Local recurrence risk factors and outcomes in minimally invasive thermal ablation for liver tumors: a single-institution analysis.

BACKGROUND: Minimally Invasive thermal ablation (MITA) of liver tumors is a commonly performed procedure, alone or in combination with liver resection. Despite being a first-option strategy for small lesions, it is technically demanding, and many concerns still exist about local disease control. METHODS: Consecutive patients undergoing MITA from 1-2019 to 12-2022 were retrospectively enrolled. Risk factors of local recurrence were investigated through univariate and multivariable cox regression analysis. RESULTS: At the multivariable analysis of the 207 nodules undergoing MITA, RFA was associated with worse local Recurrence Free Survival (lRFS) than MWA (HR 2.87 [95 % CI 0.96-8.66], p = 0.05), as well as a concomitant surgical resection (HR 3.89 [95 % CI 1.06-9.77], p = 0.02). A concomitant surgical resection showed worse lRFS in the subgroup analysis of both HCC (HR 3.98 [95 % CI 1.16-13.62], p = 0.02) and CRLM patients (HR 2.68 [95 % CI 0.66-5.92], p = 0.04). Interestingly, a tumor size between 30 and 40 mm was not associated to worse lRFS. CONCLUSION: MWA may reduce the risk of local recurrence in comparison to RFA, while MITA associated to liver resection may face an increased risk of local recurrence. Further prospective studies are needed to confirm such results.

Management of hepatocellular carcinoma recurrence after liver surgery and thermal ablations: state of the art and future perspectives.

Despite the improvements in surgical and medical therapy for hepatocellular carcinoma (HCC), recurrence still represents a major issue. Up to 70% of patients can experience HCC recurrence after liver resection (LR), as well as 20% of them even after liver transplantation (LT). The patterns of recurrence are different according to both the time and the location. Similarly, the risk factors and the management can change not only according to these patterns, but also according to the underlying liver condition and to the first treatment performed. Deep knowledge of such correlation is fundamental, since prevention and effective management of recurrence are undoubtedly the most important strategies to improve the outcomes of HCC treatment. Without adjuvant therapy, maintaining very close monitoring during the first 2 years in order to diagnose curable recurrence and continue this monitoring beyond 5 years because late recurrences exist, remains our only possibility today. Surgery represents the cornerstone treatment for HCC, including both LT and LR. However, new interesting therapeutic opportunities are coming from immunotherapy that has shown encouraging results also in the adjuvant setting. In such a complex and evolutionary scenario, the aim of this review is to summarize current strategies for the management of HCC recurrence, focusing on the different possible scenarios, as well as on future perspectives.

Evolution of laparoscopic liver resection in the last two decades: lessons from 2000 cases at a referral Korean center.

BACKGROUND AND AIMS: Laparoscopic liver resection (LLR) has evolved to become the standard surgical approach in many referral centers worldwide. The aim of this study was to analyze how LLR evolved at a single high-volume referral center since its introduction, more than two decades ago. METHODS: Data from all consecutive LLR between January 2003 and September 2022 at the Seoul National University Bundang Hospital were analyzed. Perioperative outcomes were compared between three time periods, with major technological innovations considered as landmarks: before introduction of laparoscopic-US and CUSA (2003-2006), before (2006-2015) and after (2015-2022) introduction of high-definition scope. RESULTS: During the analyzed time periods the number of technically challenging procedures increased from 39.2 to 61.1% (p < 0.001). The most recent period showed shorter median operation time (from 267.5' to 175', p < 0.001), lower median estimated blood loss (EBL) (from 500 to 300 ml, p < 0.001), lower intraoperative transfusions (from 33.8 to 9.3%, p < 0.001), shorter median postoperative hospital stay (from 12 to 6 days, p < 0.001). The time period, a technical major resection and an underlying liver cirrhosis were found to be the associated with longer operation time (p < 0.001) in the multivariable linear regression analysis, while tumor size, technically major surgeries and liver cirrhosis were associated with higher EBL (p < 0.001). CONCLUSION: During the last two decades, the indications for patients undergoing LLR have expanded significantly, including more and more challenging procedures and frail patients. Despite such challenges, perioperative outcomes improved, although technically major procedures, cirrhotic patients and huge tumors have still to be considered challenging situations.

Laparoscopic versus open liver resection for multiple hepatocellular carcinoma within and beyond the Milan criteria: An Eastern-Western propensity score-matched analysis.

BACKGROUND: There is still little knowledge about the outcomes of laparoscopic liver resection (LLR) for multiple hepatocellular carcinomas (HCC). The aim of this study was to assess the short- and long- term outcomes of LLR versus open liver resection (OLR) for patients with multiple HCC within and beyond the Milan criteria, and in both BCLC-A and -B stage. METHODS: Data regarding all consecutive patients undergoing liver resection for multiple HCC were retrospectively collected from Asian (South Korean) and European (Italian) referral HPB centers. The cases were propensity-score matched for age, BMI, center, extent of the resection, postero-superior location of the lesion, underlying liver condition, BCLB staging and the Milan criteria. RESULTS: A total of 203 patients were included in the study: 27% of patients had undergone hemi-hepatectomy, 26.6% atypical resections, 20.6% sectionectomy and 16.2% segmentectomy. After PSM two cohorts of 57 patients were obtained, with no significant differences in all preoperative characteristics. The length of hospital stay was significantly lower after LLR (median 7 vs. 9 days, p < .01), with no statistically significant differences in estimated blood loss, operation time, transfusions, postoperative bile leak, ascites, severe complications and R1 resection rates. After a median follow-up of 61 (±7) months, there were no significant differences between OLR and LLR in both median OS (69 vs. 59 months, p = .74, respectively) and median DFS (12 vs. 10 months, p = .48, respectively). CONCLUSION: LLR for multiple HCC can be safe and effective in selected cases and is able to shorten median hospital stay without affecting perioperative and long-term oncological outcomes.

Role of neoadjuvant therapy for nonmetastatic pancreatic cancer: Current evidence and future perspectives.

Pancreatic adenocarcinoma (PDAC) is one of the most common and lethal human cancers worldwide. Surgery followed by adjuvant chemotherapy offers the best chance of a long-term survival for patients with PDAC, although only approximately 20% of the patients have resectable tumors when diagnosed. Neoadjuvant chemotherapy (NACT) is recommended for borderline resectable pancreatic cancer. Several studies have investigated the role of NACT in treating resectable tumors based on the recent advances in PDAC biology, as NACT provides the potential benefit of selecting patients with favorable tumor biology and controls potential micro-metastases in high-risk patients with resectable PDAC. In such challenging cases, new potential tools, such as ct-DNA and molecular targeted therapy, are emerging as novel therapeutic options that may improve old paradigms. This review aims to summarize the current evidence regarding the role of NACT in treating non-metastatic pancreatic cancer while focusing on future perspectives in light of recent evidence.

Role of preoperative 3D rendering for minimally invasive parenchyma sparing liver resections.

BACKGROUND: 3D rendering (3DR) represents a promising approach to plan surgical strategies. The study aimed to compare the results of minimally invasive liver resections (MILS) in patients with 3DR versus conventional 2D CT-scan. METHODS: We performed 118 3DR for various indications; the patients underwent a preoperative tri-phasic CT-scan and rendered with Synapse3D® Software. Fifty-six patients undergoing MILS with pre-operative 3DR were compared to a similar cohort of 127 patients undergoing conventional pre-operative 2D CT-scan using the propensity score matching (PSM) analysis. RESULTS: The 3DR mandated pre-operative surgical plan variations in 33.9% cases, contraindicated surgery in 12.7%, providing a new surgical indication in 5.9% previously excluded cases. PSM identified 39 patients in both groups with comparable results in terms of conversion rates, blood loss, blood transfusions, parenchymal R1-margins, grade ≥3 Clavien-Dindo complications, 90-days mortality, and hospital stay respectively in 3DR and conventional 2D. Operative time was significantly increased in the 3DR group (402 vs. 347 min, p = 0.020). Vascular R1 resections were 25.6% vs 7.7% (p = 0.068), while the conversion rate was 0% vs 10.2% (p = 0.058), respectively, for 3DR group vs conventional 2D. CONCLUSION: 3DR may help in surgical planning increasing resectability rate while reducing conversion rates, allowing the precise identification of anatomical landmarks in minimally invasive parenchyma-preserving liver resections.

Liver Venous Deprivation Versus Portal Vein Embolization Before Major Hepatectomy for Colorectal Liver Metastases: A Retrospective Comparison of Short- and Medium-Term Outcomes.

BACKGROUND: Liver venous deprivation (LVD) is a recent radiological technique performed to induce hypertrophy of the future liver remnant. Medium-term results of major hepatectomy after LVD have never been compared with the actual standard of care, portal vein embolization (PVE). METHODS: We retrospectively compared data from 33 consecutive patients who had undergone LVD (n = 17) or PVE (n = 16) prior to a right hemi-hepatectomy or right extended hepatectomy indicated for colorectal liver metastases (CRLM) between May 2015 and December 2019. RESULTS: The 1-year and 3-year overall survival (OS) rates in the LVD group were 81.3% (95% confidence interval [CI]: 72-90) and 54.7% (95% CI: 46-63), respectively, against 85% (95% CI: 69-101) and 77.4% (95% CI: 54-100) in the PVE group; the differences were not statistically significant (p = 0.64). The median disease-free survival (DFS) rate was also comparable: 6 months (95% CI: 4-7) in the LVD group and 12 months (95% CI: 1.5-13) in the PVE group (p = 0.29). The overall intra-operative and post-operative complication rates were similar between the two groups. The mean daily kinetic growth rate (KGR) was found to be higher after LVD than after PVE (0.2% vs. 0.1%, p = 0.05; 10 cc/day vs. 4.8 cc/day, p = 0.03), as was the mean increase in future liver remnant volume (FLR-V) (49% vs. 27%, p = 0.01). CONCLUSIONS: The LVD technique is well tolerated in patients undergoing right hemi-hepatectomy or right extended hepatectomy for CRLM. When compared with the PVE technique, the LVD technique has similar peri-operative and medium-term outcomes, but higher KGR and FLR-V increase.

Gastrointestinal perforation in liver transplantation recipients: risk factors analysis from a 10-year retrospective study with an international multicenter survey about management strategies.

Risk factors for gastrointestinal (GI) perforations in adult liver transplantation (LT) recipients have never been deeply investigated, as well as their management. The aim of this study is to report a single-center 10 years' experience about GI perforations after LT, focusing on risk factors and management strategies according to an international survey involving expert transplant surgeons. Data regarding all consecutive patients undergoing liver transplantations from January 2009 until December 2019 in a single institution were retrospectively collected. Risk factors for GI perforation were investigated. A web survey about the management of gastrointestinal perforations was conducted among worldwide transplantation centers. On 699 adult liver transplantations performed in our center, 20 cases of GI perforations were found, with an incidence of 2.8%. A previous abdominal surgery was found to be the only risk factor (p = 0.01). Ninety-day mortality was 75%. According to the survey, a more conservative treatment was suggested in case of gastric and duodenal perforations (consisting in a direct suture or an external drain), while a more aggressive treatment was adopted for ileal or colic perforation (stoma with or without resection). The W value for inter-personal agreement was 0.41. Despite rare, GI perforations in LT recipients can represent a life-threatening complication. Surgical management can be challenging and depends on both the site of perforation and the clinical conditions of the patient.

Minimally invasive biliary anastomosis after iatrogenic bile duct injury: a systematic review.

Major bile duct injuries (BDIs) may require complex surgical repairs that are usually performed with a conventional open approach. This study aims to analyze current evidence concerning the safety and the outcomes of the minimally invasive (MI) approach for biliary anastomosis in post-cholecystectomy BDIs. A systematic search of MEDLINE, Embase, and Web-Of-Science indexed studies involving MI (laparoscopic or robotic) biliary anastomosis in patients with iatrogenic BDIs was performed. The quality of the studies was assessed using the MINORS criteria. A total of 13 studies involving 198 patients were included. One hundred and twenty-five patients (63.1%) underwent a laparoscopic biliary anastomosis, while 73 (36.1%) received an analogue robotic procedure. All the included BDIs were types D and E (E1-E5). The mean OT varied between 190 and 330 (mean = 227) minutes. Ten studies reported the mean intraoperative blood loss that ranged between 50 and 252 (mean = 135.9) mL. No conversions occurred in the robotic series, while four patients required conversion to open surgery among the laparoscopic ones. The mean length of postoperative hospital stay was 6.3 days. The reported overall morbidity was similar among the robotic and laparoscopic series. During the follow-up period, no surgery-related mortality occurred. A growing number of referral centers are showing the safety and feasibility of the MI approach for biliary anastomosis in patients with major BDIs. Further prospective comparative studies are needed to draw more definitive conclusions.

Selecting the Best Approach for the Treatment of Multiple Non-Metastatic Hepatocellular Carcinoma.

According to the Barcelona Clinic Liver Cancer (BCLC) staging system, the optimal strategy for patients with multiple HCC within the Milan Criteria is liver transplantation (LT). However, LT cannot be offered to all the patients due to organ shortages and long waiting lists, as well as because of the advanced disease carrying a high risk of poor outcomes. For early stages, liver resection (LR) or thermal ablation (TA) can be proposed, while trans-arterial chemoembolization (TACE) still remains the treatment of choice for intermediate stages (BCLC-B). Asian guidelines and the National Comprehensive Cancer Network suggest LR for resectable multinodular HCCs, even beyond Milan criteria. In this scenario, a growing body of evidence shows better outcomes after surgical resection when compared with TACE. Trans-arterial radioembolization (TARE) and stereotaxic body radiation therapy (SBRT) can also play an important role in this setting. Furthermore, the role of minimally invasive liver surgery (MILS) specifically for patients with multiple HCC is still not clear. This review aims to summarize current knowledge about the best therapeutical strategy for multiple HCC while focusing on the role of minimally invasive surgery and on the most attractive future perspectives.

Immunotherapy for hepatocellular carcinoma: A promising therapeutic option for advanced disease.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and its incidence continues to increase. Despite improvements in both medical and surgical therapies, HCC remains associated with poor outcomes due to its high rates of recurrence and mortality. Approximately 50% of patients require systemic therapies that traditionally consist of tyrosine kinase inhibitors. Recently, however, immune checkpoint inhibitors have revolutionized HCC management, providing new therapeutic options. Despite these major advances, the different factors involved in poor clinical responses and molecular pathways leading to resistance following use of these therapies remain unclear. Alternative strategies, such as adoptive T cell transfer, vaccination, and virotherapy, are currently under evaluation. Combinations of immunotherapies with other systemic or local treatments are also being investigated and may be the most promising opportunities for HCC treatment. The aim of this review is to provide updated information on currently available immunotherapies for HCC as well as future perspectives.

Portal vein embolization failure: Current strategies and future perspectives to improve liver hypertrophy before major oncological liver resection.

Portal vein embolization (PVE) is currently considered the standard of care to improve the volume of an inadequate future remnant liver (FRL) and decrease the risk of post-hepatectomy liver failure (PHLF). PHLF remains a significant limitation in performing major liver surgery and is the main cause of mortality after resection. The degree of hypertrophy obtained after PVE is variable and depends on multiple factors. Up to 20% of patients fail to undergo the planned surgery because of either an inadequate FRL growth or tumor progression after the PVE procedure (usually 6-8 wk are needed before surgery). The management of PVE failure is still debated, with a lack of consensus regarding the best clinical strategy. Different additional techniques have been proposed, such as sequential transarterial chemoembolization followed by PVE, segment 4 PVE, intra-portal administration of stem cells, dietary supplementation, and hepatic vein embolization. The aim of this review is to summarize the up-to-date strategies to overcome such difficult situations and discuss future perspectives on improving FRL hypertrophy.

Preoperative Assessment and Perioperative Management of Resectable Gallbladder Cancer in the Era of Precision Medicine and Novel Technologies: State of the Art and Future Perspectives.

Gallbladder carcinoma (GBC) is a rare malignancy, with an estimated 5-year survival rate of less than 5% in the case of advanced disease. Surgery is the only radical treatment for early stages, but its application and effectiveness depend on the depth of tumoral invasion. The extent of resection is usually determined according to the T-stage. Therefore, an early and correct preoperative assessment is important for the prognosis, as well as for the selection of the most appropriate surgical procedure, to avoid unnecessary morbid surgeries and to reach the best outcomes. Several modalities can be used to investigate the depth of invasion, from ultrasounds to CT scans and MRI, but an ideal method still does not exist. Thus, different protocols are proposed according to different recommendations and institutions. In this scenario, the indications for laparoscopic and robotic surgery are still debated, as well as the role of new technologies such as next-generation sequencing and liquid biopsies. The aim of this article is to summarize the state of the art current modalities and future perspectives for assessing the depth of invasion in GBC and to clarify their role in perioperative management accordingly.

Liver venous deprivation versus associating liver partition and portal vein ligation for staged hepatectomy for colo-rectal liver metastases: a comparison of early and late kinetic growth rates, and perioperative and oncological outcomes.

BACKGROUND: Different techniques have been developed to optimize the Future Liver Remnant (FLR). Associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) and liver venous deprivation (LVD) have shown the higher hypertrophy rates, but their place in clinical practice is still debated. METHODS: Thirty-two consecutive ALPPS and LVD procedures for CRLM performed between December 2015 and December 2019 were included. This retrospective study evaluated kinetic growth rates (KGR) as primary outcome, and perioperative and oncological outcomes as secondary endpoints. RESULTS: A total of 17 patients underwent LVD before surgery, whereas 15 underwent ALPPS. On early evaluation (7 vs 9 days, respectively), KGR did not differ between ALPPS and LVD cohort (0.8% per day vs 0.3% per day, p = 0.70; 23 cc/day vs 26 cc/day, p = 0.31). Late evaluation (21 vs 9 days) showed a KGR significantly decreased in the LVD group (0.6% per day vs 0.2% per day, p = 0.21; 20 cc/day vs 10 cc/day p = 0.02). Mean FLR-V increase was comparable in the two groups (60% vs 49%, p 0.32). Successful resection rate was 100% and 94% in LVD and ALPPS group, respectively. The hospital stay (p < 0.0001) and severe complications rate (p = 0.05) were lower after LVD. One and 3-years overall survival (OS) were 72,7% and 27,4% in the ALPSS group, versus 81,3% and 54,7% in LVD group (p = 0.10). The Median DFS was comparable between both techniques (6.1 months and 5.9 respectively, p = 0.66). CONCLUSIONS: LVD and ALPPS shows similar KGR during the early period following preparation as well as similar survival outcomes. Hospital stay and severe complications are lower after LVD.

Endoscopic Diagnosis and Management of Barrett's Esophagus with Low-Grade Dysplasia.

Barrett's Esophagus is a common condition associated with chronic gastroesophageal reflux disease. It is well known that it has an association with a higher incidence of esophageal adenocarcinoma, but this neoplastic transformation is first preceded by the onset of low and high-grade dysplasia. The evaluation of low grade dysplastic esophageal mucosa is still controversial; although endoscopic surveillance is preferred, several minimally invasive endoscopic therapeutic approaches are available. Endoscopic mucosal resection and radiofrequency ablation are the most used endoscopic treatments for the eradication of low-grade dysplasia, respectively, for nodular and flat dysplasia. Novel endoscopic treatments are cryotherapy ablation and argon plasma coagulation, that have good rates of eradication with less complications and post-procedural pain.

Leaping the Boundaries in Laparoscopic Liver Surgery for Hepatocellular Carcinoma.

The minimally invasive approach for hepatocellular carcinoma (HCC) had a slower diffusion compared to other surgical fields, mainly due to inherent peculiarities regarding the risks of uncontrollable bleeding, oncological inadequacy, and the need for both laparoscopic and liver major skills. Recently, laparoscopic liver resection (LLR) has been associated with an improved postoperative course, including reduced postoperative decompensation, intraoperative blood losses, length of hospitalization, and unaltered oncological outcomes, leading to its adoption within international guidelines. However, LLR for HCC still faces several limitations, mainly linked to the impaired function of underlying parenchyma, tumor size and numbers, and difficult tumor position. The aim of this review is to highlight the state of the art and future perspectives of LLR for HCC, focusing on key points for overcoming currents limitations and pushing the boundaries in minimally invasive liver surgery (MILS).

Progression of AFP SCORE is a Preoperative Predictive Factor of Microvascular Invasion in Selected Patients Meeting Liver Transplantation Criteria for Hepatocellular Carcinoma.

Microvascular invasion (MVI) is one of the main prognostic factors of hepatocellular carcinoma (HCC) after liver transplantation (LT), but its occurrence is unpredictable before surgery. The alpha fetoprotein (AFP) model (composite score including size, number, AFP), currently used in France, defines the selection criteria for LT. This study's aim was to evaluate the preoperative predictive value of AFP SCORE progression on MVI and overall survival during the waiting period for LT. Data regarding LT recipients for HCC from 2007 to 2015 were retrospectively collected from a single institutional database. Among 159 collected cases, 34 patients progressed according to AFP SCORE from diagnosis until LT. MVI was shown to be an independent histopathological prognostic factor according to Cox regression and competing risk analysis in our cohort. AFP SCORE progression was the only preoperative predictive factor of MVI (OR = 10.79 [2.35-49.4]; p 0.002). The 5-year overall survival in the progression and no progression groups was 63.9% vs. 86.3%, respectively (p = 0.001). Cumulative incidence of HCC recurrence was significantly different between the progression and no progression groups (Sub-HR = 4.89 [CI 2-11.98]). In selected patients, the progression of AFP SCORE during the waiting period can be a useful preoperative tool to predict MVI.

Future remnant liver optimization: preoperative assessment, volume augmentation procedures and management of PVE failure.

Surgery is the cornerstone treatment for patients with primary or metastatic hepatic tumors. Thanks to surgical and anesthetic technological advances, current indications for liver resections have been significantly expanded to include any patient in whom all disease can be resected with a negative margin (R0) while preserving an adequate future residual liver (FRL). Posthepatectomy liver failure (PHLF) is still a feared complication following major liver surgery, associated with high morbidity, mortality and cost implications. PHLF is mainly linked to both the size and quality of the FRL. Significant advances have been made in detailed preoperative assessment to predict and mitigate this complication, even if an ideal methodology has yet to be defined. Several procedures have been described to induce hypertrophy of the FRL when needed. Each technique has its advantages and limitations, and among them portal vein embolization (PVE) is still considered the standard of care. About 20% of patients after PVE fail to undergo the scheduled hepatectomy, and newer secondary procedures, such as segment 4 embolization, ALPPS and HVE, have been proposed as salvage strategies. The aim of this review was to discuss the current modalities available and new perspectives in the optimization of FRL in patients undergoing major liver resection.

Incisional hernia repair after kidney transplantation in a tertiary high-volume center: outcomes from a 10-year retrospective cohort study.

BACKGROUND AND AIM: Incisional hernia (IH) after Kidney Transplantation (KT) is a challenging complication due to both technical reasons and patients' complexity. Data regarding outcomes of hernia repair in KT recipients are uncertain, since the biggest part of previous papers focused on risk factors for incisional hernia occurrence and not on its outcomes. Aim of the study was to focus on risk factors for incisional hernia recurrence after surgical repair in KT recipients. METHODS: Data regarding all consecutive patients undergoing kidney transplantations from January 2011 until September 2020 in Montpellier University Hospital were retrospectively collected from a single institutional database. RESULTS: After a median follow-up of 48 months (IQR25-75 31-59), data from 1546 consecutive KT were collected. 83 patients underwent 99 incisional hernia surgeries after KT, with 14 patients that had one recurrence (14.4%) and 2 patients that experienced two recurrences (2.4%). Total recurrence rate was 16.8%. At univariate analysis, the only factor associated with an incisional hernia recurrence was having undergone to at least one previous abdominal surgery other than KT (p value 0.002). Overall morbidity was 15% (n = 15), with most of complications classified as mild (59%). No mortality related to incisional hernia repair occurred. CONCLUSION: IHs after KT represent an important condition. Its surgical management is challenging due to its anatomical complexity and patient's status. This is the largest sample size in the literature of patients treated for IH after KT and it shows that a previous surgery other than the KT is a risk factor for hernia recurrence after surgical repair, without regarding surgical technique or other comorbidity and therapeutical factors.