Textbook Outcome of Laparoscopic Microwave Ablation for Hepatocellular Carcinoma.

In the context of spreading interest in textbook outcome (TO) evaluation in different fields, we aimed to investigate an uncharted procedure, that is, laparoscopic microwave ablation (MWA) for hepatocellular carcinoma (HCC). Absence of post-MWA complications, a hospital stay of three days, no mortality nor readmission within 30 days, and complete response of the target lesion at post-MWA CT scan defined TO achievement. Patients treated between January 2014 and March 2021 were retrospectively reviewed, and of the 521 patients eligible for the study, 337 (64.7%) fulfilled all the quality indicators to achieve the TO. The absence of complications was the main limiting factor for accomplishing TO. At multivariable analysis, Child-Pugh B cirrhosis, age of more than 70 years old, three nodules, and MELD score ≥ 15 were associated with decreased probabilities of TO achievement. A score based on these factors was derived from multivariable analysis, and patients were divided into three risk groups for TO achievement. At survival analysis, overall survival (OS) was significantly (p = 0.001) higher in patients who achieved TO than those who did not. Moreover, OS evaluation in the three risk groups showed a trend coherent with TO achievement probability. The present study, having assessed the first TO for laparoscopic MWA for HCC, encourages further broader consensus on its definition and, on its basis, on the development of clinically relevant tools for managing treatment allocation.

Epidemiology and outcomes of surgical site infections among pediatric liver transplant recipients.

INTRODUCTION: Surgical site infections (SSI) are a significant cause of morbidity in liver transplant recipients, and the current data in the pediatric population are limited. The goal of this study was to identify the incidence, classification, risk factors, and outcomes of SSIs among children undergoing liver transplantation (LT). METHODS: A single-center, retrospective descriptive analysis was performed of patients age ≤18 years undergoing LT between September 2007 and April 2017. SSI identified within the first 30 days were analyzed. Primary endpoints included incidence, classification, risk factors, and outcomes associated with SSIs. RESULTS: We included 86 patients, eight patients (9.3%) developed SSIs. Among segmental grafts (SG) recipients, 7/61 (11.4%) developed SSI. Among whole grafts recipients, 1/25 (4%) developed SSI. SSIs were associated with the presence of biliary complications (35% vs. 3%, p < .01; odds ratios 24, 95% CI: 3.41-487.37, p<.01). There were no differences in long term graft or patient survival associated with SSI. Patients who developed SSI were more likely to undergo reoperation (50% vs. 16.7%, p = .045) and had an increased total number of hospital days in the first 60 days post-transplant (30.5 vs. 12.5 days, p = .001). CONCLUSIONS: SSIs after pediatric LT was less frequent than what has been previously reported in literature. SSIs were associated with the presence of biliary complications without an increase in mortality. SG had an increased rate of biliary complications without an association to SSIs but, considering its positive impact on organ shortage barriers, should not be a deterrent to the utilization of SGs.

Colon Rectal Liver Metastases: The Role of the Liver Transplantation in the Era of the Transplant Oncology and Precision Medicine.

The development of liver metastases in colon rectal cancer has a strong impact on the overall survival (OS) of the patient, with a 5-year survival rate of 5% with palliative treatment. Surgical resection combined with pharmacological treatment can achieve a 5-year OS rate of 31-58%. However, in only 20% of patients with colon rectal liver metastases (CRLMs), liver resection is feasible. In highly selected patients, recent trials and studies proved that liver transplantation (LT) for non-resectable CRLM is a surgical option with an excellent long-term OS. The paper aims to review the indications and outcome of LT for CRLMs, with a special focus on immunosuppressive therapy and the management of local and extrahepatic recurrence after LT.

Sustained Complete Response after Biological Downstaging in Patients with Hepatocellular Carcinoma: XXL-Like Prioritization for Liver Transplantation or "Wait and See" Strategy?

The XXL trial represents the first prospective validation of "biological downstaging" in liver transplantation (LT) for hepatocellular carcinoma. The aim of this study was to compare the Padua downstaging protocol to the XXL protocol in terms of downstaging failure rates and patient outcome. A total of 191 patients undergoing aggressive surgical downstaging and potentially eligible for LT from 2012 to 2018 at our center were retrospectively selected according to XXL trial criteria. Unlike the XXL trial, patients with a complete response to downstaging did not receive any prioritization for LT. Downstaging failure was defined as stable progressive disease or post-treatment mortality. The statistical method of "matching-adjusted indirect comparison" was used to match the study group to the XXL population. Downstaging failure rate was considerably lower in the study group than in the XXL trial (12% vs. 32%, d value = |0.683|). The survival curves of our LT group (n = 68) overlapped with those of the LT-XXL group (p = 0.846). Survival curves of non-LT candidates with a sustained complete response (n = 64) were similar to those of transplanted patients (p = 0.281). Our study represents a validation of the current Padua and Italian policies of denying rapid prioritization to patients with complete response to downstaging. Such a policy seems to spare organs without worsening patient outcome.

Thoracoscopic Ablation of Critically Located Liver Tumors: A Safety and Efficacy Cohort Study.

Background: Liver resection represents the first curative treatment to treat primary and secondary hepatic tumors. Thoracoscopic liver ablation is a viable and minimally invasive alternative treatment, especially for patients with previous multiple abdominal surgeries. The aim of the study was to evaluate the safety and efficacy of thoracoscopic ablation for liver tumors. Methods: Retrospective analysis of a prospective database of patients with liver tumors, treated with thoracoscopic trans-diagrammatic ablation (MWA or RFA) at our institution from 2012 to 2018. The primary endpoint was post-operative mortality at 30 days, while secondary endpoints were morbidity and efficacy of ablation (i.e., response rate evaluated according to mRECIST criteria, and overall patient survival). Patient demographics, operational characteristics, and complications were recorded. Results: A total of 13 nodules were treated in 10 patients with a median age of 65.5 years. Post-operative mortality was 0%, and overall morbidity was 40% (Clavien-Dindo I complications 30%, II 0%, III 10%, IV 0%). Complete radiological response was obtained in 83.3% of nodules at 3 months. After a median follow-up of 20.95 months, the local tumor progression rate was 30%, with an intra-segmental-recurrence of 30%, and an intra-hepatic-recurrence of 30%. The overall 1-, 2-, and 3-years survival rates were 80%, 58%, and 58%. Conclusion: Thoracoscopic trans-diaphragmatic ablation proved to be a safe and effective way to treat liver tumors when abdominal approach is not feasible. Considering the low morbidity, it is a viable option to treat patients with recurrent disease and/or previous multiple abdominal surgeries.

Bile Microbiota in Liver Transplantation: Proof of Concept Using Gene Amplification in a Heterogeneous Clinical Scenario.

Objective: Historically, bile in the biliary tract has been considered sterile. Most of the series are based on patients with biliary tract diseases or the bile has been obtained with procedures susceptible to contamination. Methods: We evaluated the bile in a heterogeneous cohort of liver donors and recipient patients, with samples obtained in a sterile way, directly from the gallbladder and the common bile duct. Results: We assessed the bile microbiota in six liver donors and in six liver recipients after whole or split liver procedures in adult or pediatric recipients. Bile samples were studied using PCR sequencing of the 16S ribosomal RNA gene amplification (rDNA). Conclusions: We demonstrated that the bile is sterile, thereby ruling this out as a source of contamination following transplant.

Human Small Intestine Transplantation: Segmental Susceptibility to Ischemia Using Different Preservation Solutions and Conditions.

BACKGROUND AND AIMS: Among all transplanted abdominal organs, the small intestine is one of the most ischemia sensitive. Appropriate graft selection, procurement, and preservation are crucial for optimum graft and patient survival. We evaluated ischemic damage in human small intestine grafts under different hypothermic preservation conditions (cold static and continuous perfusion) and solutions: histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW). METHODS: Fourteen small intestinal grafts were procured from deceased donors. HTK and UW were used for the vascular perfusion at the cross clamp, and UW, HTK, or Ringer Lactate were used for the luminal flush at the back table. Therefore, part of the same harvested intestine was stored in cold static storage and in continuous perfusion preservation (with intestinal perfusion unit) simultaneously. Histological samples were collected from the jejunum and ileum at different time points and different preservation conditions. The samples were collected before the initiation of cold storage (T0), after 8 hours of cold static (ST8), or after 8 hours of continuous perfusion preservation (PT8) (n = 161 samples). Blinded histological evaluation was conducted and ischemic damage was determined using the Park/Chiu scale. RESULTS: The ileum had less ischemic damage than the jejunum, regardless of using static or continuous perfusion preservation. There was no significantly ischemic damage difference between intestinal grafts flushed and perfused with UW or HTK. CONCLUSION: The jejunum is more susceptible to ischemic injury than the ileum. UW and HTK are equivalent to preserve intestinal graft. This suggests that selective transplantation of ileum could reduce ischemia-related postoperative complications.

Sorafenib treatment has the potential to downstage advanced hepatocellular carcinoma before liver resection.

Sorafenib is acknowledged as the standard therapy for advanced hepatocellular carcinoma (HCC) but in the clinical practice the treatment of these patients is extremely complex and needs to be personalized. New evidence suggests that surgical resection-based multimodal treatments may improve outcome in these patients. There is no strong evidence supporting the ability of sorafenib in downstage HCC before surgery. We presented a case of a 53-year-old man with well-compensated HCV-cirrhosis complicated with HCC and neoplastic portal vein thrombosis. The patient was treated initially with sorafenib with optimal radiological and serological response and subsequently with liver resection. Pathological examination showed necrotic portal thrombosis and massive necrosis of a metastatic regional node confirming radiological evidence. This finding suggests that sorafenib exhibits a potential to downstage advanced HCC which is not irrelevant. A possible combination of different modalities has to be considered in the view of a personalized medicine.

Videolaparoscopic microwave ablation in patients with HCC at a European high-volume center: Results of 815 procedures.

BACKGROUND: Videolaparoscopic (VL) microwave ablation (MWA) is not included in most of the international guidelines as a therapeutic option for hepatocellular carcinoma (HCC). Aim of this study was to assess the safety of VL MWA in patients with HCC for whom resection or percutaneous ablation is unsuitable. METHODS: A retrospective analysis was performed on a prospective database of patients with HCC treated with VL MWA at our institution from 2009 to 2016. Patient demographics, operational characteristics, and complications were recorded. Statistical analysis was performed to identify safety profile, overall survival and recurrence rate. RESULTS: A total of 815 VL MWA were performed in 674 patients with a mean age of 64 years. Patients had a mean Model for End-stage Liver Disease score of 10 (±3); 32.8% were Child B, 44.1% Barcelona Clinic Liver Cancer B-C. Perioperative mortality was 0.4%. Overall morbidity was 30.8%, with Dindo-Clavien complications ≥3 in 2%. The median length of stay was 2 days. In 43.1% VL MWA was the first-line therapy. Overall 1-, 3-, and 5-year survival rates were 81.9%, 54.9%, and 35.9%. CONCLUSIONS: The present is the largest series of VL ablation and the bigger number of patients with HCC treated with MW reported nowadays. It confirms the safety of a minimally invasive procedure for patients with HCC when resection or percutaneous ablation is not feasible.

Very Early Introduction of Everolimus in De Novo Liver Transplantation: Results of a Multicenter, Prospective, Randomized Trial.

Early everolimus (EVR) introduction and tacrolimus (TAC) minimization after liver transplantation may represent a novel immunosuppressant approach. This phase 2, multicenter, randomized, open-label trial evaluated the safety and efficacy of early EVR initiation. Patients treated with corticosteroids, TAC, and basiliximab were randomized (2:1) to receive EVR (1.5 mg twice daily) on day 8 and to gradually minimize or withdraw TAC when EVR was stable at >5 ng/mL or to continue TAC at 6-12 ng/mL. The primary endpoint was the proportion of treated biopsy-proven acute rejection (tBPAR)-free patients at 3 months after transplant. As secondary endpoints, composite tBPAR plus graft/patient loss rate, renal function, TAC discontinuation rate, and adverse events were assessed. A total of 93 patients were treated with EVR, and 47 were controls. After 3 months from transplantation, 87.1% of patients with EVR and 95.7% of controls were tBPAR-free (P = 0.09); composite endpoint-free patients with EVR were 85% (versus 94%; P = 0.15). Also at 3 months, 37.6% patients were in monotherapy with EVR, and the tBPAR rate was 11.4%. Estimated glomerular filtration rate was significantly higher with EVR, as early as 2 weeks after randomization. In the study group, higher rates of dyslipidemia (15% versus 6.4%), wound complication (18.32% versus 0%), and incisional hernia (25.8% versus 6.4%) were observed, whereas neurological disorders were more frequent in the control group (13.9% versus 31.9%; P < 0.05). In conclusion, an early EVR introduction and TAC minimization may represent a suitable approach when immediate preservation of renal function is crucial.

Resection for hepatocellular cancer: overpassing old barriers.

Several recent studies have shown that the selection limits commonly used for patients with hepatocellular cancer (HCC) potentially requiring a liver resection (LR) are too restrictive. The present review aims at investigating the studies showing that LR is no longer a treatment suitable only for highly selected patients, but also for patients selectively presenting one-to-more negative factors. Several specific variables have been investigated, none of them showing to be an absolute contraindication for LR: age; single vs. multiple diseases; the dimension of the nodule; hyperbilirubinemia; clinically relevant portal hypertension; Child-Pugh status; macrovascular invasion. As a consequence, LR for the treatment of HCC-on-cirrhosis is a safe and effective procedure not only in "ideal cases", but also for selected patients presenting risk factors. The presence of only one of these factors does not represent an absolute contraindication for LR. On the opposite, the contemporaneous presence of risk factors should contraindicate the procedure. Further studies investigating the "borderline" cases are required, mainly looking at the possible decisive role of laparoscopy in this setting.

Microwave Thermal Ablation in an Unusual Case of Malignant and Locally Advanced Rare Tumor of Pancreas in ASA IV Old Male Patient and Literature Review.

Pancreatic intraductal papillary-mucinous neoplasm is a rare primary neoplasm of unknown pathogenesis. This kind of tumor represents 0.2-2.7% of all pancreatic cancers and they may proceed to malignant lesions. In this study, we describe a case of pancreatic intraductal papillary-mucinous tumor (4.3 cm) with normal tumoral markers and nuclear atypia. We perform also a systematic review of the literature on MEDLINE and find only one relevant study that used microwave ablation for the palliative treatment of pancreatic tumor. We describe the case of a 70-year-old Caucasian male who was diagnosed with a pancreatic tumor with biliary tree dilatation. The patient underwent computed tomography (CT), percutaneous biopsy, and an endoscopic positioning of prosthesis in the biliary tree. Due to the worsening of jaundice and cholestasis, and considering the severe systemic disease status, palliative surgery with microwave thermoablation in the head of pancreas was performed. No complications were observed. The hospitalization lasted for 11 days after surgery, with normal liver and pancreatic lab tests at discharge. The patient followed a line of chemotherapy for 6 months with a complete response for 8 months. One month after the treatment, a staging CT scan was performed showing the size of the cephalopancreatic lesion had decreased from 43 to 35 mm with signs of complete ablation. The patient had a total response at the imaging of 10 months. One year later, a CT scan follow-up showed progression of the pancreatic disease. The disease remained stable for 18 months. The patient died due to cardiovascular complications with an overall survival of 30 months. Microwave ablation in our case report has been demonstrated to be feasible and safe without complications. It can be used as a phase of multimodality treatment in patients with severe systemic disease status and advanced intraductal papillary-mucinous neoplasm.

Extraordinary disease-free survival in a rare malignant extrarenal rhabdoid tumor: a case report and review of the literature.

BACKGROUND: Malignant extrarenal rhabdoid tumor of the gastrointestinal tract is rarely reported in the literature. It is characterized by poor prognosis and aggressive metastatic features. A literature review evidenced only 19 cases, with poor outcome. CASE PRESENTATION: We report a case of a colonic "pure" malignant extrarenal rhabdoid tumor with metastatic nodes in a 65-year-old Caucasian man. He was treated surgically with no recurrence, no adjuvant chemotherapy, and with 4-year survival without disease at the time of the submission of this article. CONCLUSIONS: We present an extraordinary case of long-term survival due to the extended surgical treatment. We believe that the absence of organ metastasis at presentation is a positive prognostic factor, although pathology confirmed node involvement (13/38 positive) on microscopy.

Liver radiofrequency ablation as emergency treatment for a ruptured hepatocellular carcinoma: a case report.

BACKGROUND: Hemoperitoneum is a possible complication of hepatocellular carcinoma that may require emergency surgery as an alternative to radiological locoregional therapies. CASE PRESENTATION: We present a case report of a 78-year-old white man with alcoholic-related cirrhosis and a multifocal hepatocellular carcinoma. An abdominal computed tomography scan showed multiple and bilateral foci of bleeding from broken liver cancer. He was urgently transferred from our radiology unit to our operating room for massive hemoperitoneum. A middle line laparotomy detected a massive hemoperitoneum. His liver was cirrhotic and completely subverted by a tumor; there were two spontaneous bleeding lacerations on segments II and IV, which were uncontrollable with conventional hemostatic techniques. Therefore, it was decided to carry out the coagulation of the multiple vascular afferents of each single mass by means of radiofrequency ablation cycles performed circumferentially on both nodules for a total of 40 minutes. Hemostasis was achieved; the radiofrequency ablation controlled the bleeding from his ruptured hepatocellular carcinoma. He was transferred to our intensive care unit for postoperative monitoring in terms of hemodynamic stability. On postoperative day 2 he was discharged from our intensive care unit. CONCLUSIONS: Multifocal bleeding hepatocellular carcinoma still has an extremely high mortality. The angiographic control of multiple bilateral bleeding lesions can be extremely difficult and can be contraindicated by the location of the lesions and by the overall clinical condition of the patient. In this case, treatment with radiofrequency ablation has proven to be effective in the control of multiple and bilateral hepatic lesions. This particular technique allowed us to attack the lesion at the level of the vascular pedicle in order to control the bleeding.

Modulation of Intestinal Microbiome Prevents Intestinal Ischemic Injury.

Background: Butyrate protects against ischemic injury to the small intestine by reducing inflammation and maintaining the structure of the intestinal barrier, but is expensive, short-lived, and cannot be administered easily due to its odor. Lactate, both economical and more palatable, can be converted into butyrate by the intestinal microbiome. This study aimed to assess in a rat model whether lactate perfusion can also protect against intestinal ischemia. Materials and Methods: Rat intestinal segments were loaded in an in vitro bowel perfusion device, and water absorption or secretion was assessed based on fluorescence of FITC-inulin, a fluorescent marker bound to a biologically inert sugar. Change in FITC concentration was used as a measure of ischemic injury, given the tendency of ischemic cells to retain water. Hematoxylin and eosin-stained sections at light level microscopy were examined to evaluate intestinal epithelium morphology. Comparisons between the data sets were paired Student t-tests or ANOVA with p < 0.05 performed on GraphPad. Results: Lactate administration resulted in a protective effect against intestinal ischemia of similar magnitude to that observed with butyrate. Both exhibited approximately 1.5 times the secretion exhibited by control sections (p = 0.03). Perfusion with lactate and methoxyacetate, a specific inhibitor of lactate-butyrate conversion, abolished this effect (p = 0.09). Antibiotic treatment also eliminated this effect, rendering lactate-perfused sections similar to control sections (p = 0.72). Perfusion with butyrate and methoxyacetate did not eliminate the observed increased secretion, which indicates that ischemic protection was mediated by microbial conversion of lactate to butyrate (p = 0.71). Conclusions: Lactate's protective effect against intestinal ischemia due to microbial conversion to butyrate suggests possible applications in the transplant setting for reducing ischemic injury and ameliorating intestinal preservation during transport.

Use of N-acetylcysteine during liver procurement: a prospective randomized controlled study.

Antioxidant agents have the potential to reduce ischemia/reperfusion damage to organs for liver transplantation (LT). In this prospective, randomized study, we tested the impact of an infusion of N-acetylcysteine (NAC) during liver procurement on post-LT outcomes. Between December 2006 and July 2009, 140 grafts were transplanted into adult candidates with chronic liver disease who were listed for first LT, and according to a sequential, closed-envelope, single-blinded procedure, these patients were randomly assigned in a 1/1 ratio to an NAC protocol (69 patients) or to the standard protocol without NAC [71 patients (the control group)]. The NAC protocol included a systemic NAC infusion (30 mg/kg) 1 hour before the beginning of liver procurement and a locoregional NAC infusion (300 mg through the portal vein) just before cross-clamping. The primary endpoint was graft survival. The graft survival rates at 3 and 12 months were 93% and 90%, respectively, in the NAC group and 82% and 70%, respectively, in the control group (P = 0.02). An adjusted Cox analysis showed a significant NAC effect on graft survival at both 3 months [hazard ratio = 1.65, 95% confidence interval (CI) = 1.01-2.93, P = 0.04] and 12 months (hazard ratio = 1.73, 95% CI = 1.14-2.76, P ≤ 0.01). The incidence of postoperative complications was lower in the NAC group (23%) versus the control group (51%, P < 0.01). In the subgroup of 61 patients (44%) receiving suboptimal grafts (donor risk index > 1.8), the incidence of primary dysfunction of the liver was lower (P = 0.09) for the NAC group (15%) versus the control group (32%). In conclusion, the NAC harvesting protocol significantly improves graft survival. The effect of NAC on early graft function and survival seems higher when suboptimal grafts are used.