of esomeprazole 40 mg bid and fundoplication on airway responsiveness, forced expiratory volume in 1 s (FEV1), exhaled nitric oxide (NO) and respiratory symptoms in patients with moderate-to-severe GORD. Methods Sixty-nine GORD patients had methacholine inhalation challenge performed on them, and FEV1, exhaled NO and respiratory symptoms were measured at baseline, after a 3-month treatment with esomeprazole and 3 months after fundoplication. Primary outcome variable was dose-response slope (DRS), i.e. decline in FEV1 during methacholine challenge divided with the amount of methacholine administered (%/μmol). Pre-defined subgroup analysis was performed among those with concomitant asthma (n = 12). Results There was no improvement in DRS, FEV1 or exhaled NO after esomeprazole treatment or fundoplication. Cough and dyspnoea measured with visual analog scale improved with esomeprazole treatment (P

Lynch syndrome (LS) is an autosomal dominant cancer syndrome including increased life-long risk for colorectal (CRC) and endometrial (EC) cancer, but also for cancers of other types. The risk for CRC is up to 70-80 % and for EC up to 50-60 %. Due to screening and early diagnosing the mortality related to CRC and EC seems to be low. In spite of many studies on surveillance of mutation carriers, there is no comprehensive evaluation on causes of death in LS families. The disease history and cause of death of all the deceased, tested mutation carriers and their mutation negative relatives in the Finnish LS families (N = 179) was examined utilizing hospital records and relevant national registries. Out of 1069 mutation carriers 151 had succumbed; 97 (64 %) from cancer. Out of 1146 mutation-negative family 44 members had died; 11 (25 %) of them from cancer. In 12 (7.7 %) of the deceased mutation carriers no cancer had been diagnosed. The mean age of death from cancer was 63.2 years vs. 68.8 years from non-cancer causes. Only 7.9 % of the patients with CRC had died from CRC and 5 % of those with EC, respectively. 61 % of the cancer deaths were related to extra-colonic, extra-endometrial cancers. The cumulative overall and cancer specific death rates were significantly increased in Mut+ compared to Mut- family members. Even surveillance yields decrease in the life-long risk and mortality of the most common cancers CRC and EC in LS, almost all mutation carriers will contract with cancer, and two thirds of the deceased have died from cancer. This should be taken in account in genetic counseling. Mutation carriers should be encouraged to seek help for abnormal symptoms.

To examine the impact of day-care laparoscopic cholecystectomy (LC) with ultrasonic scissors dissection versus diathermy hook dissection method in a randomized setting. From April 2012 to September 2014, a total of 169 elective day-care patients were randomized to undergo either laparoscopic cholecystectomy with ultrasonic scissors using fundus-first approach (n = 88) or diathermy hook dissection starting from the triangle of Calot (n = 79). Main measures of outcome were operative time, same-day discharge and intraoperative complications. Secondary outcome measures were postoperative pain (numeric rating scale), postoperative nausea and vomiting (PONV), readmissions and 30-day morbidity. Median operative time was similar in the ultrasonic dissection and diathermy hook dissection groups (45 vs 45 min, p = 0.95). Same-day discharge was possible in 77 patients (87 %) in the ultrasonic dissection group and in 69 patients (87 %) in the diathermy group, p = 0.98. Intraoperative gallbladder perforations, mean intraoperative bleeding, postoperative pain and PONV at 1, 2 and 4 h (p = 0.78) did not differ significantly between the study groups. Day-care LC using either diathermy hook or ultrasonic dissection resulted in excellent same-day discharge in both groups (87 %). LC with ultrasonic dissection does not offer any clinical advantages compared to diathermy dissection.

To examine the quality of surgical care and long-term oncologic outcome after D2 gastrectomy for gastric cancer.From 1999 to 2008, a total of 109 consecutive patients underwent D2 gastrectomy without routine pancreaticosplenectomy in a multimodal setting at our institution. Oncologic outcomes together with clinical and histopathologic data were analyzed in relation to the type of surgery performed. Staging was carried out according to the Union for International Cancer Control criteria of 2002. Patients were followed-up for five years at the outpatient clinic. The primary measure of outcome was long-term survival with the quality of surgery as a secondary outcome measure. Clinical data were retrospectively collected from the patient records, and causes of death were obtained from national registries.A total of 109 patients (58 men) with a mean age of 67.4 ± 11.2 years underwent total gastrectomy or gastric resection with D2 lymph node dissection. The tumor stage distribution was as follows: stage I, (27/109) 24.8%; stage II, (31/109) 28.4%; stage III, (41/109) 37.6%; and stage IV, (10/109) 9.2%. Forty patients (36.7%) received chemotherapy or chemoradiotherapy. The five-year overall survival rate for all 109 patients was 45.0%, and was 47.1% for the 104 patients treated with curative R0 resection. The five-year disease-specific survival rates were 53.0% and 55.8%, respectively. In a multivariate analysis, body mass index and tumor stage were independent prognostic factors for overall survival (both P0.01), whereas body mass index, tumor stage, tumor site, Lauren classification, and lymph node invasion were prognostic factors for cancer-specific survival (all P0.05). Postoperative 30-d mortality was 1.8% and 30-d, surgical (including three anastomotic leaks, two of which were treated conservatively), and general morbidities were 26.6%, 12.8%, and 14.7%, respectively.D2 dissection is a safe surgical option for gastric cancer, providing quality surgical care and long-term oncologic outcomes that are in line with current Western standards.

Overlap sphincteroplasty is gaining popularity in the primary repair of obstetric sphincter ruptures. This study was designed to evaluate the medium-term outcome of the overlap technique. Between August 1997 and October 2001, 31 consecutive females who were diagnosed with a complete third-degree or fourth-degree anal sphincter rupture underwent overlap sphincteroplasty immediately after delivery. Thirty of the females were followed-up for a median of 24 months. The outcome was assessed by clinical examination, anal endosonography, Wexner score, and pelvic floor electromyography. Median 24 (range, 12–63) months after delivery, 23 females (77 percent) were free of symptoms of anal incontinence. Occasional incontinence to flatus and liquid stool occurred in 17 and 7 percent of patients, respectively. Seven percent of patients had a Wexner incontinence score of > 9. The maximum mean resting pressure was 55 (range, 20–90) mmHg, and the maximum mean incremental squeeze pressure was 37 (range, 14–95) mmHg. On anal endosonography, an unrecognized internal sphincter rupture was found in one and a failed repair in two females. Overlap of the external sphincter was demonstrated in 29 patients (97 percent). One female with anal incontinence and persisting external sphincter rupture underwent redo sphincteroplasty. The median-term outcome of primary overlap repair for obstetric sphincter rupture is good; however, larger, randomized studies with a longer follow-up are needed to evaluate the advantage of this technique over the end-to-end technique.

PURPOSE: Stapled hemorrhoidectomy may be associated with less pain and faster recovery than conventional hemorrhoidectomy for prolapsing hemorrhoids. Therefore, the outcome of stapled hemorrhoidectomy was compared with that of diathermy hemorrhoidectomy in a randomized, controlled trial. METHODS: Sixty patients with third-degree hemorrhoids were randomly assigned to stapled hemorrhoidectomy (n = 30) or to diathermy hemorrhoidectomy in a day-case setting. Visual analog scale was used for postoperative pain scoring. Surgical and functional outcome was assessed at six weeks and one year after surgery. RESULTS: Operation time was a median of 21 (range, 11–59) minutes in the stapled group vs. 22 (range, 14–40) minutes in the diathermy group. Day-case surgery was successful in 24 patients (80 percent) in the stapled group vs. 29 patients (97 percent) in the diathermy group. Average pain in the stapled group was significantly lower than in the diathermy group (median, 1.8 (0.1–4.8) vs. 4.3 (1.4–6.2), 95 percent confidence interval difference medians, 1.15–3.85, P = 0.0002, Mann-Whitney U test) as was the average pain expected by the patients (median −2.7 (−0.15–0.8) vs. 0.006 (−4.05–0.5) respectively, 95 percent confidence interval difference medians, 0.5–3.55, P = 0.0018, Mann-Whitney U test). Postoperative morbidity and time off work were not significantly different between the diathermy and stapled groups. Seven treatment failures in the stapled group and one in the diathermy group necessitated other treatments at a later date. Patient satisfaction scores in the stapled and diathermy group were similar. Symptoms attributed to difficult rectal evacuation decreased significantly after surgery. CONCLUSIONS: Stapled hemorrhoidectomy is a significantly less painful operation than diathermy hemorrhoidectomy, but does not seem to offer significant advantages in terms of hospital stay or symptom control in the long term. Hemorrhoidectomy may improve symptoms of difficult rectal evacuation.

Background: The objective of the study was to examine the role of microsatellite instability (MSI) and BRAFV600Emutation 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 BRAFV600E 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, BRAFV600E 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

Juvenile polyposis (JP) is a dominantly inherited condition characterized by the development of multiple hamartomatous tumors, juvenile polyps, in the gastrointestinal tract. The aim of this study was to clarify the role of SMAD4 in JP. DNA from four unrelated JP kindreds and three sporadic JP cases was available for mutation screening. Two truncating defects (one in a familial and one in a sporadic case) and one missense change (in a familial case) that was absent in 55 control samples were detected. To study the possibility that germline mutations in other genes encoding different components of the TGF-beta signaling pathway may be present in these JP patients, mutation analyses of the SMAD2, SMAD3, and SMAD7 genes were also performed. No mutations of these genes were detected in any of the patients. Our results confirm that SMAD4 is a gene predisposing to JP and suggest the existence of further JP loci other than the SMAD2, SMAD3, or SMAD7 genes. Genes Chromosomes Cancer 26:54-61, 1999.

Carbon dioxide (CO,) insufflation with increased intraabdominal pressure (IAP) has adverse hemodynamic, pulmonary, and renal effects. To avoid these problems, an abdominal wall lift method with a retractor was used to provide the surgical view without CO2 insufflation. Twenty-six patients undergoing elective laparoscopic cholecystectomy were randomly allocated to either the gasless, retractor group, or conventional CO, pneurnoperitoneum group (CPP). Hemodynamic data, ventilatory variables, urine output, urine oxygen tension, and blood samples for determining stress hormones were collected throughout the perioperative period. Patients in the retractor group had lower mean arterial pressure, heart rate, and central venous pressure (P < 0.001). They also had higher pulmonary dynamic compliance and needed a lower minute volume of ventilation to achieve normocarbia (P < 0.001). Urine output and oxygen tension in urine were higher (P < 0.05) with the retractor method than with CPP. Increase in plasma renin activity (P < 0.05) and decrease in core temperature (P < 0.001) were smaller with the gasless method than with CPP. The gasless method for laparoscopic cholecystectomy might be beneficial, especially in patients with compromised cardiorespiratory or renal function. Implications: Totally gasless laparoscopic cholecystectomy was compared with conventional pressure pneumoperitoneum with CO, insufflation. The gasless method resulted in more stable hemodynamics and pulmonary function, as well as higher urine, output than conventional pressure pneumoperitoneum. No changes in renal oxygenation was seen with the gasless method, compared with conventional pressure pneumoperitoneum.

In contrast to normal colorectal mucosa, peanut-agglutinin(PNA)-reactive glycoconjugates are commonly expressed in most colorectal carcinomas and in some pre-malignant conditions such as adenomas and ulcerative colitis. Since enzymatically detectable galactose-β1-3-N-acetyl-galactosamine residues are found in rectal mucus obtained from patients with carcinoma of the large bowel, it was investigated here whether PNA-reactive carbohydrate structures in rectal mucus can be exploited in the detection of colorectal neoplasia. Samples of rectal mucus obtained from 261 randomly selected patients with colorectal symptoms were applied on nitrocellulose filters. The presence of PNA-reactive glycoconjugates in mucus samples was determined by a peroxidase-conjugated PNA-overlay procedure. The results were correlated to findings from total colonoscopy/surgery and histopathology. PNA-reactive carbohydrate structures were detected in 76% of patients with carcinoma (p < 0.005), in 62% of patients with adenoma (p < 0.005), in 69% of patients with inflammatory bowel disease (p < 0.005), and in 38% of patients with hyperplastic polyps (NS), in contrast to 21% of the control subjects with macroscopically normal colorectal mucosa. These results show that PNA-reactive carbohydrate alterations in rectal mucus correlates with neoplastic and hyperproliferative conditions of the colorectal mucosa. The specificity of the PNA test for colorectal neoplasia was 76%. Therefore the use of more discriminate carbohydrate probes are needed for the pre-symptomatic detection of colorectal neoplasia. Int. J. Cancer 74:648–653, 1997.© 1997 Wiley-Liss, Inc.

Carbon dioxide (CO 2 ) pneumoperitoneum together with an increased intraabdominal pressure (IAP) induces a hemodynamic stress response, diminishes urine output, and may compromise splanchnic perfusion. A new retractor method may be less traumatic. Accordingly, 30 ASA physical status I or II patients undergoing laparoscopic cholecystectomy were randomly allocated to a CO 2 pneumoperitoneum (IAP 12-13 mm Hg) (control) or to a gasless abdominal wall lift method (retractor) group. Anesthesia and intravascular fluids were standardized. Direct mean arterial pressure (MAP), urine output, urine-N-acetyl-β-D-glucosaminidase (U-NAG), arterial blood gases, gastric mucosal Pco 2 , and intramucosal pH (pHi) were measured. Normoventilation was instituted in all patients. MAP increased (P < 0.001) only with CO 2 pneumoperitoneum. Minute volume of ventilation had to be increased by 35% with CO 2 insufflation. Paco 2 was significantly higher (P < 0.05) for 3 h postoperatively in the control group. Diuresis was less (P < 0.01) and U-NAG levels (P < 0.01) higher in the control group. The pHi decreased after induction of pneumoperitoneum up to three hours postoperatively and remained intact in the retractor group. We conclude that the retractor method for laparoscopic cholecystectomy ensures stable hemodynamics, prevents respiratory acidosis, and provides protection against biochemical effects, which reveal the renal and splanchic ischemia caused by CO 2 insufflation. Implications: A mechanical retractor method (gasless) was compared with conventional CO 2 pneumoperitoneum for laparoscopic cholestectomy. The gasless method ensured stable hemodynamics, prevented respiratory acidosis, and provided protection against the renal and splanchnic ischemia seen with CO 2 pneumoperitoneum.

The aim of the study was to estimate the usefulness of measuring the circulating concentration of serum aminoterminal propeptide of type III collagen (S-PIIINP) in screening for hepatobiliary diseases in patients with ulcerative colitis. S-PIIINP was measured in 69 patients with ulcerative colitis and normal liver biochemistry, in 14 patients with ulcerative colitis and elevated catalytic concentration of alkaline phosphatases in serum (S-ALP, EC 3.1.3.1) but without primary sclerosing cholangitis (PSC), and in 20 patients with ulcerative colitis and PSC. The median S-PIIINP was 3.1 micrograms l-1 in patients with ulcerative colitis and normal liver biochemistry, 4.3 micrograms l-1 in patients with ulcerative colitis and hepatobiliary disorder other than PSC and 8.9 micrograms l-1 in those with ulcerative colitis and PSC. When the S-PIIINP cut-off level was set at 5.0 micrograms l-1, 1% of the patients with ulcerative colitis and normal liver biochemistry, 21% of those with hepatobiliary disorder, not PSC, and 90% of the patients with PSC had S-PIIINP values above that concentration. In conclusion, S-PIIINP above 5.0 micrograms l-1 in a patient with ulcerative colitis strongly suggests concomitant PSC.

There are no prospective studies available on the behavior of extraesophageal and esophageal symptoms and treatment-related side effects in patients without effective antireflux medication, receiving the most effective antireflux medication, and after laparoscopic fundoplication. Extraesophageal and esophageal reflux symptoms and treatment-related side effects were assessed in 60 patients while they were on no effective antireflux medication (three-week washout period), after three month of treatment with double-dose esomeprazole, and 3 months after laparoscopic Nissen fundoplication. Esophageal and extraesophageal reflux symptoms, rectal flatulence, and bloating were analyzed with the visual analog scale. In addition, dysphagia, rectal flatulence, and bloating were recorded as none, mild, moderate, or severe. Both extraesophageal and esophageal reflux symptoms decreased after treatment with esomeprazole and were further reduced after fundoplication. Dysphagia and flatulence did not increase from baseline after surgery. Bloating decreased both after treatment with esomeprazole and after fundoplication. In contrast, dysphagia and increased flatus were found more often after surgery than during treatment with esomeprazole. Dysphagia and rectal flatulence were less common during treatment with esomeprazole than at baseline or after surgery. Both extraesophageal and esophageal reflux symptoms decreased after treatment with esomeprazole and were reduced further after fundoplication. Any treatment-related side effect was not increased after surgery when compared to baseline. However, compared to esomeprazole there was more dysphagia and flatulence after fundoplication.

The fast-track treatment model can be regarded as the second revolution of colorectal surgery after the introduction of laparoscopic surgery. In the gastro-surgical unit of the Central Hospital of Central Finland, results equivalent to international studies in colorectal surgery have been achieved by using fast-track model. In a study setting, this treatment model has resulted in significant decrease of total treatment costs and speeded up discharge of the patients from the hospital. The fast-track treatment model requires both a motivated, trained medical team and a motivated patient.

BACKGROUND Laparoscopic resection for rectal cancer has remained controversial because of the lack of level 1 evidence regarding oncologic safety and long-term survival. OBJECTIVES The aim of this study was to assess the impact of laparoscopic versus open resection for rectal cancer on clinical and oncologic outcome in the multimodal setting. DESIGN This is a review of prospectively gathered data from a single-institution rectal cancer database. SETTINGS This study was conducted in the Central Hospital of Central Finland. PATIENTS From January 1999 to December 2006, 191 selected patients were included. INTERVENTIONS One hundred patients underwent laparoscopic resection, and 91 patients, also suitable for laparoscopic surgery, underwent open major rectal resection in the multimodal setting. MAIN OUTCOME MEASURES The main measures of outcome were early recovery and short- and long-term morbidity; local recurrence and survival were secondary outcomes. LIMITATIONS This is not a randomized study. RESULTS The study groups were balanced for baseline characteristics. Conversion rate to open surgery was 22%. Laparoscopic surgery resulted in significantly less bleeding (175 mL vs 500 mL, p < 0.001), 1 day earlier recovery of normal diet (3 days vs 4 days, p = 0.001), and shorter postoperative hospital stay (7 days vs 9 days, p < 0.001). Postoperative 30-day mortality (1% vs 3%), morbidity (31% vs 43%), readmission (11% vs 15%), and reoperation (6% vs 9%) rates were similar in the 2 groups, but significantly fewer patients in the laparoscopic group had long-term complications (19% vs 36%, p = 0.033). The 5-year disease-free survival (78% vs 80%, p = 0.74) and local recurrence (5% vs 6%, p = 0.66) rates were similar in the laparoscopic and open group for those 175 patients treated for cure. CONCLUSION Laparoscopic surgery resulted in faster postoperative recovery and fewer long-term complications than open surgery without apparently compromising the long-term oncologic outcome. Our results indicate that laparoscopic rectal resection is an acceptable alternative to open surgery in selected patients with rectal cancer.

To assess the quality of surgical care and outcome following multimodal treatment for low- and midrectal cancers, focusing on differences between low anterior and abdominoperineal resections. From 1999 to 2007, 179 patients underwent low anterior resection (LAR), abdominoperineal resection (APR), or proctocolectomy for low- or midrectal cancers. Preoperative (chemo)radiotherapy was given according to local guidelines and adjuvant postoperative chemotherapy in stage III disease. Outcome together with clinical and histopathological data were analyzed in relation to the type of surgery performed. The postoperative mortality was 2.2%; morbidity, 39.6%; reoperation rate, 8.4%; and readmission rate, 16.0%. Involved circumferential resection margin (CRM ≤ 1 mm) rate was 4.5% (APR 9.1% vs. LAR 2.6%, p = 0.046). Intraoperative bowel perforation occurred in 5.5% of APRs. Anastomotic leak rate was 15.3%. The 5-year overall survival of the 179 patients was 68.5 %; disease-specific survival, 82.2%; and local recurrence rate, 6.3%. The overall, disease-specific, and disease-free survival rates in the 162 patients treated for cure were 73.1%, 84.6%, and 78.3%, and local recurrence rate was 4.4% with no significant differences between LAR and APR. CRM was the only independent predictor of local recurrence and CRM, tumor stage, and level independent predictors of disease-free survival. Quality of surgical care was in line with the current international standards. CRM was an independent predictor for local recurrence and CRM, tumor stage, and level independent prognostic factors for disease-free survival. Neither the type of surgery (LAR vs. APR) nor the surgical approach (laparoscopic vs. open) influenced the oncologic outcome.

Laparoscopic surgery has established itself in gallbladder, adrenal and colorectal surgery as well as in anti-reflux and buriatric surgery. The technique has also been increasingly applied to hepatic, pancreatic and gastric surgery. The progress has taken place at the price of increased surgery costs, but is compensated by shortened hospitalization. Robot-assisted laparoscopy may facilitate the technical execution of surgery in hepatic and pancreatic surgery and additionally make possible the benefits of preoperative imaging, intraoperative localization of the tumor, and optimal determination of the margins of resection.

Carcinoembryonic antigen (CEA, ceacam5) is an important tumor-associated antigen with reported roles, e.g., in immunological defense, cell adhesion, cell survival and metastasis. Its overexpression in cancer cells is known to involve transcriptional activation of the CEA gene, but the underlying molecular details remain unclear. Here, we show that hypoxia and intracellular alkalinization, 2 factors commonly found in solid tumors, increase CEA protein expression in breast (MCF-7) and colorectal (CaCo-2 and HT-29) cancer cells. The increase was comparable (2-3-fold) to that observed in colorectal carcinomas in vivo. CEA promoter analyses further revealed that this upregulation involves a known binding site for HIF-1 transcription factor (5'-ACGTG-3') within one of the CEA promoter's positive regulatory elements (the FP1 site; the E-box). Accordingly, deletion or targeted mutagenesis of this motif rendered the CEA promoter unresponsive to hypoxia. Our chromatin immunoprecipitation data confirmed that endogenous HIF-1alpha binds to the CEA promoter in hypoxic cells but not in normoxic cells. Moreover, overexpression of the hypoxia-inducible factor (HIF-1alpha) was sufficient to increase CEA protein expression in the cells. In contrast, c-Myc, which is known to bind to the overlapping E-box, did not potentiate HIF-1alpha-induced CEA expression. CEA overexpression in vivo was also found to coincide with the expression of carbonic anhydrase IX, a well-known hypoxia marker. Collectively, these results define CEA as a hypoxia-inducible protein and suggest an important role for the tumor microenvironmental factors in CEA overexpression during tumorigenesis.

Quality of life is an important outcome measure that has to be considered when deciding treatment strategy for rectal cancer. The aim of this study was to find out the impact of surgery-related adverse effects on quality of life. The RAND-36 questionnaire and questionnaires assessing urinary, sexual, and bowel dysfunction were administered to 94 patients with no sign of recurrence a minimum of one year after curative surgery. Results were compared with age-matched and gender-matched general population. Eighty-two (87 percent) patients answered the questionnaires. Major bowel dysfunction was as common after high anterior resection as after low anterior resection. Urinary complaints occurred as often after anterior resection as after abdominoperineal resection, but sexual dysfunction was more common after abdominoperineal resection. Overall, the patients reported better general health perception but poorer social functioning than population controls. In particular, elderly patients reported a significantly better quality of life in many dimensions than their population controls. There was no significant difference in quality of life between treatment groups. Major bowel dysfunction after anterior resection impaired social functioning compared with that of patients without such symptoms. Urinary dysfunction impaired social functioning and impotence impaired physical and social functioning. Quality of life after rectal cancer surgery is not worse than that of the general population. The major adverse impact of bowel and urogenital dysfunction is on social functioning. These adverse effects need to be discussed with the patient and preoperative function needs to be taken into account when choosing between treatment options. Permanent colostomy is not always the factor that disrupts a person's quality of life most.

Altered glycosylation has turned out to be a universal feature of cancer cells, and in many cases, to correlate with altered expression or localization of relevant glycosyltransferases. However, no such correlation exists between observed enzymatic changes and the expression of the oncofetal Thomsen-Friedenreich (T)-antigen, a core 1 (Gal-beta1 --> 3-GalNAc-ser/thr) carbohydrate structure. Here we report that T-antigen expression, instead, correlates with elevated Golgi pH in cancer cells. Firstly, using a Golgi-targeted green fluorescent protein (GT-EGFP) as a probe, we show that the medial/trans-Golgi pH (pHG) in a high proportion of breast (MCF-7) and colorectal (HT-29, SW-48) cancer cells is significantly more alkaline (pHG > or = 6.75) than that of control cells (pHG 5.9-6.5). The pH gradient between the cytoplasm and the Golgi lumen is also markedly reduced in MCF-7 cells, suggesting a Golgi acidification defect. Secondly, we show that T-antigen expression is highly sensitive to changes in Golgi pH, as only a 0.2 pH unit increase was sufficient to increase T-antigen expression in control cells. Thirdly, we found that T-antigen expressing MCF-7 cells have 0.3 pH units more alkaline Golgi pH than non-expressing MCF-7 cells. Fourthly, in all cell types examined, we observed significant correlation between the number of T-antigen expressing cells and cells with a markedly elevated Golgi pH (pHG > or = 6.75). Consistent with these observations in cultured cells, cells in solid tumors also heterogenously expressed the T-antigen. Thus, elevated Golgi pH appears to be directly linked to T-antigen expression in cancer cells, but it may also act as a more general factor for altered glycosylation in cancer by affecting the distribution of Golgi-localized glycosyltransferases.

Background: After laparoscopy with carbon dioxide (CO2) insufflation early postoperative recovery is often complicated with drowsiness and postoperative nausea and vomiting (PONV). Methods: 25 ASA I − II patients undergoing elective laparoscopic cholecystectomy under standardized anaesthesia were studied in a randomized, prospective study. The conventional CO2 pneumoperitoneum was compared with the mechanical abdominal wall lift (AWL) method with minimal CO2 insufflation with special reference to postoperative recovery. Results: Postoperative drowsiness was of a significantly longer duration with the conventional method (p < 0.001) compared with the AWL technique. There was a positive correlation with the total amount of CO2 used and the duration of drowsiness (r = 0.75, p < 0.01). PONV was seen significantly more often in patients with CO2 insufflation of more than 121 (p < 0.05). Conclusions: Avoiding excessive CO2 is beneficial for smoother and more uneventful recovery after laparoscopic cholecystectomy.

Preoperative radiotherapy (PRT) for rectal carcinoma has been shown to cause tumour regression and increase local control and patient survival. The aim of this study was to examine the usefulness of tumour regression grading (TRG) in quantifying the effect of PRT.Depending on the tumour stage (uT), as defined by preoperative endorectal ultrasound (ERUS), fixity and distance from the anal verge, 126 patients with rectal cancer underwent either surgery alone, or received short-course 25-Gy radiotherapy or long-course 50-Gy radiotherapy combined with 5-fluorouracil (5-FU) before surgery. TRG in each group was assessed and compared with the downstaging, defined as a change in preoperative uT stage and pathologic stage (pT).Complete response (no residual tumour, TRG 1) was seen in 7% of the patients (3/44) and total or major regression (TRG 1-3) in 73% of the patients (32/44) treated with 50-Gy chemoradiation. Of those treated with 25-Gy PRT, 21% (9/42) showed major tumour regression. Of the patients who underwent ERUS and PRT, 32% (26/83) were downstaged when comparing uT with pT, but 53% (14/26) of the downstaged tumours showed no response by TRG. In comparison, 50% (28/57) of the tumours with no downstaging showed a marked response by TRG (p=0.05).Tumour regression grading offers detailed information of the effect of PRT and shows that tumour regression is more marked after long-term chemoradiation than after short-course radiotherapy (p=0.02). In contrast, T-stage downstaging was similar in both groups and did not correlate with the TRG results (p=0.05).

Juvenile polyposis syndrome (JPS) is an inherited hamartomatous-polyposis syndrome with a risk for colon cancer. JPS is a clinical diagnosis by exclusion, and, before susceptibility genes were identified, JPS could easily be confused with other inherited hamartoma syndromes, such as Bannayan-Riley-Ruvalcaba syndrome (BRRS) and Cowden syndrome (CS). Germline mutations of MADH4 (SMAD4) have been described in a variable number of probands with JPS. A series of familial and isolated European probands without MADH4 mutations were analyzed for germline mutations in BMPR1A, a member of the transforming growth-factor beta-receptor superfamily, upstream from the SMAD pathway. Overall, 10 (38%) probands were found to have germline BMPR1A mutations, 8 of which resulted in truncated receptors and 2 of which resulted in missense alterations (C124R and C376Y). Almost all available component tumors from mutation-positive cases showed loss of heterozygosity (LOH) in the BMPR1A region, whereas those from mutation-negative cases did not. One proband with CS/CS-like phenotype was also found to have a germline BMPR1A missense mutation (A338D). Thus, germline BMPR1A mutations cause a significant proportion of cases of JPS and might define a small subset of cases of CS/BRRS with specific colonic phenotype.

There have been few large series that have focused on the feasibility of the laparoscopic approach for rectal prolapse. This single-institution study prospectively examines the surgical outcome and changes in symptoms and bowel function following the laparoscopic repair of rectal prolapse.In a selected group of 34 patients (total prolapse, 28; intussusception, six), 17 patients underwent laparoscopic-assisted resection rectopexy and 17 patients received a laparoscopic sutured rectopexy. Preoperative and postoperative evaluation at 3, 6, and 12 months included assessment of the severity of anal incontinence, constipation, changes in constipation-related symptoms, and colonic transit time.Median operation time was 255 min (range, 180-360) in the resection rectopexy group and 150 min (range, 90-295) in the rectopexy alone group. Median postoperative hospital stay was 5 days (range, 3-15) and median time off work was 14 days (range, 12-21) in both groups. There were no deaths. Postoperative morbidity was 24%. Incontinence improved significantly regardless of which method was used. The main determinant of constipation was excessive straining at defecation. Constipation was cured in 70% of the patients in the rectopexy group and 64% in the resection rectopexy group. Symptoms of difficult evacuation improved, but the changes were significant only after resection rectopexy. Two patients (7%) developed recurrent total prolapse during a median follow-up of 2 years (range 12-60 months).Laparoscopic-sutured rectopexy and laparoscopic-assisted resection rectopexy are feasible and carry an acceptable morbidity rate. They eliminate prolapse and cure incontinence in the great majority of patients. Constipation and symptoms of difficult evacuation are alleviated.

Pneumoperitoneum with room temperature carbon dioxide (CO2) has been shown to decrease core temperature and urine output.The effect of 37 degrees C (warm) and room temperature (cool) CO2 pneumoperitoneum on core temperature, urine output, and central hemodynamics was compared in 26 randomized patients undergoing prolonged laparoscopic surgery (90 min).The core temperature (p0.05) and cardiac index (p0.05) were significantly higher after warm than after cool pneumoperitoneum. Urine output was significantly higher during warm (2.3 +/- 1.6 ml/kg/h) than during cool (0.9 +/- 0.7 ml/kg/h) insufflation (p0. 05). Two of 13 patients with warm and 11 of 13 patients with cool pneumoperitoneum needed mannitol to maintain adequate diuresis (p0.05).Warm insufflation probably causes a local vasodilation in the kidneys and may be beneficial to patients with borderline renal function.

Background: The aim of this study was to evaluate the role of primary sclerosing cholangitis (PSC) as a cofactor in the dysplasia-carcinoma sequence in ulcerative colitis (UC). Methods: Forty-five patients with UC and concomitant PSC and 45 pair-matched control patients with UC only were examined for colorectal dysplasia and carcinoma. Results: The median duration of UC was 11 years in the group with UC and PSC and 15 years in the control group. Thirteen of the 45 patients (29%) with UC and PSC had colorectal neoplasia: 4, carcinoma; 2, high-grade dysplasia; and 7, low-grade dysplasia. Four of the 45 control patients (9%) had neoplastic findings: 1, carcinoma; 1, high-grade dysplasia, and 2, low-grade dysplasia (P < 0.05). Conclusion: The results suggest that the risk of colorectal dysplasia and carcinoma in patients with UC is increased by concomitant PSC.