Retrospective comparison of outcomes of patients undergoing omental patch versus falciform patch repair of perforated peptic ulcers.

BACKGROUND: The omental patch repair is the gold standard for the repair of perforated peptic ulcers. This can be performed open or laparoscopically. However, in the event of non-viable or inadequate omentum available at the time of surgery the falciform ligament has been reportedly used to as an alternative. Nonetheless, evidence for its safety is scant. This study aims to determine differences in patient outcomes when comparing the two repair techniques. METHODS: Following ethics approval, patients who underwent surgical repair of perforated peptic ulcers using omental or falciform patch repair, between 1 January 2010 and 31 December 2017, across all three Western Australian tertiary hospital services and at least 18 years of age were included. Data were collected by reviewing medical records of included patients. RESULTS: Three hundred twenty-nine patients who underwent either open or laparoscopic repairs were included. Thirty-seven patients had falciform repairs and were mostly ASA of 2 compared to 292 patients receiving omental patch repair who were mostly ASA 3. Falciform patch repairs were more commonly used in duodenal ulcer perforations. There were no statistically significant differences in patient outcomes between the omental patch and falciform ligament groups. This included post-operative intra-abdominal sepsis, return to theatre, post-operative ICU admission, inpatient mortality, 30-day readmission and ulcer healing on follow-up gastroscopy. CONCLUSIONS: This study demonstrates safety, efficacy and similar outcomes for patients receiving the falciform ligament patch repair compared with omental patch repair.

Human Mesenchymal Stem Cell (hMSC) Donor Potency Selection for the "First in Cystic Fibrosis" Phase I Clinical Trial (CEASE-CF).

Human Mesenchymal Stem Cell (hMSC) immunotherapy has been shown to provide both anti-inflammatory and anti-microbial effectiveness in a variety of diseases. The clinical potency of hMSCs is based upon an initial direct hMSC effect on the pro-inflammatory and anti-microbial pathophysiology as well as sustained potency through orchestrating the host immunity to optimize the resolution of infection and tissue damage. Cystic fibrosis (CF) patients suffer from a lung disease characterized by excessive inflammation and chronic infection as well as a variety of other systemic anomalies associated with the consequences of abnormal cystic fibrosis transmembrane conductance regulator (CFTR) function. The application of hMSC immunotherapy to the CF clinical armamentarium is important even in the era of modulators when patients with an established disease still need anti-inflammatory and anti-microbial therapies. Additionally, people with CF mutations not addressed by current modulator resources need anti-inflammation and anti-infection management. Furthermore, hMSCs possess dynamic therapeutic properties, but the potency of their products is highly variable with respect to their anti-inflammatory and anti-microbial effects. Due to the variability of hMSC products, we utilized standardized in vitro and in vivo models to select hMSC donor preparations with the greatest potential for clinical efficacy. The models that were used recapitulate many of the pathophysiologic outcomes associated with CF. We applied this strategy in pursuit of identifying the optimal donor to utilize for the "First in CF" Phase I clinical trial of hMSCs as an immunotherapy and anti-microbial therapy for people with cystic fibrosis. The hMSCs screened in this study demonstrated significant diversity in antimicrobial and anti-inflammatory function using models which mimic some aspects of CF infection and inflammation. However, the variability in activity between in vitro potency and in vivo effectiveness continues to be refined. Future studies require and in-depth pursuit of hMSC molecular signatures that ultimately predict the capacity of hMSCs to function in the clinical setting.

Mesh versus non-mesh repair of groin hernias: a rapid review.

BACKGROUND: Mesh is frequently utilized intraoperatively for the repair of groin hernias. However, patients may request non-mesh hernia repairs owing to adverse events reported in other mesh procedures. To inform surgical safety, this study aimed to compare postoperative complications between mesh and non-mesh groin hernia repairs and identify other operative and patient-related risk factors associated with poor postoperative outcomes. METHODS: Ovid MEDLINE and grey literature were searched to 9 June 2021 for studies comparing mesh to non-mesh techniques for primary groin hernia repair. Outcomes of interest were postoperative complications, recurrence of hernia, pain and risk factors associated with poorer surgical outcomes. Methodological quality was appraised using the AMSTAR 2 tool. RESULTS: The systematic search returned 4268 results, which included seven systematic reviews and five registry analyses. Mesh repair techniques resulted in lower hernia recurrence rates, with no difference in chronic pain, seroma, haematoma or wound infection, compared to non-mesh techniques. Risk factors associated with increased risk of hernia recurrence were increased body mass index (BMI), positive smoking status and direct hernia. These were independent of surgical technique. Patients under 40 years of age were at increased risk of postoperative pain. CONCLUSIONS: Surgical repair of primary groin hernias using mesh achieves lower recurrence rates, with no difference in safety outcomes, compared with non-mesh repairs. Additional risk factors associated with increased recurrence include increased BMI, history of smoking and hernia subtype.

Enhancing Cystic Fibrosis Immune Regulation.

In cystic fibrosis (CF), sustained infection and exuberant inflammation results in debilitating and often fatal lung disease. Advancement in CF therapeutics has provided successful treatment regimens for a variety of clinical consequences in CF; however effective means to treat the pulmonary infection and inflammation continues to be problematic. Even with the successful development of small molecule cystic fibrosis transmembrane conductance regulator (CFTR) correctors and potentiators, there is only a modest effect on established infection and inflammation in CF patients. In the pursuit of therapeutics to treat inflammation, the conundrum to address is how to overcome the inflammatory response without jeopardizing the required immunity to manage pathogens and prevent infection. The key therapeutic would have the capacity to dull the inflammatory response, while sustaining the ability to manage infections. Advances in cell-based therapy have opened up the avenue for dynamic and versatile immune interventions that may support this requirement. Cell based therapy has the capacity to augment the patient's own ability to manage their inflammatory status while at the same time sustaining anti-pathogen immunity. The studies highlighted in this manuscript outline the potential use of cell-based therapy for CF. The data demonstrate that 1) total bone marrow aspirates containing Cftr sufficient hematopoietic and mesenchymal stem cells (hMSCs) provide Cftr deficient mice >50% improvement in survival and improved management of infection and inflammation; 2) myeloid cells can provide sufficient Cftr to provide pre-clinical anti-inflammatory and antimicrobial benefit; 3) hMSCs provide significant improvement in survival and management of infection and inflammation in CF; 4) the combined interaction between macrophages and hMSCs can potentially enhance anti-inflammatory and antimicrobial support through manipulating PPARγ. These data support the development of optimized cell-based therapeutics to enhance CF patient's own immune repertoire and capacity to maintain the balance between inflammation and pathogen management.

Donor-defined mesenchymal stem cell antimicrobial potency against nontuberculous mycobacterium.

Chronic nontuberculous mycobacterial infections with Mycobacterium avium and Mycobacterium intracellulare complicate bronchiectasis, chronic obstructive airway disease, and the health of aging individuals. These insidious intracellular pathogens cause considerable morbidity and eventual mortality in individuals colonized with these bacteria. Current treatment regimens with antibiotic macrolides are both toxic and often inefficient at providing infection resolution. In this article, we demonstrate that human marrow-derived mesenchymal stem cells are antimicrobial and anti-inflammatory in vitro and in the context of an in vivo sustained infection of either M. avium and/or M. intracellulare.

The outcome of patients on the cholecystectomy waiting list in Western Australia 1999-2005.

BACKGROUND: Surgeons are noticing increasing numbers of cholecystectomy waiting list patients presenting with complications of their gallstones. In this study, we analysed the outcome of these to ascertain natural history and outcome. METHODS: Data for 5298 waiting list patients in Western Australia, from 1999 to 2006, were analysed. Negative binomial regression was used to analyse waiting times data with Waitlist Year, Urgency Category and Aboriginality, after adjusting for Gender, Location and Age at Cholecystectomy. RESULTS: The overall median waiting time for surgery was 40 days (interquartile range (IQR) = 15-103). The median waiting times for Urgent, Semi-Urgent, and Routine categories were 21 (IQR = 8-63), 44 (IQR = 20-97) and 50 (IQR = 17-131) days, respectively. While waiting for surgery, 240 (5%) patients had gallstone-related admissions. Eighty (33.3%) patients had previous gallstone-related admissions prior to their enrolment on the waiting list. Analysis of the crude odds ratio showed that the probability of readmission during wait for surgery was three times more, when the surgery was not performed within the recommended time. Aboriginal and Torres Strait Islanders wait 1.77 times longer than non aboriginals (P < 0.001) and waiting time decreased with more recent calendar years. (P= 0.001) Patients in the metropolitan hospitals waited twice as long compared with the regional hospitals (P < 0.001). CONCLUSION: Approximately 5% of patients on the waiting list for an elective cholecystectomy were readmitted to the hospital for gallstone-related problems. Proper categorization of patients and definitive surgical treatment of acute gallbladder disease at index presentation might decrease this readmission rate. More effort needs to be made to ensure equity of access for gallstone patients.

Five-year follow-up of a multicenter, double-blind randomized clinical trial of laparoscopic Nissen vs anterior 90 degrees partial fundoplication.

HYPOTHESIS: Laparoscopic 90 degrees anterior partial fundoplication for gastroesophageal reflux disease achieves equivalent results to laparoscopic Nissen fundoplication. DESIGN: A multicenter, prospective, double-blind randomized clinical trial with a minimum of 5 years' follow-up. SETTING: Nine university teaching hospitals in 6 major cities throughout Australia and New Zealand. PARTICIPANTS: One hundred twelve patients undergoing primary antireflux surgery were randomized to undergo either laparoscopic Nissen fundoplication (52 patients) or anterior 90 degrees partial fundoplication (60 patients). INTERVENTIONS: Laparoscopic Nissen fundoplication with division of the short gastric vessels or laparoscopic anterior 90 degrees partial fundoplication. MAIN OUTCOME MEASURES: Blinded assessment at 1 and 5 years' follow-up of clinical outcome for postoperative heartburn, dysphagia, gas-related symptoms, and satisfaction with the surgical outcome. Analog scales ranging from 0 to 10 were used to assess symptom severity. RESULTS: Ninety-seven patients underwent follow-up at 5 years. Three others died during follow-up, 4 refused follow-up, and 8 were lost to follow-up; 89% remained at 5-years' follow-up. At 5 years' follow-up, mean analog scores for heartburn were 2.2 for anterior fundoplication vs 0.9 for Nissen fundoplication (P=.003). There were no significant differences between the groups for dysphagia scores. The mean score for outcome satisfaction was 7.1 after anterior fundoplication vs 8.1 after Nissen fundoplication (P=.18). Eighty-eight percent reported a good or excellent outcome following Nissen fundoplication vs 77% following anterior fundoplication. CONCLUSIONS: Laparoscopic Nissen and anterior 90 degrees partial fundoplication achieve similar levels of patient satisfaction at 5 years' follow-up, with similar adverse effect profiles. However, at 5 years' follow-up, laparoscopic Nissen fundoplication achieves superior control of reflux symptoms. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Register Identifier: ACTRN12607000298415.

Incidence of bariatric surgery and postoperative outcomes: a population-based analysis in Western Australia.

OBJECTIVE: To investigate the incidence of bariatric surgery and postoperative outcomes in a population-based cohort of patients in Western Australia over a 17-year period. DESIGN AND SETTING: A population-based incidence study of all bariatric procedures (n=1403) performed in WA hospitals over the period 1988-2004, based on hospital morbidity and death data from the WA Data Linkage System. MAIN OUTCOME MEASURES: Changes in incidence of bariatric procedures over time; mortality and complications within 30 days after surgery; survival rates after surgery relative to age-, sex-, and period-matched survival rates in the general population; factors predictive of re-admission to hospital. RESULTS: The incidence of bariatric surgery increased from 1.2 procedures per 100,000 person-years in 1988 to 24.2 procedures per 100,000 person-years in 2004. Although some of this was ascribed to a rising prevalence of obesity generally, there was a 13-fold increase in the bariatric procedure rate within the obese population itself. At 5 years, the relative survival rate in bariatric patients was the same as the survival rate in the general population. Within the 30-day postoperative period, mortality was low (0.07%) and 9.6% of patients experienced complications. Those who had bypass-type procedures were more likely to be re-admitted within 30 days than those who had gastric reduction procedures (adjusted hazard ratio, 5.80 [95% CI, 3.42-9.84]). CONCLUSION: The use of bariatric surgery increased 20-fold over the study period. Relative survival after surgery was in line with population norms. The observed low mortality rates and moderate level of complications are similar to findings in other studies in which the proportion of reduction procedures has been high.

Quality of life following laparoscopic anterior 90 degrees versus Nissen fundoplication: results from a multicenter randomized trial.

BACKGROUND: The short-term clinical outcomes from a multicenter prospective randomized trial of laparoscopic Nissen versus anterior 90 degrees partial fundoplication have been reported previously. These demonstrated a high level of satisfaction with the overall outcome following anterior 90 degrees fundoplication. However, the results of postoperative objective tests and specific clinical symptoms are not always consistent with an individual patient's functional status and general well being following surgery, and quality of life (QOL) is also an important outcome to consider following surgery for reflux. Hence, QOL information was collected in this trial to investigate the hypothesis: improvements in QOL following laparoscopic antireflux surgery are greater after anterior 90 degrees partial fundoplication than after Nissen fundoplication. METHODS: Patients undergoing a laparoscopic fundoplication for gastro-esophageal reflux at one of nine university teaching hospitals in six major cities in Australia and New Zealand were randomized to undergo either laparoscopic Nissen or anterior 90 degrees partial fundoplication. Quality of life before and after surgery was assessed using validated questionnaires - the Short Form 36 general health questionnaire (SF36) and an Illness Behavior Questionnaire (IBQ). Patients were asked to complete these questionnaires preoperatively and at 3, 6, 12 and 24 months postoperatively. RESULTS: One hundred and twelve patients were randomized to undergo a Nissen fundoplication (52) or a 90 degrees anterior fundoplication (60). Patients who underwent anterior fundoplication reported significant improvements in eight of the nine SF36 scales compared to four of the nine following a Nissen fundoplication. The majority of these improvements occurred early in the postoperative period. With respect to the illness behavior data, there were no significant differences between the two procedures. Both groups had a significant improvement in disease conviction scores at all time points compared to their preoperative scores. CONCLUSIONS: Patients undergoing laparoscopic anterior 90 degrees partial fundoplication reported more QOL improvements in the early postoperative period than patients undergoing a Nissen fundoplication. However, the QOL outcome for both procedures was similar at later follow-up.

Multicenter, prospective, double-blind, randomized trial of laparoscopic nissen vs anterior 90 degrees partial fundoplication.

HYPOTHESIS: Laparoscopic anterior 90 degrees partial fundoplication for gastroesophageal reflux is associated with a lower incidence of postoperative dysphagia and other adverse effects compared with laparoscopic Nissen fundoplication. DESIGN: A multicenter, prospective, double-blind, randomized controlled trial. SETTING: Nine university teaching hospitals in 6 major cities in Australia and New Zealand. PARTICIPANTS: One hundred twelve patients with proven gastroesophageal reflux disease presenting for laparoscopic fundoplication were randomized to undergo either a Nissen (52 patients) or an anterior 90 degrees partial procedure (60 patients). Patients with esophageal motility disorders, patients requiring a concurrent abdominal procedure, and patients who had undergone previous antireflux surgery were excluded from this study. INTERVENTIONS: Laparoscopic Nissen fundoplication with division of the short gastric vessels or laparoscopic anterior 90 degrees partial fundoplication. MAIN OUTCOME MEASURES: Independent assessment of dysphagia, heartburn, and overall satisfaction 1, 3, and 6 months after surgery using multiple clinical grading systems. Objective measurement of esophageal manometric parameters, esophageal acid exposure, and endoscopic assessment. RESULTS: Postoperative dysphagia, and wind-related adverse effects were less common after a laparoscopic anterior 90 degrees partial fundoplication. Relief of heartburn was better following laparoscopic Nissen fundoplication. Overall satisfaction was better after anterior 90 degrees partial fundoplication. Lower esophageal sphincter pressure, acid exposure, and endoscopy findings were similar for both procedures. CONCLUSIONS: At the 6-month follow-up, laparoscopic anterior 90 degrees culine partial fundoplication is followed by fewer adverse effects than laparoscopic Nissen fundoplication with full fundal mobilization, and it achieves a higher rate of satisfaction with the overall outcome. However, this is offset to some extent by a greater likelihood of recurrent gastroesophageal reflux symptoms.

Impact of laparoscopic cholecystectomy on hospital utilization.

OBJECTIVE: The objective of the present study was to assess the impact of laparoscopic cholecystectomy (LC) and associated endoscopic retrograde pancreatography (ERCP) on hospital utilization. BACKGROUND: Laparoscopic cholecystectomy (LC) has resulted in marked reductions in average length of hospital stay; but population-based studies of hospital utilization have generally not taken into account increased cholecystectomy rates or associated increases in pre and postoperative admissions. METHODS: We conducted a population-based study of all residents of Western Australia who underwent cholecystectomy in the period 1980-2000. Record linkage was used to identify pre and postoperative admissions, and to estimate aggregate length of stay per case based on all relevant admissions. We estimated trends in cholecystectomy rates, proportions of cases with related pre and postoperative hospital admissions, average aggregate length of stay per case and total bed utilization per unit of population. RESULTS: The introduction of LC was associated with a sustained increase in rates of cholecystectomy of 25%. Similar increases occurred in the percentage of cases with related preoperative and postoperative admissions. Average length of stay for index admissions declined by nearly 60% compared with 50% for all related admissions. Per capita hospital utilization for index admissions decreased by 45% compared with 38% for index and associated admissions combined, and 32% for all admissions for biliary disease. CONCLUSIONS: Reduced hospital utilization associated with LC was partly offset by increases in pre and postoperative admissions and a sustained increase in cholecystectomy rates. Record linkage is required to assess the true impact of new technologies on hospital utilization.

Changing methods of imaging the common bile duct in the laparoscopic cholecystectomy era in Western Australia: implications for surgical practice.

OBJECTIVE: To assess changes in the use of endoscopic retrograde cholangiopancreatography (ERCP), intraoperative cholangiography (IOC), and surgical exploration of the common bile duct (CBD) associated with the introduction of laparoscopic cholecystectomy (LC). SUMMARY BACKGROUND DATA: The optimal strategy for dealing with potential stones of the CBD during LC remains controversial. METHODS: The authors conducted a population-based study of all cases of cholecystectomy (20,084) in Western Australia in the periods before, during, and after the introduction of LC (1988-1994). Index admissions were linked to previous or subsequent admissions for ERCP. Factors associated with ERCP were analyzed by multivariate regression models. RESULTS: Between 1988 and 1994, admissions for ERCP almost doubled, whereas the use of IOC decreased from 71% to 51%. Different trends were found for open and laparoscopic procedures. Exploration of the CBD declined because of the infrequent use of this procedure in LC. Preoperative ERCP was significantly more common in older patients and men; the reverse was found for IOC. There was an adjusted 3.5-fold increase in preoperative ERCP both during and after the introduction of LC. The adjusted odds ratios for IOC were 0.48 and 0.52 for these periods. CONCLUSIONS: The introduction of LC was associated with increasing reliance on ERCP to image the CBD and a decrease in the use of IOC. These changes were observed in both LC and open cholecystectomy. They suggest that the use of ERCP before cholecystectomy has partly replaced IOC for visualization of the CBD for suspected stones. Although more than 40% of patients undergoing LC had IOC, surgeons appear to be reluctant to perform surgical exploration of the CBD when stones are present. Savings in terms of both complications and cost can be expected if preoperative ERCPs performed for suspicion of uncomplicated CBD stones are replaced by IOC.