A Hepatocellular Cancer Patient-derived Organoid Xenograft Model to Investigate Impact of Liver Regeneration on Tumor Growth.

Recurrence poses a notable challenge after hepatocellular carcinoma (HCC) treatment, impacting more than 70% of patients who undergo surgical resection. Recurrence stems from undetected micro-metastasis or de novo cancer, potentially triggered by postsurgical liver regeneration. Prior research employed HCC cell lines in orthotopic models to study the impact of liver regeneration, but their limited validity prompted the need for a more representative model. Here, we introduce a novel approach utilizing patient-derived HCC organoids to investigate the influence of liver regeneration on HCC. Patient tumor tissues are processed to create tumor organoids, embedded in a three-dimensional basement membrane matrix, and cultured in a liver-specific medium. One million organoids are injected into the right superior lobe (RSL) of immunodeficient mice, confirming macroscopic tumor growth through sonography. The intervention group undergoes resection of the left lateral lobe (LLL) (30% of total liver volume) or additionally, the middle lobe (ML) (65% of total liver volume) to induce liver regeneration within the tumor site. The control group experiences re-laparotomy without liver tissue resection. After 2 weeks, both groups undergo tumor and normal tissue explantation. In conclusion, this patient-derived HCC organoid model offers a robust platform to investigate the impact of liver regeneration post-cancer resection. Its multi-cellular composition, genetic diversity, and prolonged culture capabilities make it an invaluable tool for studying HCC recurrence mechanisms and potential interventions.

Omission of perioperative morphine reduces postoperative pain in proctological interventions: a single-center analysis.

There is an increase in outpatient procedures and this trend will continue in the future. For hemorrhoidectomy, it is the standard of treatment in many health care systems. Perioperative management including adequate pain control is of paramount importance to ensure successful ambulatory surgery. This study investigates the role and effect of morphine compared to short-acting opiates applied before, during, or after proctological interventions and with focus on hemorrhoidectomy. A retrospective analysis of a prospective database was conducted comparing two populations. The control cohort received morphine (Yes-Mô) intra- and postoperatively, while the intervention group did not receive morphine (No-Mô) between January 2018 and January 2020. Both cohorts were balanced by propensity score matching. The outcomes were postoperative pain measured by numeric ratings scale (NRS) one hour postoperatively, pain 24 h postoperatively, success rate of outpatient management, and complication rate including postoperative nausea and vomiting as well as urinary retention. The intervention population comprised 54 patients and the control group contained 79 patients. One hour after surgery, patients in No-Mô reported lower NRS (1.44 ± 1.41) compared to Yes-Mô (2.48 ± 2.30) (p = 0.029). However, there was no difference in NRS 24 h postoperatively (No-Mô: 1.61 ± 1.41 vs Yes-Mô: 1.63 ± 1.72; p = 0.738). 100% of No-Mô was managed as outpatients while only 50% of Yes-Mô was dismissed on the day of the operation (p = < 0.001). There was no difference in postoperative complications (including postoperative nausea and vomiting (PONV) and urinary retention) between the two groups (PONV No-Mô 7.4% vs Yes-Mô 5.6%, p = 1.0 and urinary retention No-Mô 3.7% vs Yes-Mô 7.4%, p = 0.679). No-Mô received an oral morphine equivalent of 227.25 ± 140.35 mg intraoperatively and 11.02 ± 18.02 mg postoperatively. Yes-Mô received 263.17 ± 153.60 mg intraoperatively and 15.97 ± 14.17 mg postoperatively. The difference in received morphine equivalent between the groups was not significant after matching for the intraoperative (p = 0.212) and postoperative (p = 0.119) received equivalent. Omission of perioperative morphine is a viable but yet not understood method for reducing postoperative pain. Omission of morphine leads to a lower use of total morphine equivalent to attain satisfactory analgesia. The reduction of the overall opiate load and using opiates with a very short half-life potentially leads to a reduction of side effects like sedation. This in turn promotes discharge of the patient on the day of surgery. Omission of morphine is safe and does not increase postoperative complications.

Surgical outcomes in elective sigmoid resection for diverticulitis stratified according to indication: a propensity-score matched cohort study with 903 patients.

OBJECTIVE: Weighing the perioperative risk of elective sigmoidectomy is done regardless of the specific diverticulitis classification. The aim of this study is to evaluate surgical outcomes according to the classification grade and the indication. METHODS: All patients who underwent elective colonic resection for diverticulitis during the ten-year study period were included. They were divided into two groups: relative surgery indication (RSI) and absolute surgery indication (ASI). RSI included microabscess and recurrent uncomplicated disease. ASI included macroabscess and recurrent complicated disease. Propensity score-matching (PSM, 1:1) was performed. RESULTS: 585 patients fulfilled criteria for RSI and 318 patients fulfilled criteria for ASI. In the univariate analysis, RSI patients were younger (62 vs. 67.7 years, p < 0.001), had a higher physical status (ASA score 1 or 2 in 80.7% vs. 60.8%, p < 0.001), were less immunosuppressed (3.4% vs. 6.9%, p = 0.021) and suffered less often from coronary heart disease (3.8% vs. 7.2%, p = 0.025). After PSM, 318 RSI vs. 318 ASI patients were selected; baseline characteristics results were comparable. The proportion of planned laparoscopic resection was 93% in RSI versus 75% in ASI (p < 0.001), and the conversion rate to open surgery for laparoscopic resection was 5.0% and 13.8% in RSI versus ASI, respectively (p < 0.001). Major morbidity (Clavien/Dindo ≥ IIIb) occurred less frequently in RSI (3.77% vs. 10%, p = 0.003). A defunctioning stoma was formed in 0.9% and 11.0% in RSI vs ASI, respectively (p < 0.001). CONCLUSION: The lower risk for postoperative morbidity, the higher chance for a laparoscopic resection and the decreased rate of stoma formation are attributed to patients with recurrent uncomplicated diverticulitis or diverticulitis including a microabscess as compared to patients with complicated diverticulitis or diverticulitis and a macroabscess, and this applies even after PSM.

Incidence of Liver Resection Following the Introduction of Caseload Requirements for Liver Surgery in Switzerland.

BACKGROUND: Centralization of care is an established concept in complex visceral surgery. Switzerland introduced case load requirements (CR) in 2013 in five areas of cancer surgery. The current study investigates the effects of CR on indication and mortality in liver surgery. METHODS: This is a retrospective analysis of a complete national in-hospital data set including all admissions between January 1, 2005, and December 31, 2015. Primary outcome variables were the incidence proportion and the 60-day in-hospital mortality of liver resections. Incidence proportion was calculated as the overall yearly number of liver resections performed in relation to the population living in Switzerland before and after the introduction of CR. RESULTS: Our analysis shows an increase number of liver resections compared to the period before introduction of CR from 2005-2012 (4.67 resections/100,000) to 2013-2015 (5.32 resections/100,000) after CR introduction. Age-adjusted incidence proportion increased by 14% (OR 1.14 95 CI [1.07-1.22]). National in-hospital mortality remained stable before and after CR (4.1 vs 3.7%), but increased in high-volume institutions (3.6 vs 5.6%). The number of hospitals performing liver resections decreased after the introduction of CR from 86 to 43. Half of the resections were performed in institutions reaching the stipulated numbers (53% before vs 49% after introduction of CR). After implementation of CR, patients undergoing liver surgery had more comorbidities (88 vs 92%). CONCLUSION: The introduction of CR for liver surgery in Switzerland in 2013 was accompanied by an increase in operative volume with limited effects on centralization of care.

Persistent acute cholecystitis after cholecystostomy - increased mortality due to treatment approach?

BACKGROUND: Percutaneous cholecystostomy (PC) is a treatment option for acute cholecystitis (AC) in cases where cholecystectomy (CCY) is not feasible due to limited health conditions. The use of PC remains questionable. The aim was to retrospectively analyse the outcome of patients after PC. METHODS: All patients who underwent PC for AC at a tertiary referral hospital over 10 years were included. Descriptive statistics, analysed mortality with and without CCY after PC, and a multivariable logistic regression for potential confounder and a landmark sensitivity analysis for immortal time bias were used. RESULTS: Of 158 patients, 79 were treated with PC alone and 79 had PC with subsequent CCY. Without CCY, 48% (38 patients) died compared to 9% with CCY. In the multivariable analysis CCY was associated with 85% lower risk of mortality. The landmark analysis was compatible with the main analyses. Direct PC-complications occurred in 17% patients. Histologically, 22/75 (29%) specimens showed chronic cholecystitis, and 76% AC. CONCLUSION: Due to the high mortality rate of PC alone, performing up-front CCY is proposed. PC represents no definitive treatment for AC and should remain a short-term solution because of the persistent inflammatory focus. According to these findings, almost all specimens showed persistent inflammation.

Influence of the introduction of caseload requirements on indication for visceral cancer surgery in Switzerland.

BACKGROUND: In 2013 Swiss health authorities implemented annual hospital caseload requirements (CR) for five areas of visceral surgery. We assess the impact of the implementation of CR on indication for surgery in esophageal, pancreatic and rectal cancer. MATERIALS AND METHODS: Retrospective analysis of national registry data of all inpatient admissions between January 1st, 2005 and December 31st, 2015. Primary end-point was the age-adjusted resection rate for esophageal, pancreatic and rectal cancer among patients with at least one cancer-specific hospitalization per year. We calculated age-adjusted rate ratios for period effects before and after implementation of CR and odds ratios (OR) based on a generalized estimation equation. A relative increase of 5% in age-adjusted relative risk was set a priori as relevant from a health policy perspective. RESULTS: Age-adjusted resection rates before and after the implementation of CR were 0.12 and 0.13 (Relative Risk [RR] 1.08; 95%-Confidence Interval [CI] 0.85-1.36) in esophageal cancer, 0.22 and 0.26 (RR 1.17; 95%-CI 0.85-1.58) in pancreatic cancer and 0.38 and 0.43 (RR 1.14; 95%-CI 0.99-1.30) in rectal cancer. In adjusted models OR for resection after the implementation of CR were 1.40 (95%-CI 1.24-1.58) in esophageal cancer, 1.05 (95%-CI 0.96-1.15) in pancreatic cancer and 0.92 (95%-CI 0.87-0.97) in rectal cancer. CONCLUSION: Implementation of CR was associated with an increase of resection rates above the a priori set margins in all resections groups. In adjusted models, odds for resection were significantly higher for esophageal cancer, while they remained unchanged for pancreatic and decreased for rectal cancer.

Risk of Emergency Surgery or Death After Initial Nonoperative Management of Complicated Diverticulitis in Scotland and Switzerland.

Importance: National guidelines on interval resection for prevention of recurrence after complicated diverticulitis are inconsistent. Although US and German guidelines favor interval colonic resection to prevent a perceived high risk of recurrence, UK guidelines do not. Objectives: To investigate patient management and outcomes after an index inpatient episode of nonoperatively managed complicated diverticulitis in Switzerland and Scotland and determine whether interval resection was associated with the rate of disease-specific emergency surgery or death in either country. Design, Setting, and Participants: This secondary analysis of anonymized complete national inpatient data sets included all patients with an inpatient episode of successfully nonoperatively managed complicated diverticulitis in Switzerland and Scotland from January 1, 2005, to December 31, 2015. The 2 countries have contrasting health care systems: Switzerland is insurance funded, while Scotland is state funded. Statistical analysis was conducted from February 1, 2018, to October 17, 2019. Main Outcomes and Measures: The primary end point defined a priori before the analysis was adverse outcome, defined as any disease-specific emergency surgical intervention or inpatient death after the initial successful nonsurgical inpatient management of an episode of complicated diverticulitis, including complications from interval elective surgery. Results: The study cohort comprised 13 861 inpatients in Switzerland (6967 women) and 5129 inpatients in Scotland (2804 women) with an index episode of complicated acute diverticulitis managed nonoperatively. The primary end point was observed in 698 Swiss patients (5.0%) and 255 Scottish patients (5.0%) (odds ratio, 0.98; 95% CI, 0.81-1.19). Elective interval colonic resection was undertaken in 3280 Swiss patients (23.7%; median follow-up, 53 months [interquartile range, 24-90 months]) and 231 Scottish patients (4.5%; median follow-up, 57 months [interquartile range, 27-91 months]). Death after urgent readmission for recurrent diverticulitis occurred in 104 patients (0.8%) in Switzerland and 65 patients (1.3%) in Scotland. None of the investigated confounders had a significant association with the outcome apart from comorbidity. Conclusions and Relevance: This study found no difference in the rate of adverse outcome (emergency surgery and/or inpatient death) despite a 5-fold difference in interval resection rates.

Tumor Infiltration by OX40+ Cells Enhances the Prognostic Significance of CD16+ Cell Infiltration in Colorectal Cancer.

OBJECTIVES: Analysis of tumor immune infiltration has been suggested to outperform tumor, node, metastasis staging in predicting clinical course of colorectal cancer (CRC). Infiltration by cells expressing OX40, a member of the tumor necrosis factor receptor family, or CD16, expressed by natural killer cells, monocytes, and dendritic cells, has been associated with favorable prognosis in patients with CRC. We hypothesized that assessment of CRC infiltration by both OX40+ and CD16+ cells might result in enhanced prognostic significance. METHODS: Colorectal cancer infiltration by OX40 and CD16 expressing cells was investigated in 441 primary CRCs using tissue microarrays and specific antibodies, by immunohistochemistry. Patients' survival was evaluated by Kaplan-Meier and log-rank tests. Multivariate Cox regression analysis, hazard ratios, and 95% confidence intervals were also used to evaluate prognostic significance of OX40+ and CD16+ cell infiltration. RESULTS: Colorectal cancer infiltration by OX40+ and CD16+ cells was subclassified into 4 groups with high or low infiltration levels in all possible combinations. High levels of infiltration by both OX40+ and CD16+ cells were associated with lower pT stage, absence of peritumoral lymphocytic (PTL) inflammation, and a positive prognostic impact. Patients bearing tumors with high infiltration by CD16+ and OX40+ cells were also characterized by significantly longer overall survival, as compared with the other groups. These results were confirmed by analyzing an independent validation cohort. CONCLUSIONS: Combined infiltration by OX40+ and CD16+ immune cells is an independent favorable prognostic marker in CRC. The prognostic value of CD16+ immune cell infiltration is significantly improved by the combined analysis with OX40+ cell infiltration.