Single stage management of suspected gallbladder cancer guided by intraoperative frozen section analysis: A retrospective cohort study.

BACKGROUND: The management of radiologically suspected gallbladder cancers (GBC) that lack definitive radiological features usually involves performing a first-stage routine laparoscopic cholecystectomy, followed by an open second-stage liver resection (segments IVB and V) and hilar lymphadenectomy (extended cholecystectomy) if subsequent formal histology confirms a malignancy. Performing a cholecystectomy with an intraoperative frozen section to guide the need for conversion to an extended cholecystectomy as a single-stage procedure has multiple benefits compared to a two-stage approach. However, the safety and efficacy of this approach have not yet been evaluated in a tertiary setting. METHODS: A retrospective cohort study was performed using a database of all consecutive patients with suspected GBC who had been referred to our tertiary unit. Following routine cholecystectomy, depending on the operative findings, the gallbladder specimen was removed and sent for frozen-section analysis. If malignancy was confirmed, the depth of tumour invasion was evaluated, followed by simultaneous extended cholecystectomy, when appropriate. The sensitivity and specificity of frozen section analysis for the diagnosis of GBC were measured using formal histopathology as a reference standard. RESULTS: A total of 37 consecutive cholecystectomies were performed. In nine cases, GBC was confirmed by intraoperative frozen section analysis, three of which had standard cholecystectomy only as their frozen section showed adenocarcinoma to be T1a or below (n=2) or were undetermined (n=1). In the remaining six cases, malignant invasion beyond the muscularis propria (T1b or above) was confirmed; thus, a synchronous extended cholecystectomy was performed. The sensitivity (95% CI 66.4%-100%) and specificity (95% CI 87.7%-100%) for identifying GBC using frozen section analysis were both 100%. The net cost of the single-stage pathway in comparison to the two-stage pathway resulted in overall savings of £3894. CONCLUSION: Intraoperative frozen section analysis is a reliable tool for guiding the use of a safe, single-stage approach for the management of GBC in radiologically equivocal cases. In addition to its lower costs compared to a conventional two-stage procedure, intraoperative analysis also affords the benefit of a single hospital admission and single administration of general anaesthesia, thus greatly enhancing the patient's experience and relieving the burden on waiting lists.

Tumour Heterogeneity and the Consequent Practical Challenges in the Management of Gastroenteropancreatic Neuroendocrine Neoplasms.

Tumour heterogeneity is a common phenomenon in neuroendocrine neoplasms (NENs) and a significant cause of treatment failure and disease progression. Genetic and epigenetic instability, along with proliferation of cancer stem cells and alterations in the tumour microenvironment, manifest as intra-tumoural variability in tumour biology in primary tumours and metastases. This may change over time, especially under selective pressure during treatment. The gastroenteropancreatic (GEP) tract is the most common site for NENs, and their diagnosis and treatment depends on the specific characteristics of the disease, in particular proliferation activity, expression of somatostatin receptors and grading. Somatostatin receptor expression has a major role in the diagnosis and treatment of GEP-NENs, while Ki-67 is also a valuable prognostic marker. Intra- and inter-tumour heterogeneity in GEP-NENS, however, may lead to inaccurate assessment of the disease and affect the reliability of the available diagnostic, prognostic and predictive tests. In this review, we summarise the current available evidence of the impact of tumour heterogeneity on tumour diagnosis and treatment of GEP-NENs. Understanding and accurately measuring tumour heterogeneity could better inform clinical decision making in NENs.

Efficacy of local anaesthetic infiltration via wound catheters after open hepatic surgery: a systematic review and meta-analysis.

BACKGROUND: This study analysed whether local anaesthetic wound catheter infiltration (LA-WCI) as an adjunct to intravenous patient-controlled analgesia (IV-PCA) provides superior outcomes compared to IV-PCA alone following liver resection. METHODS: A systematic review and meta-analysis was conducted for randomised control trials (RCTs) comparing LA-WCI with IV-PCA(LA-WCI group) versus IV-PCA alone (IV-PCA group). PubMed and the Cochrane Library were searched for relevant articles. RESULTS: Six RCTs with a total of 440 patients were included. Opioid use in the initial 48 h was less in the LA-WCI group [MD -21.27 mg (-39.39,-3.15), p = 0.02]. Pain scores were lower in the LA-WCI group at rest at POD0 (post-operative day 0)6-8 h (p = 0.0009), POD1AM(p = 0.01), POD1PM(p = 0.02) and POD2 (p = 0.0006), and exertion at POD0 0-2 h (p = 0.05), POD1AM(p = 0.03), POD1PM(p = 0.03), POD2 (p = 0.03) and POD3 (p = 0.01). LA-WCI group had reduced length of hospital stay [MD -1.32 days (-2.23,-0.40),p = 0.005], time to ambulation [MD -5.94 h (-8.47,-3.42),p = 0.00001] and incidence of nausea and vomiting (PONV) [OR 0.17 (0.07,0.43),p = 0.0002]. No differences were observed in length of intensive care unit (ICU) stay or incidence of surgical site infections. DISCUSSION: LA-WCI as an adjunct to opiate IV-PCA post-hepatectomy reduces opioid use, pain scores at multiple time points at rest and exertion, length of hospital stay, time to ambulation and PONV. However, LA-WCI use does not alter length of ICU stay or incidence of wound infection.

Pancreaticoduodenectomy with right hemicolectomy for advanced malignancy: a single UK hepatopancreaticobiliary centre experience.

AIM: Locally advanced intestinal neoplasms including colon cancer may require radical en bloc pancreaticoduodenectomy and right hemicolectomy (PD-RC) to achieve curative, margin-negative resection, but the safety and benefit of this uncommon procedure has not been established. The Association of Coloproctology of Great Britain and Ireland IMPACT initiative has also highlighted a lack of awareness about current services available within the UK for patients with advanced colorectal cancer and concerns about low-volume centres managing complex cases. Thus, we aimed to review the feasibility, safety and long-term outcomes of this procedure at a single high-volume hepatopancreaticobiliary surgery unit in the UK. METHOD: A retrospective cohort study was performed using a database of all consecutive patients with intestinal cancer who had been referred to our regional advanced multidisciplinary team and undergone PD-RC in a 7-year period (2013-2020). Clinico-pathological and outcome data were reviewed. RESULTS: Ten patients (mean age 54 ± 13, 8/10 men) were identified. Final histology revealed the primary tumour sites were colon (n = 7) and duodenum (n = 3). R0 resection was achieved in all cases. The major complication rate (Clavien-Dindo ≥ 3) was 10% (1/10) with no deaths within 90 days of surgery. The Kaplan-Meier estimated 5-year overall survival was 83.3% (95% CI 58.3%-100%). Univariate survival analysis identified perineural invasion and extra-colonic origin as predictors of poor survival (log-rank P < 0.05). CONCLUSION: En bloc PD-RC for locally advanced intestinal cancer can be performed safely with a high proportion of margin-negative resections and resultant long-term survival in carefully selected patients.

HOW TO PERFORM LAPAROSCOPIC DISTAL PANCREATECTOMY USING THE CLOCKWISE TECHNIQUE.

BACKGROUND: Laparoscopic pancreatectomy is currently a widely used approach for benign and malignant lesions of the pancreas. AIMS: This study aimed to describe how to perform a laparoscopic distal pancreatectomy using The Clockwise Technique. METHODS: An 18-year-old female patient presented with a well-defined tumor in the pancreatic body with 4 cm in diameter that suggested a diagnosis of solid pseudopapillary tumor (Frantz's tumor). The patient was recommended for laparoscopic distal pancreatectomy by using The Clockwise Technique. RESULTS: The clockwise, caudal-to-cephalic approach appears to have other significant technical advantages that facilitate the performance of the procedure. CONCLUSIONS: A laparoscopic distal pancreatectomy performed using The Clockwise Technique provides satisfactory outcomes.

How to perform laparoscopic distal pancreatectomy using the clockwise technique / Como realizar a pancreatectomia distal laparoscópica usando a clockwise technique

ABSTRACT - BACKGROUND: Laparoscopic pancreatectomy is currently a widely used approach for benign and malignant lesions of the pancreas. AIMS: This study aimed to describe how to perform a laparoscopic distal pancreatectomy using The Clockwise Technique. METHODS: An 18-year-old female patient presented with a well-defined tumor in the pancreatic body with 4 cm in diameter that suggested a diagnosis of solid pseudopapillary tumor (Frantz's tumor). The patient was recommended for laparoscopic distal pancreatectomy by using The Clockwise Technique. RESULTS: The clockwise, caudal-to-cephalic approach appears to have other significant technical advantages that facilitate the performance of the procedure. CONCLUSIONS: A laparoscopic distal pancreatectomy performed using The Clockwise Technique provides satisfactory outcomes.

RESUMO - RACIONAL: A pancreatectomia laparoscópica está se tornando uma abordagem amplamente usada para lesões benignas e malignas do pâncreas. OBJETIVOS: Descrever como realizar a pancreatectomia distal laparoscópica usando a Clockwise Technique. MÉTODOS: Paciente feminina com 18 anos de idade, apresentando tumor bem definido no corpo pancreático com 4 cm de diâmetro que sugeria o diagnóstico de tumor sólido pseudopapilar (tumor de Frantz). O paciente foi considerado para pancreatectomia distal laparoscópica pela Clockwise Technique. RESULTADOS: A Clockwise Technique parece apresentar outras vantagens técnicas significativas que facilitam a realização do procedimento. CONCLUSÕES: A pancreatectomia distal laparoscópica foi realizada com a clockwise technique, obtendo-se resultados satisfatórios.

Upregulation of C/EBPα Inhibits Suppressive Activity of Myeloid Cells and Potentiates Antitumor Response in Mice and Patients with Cancer.

PURPOSE: To evaluate the mechanisms of how therapeutic upregulation of the transcription factor, CCAAT/enhancer-binding protein alpha (C/EBPα), prevents tumor progression in patients with advanced hepatocellular carcinoma (HCC) and in different mouse tumor models. EXPERIMENTAL DESIGN: We conducted a phase I trial in 36 patients with HCC (NCT02716012) who received sorafenib as part of their standard care, and were given therapeutic C/EBPα small activating RNA (saRNA; MTL-CEBPA) as either neoadjuvant or adjuvant treatment. In the preclinical setting, the effects of MTL-CEBPA were assessed in several mouse models, including BNL-1ME liver cancer, Lewis lung carcinoma (LLC), and colon adenocarcinoma (MC38). RESULTS: MTL-CEBPA treatment caused radiologic regression of tumors in 26.7% of HCC patients with an underlying viral etiology with 3 complete responders. MTL-CEBPA treatment in those patients caused a marked decrease in peripheral blood monocytic myeloid-derived suppressor cell (M-MDSC) numbers and an overall reduction in the numbers of protumoral M2 tumor-associated macrophages (TAM). Gene and protein analysis of patient leukocytes following treatment showed CEBPA activation affected regulation of factors involved in immune-suppressive activity. To corroborate this observation, treatment of all the mouse tumor models with MTL-CEBPA led to a reversal in the suppressive activity of M-MDSCs and TAMs, but not polymorphonuclear MDSCs (PMN-MDSC). The antitumor effects of MTL-CEBPA in these tumor models showed dependency on T cells. This was accentuated when MTL-CEBPA was combined with checkpoint inhibitors or with PMN-MDSC-targeted immunotherapy. CONCLUSIONS: This report demonstrates that therapeutic upregulation of the transcription factor C/EBPα causes inactivation of immune-suppressive myeloid cells with potent antitumor responses across different tumor models and in cancer patients. MTL-CEBPA is currently being investigated in combination with pembrolizumab in a phase I/Ib multicenter clinical study (NCT04105335).

PRIME-HCC: phase Ib study of neoadjuvant ipilimumab and nivolumab prior to liver resection for hepatocellular carcinoma.

BACKGROUND: After liver resection (LR), patients with hepatocellular cancer (HCC) are at high risk of recurrence. There are no approved anti-cancer therapies known to affect such risk, highlighting the acute need for novel systemic therapies to control the probability of disease relapse. Immunotherapy is expanding as a novel treatment option for HCC. Emerging data from cohort 4 of the CA209-040 study, which investigated the safety and preliminary efficacy of nivolumab/ipilimumab co-administration in advanced HCC, suggest that the combination can be delivered safely with an acceptable proportion of reversible grade 3-4 toxicities (27.1%) and a low discontinuation rate (2%) in patients with HCC. Here, we describe the design and rationale of PRIME-HCC, a two-part, multi-centre, phase Ib study to assess safety and bioactivity of the nivolumab/ipilimumab combination prior to LR in early-stage HCC. METHODS: The study involves an initial safety run-in phase (Part 1) to allow for preliminary safety characterisation within the first 6 patients enrolled and a subsequent expansion (Part 2). Ipilimumab will be administered once only on Day 1. Nivolumab will be administered on Day 1 and Day 22 (± 3 days) for a total of two 21-day cycles (i.e. 6 weeks of treatment). The primary objective of the study is to determine the safety and tolerability of the nivolumab/ipilimumab combination prior to LR. The secondary objective is to preliminarily characterize the efficacy of the combination prior to LR, including objective response rate (ORR) and pathologic response rates. Additional exploratory objectives include preliminary evidence of long-term disease control and to identify predictive correlates of response to the nivolumab/ipilimumab combination in HCC. DISCUSSION: The results of this study will help define the positioning of neoadjuvant nivolumab/ipilimumab combination in the perioperative management of HCC, with potential to improve survival outcomes in this patient population. TRIAL REGISTRATION: EudraCT Number: 2018-000987-27 Clinical trial registry & ID: ClinicalTrials.gov : NCT03682276 .

A systematic review into patient reported outcomes following pancreaticoduodenectomy for malignancy.

BACKGROUND: Pancreaticoduodenectomy is associated with high rates of morbidity. This combined with the psychological burden of cancer, may impact on a patient's quality of life (QoL), which can be measured by using patient-reported outcomes (PRO). OBJECTIVE: To perform a systematic review to evaluate the measurement of PRO after pancreaticoduodenectomy for cancer. METHODS: 7 different databases were searched using 2 groups of search terms, one relating to pancreaticoduodenectomy, and one to PRO. Three authors screened the search results independently in a systematic manner based on predefined inclusion and exclusion criteria. RESULTS: 27 studies, with 2173 eligible patients were included in the final analysis. Most of the included studies used validated instruments. The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire was most popular and used in 12 studies. The methodology of all included studies was also scrutinised. 12 studies were deemed to have high quality methodology according to pre-defined criteria. CONCLUSION: The instruments and methods used to measure PRO are variable. The quality of PRO within the available literature has improved over time, as has the number of studies measuring PRO. PRO should be measured with uniformity in future trials so that patients can be provided with more comprehensive information regarding post-operative recovery and QoL during the shared decision-making process preoperatively.

Effectiveness of Terlipressin on Modulation of Portal Vein Pressure after Hepatic Resections in Non-Cirrhotic Patients. A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Background-Objectives: It has been reported, that high posthepatectomy portal vein pressure (PVP) has deleterious effect on the liver parenchyma and causes posthepatectomy liver failure (PHLF) and increased 90-day mortality. Terlipressin, is widely used to mitigate the effects of portal hyper-tension. Randomised clinical trials (RCTs) demonstrated encouraging results of use of terlipressin for modulation of increased posthepatectomy PVP. The aim of the present study was to evaluate the effectiveness of the pharmacological modulation of the increased posthepatectomy PVP after major hepatectomy. Methods: Systematic literature searches of electronic databases in accordance with PRISMA was conducted. Meta-analysis was conducted using both fixed- and random-effects models. Results: Three randomised controlled trials (RCTs) comparing terlipressin versus placebo including 284 patients of pooled 60 studies were selected. Placebo cohort patients were significantly younger by 5 years compared to terlipressin cohort. However, the terlipressin cohort demonstrated significantly shorter intensive care unit (ICU) stay compared to placebo cohort. Conclusions: The first meta-analysis demonstrated that terlipressin cohort patients although significantly older by 5 years had significantly shorter ICU stay compared to placebo cohort. Furthermore, though statistically nonsignificant only 6% of terlipressin patients needed inotropic support compared to 16.4% of placebo cohort.

No difference in mortality among ALPPS, two-staged hepatectomy, and portal vein embolization/ligation: A systematic review by updated traditional and network meta-analyses.

BACKGROUND: There is an ongoing debate on the feasibility, safety, and oncological efficacy of the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) technique. The aim of this study was to compare ALPPS, two-staged hepatectomy (TSH), and portal vein embolization (PVE)/ligation (PVL) using updated traditional meta-analysis and network meta-analysis (NMA). DATA SOURCES: Electronic databases were used in a systematic literature search. Updated traditional meta-analysis and NMA were performed and compared. Mortality and major morbidity were selected as primary outcomes. RESULTS: Nineteen studies including 1200 patients were selected from the pool of 436 studies. Of these patients, 315 (31%) and 702 (69%) underwent ALPPS and portal vein occlusion (PVO), respectively. Ninety-day mortality based on updated traditional meta-analysis, subgroup analysis of the randomized controlled trials (RCTs), and both Bayesian and frequentist NMA did not demonstrate significant differences between the ALPPS cohort and the PVE, PVL, and TSH cohorts. Moreover, analysis of RCTs did not demonstrate significant differences of major morbidity between the ALPPS and PVO cohorts. The ALPPS cohort demonstrated significantly more favorable outcomes in hypertrophy parameters, time to operation, definitive hepatectomy, and R0 margins rates compared with the PVO cohort. In contrast, 1-year disease-free survival was significantly higher in the PVO cohort compared to the ALPPS cohort. CONCLUSIONS: This study is the first to use updated traditional meta-analysis and both Bayesian and frequentist NMA and demonstrated no significant differences in 90-day mortality between the ALPPS and other hepatic hypertrophy approaches. Furthermore, two high quality RCTs including 147 patients demonstrated no significant differences in major morbidity between the ALPPS and PVO cohorts.

The Impact of COVID-19 Global Pandemic on Morbidity and Mortality of Liver Transplant Recipients Children and Adults: A Systematic Review of Case Series.

The pandemic of coronavirus disease 2019 (COVID-19) changed the surgical everyday practice overnight. Currently, the first articles reporting outcomes of liver transplant recipients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are published. The aim of the present study was to summarise the existing evidence of impact of COVID-19 global pandemic on liver transplant recipients. Electronic databases were searched in accordance with Preferred Reporting Items in Systematic Reviews and Meta-Analyses (PRISMA). Five studies were selected from a pool of 12 studies with a total of 854 liver transplant recipients of whom 700 were children and the rest 154 were adults. The present evidence, based on case reports and series demonstrated lower mortality in liver transplant recipients compared to general population.

Radiofrequency combined with immunomodulation for hepatocellular carcinoma: State of the art and innovations.

Hepatocellular carcinoma (HCC) is the most common primary liver tumor and has been considered a very immunogenic tumor. The treatment with radiofrequency ablation (RFA) has been established as the standard ablative therapy for early HCC, and is currently recognized as the main ablative tool for HCC tumors < 5 cm in size; however, progression and local recurrence remain the main disadvantages of this approach. To solve this clinical problem, recent efforts were concentrated on multimodal treatment, combining different strategies, including the combination of RFA and immunotherapy. This article reviewed the combination treatment of RFA with immunotherapy and found that this treatment strategy leads to an increased response of anti-tumor T cells, significantly reduces the risk of recurrence and improves survival rates compared to RFA alone. This review highlighted scientific evidence that supports the current recommendations for pre-clinical studies, and discuss the need for further research on this topic.

MTL-CEBPA, a Small Activating RNA Therapeutic Upregulating C/EBP-α, in Patients with Advanced Liver Cancer: A First-in-Human, Multicenter, Open-Label, Phase I Trial.

PURPOSE: Transcription factor C/EBP-α (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions and multiple oncogenic processes. MTL-CEBPA is a first-in-class small activating RNA oligonucleotide drug that upregulates C/EBP-α. PATIENTS AND METHODS: We conducted a phase I, open-label, dose-escalation trial of MTL-CEBPA in adults with advanced hepatocellular carcinoma (HCC) with cirrhosis, or resulting from nonalcoholic steatohepatitis or with liver metastases. Patients received intravenous MTL-CEBPA once a week for 3 weeks followed by a rest period of 1 week per treatment cycle in the dose-escalation phase (3+3 design). RESULTS: Thirty-eight participants have been treated across six dose levels (28-160 mg/m2) and three dosing schedules. Thirty-four patients were evaluable for safety endpoints at 28 days. MTL-CEBPA treatment-related adverse events were not associated with dose, and no maximum dose was reached across the three schedules evaluated. Grade 3 treatment-related adverse events occurred in nine (24%) patients. In 24 patients with HCC evaluable for efficacy, an objective tumor response was achieved in one patient [4%; partial response (PR) for over 2 years] and stable disease (SD) in 12 (50%). After discontinuation of MTL-CEBPA, seven patients were treated with tyrosine kinase inhibitors (TKIs); three patients had a complete response with one further PR and two with SD. CONCLUSIONS: MTL-CEBPA is the first saRNA in clinical trials and demonstrates an acceptable safety profile and potential synergistic efficacy with TKIs in HCC. These encouraging phase I data validate targeting of C/EBP-α and have prompted MTL-CEBPA + sorafenib combination studies in HCC.

Rapid Induction of Liver Regeneration for Major Hepatectomy (REBIRTH): A Randomized Controlled Trial of Portal Vein Embolisation versus ALPPS Assisted with Radiofrequency.

To avoid liver insufficiency following major hepatic resection, portal vein embolisation (PVE) is used to induce liver hypertrophy pre-operatively. Associating liver partition with portal vein ligation for staged hepatectomy assisted with radiofrequency (RALPPS) was introduced as an alternative method. A randomized controlled trial comparing PVE with RALPPS for the pre-operative manipulation of liver volume in patients with a future liver remnant volume (FLRV) ≤25% (or ≤35% if receiving preoperative chemotherapy) was conducted. The primary endpoint was increase in size of the FLRV. The secondary endpoints were length of time taken for the volume gain, morbidity, operation length and post-operative liver function. Between July 2015 and October 2017, 57 patients were randomised to RALPPS (n = 29) and PVE (n = 28). The mean percentage of increase in the FLRV was 80.7 ± 13.7% after a median 20 days following RALPPS compared to 18.4 ± 9.8% after 35 days (p < 0.001) following PVE. Twenty-four patients after RALPPS and 21 after PVE underwent stage-2 operation. Final resection was achieved in 92.3% and 66.6% patients in RALPPS and PVE, respectively (p = 0.007). There was no difference in morbidity, and one 30-day mortality after RALPPS (p = 0.991) was reported. RALPPS is more effective than PVE in increasing FLRV and the number of patients for surgical resection.

Can we predict long-term survival in resectable pancreatic ductal adenocarcinoma?

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumour associated with poor 5-year survival. We aimed to determine factors which differentiate short and long-term survivors and identify a prognostic biomarker. METHODS: Over a ten-year period, patients with resected PDAC who developed disease recurrence within 12 months (Group I) and those who had no disease recurrence for 24 months (Group II) were identified. Clinicopathological data was analysed. Ion Torrent high-throughput sequencing on DNA extracted from FFPE tumour samples was used to identify mutations. Additionally, peripheral blood samples were analysed for variants in cell-free DNA, circulating tumour cells (CTCs), and microRNAs. RESULTS: Multivariable analysis of clinicopathological factors showed that a positive medial resection margin was significantly associated with short disease-free survival (p = 0.007). Group I patients (n = 21) had a higher frequency of the KRAS mutant mean variant allele (16.93% ± 11.04) compared to those in Group II (n = 13; 7.55% ± 5.76, p = 0.0078). Group I patients also trended towards having a KRAS c.35G>A p.Gly12Asp mutation in addition to variants in other genes, such as TP53, CDKN2A, and SMAD4. Mutational status of cell-free DNA, and number of CTCs, was not found to be useful in this study. A circulating miRNA (hsa-miR-548ah-5p) was found to be significantly differentially expressed. CONCLUSIONS: Medial resection margin status and the frequency of KRAS mutation in the tumour tissue are independent prognostic indicators for resectable PDAC. Circulating miRNA hsa-miR-548ah-5p has the potential to be used as a prognostic biomarker.

A Systematic Review and Meta-Analysis Comparing Liver Resection with the Rf-Based Device Habib™-4X with the Clamp-Crush Technique.

Liver cancer is the sixth most common cancer and third most common cause of cancer-related mortality. Presently, indications for liver resections for liver cancers are widening, but the response is varied owing to the multitude of factors including excess intraoperative bleeding, increased blood transfusion requirement, post-hepatectomy liver failure and morbidity. The advent of the radiofrequency energy-based bipolar device Habib™-4X has made bloodless hepatic resection possible. The radiofrequency-generated coagulative necrosis on normal liver parenchyma provides a firm underpinning for the bloodless liver resection. This meta-analysis was undertaken to analyse the available data on the clinical effectiveness or outcomes of liver resection with Habib™-4X in comparison to the clamp-crush technique. The RF-assisted device Habib™-4X is considered a safe and feasible modality for liver resection compared to the clamp-crush technique owing to the multitude of benefits and mounting clinical evidence supporting its role as a superior liver resection device. The most intriguing advantage of the RF-device is its ability to induce systemic and local immunomodulatory changes that further expand the boundaries of survival outcomes following liver resection.

Study to evaluate the immunomodulatory effects of radiofrequency ablation compared to surgical resection for liver cancer.

Introduction: Hepatic cancer is a highly lethal tumour with increasing worldwide incidence. These tumours are characterized by the proliferation of malignant cells, generalised immunosuppression and chronic inflammation marked with an increase in inflammatory markers as a neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR) and overexpression of CD4+CD39+ on T lymphocytes. The studies have outlined immunomodulatory changes in liver cancer patients as the plausible explanation for the better survival. The aim of this pilot study was understand the possible immunomodulatory effect of radiofrequency (RF) energy and liver resection (non-radiofrequency based devices; non-RF device) in relation to NLR, PLR and expression of CD4+CD39+ T lymphocytes and compare the magnitude of these changes. Material and Methods: In the present study, 17 patients with hepatic cancer were prospectively divided into treatment groups radiofrequency ablation (RFA group) and Liver resection using non-RF devices (LR group). A blood sample was collected from each patient, one month before and after the procedure and compared with the blood samples of age-matched healthy volunteers for group wise comparison. The Mann-Whitney U test, Mc Nemar test and Wilcoxon rank test were used for statistical comparisons as appropriate. Results: A decrease in NLR was reported after RFA from 4.7±3.3 to 3.8±1.8 (P=0.283), in contrary to an increase from 3.5±2.8 to 4.5±3.2 (P=0.183) in LR group. Likewise, a decrease was discerned in PLR following RFA from 140.5±79.5 to 137±69.2 respectively (P=0.386) and increase in the LR group from 116±42.2 to 120.8±29 respectively (P=0.391). A significant decrease in CD4+CD39+ lymphocytes from 55.8±13.8 to 24.6±21.1 (P=0.03) was observed in RFA group whilst a significant increase was reported in LR group from 47.6±8.8 to 55.7±33.2 (P=0.38). Conclusion: Studies have shown that decrease in the NLR, PLR and expression of CD4+CD39+ on T lymphocytes as the marker of better survival in hepatic cancer patients and our findings have confirmed that these changes can be induced following application of RF energy. Moreover, this could be the explanation of better survival observed in different studies using RFA or other RF-based devices in comparison to non-RF based liver resection techniques. However, further larger studies are needed to confirm these findings.

Radiofrequency-assisted liver resection: Technique and results.

BACKGROUND: Radiofrequency (RF)-assisted liver resection allows non-anatomical liver resection with reduced blood loss and offers the opportunity for a combination of resection and ablation. However, there are still concerns with regard to postoperative complications related to this technique. In the present study, we discuss the technical aspects of RF-assisted liver resections and analyse the rate of perioperative complications, focusing on post-hepatectomy liver failure (PLF), bile leak and abscess, and mortality. METHODS: Between 2001 and 2015, 857 consecutive open and laparoscopic elective RF-assisted liver resections for benign and malignant liver tumours were reviewed retrospectively to assess perioperative outcomes. RESULTS: Median intraoperative blood loss was 130 mL, with 9.8% of patients requiring blood transfusion. Intra-abdominal collections requiring percutaneous drainage developed in 8.7% of all patients, while bile leak at resection margin developed in 2.8% of the cases. Major liver resection was performed in 34% of patients and the incidence of PLF was 1.5% with one directly related mortality (0.1%). CONCLUSION: RF-assisted liver resection has evolved into a feasible and safe technique of liver resection with an acceptable incidence of perioperative morbidity and a low incidence of PLF and related mortality.

Radiofrequency assisted pancreaticoduodenectomy for palliative surgical resection of locally advanced pancreatic adenocarcinoma.

BACKGROUND: Despite careful patient selection and preoperative investigations curative resection rate (R0) in pancreaticoduodenectomy ranges from 15% to 87%. Here we describe a new palliative approach for pancreaticoduodenectomy using a radiofrequency energy device to ablate tumor in situ in patients undergoing R1/R2 resections for locally advanced pancreatic ductal adenocarcinoma where vascular reconstruction was not feasible. RESULTS: There was neither postoperative mortality nor significant morbidity. Each time the ablation lasted less than 15 minutes. Following radiofrequency ablation it was observed that the tumor remnant attached to the vessel had shrunk significantly. In four patients this allowed easier separation and dissection of the ablated tumor from the adherent vessel leading to R1 resection. In the other two patients, the ablated tumor did not separate from vessel due to true tumor invasion and patients had an R2 resection. The ablated remnant part of the tumor was left in situ. CONCLUSION: Whenever pancreaticoduodenectomy with R0 resection cannot be achieved, this new palliative procedure could be considered in order to facilitate resection and enable maximum destruction in remnant tumors. METHOD: Six patients with suspected tumor infiltration and where vascular reconstruction was not warranted underwent radiofrequency-assisted pancreaticoduodenectomy for locally advanced pancreatic ductal adenocarcinoma. Radiofrequency was applied across the tumor vertically 5-10 mm from the edge of the mesenteric and portal veins. Following ablation, the duodenum and the head of pancreas were removed after knife excision along the ablated line. The remaining ablated tissue was left in situ attached to the vessel.