Days of symptoms and days of hospital admission before surgery do not influence the results of cholecystectomy in moderate acute calculous cholecystitis-Cholecystectomy remains the best treatment.

BACKGROUND AND AIMS: early cholecystectomy is the gold-standard treatment for acute calculous cholecystitis (ACC), although many surgeons still prefer delayed cholecystectomy for grade II to avoid surgical complications. The aim of this study was to analyze the postoperative morbidity and mortality of Tokyo Guidelines grade-II ACC as treated with cholecystectomy, taking into account the days of symptoms and days since hospital admission. MATERIALS AND METHODS: a unicenter, retrospective study was performed based on a prospective database. Patients with grade-II ACC treated with cholecystectomy were selected. Patients were analyzed according to days of symptoms (DS) and days of hospital admission (DHA) until cholecystectomy. Patients were subdivided into 3 groups: < 3 days, 3-5 days, and > 5 days. Univariate and multivariate analyses were performed for morbidity and mortality. Categorical variables were compared using the Chi-squared or Fischer's exact test. Continuous variables were compared using the Mann-Whitney U-test. The level of statistical significance was set at p < 0.05. RESULTS: a total of 998 patients with ACC diagnosis were included; 567 with grade-II ACC and 368 treated with cholecystectomy. Nearly 90 % were treated laparoscopically and 48.1 % underwent surgery the same day of emergency admission. With regard to DS and DHA, there were no statistical differences for severe postoperative complications, although a greater number of complications were detected in the > 5 DS group (p: 0.32) and > 5 DHA group (p: 0.00). Statistically significant differences were found in DS for mortality (p: 0.04). Postoperative length of stay was longer for > 5 DHA group cholecystectomies (p > 0.05). There were no differences with regard to hospital readmission. CONCLUSION: with regard to DS or DHA until cholecystectomy, there were no statistically significant differences related to severe postoperative complications, length of stay, or mortality.

Failure to perform index cholecystectomy during acute cholecystitis results in significant morbidity for patients who present with recurrence.

BACKGROUND: Although index cholecystectomy is considered the treatment of choice for acute cholecystitis (AC), many hospital systems struggle to provide such a service. The aim of this study was to analyze the effect of failure to perform index cholecystectomy in patients presenting with acute cholecystitis. METHODS: Between June 2010 and December 2015, all patients presenting to one hospital with an initial attack of AC were enrolled into a prospective database. Patient's records were reviewed up until point of delayed cholecystectomy or for a minimum of 24 months after the initial presentation with AC. Recurrent AC was defined as early (<6 weeks from initial discharge) or late (>6 weeks from initial discharge). RESULTS: In total 998 patients presented with AC, 409 (41%) of whom were discharged without index cholecystectomy. Eighty-three (20%) patients presented with AC recurrence (ACR). Compared to the first AC episode, patients were more likely to present with grade III AC and suffer significantly greater morbidity (p < 0.05 for all comparisons). A prior history of biliary disease was associated with ACR (p = 0.002). ACR occurred early in 48 (58%) patients and delayed in 35 (42%) patients. CONCLUSIONS: Twenty percent of patients discharged without cholecystectomy after their first attack of ACR will develop recurrence within the first two years. Half of ACR will occur within 6 weeks. Patients who present with ACR are more likely to develop more severe AC and are likely to suffer greater morbidity as compared to their first attack.

Robotic versus open approach in total gastrectomy for gastric cancer: a comparative single-center study of perioperative outcomes.

The robotic approach to gastric cancer has been gaining interest in recent years; however, its benefit over the open procedure in total gastrectomy with D2 lymphadenectomy is still controversial. The aims of the study were to compare postoperative morbidity and mortality, hospital stay, and anatomopathological findings between the robotic and open approaches to oncologic total gastrectomy. We analyzed a prospectively collected database, which included patients who underwent total gastrectomy with D2 lymphadenectomy in our center using a robotic or an open approach between 2014 and 2021. Comparative analysis of clinicopathological, intraoperative, postoperative and anatomopathological variables between the robot-assisted group and the open group was performed. Thirty patients underwent total gastrectomy with D2 lymphadenectomy by a robotic approach and 48 patients by an open procedure. Both groups were comparable. The robot-assisted group presented a lower rate of Clavien-Dindo complications ≥ stage II (20 vs. 48%, p = 0.048), a shorter hospital stay (7 days vs. 9 days, p = 0.003) and had a higher total number of lymph nodes resected (22 nodes vs. 15 nodes, p = 0.001) compared to the open approach. Operative time was longer in the robotic group (325 min vs. 195 min, p < 0.001) compared to the open group. The robotic approach is associated with a longer surgical time, a lower rate of Clavien-Dindo complications ≥ stage II and a shorter hospital stay, and more lymph nodes were resected compared to the open approach.

Litiasic acute cholecystitis: application of Tokyo Guidelines in severity grading.

BACKGROUND: Acute calculous cholecystitis (AC) is one of the most frequent surgical emergencies in our field. Laparoscopic cholecystectomy is considered the treatment of choice, although not sufficiently widespread. OBJECTIVE: To analyze the application of the Tokyo Guidelines in the management of AC and to determine the influence of the degree of severity on management and prognosis. METHOD: Prospective, observational study of patients with a primary diagnosis of AC between 2010 and 2015.. Exclusion criteria: AC recurrence; AC as a secondary diagnosis; acalculous cholecystitis; concurrent biliary pathology. Severity was classified according Tokyo 2013 Guidelines. RESULTS: 998 patients were included: 338 (33.9%) mild AC, 567 (56.8%) moderate AC, and 93 (9.3%) severe AC. A total of 582 (58.3%) patients were operated on. Postoperative complications Dindo-Clavien grade ≥ II 12.6%: mild AC 3.6%; moderate AC 12.2%; severe AC 49.0% (p < 0.001). Overall mortality 2%: mild AC 0%; moderate AC 0.5%; severe AC 18.0% (p < 0.001). CONCLUSION: Urgent laparoscopic cholecystectomy remains the treatment of choice for mild and moderate AC. In patients with severe AC, the risks and benefits of surgery should be assessed, given the high degree of complications and associated mortality.

ANTECEDENTES: La colecistitis aguda litiásica (CA) es una de las urgencias quirúrgicas más frecuentes en nuestro medio. La colecistectomía laparoscópica se considera el tratamiento de elección, aunque sigue sin ser una realidad su práctica generalizada. OBJETIVO: Analizar la aplicación de las Guías de Tokio en el manejo de la CA y determinar la influencia de la gravedad en el manejo y el pronóstico. MÉTODO: Estudio prospectivo, observacional, de pacientes con diagnóstico primario de CA entre 2010 y 2015. Criterios de exclusión: recidiva de CA, CA como diagnóstico secundario, CA alitiásica u otra patología biliar concomitante. Se ha clasificado la gravedad según las Guías de Tokio de 2013. RESULTADOS: Se incluyen 998 CA: 338 (33.9%) leves, 567 (56.8%) moderadas y 93 (9.3%) graves. Se operaron 582 pacientes (58.3%), y posteriormente 15 precisaron rescate. Complicaciones posoperatorias Dindo-Clavien ≥ 12,6%: CA leve 3,6%, CA moderada 12,2%, CA grave 49% (p < 0.001). Mortalidad global 2%: CA leve 0%, CA moderada 0.5%, CA grave 18% (p < 0.001). CONCLUSIÓN: La colecistectomía laparoscópica sigue siendo el tratamiento de elección para la CA leve y moderada. En pacientes con CA grave debe valorarse el riesgo-beneficio de la cirugía, dadas las complicaciones y la mortalidad asociadas.

Acute Cholecystitis in Very Elderly Patients: Disease Management, Outcomes, and Risk Factors for Complications.

BACKGROUND: The aim of this study was to evaluate the characteristics, management, and outcomes of acute cholecystitis in patients ≥80 years. METHODS: This was a retrospective analysis of data from a prospective single-center patient registry. RESULTS: The study population was composed of 348 patients, which were divided into two groups: those younger (Group A) and those older (Group B) than the median age (85.4 years). Although demographic and clinical characteristics of the two groups were similar, the disease management was clearly different, with older patients undergoing cholecystectomy less frequently (n=80 46.0% in Group A vs n=39 22.4% in Group B; p < 0.001). The outcomes in both groups of age were similar, with 30-day mortality of 3.7%, morbidity of 17.2%, and readmissions of 4.2% and two-year AC recurrence in nonoperated patients of 22.5%. No differences were seen between operated and no operated patients. Severe (Grade III) AC was the only independent factor significantly associated with mortality (OR 86.05 (95% CI: 11-679); p < 0.001). CONCLUSIONS: In elderly patients with AC, the choice of therapeutic options was not limited by the age per se, but rather by the disease severity (grade III AC) and/or poor physical status (ASA III-IV). In case of grade I-II AC, laparoscopic cholecystectomy can be safely performed and yield good results even in very old patients. Patients with grade III AC present high risk of morbidity and mortality, and the treatment should be individualized. ASA IV patients should avoid cholecystectomy, being antibiotic treatment and cholecystectomy the best option.

Hepatic resection for liver metastases as part of the "oncosurgical" treatment of metastatic breast cancer.

BACKGROUND: Metastatic breast cancer is considered an incurable disease despite new therapies. Recent studies suggest that liver resection associated with systemic treatment may improve patient survival. PATIENTS AND METHODS: Patient selection criteria were: good performance status, the feasibility of a complete and safe surgical procedure, and absence of uncontrolled extrahepatic metastases. The information was collected prospectively and analyzed retrospectively from our database. RESULTS: Between 1988 and 2006, 13 liver resections were performed in 12 patients owing to metastatic breast cancer. Two patients had synchronous metastases and ten metachronous metastases. One patient had extrahepatic bone metastases at the time of liver resection. Median follow-up was 35.9 months (range 12-113.4 months). Median age at liver resection was 58.4 years (range 36-76 years). Median hospital stay was 8 days (range 6-24 days); two patients had biliary leak but none died during the postoperative course. Seven patients (58.3%) developed hepatic recurrence. One-, 3-, and 5-year actuarial patient survival was 100%, 79%, and 33%, respectively. Patients who developed liver metastases within the first 24 months and after the first 24 months post-breast surgery had 1-, 3-, and 5-year actuarial patient survival of 100%, 0%, and 0% and 100%, 83%, and 60%, respectively (P < 0.025). CONCLUSION: Liver resection for breast cancer liver metastases has an important role in the oncosurgical treatment of metastatic breast cancer with excellent 3-year survival.

Our experience in liver transplantation in patients over 65 yr of age.

OBJECTIVES: The aim of this study was to analyze short- and long-term results of liver transplantation (LT) in patients over 65 yr. MATERIAL AND METHODS: Between 1996 and 2004, 386 patients underwent 415 LT at our center. The main indication for LT was post-necrotic cirrhosis in 59%, followed by hepatocellular carcinoma (HCC) over cirrhosis in 33%. Half of the patients (53%) were hepatitis C virus (HCV) +. Overall, 72 patients were >65 yr of age. Actuarial survival, causes of mortality and postoperative complications were compared between groups: patients under and over 65 yr. Risk factors for poor outcome in patients over 65 yr were also analyzed. RESULTS: The older group had more patients at Child A stage, more HCC as an indication for LT and more HCV (+) patients, p < 0.05. No differences were observed in donor and surgery characteristics, except for lower multi-transfusion and higher incidence of grafts with steatosis in the older group (p < 0.05). Actuarial survival at one, three, five and 10 yr was 82%, 75%, 72%, and 70% for the <65 yr group vs. 77%, 66%, 55%, and 55% for the >65 yr group (p = 0.03). Main causes of mortality in patients >65 yr were recurrence of underlying disease and medical causes. In the older age group, fewer infections (p = ns) and rejections (p = 0.017) occurred in the postoperative period. Risk factor for poor outcome in the group of patients over 65 yr in multivariate analyses was pre-LT renal insufficiency (odds ratio 3.5, p = 0.002, 95% confidence interval 1.58-7.82). CONCLUSION: Results in patients >65 yr are comparable to those <65 yr if older LT candidates are carefully selected. Overimmunosuppression should be avoided in older candidates, as its effects could worsen the pre-existing diseases common in elderly patients.

Liver transplantation in HIV-HCV coinfected patients: a case-control study.

Liver transplantation (LT) for hepatitis C virus (HCV)-associated cirrhosis in human immunodeficiency virus (HIV)-infected patients was compared with non-HIV patients. Nine patients with HIV-HCV coinfection were compared with patients transplanted before and after each HIV patient (control group). Immunosuppression consisted in tacrolimus with steroids or mycophenolate mofetil. Acute cellular rejection and three-year actuarial patient survival were respectively 44% and 87.5% in HIV group and 22% and 93.7% in the control group (P=NS). Acute hepatitis C virus occurred earlier (2.3 vs. 4.3 months) and was more cholestatic (mean bilirubin: 10.8 vs. 1.6 mg/dL) in the HIV group. Eight (100%) HIV and nine (64.3%) control patients received antiviral treatment with pegylated interferon and ribavirin. One patient (11.1%) of the control group and one patient (20%) of the HIV group presented a sustained virologic response (P=NS). Short- to midterm results of LT in HIV-HCV co-infected patients were excellent and similar to non-HIV patients.

Superoxide dismutase prevents development of adenocarcinoma in a rat model of Barrett's esophagus.

AIM: To test whether antioxidant treatment could prevent the progression of Barrett's esophagus to adenocarcinoma. METHODS: In a rat model of gastroduodenoesophageal reflux by esophagojejunal anastomosis with gastric preservation, groups of 6-10 rats were randomized to receive treatment with superoxide dismutase (SOD) or vehicle and followed up for 4 mo. Rat's esophagus was assessed by histological analysis, superoxide anion and peroxinitrite generation, SOD levels and DNA oxidative damage. RESULTS: All rats undergoing esophagojejunostomy developed extensive esophageal mucosal ulceration and inflammation by mo 4. The process was associated with a progressive presence of intestinal metaplasia beyond the anastomotic area (9% 1st mo and 50% 4th mo) (94% at the anastomotic level) and adenocarcinoma (11% 1st mo and 60% 4th mo). These changes were associated with superoxide anion and peroxinitrite mucosal generation, an early and significant increase of DNA oxidative damage and a significant decrease in SOD levels (P<0.05). Exogenous administration of SOD decreased mucosal superoxide levels, increased mucosal SOD levels and reduced the risk of developing intestinal metaplasia beyond the anastomotic area (odds ratio = 0.326; 95%CI: 0.108-0.981; P = 0.046), and esophageal adenocarcinoma (odds ratio = 0.243; 95%CI: 0.073-0.804; P = 0.021). CONCLUSION: Superoxide dismutase prevents the progression of esophagitis to Barrett's esophagus and adenocarcinoma in this rat model of gastrointestinal reflux, supporting a role of antioxidants in the chemoprevention of esophageal adenocarcinoma.

Selective COX-2 inhibition is associated with decreased mucosal damage induced by acid and pepsin in rabbit esophagitis.

OBJECTIVE: To evaluate the effects of COX-1 and/or COX-2 inhibition in a model of chronic esophagitis in rabbits. METHODS: Both high- and low-grade esophagitis were induced in rabbits by the perfusion of acidified pepsin. Rabbits were treated with either a selective COX-2 inhibitor (DFU[3-(3-Fluorophenyl)-4-(4-Methanesulfonyl)-5,5-Dimethyl-5H-Furan-2-One];30 mg/Kg/day), a nonspecific COX inhibitor (indomethacin; 2 mg/Kg/day), or a COX-1 preferential inhibitor (piroxicam; 2 mg/Kg/12 h). RESULTS: Prostaglandins are derived from COX-1 activity in the normal esophagus. Both low- and high-grade esophagitis are associated with a progressive increase of COX activity, which is partially dependent on the COX-2 isoform. DFU reduced muscosal damage in both models of esophagitis. However, indomethacin did not affect significantly mucosal damage, and piroxicam increased damage in low-grade esophagitis. CONCLUSIONS: COX-1 activity is constitutive in the rabbit esophageal mucosa, but both COX-2 and COX-1 activity are increased under the impact of acidified pepsin. Treatment with the COX-2 inhibitor DFU is associated with improvement of mucosal damage, which may have therapeutic implications.

Indomethacin but not a selective cyclooxygenase-2 inhibitor inhibits esophageal adenocarcinogenesis in rats.

AIM: To evaluate the effects of indomethacin [dual cyclooxygenase (COX)-1/COX-2 inhibitor] and 3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl) phenyl)-2-(5H)-furanone (MF-tricyclic) (COX-2 selective inhibitor) in a rat experimental model of Barrett's esophagus and esophageal adenocarcinoma. METHODS: A total of 112 surviving post-surgery rats were randomly divided into three groups: the control group (n = 48), which did not receive any treatment; the indomethacin group (n = 32), which were given 2 mg/kg per day of the COX-1/COX-2 inhibitor; and the MF-tricyclic group (n = 32), which received 10 mg/kg per day of the selective COX-2 inhibitor. Randomly selected rats were killed either 8 wk or 16 wk after surgery. The timing of the deaths was in accordance with a previous study performed in our group. Only rats that were killed at the times designated by the protocol were included in the study. We then assessed the histology and prostaglandin E2 (PGE2) expression levels in the rat esophagi. An additional group of eight animals that did not undergo esophagojejunostomy were included in order to obtain normal esophageal tissue as a control. RESULTS: Compared to a control group with no treatment (vehicle-treated rats), indomethacin treatment was associated with decreases in ulcerated esophageal mucosa (16% vs 35% and 14% vs 17%, 2 mo and 4 mo after surgery, respectively; P = 0.021), length of intestinal metaplasia in continuity with anastomosis (2 ± 1.17 mm vs 2.29 ± 0.75 mm and 1.25 ± 0.42 mm vs 3.5 ± 1.54 mm, 2 mo and 4 mo after surgery, respectively; P = 0.007), presence of intestinal metaplasia beyond anastomosis (20% vs 71.4% and 0% vs 60%, 2 mo and 4 mo after surgery, respectively; P = 0.009), severity of dysplasia (0% vs 71.4% and 20% vs 85.7% high-grade dysplasia, 2 mo and 4 mo after surgery, respectively; P = 0.002), and adenocarcinoma incidence (0% vs 57.1% and 0% vs 60%, 2 mo and 4 mo after surgery, respectively; P < 0.0001). Treatment with the selective COX-2 inhibitor, MF-tricyclic, did not prevent development of intestinal metaplasia or adenocarcinoma. In parallel, we observed a significant decrease in PGE2 levels in indomethacin-treated rats, but not in those treated with MF-tricyclic, at both 2 mo and 4 mo. Compared to control rats that did not undergo surgery (68 ± 8 ng/g, P = 0.0022 Kruskal-Wallis test) there was a significant increase in PGE2 levels in the esophageal tissue of the rats that underwent surgery either 2 mo (1332 ± 656 ng/g) or 4 mo (1121 ± 1015 ng/g) after esophagojejunostomy. However, no differences were found when esophageal PGE2 levels were compared 2 mo vs 4 mo post-esophagojejunostomy. At both the 2- and 4-mo timepoints, we observed a significant decrease in PGE2 levels in indomethacin-treated rat esophagi compared to those in either the control or MF-tricyclic groups (P = 0.049 and P = 0.017, respectively). No differences in PGE2 levels were found when we compared levels in rats treated with MF-tricyclic to not-treated rats. CONCLUSION: In this rat model of gastrointestinal reflux, indomethacin was associated with a decrease in the severity of esophagitis and reduced development of esophageal intestinal metaplasia and adenocarcinoma.

A prospective randomized trial comparing tacrolimus and steroids with tacrolimus monotherapy in liver transplantation: the impact on recurrence of hepatitis C.

The aim of this prospective randomized trial was to study the efficacy and safety of tacrolimus monotherapy (TACRO) and compare it with our standard treatment of tacrolimus plus steroids (TACRO + ST) after liver transplant (LT). Furthermore, the impact of steroid-free immunosuppression on outcome of hepatitis C virus (HCV) was analysed. Between 1998 and 2000, 60 patients (mean age: 57 years) were included in the study and randomized to receive TACRO (n = 28) or TACRO + ST (n = 32). Indication for LT was postnecrotic cirrhosis in all cases (58.3% were HCV-positive). Mean follow-up was 44 months. Survival, incidence of rejection, infection and side-effects were compared between the two groups. In patients with HCV infection, incidence and severity of acute hepatitis C, long-term outcome of recurrent hepatitis C and survival were studied in an intention-to-treat analysis or in the real group analysis (real-TACRO versus real-TACRO + ST). Patient survival at 1, 3 and 5 years, tacrolimus pharmacokinetics, incidence of rejection infections and side-effects were similar. In patients with HCV, the incidence and severity of graft hepatitis C tended to be lower in TACRO (47%) compared with TACRO + ST (67%) (P = NS), and also in real-TACRO (42%) compared with real-TACRO + ST (61%) (P = NS). A poor outcome considered as evolution to cirrhosis at 3 years was observed in one (9%) living patient in real-TACRO and nine (45%) in real-TACRO + ST (P = 0.04). Patient survival at 1, 3 and 5 years was 92%, 92% and 73% for real-TACRO and 78%, 61% and 51% for real TACRO + ST (P = 0.07). Steroid-free immunosuppression appears to be safe and efficacious. The main advantage of this regimen could be in HCV patients, as recurrence of hepatitis in the graft was less severe in the group of patients in whom steroids could be avoided completely.

Resection for hepatocellular carcinoma is a good option in Child-Turcotte-Pugh class A patients with cirrhosis who are eligible for liver transplantation.

The best treatment option for patients with single, early hepatocellular carcinoma (HCC) and cirrhosis, good liver function, and absence of portal hypertension remains to be established. The aim of this work was to compare the outcome of liver resection (LR) with that of liver transplantation (LT) for single, early HCC in Child-Turcotte-Pugh class A patients with cirrhosis younger than 70 years of age. Thirty-seven of 134 patients who underwent LR and 36 of 125 who underwent LT for HCC in our unit fulfilled the inclusion criteria. No differences were observed in mean tumor size (3 cm); HCV cirrhosis predominated in the LT group and older age in the LR group. Postoperative mortality was higher and hospital stay longer in the LT group. Patient survival was similar in both groups. Tumor recurrence was higher in the LR group (59% vs. 11%), extrahepatic recurrences predominated after LT and hepatic recurrences after LR. Disease-free survival was significantly better after LT. Eighteen patients presented hepatic recurrence after LR: 5 advanced and 13 early. Seventeen patients--13 with early HCC recurrence and 4 with liver failure--were potential candidates for salvage LT. However, 10 of 17 patients were older than 70 years at this time. Salvage LT could only be performed in 6 patients: 5 for HCC recurrence and 1 for liver failure. Results of salvage LT were similar to those of primary LT. In conclusion, only 27.6% of resected patients were eligible for LT. LR is a good option since it offers similar survival to LT. Salvage liver transplantation was performed in 16.2% of resected patients, with older age being the main contraindication. Outcome of salvage LT was similar to that of primary LT.