Systematic Reviews and Meta-analyses of the Procedure-specific Risks of Thrombosis and Bleeding in General Abdominal, Colorectal, Upper Gastrointestinal, and Hepatopancreatobiliary Surgery.

OBJECTIVE: To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery. BACKGROUND: The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain. METHODS: We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty. RESULTS: After eligibility screening, 285 studies (8,048,635 patients) reporting on 40 general abdominal, 36 colorectal, 15 upper gastrointestinal, and 24 hepatopancreatobiliary surgery procedures proved eligible. Evidence certainty proved generally moderate or low for VTE and low or very low for bleeding requiring reintervention. The risk of VTE varied substantially among procedures: in general abdominal surgery from a median of <0.1% in laparoscopic cholecystectomy to a median of 3.7% in open small bowel resection, in colorectal from 0.3% in minimally invasive sigmoid colectomy to 10.0% in emergency open total proctocolectomy, and in upper gastrointestinal/hepatopancreatobiliary from 0.2% in laparoscopic sleeve gastrectomy to 6.8% in open distal pancreatectomy for cancer. CONCLUSIONS: VTE thromboprophylaxis provides net benefit through VTE reduction with a small increase in bleeding in some procedures (eg, open colectomy and open pancreaticoduodenectomy), whereas the opposite is true in others (eg, laparoscopic cholecystectomy and elective groin hernia repairs). In many procedures, thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding.

Prevention of incisional hernia with retrorectus synthetic mesh versus biological mesh following loop ileostomy closure (Preloop trial).

BACKGROUND: The rate of incisional hernia after closure of a temporary loop ileostomy is significant. Synthetic meshes are still commonly avoided in contaminated wounds. The Preloop trial was a multicentre RCT designed to evaluate the benefits of synthetic mesh in incisional hernia prevention, and its safety for use in a contaminated surgical site compared with biological mesh. METHODS: Study patients who underwent closure of a loop ileostomy after anterior resection for rectal cancer were assigned to receive either retrorectus synthetic or biological mesh to prevent incisional hernia. The primary outcomes were surgical-site infections within 30 days, and clinical or radiological incisional hernia incidence at 10 months. Secondary outcomes were reoperation rate, operating time, duration of hospital stay, other complications within 30 days of surgery, 5-year quality of life measured by RAND-36, and incisional hernia incidence within 5 years of follow-up. RESULTS: Between November 2018 and September 2021, 102 patients were randomised, of whom 97 received the intended allocation. At 10-month follow-up, 90 patients had undergone clinical evaluation and 88 radiological evaluation. One patient in each group (2 per cent) had a clinical diagnosis of incisional hernia (P = 0.950) and one further patient in each group had a CT-confirmed incisional hernia (P = 0.949). The number of other complications, reoperation rate, operating time, and duration of hospital stay did not differ between the study groups. CONCLUSION: Synthetic mesh appeared comparable to biological mesh in efficacy and safety for incisional hernia prevention at the time of loop ileostomy closure. REGISTRATION NUMBER: NCT03445936 (http://www.clinicaltrials.gov).

Novel human lymph node-derived matrix supports the adhesion of metastatic oral carcinoma cells.

BACKGROUND: 3D culture is increasingly used in cancer research, as it allows the growth of cells in an environment that mimics in vivo conditions. Metastases are the primary cause of morbidity and mortality in cancer patients, and solid tumour metastases are mostly located in lymph nodes. Currently, there are no techniques that model the pre-metastatic lymph node microenvironment in vitro. In this study, we prepared a novel extracellular matrix, Lymphogel, which is derived from lymph nodes, mimicking the tumour microenvironment (TME) of metastatic carcinoma cells. We tested the suitability of the new matrix in various functional experiments and compared the results with those obtained using existing matrices. METHODS: We used both commercial and patient-derived primary and metastatic oral tongue squamous cell carcinoma (OTSCC) cell lines. We characterized the functional differences of these cells using three different matrices (human uterine leiomyoma-derived Myogel, human pre-metastatic neck lymph node-derived Lymphogel (h-LG), porcine normal neck lymph node-derived Lymphogel (p-LG) in proliferation, adhesion, migration and invasion assays. We also performed proteomic analyses to compare the different matrices in relation to their functional properties. RESULTS: OTSCC cells exhibited different adhesion and invasion patterns depending on the matrix. Metastatic cell lines showed improved ability to adhere to h-LG, but the effects of the matrices on cell invasion fluctuated non-significantly between the cell lines. Proteomic analyses showed that the protein composition between matrices was highly variable; Myogel contained 618, p-LG 1823 and h-LG 1520 different proteins. The comparison of all three matrices revealed only 120 common proteins. Analysis of cellular pathways and processes associated with proteomes of each matrix revealed similarities of Myogel with h-LG but less with p-LG. Similarly, p-LG contained the least adhesion-related proteins compared with Myogel and h-LG. The highest number of unique adhesion-related proteins was present in h-LG. CONCLUSIONS: We demonstrated that human pre-metastatic neck lymph node-derived matrix is suitable for studying metastatic OTSCC cells. As a whole-protein extract, h-LG provides new opportunities for in vitro carcinoma cell culture experiments.

Long-term results of a prospective randomized trial comparing tension-free vaginal tape versus transobturator tape in stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: This study was aimed at investigating the long-term effectiveness of minimally invasive mid-urethral sling (MUS) surgery and at comparing the outcomes between retropubic (tension-free vaginal tape, TVT) and transobturator tape (TOT) methods in the treatment of stress urinary incontinence (SUI) and mixed urinary incontinence (MUI) with a predominant stress component in a long-term follow-up of a randomized controlled trial. METHODS: This work is a long-term follow-up study of a previous prospective randomized trial conducted in the Department of Obstetrics and Gynecology at Oulu University Hospital between January 2004 and November 2006. The original 100 patients were randomized into the TVT (n=50) or TOT (n=50) group. The median follow-up time was 16 years, and the subjective outcomes were evaluated using internationally standardized and validated questionnaires. RESULTS: Long-term follow-up data were obtained from 34 TVT patients and 38 TOT patients. At 16 years after MUS surgery, the UISS significantly decreased from a preoperative score in the TVT (11.88 vs 5.00, p<0.001) and TOT (11.05 vs 4.95, p<0.001) groups, showing a good long-term success of the MUS surgery in both groups. In comparing the TVT and TOT procedures, the subjective cure rates did not differ significantly between the study groups in long-term follow-up according to validated questionnaires. CONCLUSION: Midurethral sling surgery had good long-term outcomes in the treatment of SUI and MUI with a predominant stress component. The subjective outcomes of the TVT and TOT procedures were similar after a 16-year follow-up.

Laparoscopic bile duct exploration during pregnancy: a multi-center case series and literature review.

BACKGROUND: The physiological changes of pregnancy increase the risk of gallstone formation and choledocholithiasis. Traditionally, endoscopic retrograde cholangiopancreatography (ERCP) has been the main approach for managing choledocholithiasis during pregnancy, but recent progress in laparoscopic bile duct exploration (LBDE) has demonstrated this technique as a safe and effective alternative option. METHODS: A retrospective multicenter study of all patients who underwent LBDE during pregnancy from five centers with proven experience in LBDE between January 2010 and June 2020 was performed. The primary endpoint was to analyze the role of LBDE during pregnancy and to further characterize its position as a safe and effective alternative for the management of choledocholithiasis. A systematic review of the published literature relating to LBDE during pregnancy until February 2022 was also performed. RESULTS: Five institutions reported performing LBDE during pregnancy in 8 patients. Median surgical time was 75 min (range: 60-140 min). The bile duct was cleared successfully in all patients, and the median hospital stay was 2 days (range: 1-3 days). The literature review identified a total of 7 patients with a successful CBD clearance rate of 86%. There were no major maternal, fetal, or pregnancy-related complications in any of the total 15 patients included. The symptomatic common bile duct lithiasis with deranged liver function tests was the most frequent indication (n=7). CONCLUSION: LBDE during pregnancy appears to be safe and effective. More evidence reporting outcomes of LBDE during pregnancy is needed before any strong recommendations can be made.

Synthetic mesh versus biological mesh to prevent incisional hernia after loop-ileostomy closure: a randomized feasibility trial.

BACKGROUND: Incisional hernia is a frequent complication after loop-ileostomy closure, rationalizing hernia prevention. Biological meshes have been widely used in contaminated surgical sites instead of synthetic meshes in fear of mesh related complications. However, previous studies on meshes does not support this practice. The aim of Preloop trial was to study the safety and efficacy of synthetic mesh compared to a biological mesh in incisional hernia prevention after loop-ileostomy closure. METHODS: The Preloop randomized, feasibility trial was conducted from April 2018 until November 2021 in four hospitals in Finland. The trial enrolled 102 patients with temporary loop-ileostomy after anterior resection for rectal cancer. The study patients were randomized 1:1 to receive either a light-weight synthetic polypropylene mesh (Parietene Macro™, Medtronic) (SM) or a biological mesh (Permacol™, Medtronic) (BM) to the retrorectus space at ileostomy closure. The primary end points were rate of surgical site infections (SSI) at 30-day follow-up and incisional hernia rate during 10 months' follow-up period. RESULTS: Of 102 patients randomized, 97 received the intended allocation. At 30-day follow-up, 94 (97%) patients were evaluated. In the SM group, 1/46 (2%) had SSI. Uneventful recovery was reported in 38/46 (86%) in SM group. In the BM group, 2/48 (4%) had SSI (p > 0.90) and in 43/48 (90%) uneventful recovery was reported. The mesh was removed from one patient in both groups (p > 0.90). CONCLUSIONS: Both a synthetic mesh and biological mesh were safe in terms of SSI after loop-ileostomy closure. Hernia prevention efficacy will be published after the study patients have completed the 10 months' follow-up.

The Clinical Frailty Scale is a useful tool for predicting postoperative complications following elective colon cancer surgery at the age of 80 years and above: A prospective, multicentre observational study.

AIM: Identification of the risks of postoperative complications may be challenging in older patients with heterogeneous physical and cognitive status. The aim of this multicentre, observational study was to identify variables that affect the outcomes of colon cancer surgery and, especially, to find tools to quantify the risks related to surgery. METHOD: Patients aged ≥80 years with electively operated Stage I-III colon cancer were recruited. The prospectively collected data included comorbidities, results of the onco-geriatric screening tool (G8), Clinical Frailty Scale (CFS), Charlson Comorbidity Index (CCI) and Mini Nutritional Assessment-Short Form (MNA-SF), and operative and postoperative outcomes. RESULTS: A total of 161 patients (mean 84.5 years, range 80-97, 60% female) were included. History of cerebral stroke (64% vs. 37%, p = 0.02), albumin level 31-34 g/l compared with ≥35 g/l (57% vs. 32%, p = 0.007), CFS 3-4 and 5-9 compared with CFS 1-2 (49% and 47% vs. 16%, respectively) and American Society of Anesthesiologists score >3 (77% vs. 28%, P = 0.006) were related to a higher risk of complications. In multivariate logistic regression analysis CFS ≥3 (OR 6.06, 95% CI 1.88-19.5, p = 0.003) and albumin level 31-34 g/l (OR 3.88, 1.61-9.38, p = 0.003) were significantly associated with postoperative complications. Severe complications were more common in patients with chronic obstructive pulmonary disease (43% vs. 13%, p = 0.047), renal failure (25% vs. 12%, p = 0.021), albumin level 31-34 g/l (26% vs. 8%, p = 0.014) and CCI >6 (23% vs. 10%, p = 0.034). CONCLUSION: Surgery on physically and cognitively fit aged colon cancer patients with CFS 1-2 can lead to excellent operative outcomes similar to those of younger patients. The CFS could be a useful screening tool for predicting postoperative complications.

Parastomal Hernia: A Retrospective Nationwide Cohort Study Comparing Different Techniques with Long-Term Follow-Up.

BACKGROUND: Parastomal hernia repair is a complex surgical procedure with high recurrence and complication rates. This retrospective nationwide cohort study presents the results of different parastomal hernia repair techniques in Finland. METHODS: All patients who underwent a primary end ostomy parastomal hernia repair in the nine participating hospitals during 2007-2017 were included in the study. The primary outcome measure was recurrence rate. Secondary outcomes were complications and re-operation rate. RESULTS: In total, 235 primary elective parastomal hernia repairs were performed in five university hospitals and four central hospitals in Finland during 2007-2017. The major techniques used were the Sugarbaker (38.8%), keyhole (16.3%), and sandwich techniques (15.4%). In addition, a specific intra-abdominal keyhole technique with a funnel-shaped mesh was utilized in 8.3% of the techniques; other parastomal hernia repair techniques were used in 21.3% of the cases. The median follow-up time was 39.0 months (0-146, SD 35.3). The recurrence rates after the keyhole, Sugarbaker, sandwich, specific funnel-shaped mesh, and other techniques were 35.9%, 21.5%, 13.5%, 15%, and 35.3%, respectively. The overall re-operation rate was 20.4%, while complications occurred in 26.3% of patients. CONCLUSION: The recurrence rate after parastomal hernia repair is unacceptable in this nationwide cohort study. As PSH repair volumes are low, further multinational, randomized controlled trials and hernia registry data are needed to improve the results.

Keyhole versus Sugarbaker techniques in parastomal hernia repair following ileal conduit urinary diversion: a retrospective nationwide cohort study.

BACKGROUND: Previous research on parastomal hernia repair following ileal conduit urinary diversion is limited. This nationwide cohort study aims to present the results of keyhole and Sugarbaker techniques in parastomal hernia repair in the setting of ileal conduit urinary diversion. METHOD: All patients in this cohort underwent primary elective parastomal hernia repair following ileal conduit urinary diversion in four university hospitals and one central hospital in Finland in 2007-2017. Retrospective clinical data were collected from patient registries to compare keyhole and Sugarbaker parastomal hernia repair techniques. The primary outcome was parastomal hernia recurrence during the follow-up from primary surgery to the last confirmed follow-up date of the patient. The secondary outcomes were reoperations during the follow-up and complication rate at 30 days' follow-up. RESULTS: The results of 28 hernioplasties were evaluated. The overall parastomal hernia recurrence rate was 18%, the re-operation rate was 14%, and the complication rate was 14% during the median follow-up time of 30 (21-64) months. Recurrence rates were 22% (4/18) after keyhole repair and 10% (1/10) after Sugarbaker repair. Re-operation rates referred to keyhole repair were 22% and Sugarbaker repair 0% during follow-up. The majority of reoperations were indicated by recurrence. Complication rates were 17% after keyhole and 10% after Sugarbaker repair during the 30 days' follow-up. CONCLUSION: The results of parastomal hernia repair in the setting of ileal conduits are below optimal in this nationwide cohort comparing keyhole to Sugarbaker repair in elective parastomal hernia repair. Nonetheless, the Sugarbaker technique should be further studied to confirm the encouraging results of this cohort in terms of recurrence.

Effect of Oral Moxifloxacin vs Intravenous Ertapenem Plus Oral Levofloxacin for Treatment of Uncomplicated Acute Appendicitis: The APPAC II Randomized Clinical Trial.

Importance: Antibiotics are an effective and safe alternative to appendectomy for managing uncomplicated acute appendicitis, but the optimal antibiotic regimen is not known. Objective: To compare oral antibiotics with combined intravenous followed by oral antibiotics in the management of computed tomography-confirmed uncomplicated acute appendicitis. Design, Setting, and Participants: The Appendicitis Acuta (APPAC) II multicenter, open-label, noninferiority randomized clinical trial was conducted from April 2017 until November 2018 in 9 Finnish hospitals. A total of 599 patients aged 18 to 60 years with computed tomography-confirmed uncomplicated acute appendicitis were enrolled in the trial. The last date of follow-up was November 29, 2019. Interventions: Patients randomized to receive oral monotherapy (n = 295) received oral moxifloxacin (400 mg/d) for 7 days. Patients randomized to receive intravenous antibiotics followed by oral antibiotics (n = 288) received intravenous ertapenem (1 g/d) for 2 days followed by oral levofloxacin (500 mg/d) and metronidazole (500 mg 3 times/d) for 5 days. Main Outcomes and Measures: The primary end point was treatment success (≥65%) for both groups, defined as discharge from hospital without surgery and no recurrent appendicitis during 1-year follow-up, and to determine whether oral antibiotics alone were noninferior to intravenous and oral antibiotics, with a margin of 6% for difference. Results: Among 599 patients who were randomized (mean [SD] age, 36 [12] years; 263 [44%] women), 581 (99.7%) were available for the 1-year follow-up. The treatment success rate at 1 year was 70.2% (1-sided 95% CI, 65.8% to ∞) for patients treated with oral antibiotics and 73.8% (1-sided 95% CI, 69.5% to ∞) for patients treated with intravenous followed by oral antibiotics. The difference was -3.6% ([1-sided 95% CI, -9.7% to ∞]; P = .26 for noninferiority), with the confidence limit exceeding the noninferiority margin. Conclusion and Relevance: Among adults with uncomplicated acute appendicitis, treatment with 7 days of oral moxifloxacin compared with 2 days of intravenous ertapenem followed by 5 days of levofloxacin and metronidazole resulted in treatment success rates greater than 65% in both groups, but failed to demonstrate noninferiority for treatment success of oral antibiotics compared with intravenous followed by oral antibiotics. Trial Registration: ClinicalTrials.gov Identifier: NCT03236961; EudraCT Identifier: 2015-003633-10.

Cost-analysis and effectiveness of one-stage laparoscopic versus two-stage endolaparoscopic management of cholecystocholedocholithiasis: a retrospective cohort study.

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 .

Day-care laparoscopic cholecystectomy with diathermy hook versus fundus-first ultrasonic dissection: a randomized study.

BACKGROUND AND AIM: To examine the impact of day-care laparoscopic cholecystectomy (LC) with ultrasonic scissors dissection versus diathermy hook dissection method in a randomized setting. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Mifepristone and misoprostol is safe and effective method in the second-trimester pregnancy termination.

PURPOSE: The second-trimester medical abortions constitute 10-15 % of all induced abortions worldwide, but are responsible for two-thirds of major abortion related complications. During the last decade, medical methods for the second-trimester-induced abortion have been become safer and more accessible. The aim of this study is to evaluate factors affecting clinical effectiveness of the second-trimester medical terminations using mifepristone and misoprostol combination. METHODS: In this retrospective observational study, 142 consecutive women underwent medical abortion on 12-24 weeks of gestation. Clinical data were collected from Oulu University Hospital patients' records for the period between January 2008 and June 2011. The associations between patient characteristics and different outcomes were evaluated using the standard statistical test for correlation. RESULTS: The majority (92 %) of women aborted successfully within 24 h and were considered as day cases with small complication rate, as compared to hospitalized patients. In nulliparous patients, the time for complete abortion was longer than in other groups (P < 0.0019). Nulliparous women and women with gestation more than 16 weeks required opiate analgesia more often (P = 0.003 and <0.001, respectively). CONCLUSION: Women with previous live births aborted more often within 8 h than women with no previous births. Mifepristone and misoprostol is safe and effective method for the second-trimester pregnancy termination. The second-trimester medical abortion can be provided by a nurse-midwife with the back-up of a gynecologist.

Prognostic value of cyclin B in endometrial endometrioid adenocarcinoma.

Cyclins are a group of cell cycle regulatory proteins. Cyclin B acts as an activator to cyclin-dependent kinase 1 (CDK1), a protein kinase essential for G2/M phase transition. Deregulation of cyclins has been linked to a number of malignant neoplasms, but the impact on clinicopathological parameters seems to be cancer-specific. Overexpression of cyclin B has been shown to affect survival in some malignant tumors, including breast and esophageal cancer, but its impact on endometrial cancer has not been extensively studied. For this study, 211 endometrial endometrioid adenocarcinoma samples were obtained from patients surgically treated at the Oulu University Hospital. The samples were immunohistochemically stained and analyzed for cyclin B expression. The relationships between cyclin B expression and conventional prognostic factors were analyzed. A discrimination threshold for survival analyses was calculated by utilizing the receiver operator characteristic (ROC) method. Cyclin B expression correlated with grade and advanced stage. Survival analyses showed that cyclin B expression affects cancer-specific survival in univariate analysis. In multivariate analysis, the results were indicative that cyclin B may hold independent prognostic significance, but further studies are required to assess this.

High expression of cyclin A is associated with poor prognosis in endometrial endometrioid adenocarcinoma.

Cyclins are a group of proteins that act as activators to cyclin-dependent kinases and are required for normal cell cycle transitions. Cyclin A is involved in the transitions between G1 to S and G2 to M. Its deregulation has been linked to a number of neoplasms, including endometrial cancer. The prognostic significance of cyclin A expression seems to be cancer-specific, and current knowledge on its impact on survival of endometrial cancer is limited. This study aimed to investigate the effect of cyclin A expression on cancer-specific survival and its correlation with conventional prognostic factors in endometrioid adenocarcinoma. Biopsies obtained from 211 patients were immunohistochemically stained for cyclin A and differences in expression analyzed at the Oulu University Hospital. Patients were divided into two groups utilizing the ROC curve. Further survival analyses were carried out between these two groups. In this study, we show that cyclin A expression correlates with tumor grade and FIGO stage. We also show that cyclin A is an independent prognostic factor in endometrioid adenocarcinoma. Whether cyclin A plays a role in tumorigenesis or merely is a marker of increased proliferation requires further studies.

An audit of short- and long-term outcomes after laparoscopic removal of common bile duct stones in Finland.

BACKGROUND AND AIM: To audit short- and long-term outcomes after laparoscopic common bile duct exploration (LCBDE) and factors influencing the success of the laparoscopic treatment. METHODS: 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. RESULTS: 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 < 0.001] and transcholedochal approach [OR 2.98 (1.37-4.47), p = 0.006]. Laparoscopic stone clearance also failed in all 11 patients having impacted stones at the ampulla of Vater. Cumulative long-term recurrence rate was 3.6% at 5 years and 6.0 % at 10 years. Thirty-day mortality was 0.3% and morbidity 12.2%. Postoperative hospital stay was median 2 (IQR 1-3) days after transcystic CBD removal and 4 (IQR 3-7) days after transcholedochal CBD removal, p < 0.001. CONCLUSION: Our results show that one-stage LC combined with LCBDE stone clearance is safe and effective in most patients thus reducing the number of additional, potentially dangerous endoscopic procedures. Moreover, large or impacted stones are a risk factor for failed stone clearance.

Three-Year Outcomes of Oral Antibiotics vs Intravenous and Oral Antibiotics for Uncomplicated Acute Appendicitis: A Secondary Analysis of the APPAC II Randomized Clinical Trial.

Importance: Current short-term evidence has shown that uncomplicated acute appendicitis can be treated successfully with oral antibiotics alone, but longer-term results are lacking. Objective: To assess the treatment effectiveness of oral antibiotic monotherapy compared with combined intravenous (IV) and oral antibiotics in computed tomography-confirmed uncomplicated acute appendicitis at a longer-term follow-up. Design, Setting, and Participants: This secondary analysis of a predefined year 3 follow-up of the Appendicitis Acuta II (APPAC II) noninferiority, multicenter randomized clinical trial compared oral moxifloxacin with combined IV ertapenem plus oral levofloxacin and metronidazole for the treatment of uncomplicated acute appendicitis. The trial was conducted at 9 university and central hospitals in Finland from April 2017 to November 2018, with the last follow-up in November 2022. Participants included patients aged 18 to 60 years, who were randomized to receive either oral antibiotics monotherapy (n = 301) or combined IV and oral antibiotics (n = 298). Interventions: Antibiotics monotherapy consisted of oral moxifloxacin, 400 mg/d, for 7 days. Combined IV and oral antibiotics consisted of IV ertapenem sodium, 1 g/d, for 2 days plus oral levofloxacin, 500 mg/d, and metronidazole, 500 mg 3 times/d, for 5 days. Main Outcomes and Measures: The primary end point was treatment success, defined as the resolution of acute appendicitis and discharge from hospital without the need for surgical intervention and no appendicitis recurrence at the year 3 follow-up evaluated using a noninferiority design. The secondary end points included late (after 1 year) appendicitis recurrence as well as treatment-related adverse events, quality of life, length of hospital stay, and length of sick leave, which were evaluated using a superiority design. Results: After exclusions, 599 patients (mean [SD] age, 36 [12] years; 336 males [56.1%]) were randomized; after withdrawal and loss to follow-up, 582 patients (99.8%) were available for the year 3 follow-up. The treatment success at year 3 was 63.4% (1-sided 95% CI, 58.8% to ∞) in the oral antibiotic monotherapy group and 65.2% (1-sided 95% CI, 60.5% to ∞) in the combined IV and oral antibiotics group. The difference in treatment success rate between the groups at year 3 was -1.8 percentage points (1-sided 95% CI, -8.3 percentage points to ∞; P = .14 for noninferiority), with the CI limit exceeding the noninferiority margin. There were no significant differences between groups in treatment-related adverse events, quality of life, length of hospital stay, or length of sick leave. Conclusions and Relevance: This secondary analysis of the APPAC II trial found a slightly higher appendectomy rate in patients who received oral antibiotic monotherapy; however, noninferiority of oral antibiotic monotherapy compared with combined IV and oral antibiotics could not be demonstrated. The results encourage future studies to assess oral antibiotic monotherapy as a viable treatment alternative for uncomplicated acute appendicitis. Trial Registration: ClinicalTrials.gov Identifier: NCT03236961.

Circulating matrix metalloproteinase MMP-9 and MMP-2/TIMP-2 complex are associated with spontaneous early pregnancy failure.

BACKGROUND: Trophoblast cell (CTB) invasion into the maternal endometrium plays a crucial role during human embryo implantation and placentation. This invasion is facilitated by the activity of matrix metalloproteinases, which are regulated by tissue inhibitors of MMPs (TIMPs). METHODS: This study compares the serum levels of MMP-9, MMP-2/TIMP-2 complex, TIMP-1 and TIMP-2 in 129 patients with ongoing pregnancy (n = 40) or spontaneous early pregnancy failure (n = 89). RESULTS: MMP-9 was markedly (p < 0.0001) elevated in missed abortions, as was MMP-2/TIMP-2 complex (p < 0.0005). However, the serum levels of TIMP-1 and TIMP-2 were markedly elevated (p < 0.0001) in ongoing pregnancies. CONCLUSIONS: Human placentation is mediated by fetal trophoblastic cells that invade the maternal uterine endometrium. Trophoblast invasion requires a precisely regulated secretion of specific proteolytic enzymes able to degrade the endometrial basement membrane and extracellular matrix. The elevated levels of MMP-9 and MMP-2/TIMP-2 complex may play a role in spontaneous termination of pregnancy.

Preoperative MRCP Can Rule Out Choledocholithiasis in Acute Cholecystitis with a High Negative Predictive Value: Prospective Cohort Study with Intraoperative Cholangiography.

BACKGROUND: Magnetic resonance cholangiopancreatography (MRCP) provides a noninvasive and fast modality for imaging the biliary tree when choledocholithiasis is suspected. Guidelines suggest that MRCP is recommended when strong or moderate signs of common bile duct (CBD) stones are present. Well-performed prospective studies are scarce regarding the sensitivity and specificity of preoperative MRCP in patients with acute cholecystitis in comparison with intraoperative cholangiography, ERCP, or choledochoscopy. METHODS: We performed a prospective, observational population-based feasibility study in Central Finland Hospital Nova between January 2019 and December 2019. We examined the diagnostic performance of preoperative MRCP on consecutive patients with acute cholecystitis scheduled for index admission cholecystectomy. The accuracy of MRCP was verified with IOC, choledochoscopy, or ERCP. The interobserver reliability of the image quality of MRCP and the sensitivity and specificity of choledocholithiasis were observed independently by three experienced radiologists. RESULTS: A total of 180 consecutive patients diagnosed with acute cholecystitis followed by index admission cholecystectomy were identified. MRCP was performed in 113/180 (62.8%) patients, and complementary perioperative imaging of the bile ducts was performed in 72/113 (63.7%) patients. The incidence of choledocholithiasis was high (29.2%). In acute cholecystitis, the sensitivity (76.2-85.7%) and specificity (84.3-92.2%) of MRCP were equally compared to the literature with unselected patient groups. The best visibility was observed in the common hepatic duct, the inferior CBD, and the central hepatic duct. The interobserver reliability was excellent for determining the size and quantity of CBD stones. CONCLUSION: In acute cholecystitis, MRCP yields high negative predictive value regarding detection of choledocholithiasis. If CBD stones were discovered, the interobserver reliability was excellent when measuring the size and number of CBD stones. The best-visualized area was the distal part of the biliary tract, which provides good preoperative workup if choledocholithiasis is present.

Routine preoperative MRCP in screening choledocholithiasis in acute cholecystitis compared to selective approach: a population-based study.

Choledocholithiasis is more common in acute cholecystitis than in elective situations. Preoperative diagnosis of choledocholithiasis is essential to facilitate adequate planning of CBD (common bile duct) stone removal, preferably performed as a single-stage procedure. The purpose of this study was to test the feasibility of routine preoperative magnetic resonance cholangiopancreatography (MRCP) in acute cholecystitis followed by consequent cholecystectomy. A total of 180 consecutive patients operated for acute cholecystitis between January 2019 and December 2019 were prospectively enrolled. Preoperative routine MRCP was performed for bile duct evaluation when feasible. The control cohort consisted of 180 consecutive patients undergoing emergency laparoscopic cholecystectomy before the study period. Intraoperative cholangiography was used routinely in both groups when technically achievable. We examined the proportion of patients recruited in preoperative MRCP, possible time delay to MRCP and surgery, and the incidence of CBD stones compared to the control cohort. Routine MRCP in acute cholecystitis was achieved in 114/180 (63%) patients compared to 42/180 (23.3%) patients of the control group. The triage time from emergency to MRCP and the operating theatre was similar in both cohorts. The percentage of patients diagnosed with choledocholithiasis in the study group was notably higher (almost 18% vs 11%), p < 0.05. After a median follow-up time of 2.5 years in the study group and almost 4 years in the control group, recurrent choledocholithiasis was not detected in either group. Routine MRCP in patients with acute cholecystitis can be implemented with a fair execution rate in a population-based setting with minor effects on hospital stay and delays but higher detection of choledocholithiasis. We observed no additional benefit compared to the selective use of MRCP. However, routine preoperative MRCP allows an advantage when considering the appropriate exploration method if choledocholithiasis is detected.