Graft Reduction in Adult Liver Transplantation: Indications, Techniques, and Outcomes.

PURPOSE: Graft reduction can be a patients and graft-saving option to avoid large-for-size syndrome. The aim of this article was to summarize the literature on graft reduction in adult liver transplantation and to show the technique of H 6/7 graft hepatectomy. METHODS: The technique, showed in a didactical video, entails an ex-situ posterior sectionectomy under hypothermic perfusion. The right hepatic vein is identified, and the transection line follows the right hepatic fissure. The Glissonean pedicles are ligated during parenchymal transection. RESULTS: A narrative review of the literature yielded seven studies. A total of 15 liver grafts were reduced in adult liver transplantations. Most of the reduction were ex situ (11/15; 73.3%); graft reduction entailed an H6,7 sectionectomy in 10 cases and one H2, 3 in one case. In-situ reduction included one right hepatectomy (H5, 6, 7,8), two H6, 7 sectionectomy, and one H2, 3 left lateral sectionectomy. The duration of ex-situ reduction averaged 56minutes (median 40.5minutes, range 33-130minutes), and the graft weight to recipient weight ratio (GWRW) decreased from 3.57±0.4 to 2.70±0.5% after graft reduction. The average cold ischemia time was 390minutes (range 230-570minutes). There were no liver retransplantations. CONCLUSION: Graft reduction in adult liver transplantation can become necessary to avoid large-for-size syndrome. Ex-situ H6, 7 sectionectomy represents the easiest "graft reduction hepatectomy" and is able to minimize the occurrence of graft compression while leaving enough functional liver parenchyma.

REDISCOVER International Guidelines on the Perioperative Care of Surgical Patients With Borderline-resectable and Locally Advanced Pancreatic Cancer.

OBJECTIVE: The REDISCOVER consensus conference aimed at developing and validate guidelines on the perioperative care of patients with borderline resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking. METHODS: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to non-surgical guidelines. RESULTS: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive mean to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ ). CONCLUSIONS: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR- and LA-PDAC, and serve as the basis of a new international registry for this patient population.

Preoperative pancreatic radiologic characteristics predict pancreatic-specific complications before pancreaticoduodenectomy: the pancreatic acinar radiologic score.

BACKGROUND: High acinar pancreatic contents are associated with a higher rate of postpancreatectomy acute pancreatitis and pancreatic fistula formation (POPF). Predicting acinar contents preoperatively might identify those at high risk of developing postoperative complications. METHODS: A multivariable analysis was performed to identify radiological factors associated with high pancreatic acinar content at histology in patients undergoing pancreaticoduodenectomy. Clinical and radiological variables identified were used to build a composite score predicting low, moderate, and high acinar pancreatic contents. RESULTS: Pancreatic density, wirsung caliber, and pancreatic thickness on preoperative CT-scan predicted acinar contents. These three variables predicted low, moderate, and high acinar content in 94 (26%), 122 (33.6%), and 147 (40.5%) patients, respectively. Patients with high radiological acinar scores compared with patients with intermediate-low risk scores were more frequently male (73.4% vs. 54.1%; p = 0.0003), obese (14% vs. 6%; p = 0.01), and had a statistically significant higher rate of pancreatic-specific complications (23.8% vs. 8.33%; p = 0.01), POPF (12.9% vs. 4.63%; p = 0.005) and pancreaticogastrostomy bleeding (10.8% vs. 4.17%; p = 0.01). CONCLUSION: A simple radiological score combining pancreatic thickness, density, and wirsung caliber at CT scan preoperatively predicts patients with pancreatic parenchyma that are at higher risk of postoperative pancreatic-specific complications.

Management and outcomes of hemorrhage after distal pancreatectomy: a multicenter study at high volume centers.

BACKGROUND: Data on clinically relevant post-pancreatectomy hemorrhage (CR-PPH) are derived from series mostly focused on pancreatoduodenectomy, and data after distal pancreatectomy (DP) are scarce. METHODS: All non-extended DP performed from 2014 to 2018 were included. CR-PPH encompassed grade B and C PPH. Risk factors, management, and outcomes of CR-PPH were evaluated. RESULTS: Overall, 1188 patients were included, of which 561 (47.2 %) were operated on minimally invasively. Spleen-preserving DP was performed in 574 patients (48.4 %). Ninety-day mortality, severe morbidity and CR-POPF rates were 1.1 % (n = 13), 17.4 % (n = 196) and 15.5 % (n = 115), respectively. After a median interval of 8 days (range, 0-37), 65 patients (5.5 %) developed CR-PPH, including 28 grade B and 37 grade C. Reintervention was required in 57 patients (87.7 %). CR-PPH was associated with a significant increase of 90-day mortality, morbidity and hospital stay (p < 0.001). Upon multivariable analysis, prolonged operative time and co-existing POPF were independently associated with CR-PPH (p < 0.005) while a chronic use of antithrombotic agent trended towards an increase of CR-PPH (p = 0.081). As compared to CR-POPF, the failure-to-rescue rate in patients who developed CR-PPH was significantly higher (13.8 % vs. 1.3 %, p < 0.001). CONCLUSION: CR-PPH after DP remains rare but significantly associated with an increased risk of 90-day mortality and failure-to-rescue.

Volumetric Remodeling of the Left Liver After Right Hepatectomy: Analysis of Factors Predicting Degree of Hypertrophy and Post-hepatectomy Liver Failure.

BACKGROUND: This study investigated the volumetric remodeling of the left liver after right hepatectomy looking for factors predicting the degree of hypertrophy and severe post-hepatectomy liver failure (PHLF). METHODS: In a cohort of 121 right hepatectomies, we performed CT volumetrics study of the future left liver remnant (FLR) preoperatively and postoperatively. Factors influencing FLR degree of hypertrophy and severe PHLF were identified by multivariate analysis. RESULTS: After right hepatectomy, the mean degree of hypertrophy and kinetic growth rate of the left liver remnant were 25% and 3%/day respectively. The mean liver volume recovery rate was 77%. Liver remodeling volume was distributed for 79% on segments 2 and 3 and 21% on the segment 4 (p<0.001). Women showed a greater hypertrophy of segments 2 and 3 compared with men (p=0.002). The degree of hypertrophy of segment 4 was lower in case of middle hepatic vein resection (p=0.004). Left liver remnant kinetic growth rate was associated with the standardized future liver remnant (sFLR) (p<0.001) and a two-stage hepatectomy (p=0.023). Severe PHLF were predicted by intraoperative transfusion (p=0.009), biliary tumors (p=0.013), and male gender (p=0.022). CONCLUSIONS: Volumetric remodeling of the left liver after right hepatectomy is not uniform and is mainly influenced by gender and sacrifice of middle hepatic vein. Male gender, intraoperative transfusion, and biliary tumors increase the risk of postoperative liver failure after right hepatectomy.

Extended Right Hepatectomy to Inferior Vena Cava Under Total Vascular Exclusion, Veno-Venous Bypass and In Situ Hypothermic Perfusion of the Future Liver Remnant.

BACKGROUND: Venous obstruction at the hepatic veins-inferior vena cava confluence can be particularly challenging to manage if an associated liver resection is needed. Total vascular exclusion (TVE) with veno-venous bypass (VVB) and hypothermic in situ perfusion (HP) of the future liver remnant can be used in these conditions.1,2 METHODS: The patient was a 58-year-old with a voluminous adrenal cancer invading the kidney, the right liver and the retrohepatic inferior vena cava with intraluminal thrombus extending up to the hepatic veins confluence. A right hepatectomy, extended to segment 1, the right kidney, and the retrohepatic inferior vena cava was planned. RESULTS: The parenchymal liver transection was performed under a TVE, VVB, and HP of the left liver to decrease blood losses and risk of postoperative liver failure. Vena cava reconstruction was achieved by a ringed Gore-Tex prosthesis with reimplantation of the left renal vein. Total duration of veno-venous bypass and liver vascular exclusion were 2 h 40 min and 2 h 10 min, respectively. The patient was discharged on postoperative day 17. CONCLUSIONS: Total vascular exclusion with veno-venous bypass and in-situ liver hypothermic perfusion increases the safety of major liver resection requiring complex vascular reconstruction.1,2 TVE under VVB and HP of the future liver remnant is used at our institution when: (1) TVE will last more than 30 min; (2) vascular reconstruction is needed; (3) in the presence of venous obstruction; (4) in the presence of injured liver parenchyma; and (5) in the presence of cardiovascular comorbidities.

Sequential Y90 liver radioembolization and portal vein embolization: an additional strategy to downstage liver tumors and to enhance liver hypertrophy before major hepatectomies.

BACKGROUND: Yttrium (Y)90 liver radioembolization (TARE) induces both tumor downsizing and contralateral liver hypertrophy. In this study, we report the preliminary results of a sequential strategy combining Y90 radioembolization and portal vein embolization (PVE) before major right liver resections. METHODS: We retrospectively reviewed clinical, radiological, and biological data of 5 consecutive patients undergoing Y90 TARE-PVE before major right liver resections. Comparison was made with patients undergoing PVE alone or liver venous deprivation (LVD) during the same period. RESULTS: Between January 2019 and September 2022, five patients underwent sequential TARE-PVE. Type of resection included the following: right hepatectomy (n = 1), right hepatectomy + 1 (n = 2), and right hepatectomy + 1 + 4 (n = 2) with no postoperative mortality. Volumetric data showed a mean hypertrophy ratio of 30.4% after TARE and an additional 37.4% after sequential PVE. Patients undergoing sequential TARE-PVE had higher hypertrophy ratio (p = 0.02; p = 0.004), hypertrophy degree (p = 0.02; p < 0.0001), shorter time to normalize bilirubin (p = 0.04), and prothrombin time (p = 0.003; p < 0.0001) compared with patients receiving LVD or PVE. Time from diagnosis to surgery was statistically significant longer in patients undergoing sequential TARE-PVE compared with LVD or PVE (293.4 ± 169.1 vs 54.18 ±18.26 vs 58.62±13.15; p = 0.0008; p = <0.0001). CONCLUSIONS: This preliminary report suggests that sequential PVE and TARE can represent a safe and an alternative strategy to downstage liver tumors and to enhance liver hypertrophy before major hepatectomies. When compared with PVE and LVD, sequential TARE/PVE takes longer times but achieves some advantages which warrant further evaluation in a larger setting.

Incidence and outcomes of post-hepatectomy diaphragmatic hernia: a systematic review.

BACKGROUND: Post-hepatectomy diaphragmatic hernia is the second most common cause of acquired diaphragmatic hernia. This study aims to review the literature on this complication's incidence, treatment and prognosis. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched PubMed for all studies related to acquired diaphragmatic hernias after hepatectomy. RESULTS: We included 28 studies in our final analysis, comprising 11,368 hepatectomies. The incidence of post-hepatectomy diaphragmatic hernia was 0.75% (n = 86). The most frequent type of hepatectomy performed was right hepatectomy (79%, n = 68), and the indications for liver resection were a liver donation for living donor transplantation (n = 40), malignant liver tumors (n = 13), and benign tumors (n = 11). The mean onset between liver resection and the diagnosis of diaphragmatic hernia was 25.7 months (range, 1-72 months), and the hernia was located on the right diaphragm in 77 patients (89.5%). Pain was the most common presenting symptom (n = 52, 60.4%), while six patients were asymptomatic (6.9%). Primary repair by direct suture was the most frequently performed technique (88.3%, n = 76). Six patients experienced recurrence (6.9%), and three died before diaphragmatic hernia repair (3.5%). CONCLUSION: Diaphragmatic hernia is a rare complication occurring mainly after right liver resection. Repair should be performed once detected, given the not-negligible associated mortality in the emergency setting.

Novel Benchmark Values for Open Major Anatomic Liver Resection in Non-cirrhotic Patients: A Multicentric Study of 44 International Expert Centers.

OBJECTIVE: This study aims at establishing benchmark values for best achievable outcomes following open major anatomic hepatectomy for liver tumors of all dignities. BACKGROUND: Outcomes after open major hepatectomies vary widely lacking reference values for comparisons among centers, indications, types of resections, and minimally invasive procedures. METHODS: A standard benchmark methodology was used covering consecutive patients, who underwent open major anatomic hepatectomy from 44 high-volume liver centers from 5 continents over a 5-year period (2016-2020). Benchmark cases were low-risk non-cirrhotic patients without significant comorbidities treated in high-volume centers (≥30 major liver resections/year). Benchmark values were set at the 75th percentile of median values of all centers. Minimum follow-up period was 1 year in each patient. RESULTS: Of 8044 patients, 2908 (36%) qualified as benchmark (low-risk) cases. Benchmark cutoffs for all indications include R0 resection ≥78%; liver failure (grade B/C) ≤10%; bile leak (grade B/C) ≤18%; complications ≥grade 3 and CCI ® ≤46% and ≤9 at 3 months, respectively. Benchmark values differed significantly between malignant and benign conditions so that reference values must be adjusted accordingly. Extended right hepatectomy (H1, 4-8 or H4-8) disclosed a higher cutoff for liver failure, while extended left (H1-5,8 or H2-5,8) were associated with higher cutoffs for bile leaks, but had superior oncologic outcomes, when compared to formal left hepatectomy (H1-4 or H2-4). The minimal follow-up for a conclusive outcome evaluation following open anatomic major resection must be 3 months. CONCLUSION: These new benchmark cutoffs for open major hepatectomy provide a powerful tool to convincingly evaluate other approaches including parenchymal-sparing procedures, laparoscopic/robotic approaches, and alternative treatments, such as ablation therapy, irradiation, or novel chemotherapy regimens.

Additional value of interleukin-6 level to predict histopathological features of hepatocellular carcinoma before liver transplantation.

BACKGROUND & AIMS: Inflammatory biomarkers are increasingly used as outcome predictors in the field of oncology and liver transplantation for HCC, but no study has shown the prognostic value of IL6 after LT. The goal of this study was to evaluate the predictive value of IL-6 on histopathological features of HCC on explant, its predictive value on recurrence risk and its additional value to other scores and inflammatory markers at the time of transplantation. METHODS: From 2009 to 2019, all adults transplanted with a first liver graft and diagnosed with HCC on the explant analysis were retrospectively included (n = 229). Only patients who had a pre-LT IL6 level determination were analysed in this study (n = 204). RESULTS: High IL-6 level at transplantation was associated with a significantly higher risk of vascular invasion (15% vs 6%; p = 0.023), microsatellitosis (11% vs 3%; p = 0.013), lower rate of histological response both in terms of complete response (2% vs 14%, p = 0.004) and of necrosis (p = 0.010). Patients with pre-LT IL-6 level > 15 ng/ml had a lower overall and cancer-specific survival (p = 0.013). Recurrence-free survival was lower in patients with IL-6 > 15 ng/ml with a 3-year recurrence-free survival of 88% versus 78% (p = 0.034). IL6 levels were significantly higher in patients with early recurrence compared to patients without (p = 0.002) or with late recurrence (p = 0.044). CONCLUSIONS: IL6 level at transplantation is an independent predictor of pejorative histological features of HCC and is associated to the risk of recurrence.

Predicting Limited Survival After Resection of Synchronous Colorectal Liver Metastases: a Propensity Score Matched Comparison Between The Primary First And The Simultaneous Strategy.

BACKGROUND: The best surgical approach to treat synchronous colorectal liver metastases (CRLM) remains unclear. Here, we aimed to identify prognostic factors associated with limited survival comparing patients undergoing primary-first resection (PF) and simultaneous resection (SR) approaches. METHODS: We retrospectively reviewed clinical data of 217 patients who underwent resection for synchronous CRLMs between January 1, 2011, and December 31, 2021. There were 133 (61.2%) PF resection and 84 (38.8%) SRS. The two groups of patients were compared using propensity score matching (PSM) analysis and cox analysis was performed to identify prognostic factors for overall survival (OS). RESULTS: After PSM, two groups of 71 patients were compared. Patients undergoing SR had longer operative time (324 ± 104 min vs 250 ± 101 min; p < 0.0001), similar transfusion (33.3% vs 28.1%; p = 0.57), and similar complication rates (35.9% vs 27.2%; p = 0.34) than patients undergoing PF. The median overall survival and 5-year survival rates were comparable (p = 0.94) between patients undergoing PF (48.2 months and 44%) and patients undergoing SR (45.9 months and 30%). Multivariate Cox analysis identified pre-resection elevated CEA levels (HR: 2.38; 95% CI: 1.20-4.70; P = .01), left colonic tumors (HR: 0.34; 95% CI: 0.17-0.68; P = .002), and adjuvant treatment (HR: 0.43; 95% CI: 0.22-0.83; P = .01) as independent prognostic factors for OS. CONCLUSIONS: In the presence of synchronous CRLM, right colonic tumors, persistent high CEA levels before surgery, and the absence of adjuvant treatment identified patients characterized by a limited survival rate after resection. The approach used (PF vs SR) does not influence short and long-term outcomes.

Gemcitabine-induced peripheral vascular disease and prolonged response in a patient with metastatic pancreatic adenocarcinoma: A case report.

BACKGROUND: Gemcitabine is an antimetabolite used in the treatment of pancreatic cancer. One of the side effects of gemcitabine is vascular toxicity. Here, we report the case of a patient treated with gemcitabine who had peripheral vascular disease concomitant with a prolonged antitumor response. CASE SUMMARY: A 75-year-old man was diagnosed with locally recurrent pancreatic cancer. Partial response was achieved after 9 mo of gemcitabine. At the same time, the patient reported peripheral vascular disease without necrosis. Chemotherapy was suspended, and after one month the Positron Emission Tomography (PET) scan showed locoregional tumor recurrence. Gemcitabine was resumed and partial response was obtained, but peripheral vascular disease occurred. CONCLUSION: Our results suggest that the appearance of peripheral vascular disease may be related to a prolonged response to gemcitabine.