Autologous Pancreatic Islet Cell Transplantation Following Pancreatectomy for Pancreas Diseases Other Than Chronic Pancreatitis: A 15-y Study of the Milan Protocol.

BACKGROUND: Pancreatogenic diabetes, a consequence of pancreatic tissue loss following pancreatectomy, poses a significant challenge for patients undergoing pancreatic surgery. Islet autotransplantation (IAT) offers a promising approach to prevent or alleviate pancreatogenic diabetes, but its application has been limited to individuals with painful chronic pancreatitis. METHODS: This study presents a 15-y clinical experience with the Milan Protocol, which expands IAT after pancreatectomy to a broader spectrum of patients with malignant and nonmalignant pancreatic diseases. The analysis evaluates feasibility, efficacy, and safety of IAT. Modified Igls criteria validated through the arginine test and mixed meal tolerance tests were used to assess long-term metabolic outcomes. RESULTS: Between November 2008 and June 2023, IAT procedures were performed on 114 of 147 candidates. IAT-related complications occurred in 19 of 114 patients (16.7%), with 5 being potentially serious. Patients exhibited sustained C-peptide secretion over the 10-y follow-up period, demonstrating a prevalence of optimal and good beta-cell function. Individuals who underwent partial pancreatectomy demonstrated superior metabolic outcomes, including sustained C-peptide secretion and a reduced risk of developing diabetes or insulin dependence compared with those who underwent total pancreatectomy. For patients who had total pancreatectomy, the quantity of infused islets and tissue volume were identified as critical factors influencing metabolic outcomes. An increased risk of recurrence or progression of baseline diseases was not observed in subjects with neoplasms. CONCLUSIONS: These findings provide valuable insights into the benefits and applications of IAT as a therapeutic option for pancreatogenic diabetes after pancreatic surgery, expanding its potential beyond painful chronic pancreatitis.

Total Pancreatectomy With Islet Autotransplantation as an Alternative to High-risk Pancreatojejunostomy After Pancreaticoduodenectomy: A Prospective Randomized Trial.

OBJECTIVE: To compare pancreaticoduodenectomy (PD) and total pancreatectomy (TP) with islet autotransplantation (IAT) in patients at high risk of postoperative pancreatic fistula (POPF). BACKGROUND: Criteria to predict the risk of POPF occurrence after PD are available. However, even when a high risk of POPF is predicted, TP is not currently accepted as an alternative to PD, because of its severe consequences on glycaemic control. Combining IAT with TP may mitigate such consequences. METHODS: Randomized, open-label, controlled, bicentric trial (NCT01346098). Candidates for PD at high-risk pancreatic anastomosis (ie, soft pancreas and duct diameter ≤3 mm) were randomly assigned (1:1) to undergo either PD or TP-IAT. The primary endpoint was the incidence of complications within 90 days after surgery. RESULTS: Between 2010 and 2019, 61 patients were assigned to PD (n=31) or TP-IAT (n=30). In the intention-to-treat analysis, morbidity rate was 90·3% after PD and 60% after TP-IAT ( P =0.008). According to complications' severity, PD was associated with an increased risk of grade ≥2 [odds ratio (OR)=7.64 (95% CI: 1.35-43.3), P =0.022], while the OR for grade ≥3 complications was 2.82 (95% CI: 0.86-9.24, P =0.086). After TP-IAT, the postoperative stay was shorter [median: 10.5 vs 16.0 days; P <0.001). No differences were observed in disease-free survival, site of recurrence, disease-specific survival, and overall survival. TP-IAT was associated with a higher risk of diabetes [hazard ratio=9.1 (95% CI: 3.76-21.9), P <0.0001], but most patients maintained good metabolic control and showed sustained C-peptide production over time. CONCLUSIONS: TP-IAT may become the standard treatment in candidates for PD, when a high risk of POPF is predicted.

Stereotactic Radiotherapy after Incomplete Transarterial (Chemo-) Embolization (TAE\TACE) versus Exclusive TAE or TACE for Treatment of Inoperable HCC: A Phase III Trial (NCT02323360).

Background: Hepatocellular carcinoma (HCC) is the most frequent liver malignancy and a leading cause of cancer death in the world. In unresectable HCC patients, transcatheter arterial (chemo-) embolization (TAE/TACE) has shown a disease response in 15-55% of cases. Though multiple TAE/TACE courses can be administered in principle, Stereotactic Body Radiotherapy (SBRT) has emerged as an alternative option in the case of local relapse following multiple TAE/TACE courses. Methods: This is a single-center, prospective, randomized, controlled, parallel-group superiority trial of SBRT versus standard TAE/TACE for the curative treatment of the intermediate stage of HCC after an incomplete response following TAE/TACE (NCT02323360). The primary endpoint is 1-year local control (LC): 18 events were needed to assess a 45% difference (HR: 0.18) in favor of SBRT. The secondary endpoints are 1-year Progression-Free Survival (PFS), Distant Recurrence-Free Survival (DRFS), Overall Survival (OS) and the incidence of acute and late complications. Results: At the time of the final analysis, 40 patients were enrolled, 19 (49%) in the TAE/TACE arm and 21 (51%) in the SBRT arm. The trial was prematurely closed due to slow accrual. The 1- and 2-year LC rates were 57% and 36%. The use of SBRT resulted in superior LC as compared to TAE/TACE rechallenge (median not reached versus 8 months, p = 0.0002). PFS was 29% and 16% at 1 and 2 years, respectively. OS was 86% and 62% at 1 year and 2 years, respectively. In the TAE arm, PFS was 13% and 6% at 1 and 2 years, respectively. In the SBRT arm, at 1 and 2 years, PFS was 37% and 21%, respectively. OS at 1 and 2 years was 75% and 64% in the SBRT arm and 95% and 57% in the TACE arm, respectively. No grade >3 toxicity was recorded. Conclusions: SBRT is an effective treatment option in patients affected by inoperable HCC experiencing an incomplete response following ≥1 cycle of TAE/TAC.

Multidisciplinary Tumor Board in the Management of Patients with Colorectal Liver Metastases: A Single-Center Review of 847 Patients.

There is still debate over how reviewing oncological histories and addressing appropriate therapies in multidisciplinary team (MDT) discussions may affect patients' overall survival (OS). The aim of this study was to describe MDT outcomes for a single cancer center's patients affected by colorectal liver metastases (CRLMs). From 2010 to 2020, a total of 847 patients with CRLMs were discussed at our weekly MDT meeting. Patients' characteristics and MDT decisions were analyzed in two groups: patients receiving systemic therapy (ST) versus patients receiving locoregional treatment (LRT). Propensity-score matching (PSM) was run to reduce the risk of selection bias. The median time from MDT indication to treatment was 27 (IQR 13−51) days. The median OS was 30 (95%CI = 27−34) months. After PSM, OS for patients undergoing LRT was 51 (95%CI = 36−64) months compared with 15 (95%CI = 13−20) months for ST patients (p < 0.0001). In this large retrospective study, the MDT discussions were useful in providing the patients with all available locoregional options.

Myosteatosis Is Not Associated with Complications or Survival in HCC Patients Undergoing Trans Arterial Embolization.

Alterations in nutritional status, in particular sarcopenia, have been extensively associated with a poor prognosis in cirrhotic patients regardless of the etiology of liver disease. Less is known about the predictive value of myosteatosis, defined as pathological fat infiltration into the skeletal muscle. We retrospectively analyzed a cohort of 151 cirrhotic patients with unresectable hepatocellular carcinoma (HCC) who underwent their first trans-arterial embolization (TAE) between 1 March 2011 and 1 July 2019 at our Institution. Clinical and biochemical data were collected. Sarcopenia was assessed using the L3-SMI method while myosteatosis with a dedicated segmentation suite (3D Slicer), using a single slice at an axial plane located at L3 and calculating the IMAC (Intramuscular Adipose Tissue Content Index). The sex-specific cut-off values for defining myosteatosis were IMAC > −0.44 in males and >−0.31 in females. In our cohort, 115 (76%) patients were included in the myosteatosis group; 128 (85%) patients had a coexistent diagnosis of sarcopenia. Patients with myosteatosis were significantly older and showed higher BMI than patients without myosteatosis. In addition, male gender and alcoholic- or metabolic-related cirrhosis were most represented in the myosteatosis group. Myosteatosis was not associated with a different HCC burden, length of hospitalization, complication rate, and readmission in the first 30 days after discharge. Overall survival was not influenced by the presence of myosteatosis.

Adhesive small bowel obstruction: Single band or matted adhesions? A predictive model based on computed tomography scan.

BACKGROUND: Preoperative identification of the cause of adhesive small bowel obstruction (ASBO) is crucial for decision making. Some computed tomography (CT) findings can be indicative of single adhesive bands or matted adhesions. Our aim was to build a predictive model based on CT data to discriminate ASBO due to single adhesive band or matted adhesions. METHODS: A retrospective single center study was conducted, covering all consecutive patients with a preoperative CT scan, undergoing urgent surgery for ASBO between January 1, 2005, and December 31, 2017. Preoperative CT scans were blindly reviewed, and all the CT findings indicative of single adhesive band or matted adhesions described in literature were recorded. According to intraoperative findings, ASBOs were retrospectively classified into single band and matted ASBO. All observed CT findings were compared between the two groups. A predictive model based on logistic regression was developed, and its ability was quantified by discrimination and calibration. Internal cross-validation was conducted by bootstrap resampling. RESULTS: A total of 116 patients were analyzed (males, 53.5%; median age, 68 years; single band ASBO in 65.5% of cases). The odds of single band ASBO were increased four times in presence of complete obstruction (odds ratios, 4.19; 95% confidence interval, 1.49-12.56) and seven times in presence of fat notch sign (odds ratios, 7.37; 95% confidence interval, 1.83-40.03). The predictive model combining all CT findings had an accuracy of 86% in single band ASBO prediction. Accuracy decreased to 79% in the internal validation. Sensitivity, specificity, and positive and negative predictive values were calculated at different cut-points of the predicted risk: using a 0.70 cut-point, the specificity is 80%, the sensitivity is 68%, and the positive and negative predictive values are 87% and 57%, respectively. CONCLUSION: The proposed predictive model based on combination of specific CT findings may elucidate whether ASBO is caused by single bands or matted adhesions and, consequently, influence the clinical pathway. LEVEL OF EVIDENCE: Prognostic study, level IV.

Percutaneous ablation of post-surgical solitary early recurrence of colorectal liver metastases is an effective "test-of-time" approach.

Standard treatment of early recurrence of colorectal liver metastases (CLM) after liver resection (LR) is chemotherapy followed by loco-regional therapy. We reviewed the outcome of a different strategy ("test-of-time" approach): upfront percutaneous ablation without chemotherapy. Twenty-six consecutive patients with early solitary liver-only recurrence amenable to both resection and ablation (< 30 mm, distant from vessels) undergone "test-of-time" approach were analyzed. Early recurrence had a median size of 17 mm and occurred after a median interval from LR of 4 months. Primary efficacy rate of ablation was 100%. Five patients are alive and disease-free after a mean follow-up of 46 months. Five patients had local-only recurrence; all had repeat treatment (LR = 4; Ablation = 1) without chemotherapy. Local recurrence risk was associated with incomplete ablation of 1-cm thick peritumoral margin. The remaining 16 patients had non-local recurrence, 13 early after ablation. Overall, six (23%) patients had ablation as unique treatment and 13 (50%) avoided or postponed chemotherapy (mean chemotherapy-free interval 33.5 months). Ablation without chemotherapy of early liver-only recurrence is a reliable "test-of-time" approach. It minimized the invasiveness of treatment with good effectiveness and high salvageability in case of local failure, avoided worthless surgery, and saved chemotherapy for further disease progression.