Daniela Campani

Background: Small intestine bacterial overgrowth (SIBO) is associated with steatohepatitis (SH) in subjects with metabolic-associated steatotic liver disease (MASLD). The impact of ileocecal valve (ICV) incontinence, a major cause of SIBO in patients with MASLD, remains unknown because of the unmet need for a non-X-ray-dependent diagnosis. Methods: Exploiting water as contrast medium and colonic irrigation via a hydro-colon machine (Clean Colon Srl, Monza, Italy), we developed a new abdominal ultrasound (US) procedure for diagnosing and grading ICV incontinence. In a pilot, observational, feasibility and safety study, we correlated a new ICV incontinence parameter with irritable bowel syndrome (IBS, ROMA IV criteria), serum transaminases (AST, ALT), platelet counts, FIB-4, US liver steatosis and stiffness (LS, measured by Shear Wave and Transient Elastography, SWE and TE). Results: We prospectively studied 32 consecutive subjects with IBS who underwent a pre-colonoscopy colon cleansing after informed consent: 19 males (59%), body mass index (BMI) 26.6 ± 2.6 kg/m², age 57 ± 19 years, 16 (50%) with US liver steatosis. The half-hour (27 min, range 20–35 min) procedure was safe and well tolerated except in two males with prostate hypertrophy. ICV incontinence was graded (after 2500–3000 mL irrigation) according to cecum/right-colon distention with/without (immediate or delayed) reflux into terminal ileum (TI): 0 = cecum distension without TI reflux; 1 = cecum distension with TI reflux; 2 = absence of cecum distension with TI reflux. Cecum/right-colon distention (grade 0 or 1) was perceived by the patients whereas the right colon irrigation with complete ICV incontinence (grade 2) was symptomless. ICV continence associated with LS (p ≤ 0.0001). A histologic diagnosis of non-alcoholic steatohepatitis was confirmed in a 35-year-old obese male with SIBO and LS > 8 kPa (8.7/8.5 kPa by SWE/TE):steatosis (grade S3) with hepatocyte ballooning, lobular inflammation (grade 6/8) without fibrosis (stage 0/4, F0). Conclusions: The new US-based approach provides a feasible, easy-to-perform, mini-invasive tool for the diagnosis and grading of ICV incontinence. Preliminary results prompt prospective studies investigating the impact of ICV incontinence as a possible co-factor of steatohepatitis in patients with MASLD.

Background: Gut dysbiosis may trigger inflammation and steatohepatitis (SH) in subjects with metabolic associated steatotic liver disease (MASLD). Both incidence and impact of ileocecal valve (ICV) dysfunction as cause of small intestine bacterial overgrowth in MASLD remain unknown because of the unmet need of non-radiology dependent diagnostic procedures. Methods: Exploiting water as contrast medium and a hydro colon machine (Clean Colon Srl, Monza, Italy) for automated retrograde gentle colonic irrigation, we developed a new abdominal ultrasound procedure for diagnosis of ICV incontinence and we present the results of a pilot feasibility study for the assessment of its relationship with triggering of inflammation in steatotic liver disease. Results: Consecutive patients (32) performing colonic irrigation in colonoscopy preparation underwent concomitant abdominal ultrasound examination. Patients were predominantly males (59%) with body mass index (BMI) 26,6±2,6 kg/m2 and liver steatosis was present in half of the patients. Liver stiffness was 26,6±2,6 kPa, while serum transaminases ALT and AST were 33,1±9,5 and 25,9±8,4 U.I., respectively. The procedure that lasted a mean of 27min (range 20-35 min) was well tolerated in all, but 2 males with large prostate hypertrophy. Three ICV continence patterns (A - Early reflux, already at small water volume without evident cecum distension; B - Late reflux, after evident cecum distension; C - No reflux, either early or late after overall water irrigation and significant cecum distension) were observed during water irrigation (4266 ml mean, range 2000-8000 ml). ICV continence was significantly associated with IBS, steatosis, and liver stiffness (all p ≤ 0.0001). Furthermore, IBS (OR 3.97), steatosis (OR 3.30), and liver stiffness (OR 2.43 per unit increase) were also independently associated with dichotomization of impaired ICV continence.A 35-year-old male with SIBO and LS = 8.7 kPa underwent a liver biopsy showing histologically-determined high level of steatosis (S3), hepatocyte ballooning, lobular inflammation (Grade 6/8) in absence of fibrosis (Stage 0/4 F0).Conclusion: This proof-of-concept study indicates that an easy and quick mini-invasive diagnosis of ICV incontinence is feasible using water as contrast medium during abdominal ultrasound examination. Preliminary results suggest that this new technique is worth of being validated in prospective studies investigating the impact ICV incontinence as possible co-factor of steatohepatitis in patients with MAFLD.

Amebiasis is a rare condition in industrialised countries but is epidemiologically growing. Clinical manifestations may range from asymptomatic to invasive disease. An amebic abscess can be the result of extraintestinal amebiasis, and it is associated with relatively high morbidity and mortality. We present three indigenous cases of amoebic liver abscesses observed within a few weeks (October–November 2023) in patients living in a small area near Lucca in Tuscany, Central Italy. Fever accompanied by abdominal pain and liver abscess was observed in all three patients, and one of them presented necrotising colitis and pleural effusion, too. The parasitological diagnosis was performed by microscopy and confirmed with real-time PCR in liver abscess drainage fluid and stools.

To obtain long-term data on the use of everolimus in patients who underwent liver transplantation for hepatocellular carcinoma, we conducted a retrospective, single-center analysis of adult recipients transplanted between 2013 and 2021. Patients on everolimus-incorporating immunosuppression were matched with those on tacrolimus using an inverse probability of treatment weighting methodology. Two propensity-matched groups of patients were thus compared: 233 (45.6%) receiving everolimus versus 278 (54.4%) on tacrolimus. At a median (interquartile range) follow-up of 4.4 (3.8) years after transplantation, everolimus patients showed a reduced risk of recurrence versus tacrolimus (7.7% versus 16.9%; RR = 0.45; p = 0.002). At multivariable analysis, microvascular infiltration (HR = 1.22; p < 0.04) and a higher tumor grading (HR = 1.27; p < 0.04) were associated with higher recurrence rate while being within Milan criteria at transplant (HR = 0.56; p < 0.001), a successful pre-transplant downstaging (HR = 0.63; p = 0.01) and use of everolimus (HR = 0.46; p < 0.001) had a positive impact on the risk of post-transplant recurrence. EVR patients with earlier drug introduction (≤30 days; p < 0.001), longer treatment duration (p < 0.001), and higher drug exposure (≥5.9 ng/mL; p < 0.001) showed lower recurrence rates versus TAC. Based on our experience, everolimus provides a reduction in the relative risk of hepatocellular carcinoma recurrence, especially for advanced-stage patients and those with earlier drug administration, higher drug exposure, and longer time on treatment. These data advocate for early everolimus introduction after liver transplantation to reduce the attrition rate consequent to chronic immunosuppression.

Background: In Italy, data on long-term survivors after liver transplantation are lacking. Materials and Methods: We conducted a hybrid design study on a cohort of 359 adult recipients who received transplants between 1996 and 2002 to identify predictors of survival and the prevalence of co-morbidities among long-term survivors. Results: The actuarial (95% CI) patient survival was 96% (94.6–98.3%), 69% (64.2–73.6%), 55% (49.8–59.9%), 42.8% (37.6–47.8%), and 34% (29.2–38.9%) at 1, 5, 10, 15, and 20 years, respectively. The leading causes of death were hepatitis C virus recurrence (24.6%), extrahepatic malignancies (16.9%), infection (14.4%), and hepatocellular carcinoma recurrence (14.4%). The factors associated with the survival probability were younger donor and recipient ages (p = 0.001 and 0.004, respectively), female recipient sex (p < 0.001), absence of HCV (p < 0.01), absence of HCC (p = 0.001), and absence of diabetes mellitus at one year (p < 0.01). At the latest follow-up, the leading comorbidities were hypertension (53.6%), obesity (18.7%), diabetes mellitus (17.1%), hyperlipidemia (14.7%), chronic kidney dysfunction (14.7%), and extrahepatic malignancies (13.8%), with 73.9% of patients having more than one complication. Conclusions: Aging with a liver graft is associated with an increased risk of complications and requires ongoing care to reduce the long-term attrition rate resulting from chronic immunosuppression.

Background and Aims: The present study analyzed retrospectively the association between socioeconomic deprivation and graft and patient survival in a cohort of 2,568 adult recipients of a liver transplant between 1996 and 2022. Materials and methods: The primary exposure was a nationally validated socioeconomic deprivation index (DI) at census block level and ranking from 1-5, with higher ranks indicating more significant socioeconomic deprivation. Results: At a median (IQR) follow-up of 144.8 (204) months, the overall patient and graft survival rates were 92% and 90.4% at 1 year, 78.4% and 72.2% at 5 years, and 58% and 56.7% at 10 years. Recipients with a DI rank above the median (i.e., more deprived) had 1, 5, and 10-year patient and graft survival rates of 91% and 89.5%, 70.4% and 68.4%, 48% and 46.7%, respectively, versus 92% and 90.4%, 78.4% and 72.2%, and 58% and 56.7% for less deprived patients (log-rank p<0.001). More deprived patients had a higher risk of death (p<0.0001), hypertension (p<0.0001), obesity (p=0.02), diabetes mellitus (p=0.02), graft rejection (p<0.0001), chronic kidney dysfunction (p<0.0001), major cardiovascular events (p<0.0001) and de novo malignancies (p<0.0001) than less deprived recipients. The factors associated with the survival probability were younger donor and recipient ages (p=0.03 and 0.02, respectively), female recipient sex (p=0.04), absence of HCV (p<0.01), absence of HCC (p=0.02), absence of DM at transplantation (p=0.03) and 1 year (p=0.01), lower DI (p=0.02), lower MELD (0.02), shorter CIT (p=0.03), TAC (p=0.01), and EVR in the immunosuppressive regimen (p=0.02). Conclusions: Patients from more deprived areas have a higher risk of death after liver transplantation. Pre- and post-transplant socioeconomic risk profiling is warranted to better tailor care to patient’s needs and expectations.

To obtain long-term data on the use of everolimus in patients who underwent liver transplantation for hepatocellular carcinoma, we conducted a retrospective, single-center analysis of adult recipients transplanted between 2013 and 2021. Patients on everolimus-incorporating immunosuppression were matched with those on tacrolimus using an inverse probability of treatment weighting methodology. Two propensity-matched groups of patients were thus compared: 233 (45.6%) receiving everolimus versus 278 (54.4%) on tacrolimus. At a median (interquartile range) follow-up of 4.4 (3.8) years after transplantation, everolimus patients showed a reduced risk of recurrence versus tacrolimus (7.7% versus 16.9%; RR=0.45; P=0.002). At multivariable analysis, microvascular infiltration (HR=1.22; P<0.04) and a higher tumor grading (HR=1.27; P<0.04) were associated with higher recurrence rate while being within Milan criteria at transplant (HR=0.56; P<0.001), a successful pre-transplant downstaging (HR=0.63; P=0.01) and use of everolimus (HR=0.46; P<0.001) had a positive impact on the risk of post-transplant recurrence. EVR patients with earlier drug introduction (30 days; P<0.001), longer treatment duration (P<0.001), and higher drug exposure (5.9ng/mL; P<0.001) showed lower recurrence rates versus TAC. Based on our experience, everolimus provides a reduction of the relative risk of hepatocellular carcinoma recurrence, especially for advanced-stage patients and those with earlier drug administration, higher drug exposure, and longer time on treatment. These data advocate for early everolimus introduction after liver transplantation to reduce the attrition rate consequent to chronic immunosuppression.

We conducted a hybrid-design study on a historical cohort of 359 adult recipients of a liver graft who received transplants between 1996 and 2002. The study aimed to identify predictors of survival and investigate the prevalence of co-morbidities among long-term survivors. The actuarial (95% CI) patient survival of the overall study cohort was 96% (94.6%-98.3%), 69% (64.2%-73.6%), 55% (49.8%-59.9%), 42.8% (37.6%-47.8%), and 34% (29.2%-38.9%) at 1, 5, 10, 15, and 20 years, respectively. The actuarial (95% CI) graft survival was 93.8% (91.6%-97.2%), 67.6% (62.2%-71.5%), 54.3% (49.6%-59.3%), 42.1% (37.3%-47.4%), and 33.8% (29.0%-38.4%) at 1, 5, 10, 15, and 20 years, respectively. The leading cause of death was hepatitis C virus recurrence (24.6%), followed by extrahepatic malignancies (16.9%), infection (14.4%), and hepatocellular carcinoma recurrence (14.4%). The Cox proportional hazards analysis revealed that several independent factors were associated with the survival probability. These factors include younger donor and recipient ages (p=0.001 and 0.004, respectively), female recipient sex (p<0.001), absence of HCV (p<0.01), absence of HCC (p=0.001), and absence of diabetes mellitus at one year (p<0.01). At the latest follow-up, the leading comorbidities in the long-term survivors were hypertension (53.6%), obesity (18.7%), diabetes mellitus (17.1%), hyperlipidemia (14.7%), chronic kidney dysfunction (14.7%), and extrahepatic malignancies (13.8%), with 73.9% of patients having more than one complication. The Kaplan-Meier probability (95% CI) of complication-free survival was 65.4% (60.2%-70.3%), 38.4% (33.4%-43.7%), 17.8% (14.1%-22.2%), 7.2% (4.8%-10.5%), and 1.94% (0.85%-4.15%) at 1, 5, 10, 15, and 20 years, respectively. Aging with a liver graft is associated with an increased risk of complications and requires ongoing care to reduce the long-term attrition rate resulting from chronic immunosuppression.

Background: Newer chemotherapy regimens are reviving the role of pancreatectomy with arterial resection (PAR) in locally advanced pancreatic cancer. However, concerns about the early outcomes and learning curve of PAR remain. This study aimed to define the postoperative results and learning curve of PAR and provide preliminary data on oncologic outcomes. Materials and methods: A single center’s experiences (1993–2023) were retrospectively analyzed to define the postoperative outcomes and learning curve of PAR. Oncologic results were also reported. Results: During the study period 236 patients underwent PAR. Eighty PAR (33.9%) were performed until 2012, and 156 were performed thereafter (66.1%). Pancreatic cancer was diagnosed histologically in 183 patients (77.5%). Induction therapy was delivered to 18 of these patients (31.0%) in the early experience and to 101 patients (80.8%) in the last decade (PP=0.0055]. Comparison between the PAR-SMA and PAR-CT/HA groups showed no differences in severe postoperative complications (25.3 vs. 20.6%), 90-day mortality (12.6 vs. 7.8%), and median overall survival. Vascular invasion was confirmed in 123 patients (67.2%). The median number (interquartile range) of examined lymph nodes was 60.5 (41.3–83) and rate of R0 resection was 66.1% (121/183). Median overall survival for PAR was 20.9 (12.5–42.8) months, for PAR-SMA was 20.2 (14.4–44) months, and for PAR-CT/HA was 20.2 (11.4–42.7). Long-term prognosis improved by study decade [1993–2002: 12.0 (5.4–25.9) months, 2003–2012: 15.1 (9.8–23.4) months, and 2013–present: 26.2 (14.3–51.5) months; P<0.0001]. Conclusions: In recent times, PAR is associated with improved outcomes despite a steep learning curve. Pancreatic surgeons should be prepared to face the technical challenge posed by PAR.