Selective hanging maneuver and rubber band retraction technique for pure laparoscopic donor right hepatectomy.

BACKGROUND: Pure laparoscopic donor hepatectomy (PLDH) is an increasingly performed procedure despite its technical difficulties. This study introduced a selective liver parenchymal hanging maneuver and rubber band retraction technique for PLDH. METHODS: We retrospectively reviewed perioperative data from 58 patients who underwent donor right hepatectomy (including right extended) between March 2009 and February 2021. Eighteen patients underwent open donor right hepatectomy (ODRH) and 38 patients underwent pure laparoscopic donor right hepatectomy (PLDRH). RESULTS: All PLDRH donors underwent the procedure without the need for open conversion. The median PLDRH operative time was 396.84 ± 72.459 min, the median PLDRH intraoperative bleeding amount was 496.05 ± 272.591 ml, and the warm ischemic time was 8.77 ± 3.062 min. Compared to ODRH, laparoscopic surgery showed further advantages in terms of postoperative hospital stay (10.94 ± 4.036 days vs. 8.03 ± 2.646 days, respectively, P = 0.01) and estimated blood loss (676.67 ± 321.046 ml vs. 496.05 ± 272.591 ml, respectively, P = 0.033). CONCLUSIONS: The selective liver parenchymal hanging maneuver and rubber band retraction technique is a simple and effective pure laparoscopic procedure for donor hepatectomy. Our results demonstrate the safety and feasibility of this technique.

Early experiences in robotic single-site plus one port platform for complex hepatobiliary and pancreatic surgery.

BACKGROUND: Minimal invasive surgery in hepatobiliary and pancreatic (HBP) surgery has been accepted worldwide in recent years. However, applications of single-site laparoscopic surgery in complex HBP surgery have been limited due to difficulty in manoeuvring instruments and the limited range of motion resulting from clashing instruments. METHODS: To overcome the limitations, we have used the Da Vinci single-site surgical platform with one additional port in a Da Vinci Xi system to perform donor right hepatectomy, pancreaticoduodenectomy, and combined resection of the common bile duct and spleen vessels preserving distal pancreatectomy. RESULTS: In selected patients, using a robotic single-site plus one port system allowed the successful completion of complex HBP surgery. DISCUSSION: Complex HBP surgery can be performed safely in a stable environment using the robotic single-site plus one port system. Further exploration of a robotic single-site plus one port in complex HBP surgery is necessary.

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.

The care cascade for hepatitis C virus and prognosis of chronic hepatitis C patients treated with antiviral agents in a tertiary hospital.

BACKGROUND: Some studies have analyzed the frequency of HCV RNA testing and actual treatment among anti-HCV positive patients in Korea, which has a low prevalence of HCV infection. This study aimed to analyze the diagnosis process, treatment results, and prognosis according to care cascade in patients who are anti-HCV positive. METHODS: Three thousand two hundred fifty-three anti-HCV positive patients presented to a tertiary hospital between January 2005 and December 2020. The number of patients who underwent HCV RNA testing, treatment, and proportion of sustained virologic response (SVR) according to the type of antivirals was investigated. We investigated the cumulative incidence of hepatocellular carcinoma (HCC) and liver cirrhosis. RESULTS: Of a total of 3,253 people, 1,177 (36.2%) underwent HCV RNA testing and 858 (72.9%) were positive for HCV RNA. 494 (57.6%) of HCV RNA positive patients received antiviral treatment, and 443 (89.7%) of initiated hepatitis C treatment experienced SVR. Of the 421 treated patients, 16 (14.2%) developed HCC. The cumulative incidence of HCC at 15 years was significantly different according to the presence of liver cirrhosis (10/83, 29.5% vs. 6/338, 10.8%, p < 0.001). The cumulative incidences of HCC or liver cirrhosis did not show significant differences according to the presence of SVR12 (14/388, 13.2% vs. 2/33, 52.5%, p = 0.084, 21/319, 15.0%, vs. 3/22, 28.7%, p = 0.051). CONCLUSIONS: Owing to the introduction of direct-acting antivirals, high SVR12 was achieved, but the proportion of anti-HCV positive patients who received HCV RNA testing and treatment was not high. HCC surveillance after SVR12 is recommended for chronic hepatitis C patients with cirrhosis.

PMCA inhibition reverses drug resistance in clinically refractory cancer patient-derived models.

BACKGROUND: Cancer cells have developed molecular strategies to cope with evolutionary stressors in the dynamic tumor microenvironment. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) is a metabolic rheostat that regulates diverse cellular adaptive behaviors, including growth and survival. However, the mechanistic role of PGC1α in regulating cancer cell viability under metabolic and genotoxic stress remains elusive. METHODS: We investigated the PGC1α-mediated survival mechanisms in metabolic stress (i.e., glucose deprivation-induced metabolic stress condition)-resistant cancer cells. We established glucose deprivation-induced metabolic stress-resistant cells (selected cells) from parental tumor cells and silenced or overexpressed PGC1α in selected and parental tumor cells. RESULTS: Several in vitro and in vivo mouse experiments were conducted to elucidate the contribution of PGC1α to cell viability in metabolic stress conditions. Interestingly, in the mouse xenograft model of patient-derived drug-resistant cancer cells, each group treated with an anti-cancer drug alone showed no drastic effects, whereas a group that was co-administered an anti-cancer drug and a specific PMCA inhibitor (caloxin or candidate 13) showed marked tumor shrinkage. CONCLUSIONS: Our results suggest that PGC1α is a key regulator of anti-apoptosis in metabolic and genotoxic stress-resistant cells, inducing PMCA expression and allowing survival in glucose-deprived conditions. We have discovered a novel therapeutic target candidate that could be employed for the treatment of patients with refractory cancers.

Potential Therapeutic Agents against Paclitaxel-And Sorafenib-Resistant Papillary Thyroid Carcinoma.

Thyroid carcinoma, a disease in which malignant cells form in the thyroid tissue, is the most common endocrine carcinoma, with papillary thyroid carcinoma (PTC) accounting for nearly 80% of total thyroid carcinoma cases. However, the management of metastatic or recurrent therapy-refractory PTC is challenging and requires complex carcinoma therapy. In this study, we proposed a new clinical approach for the treatment of therapy-refractory PTC. We identified sarco/endoplasmic reticulum calcium ATPase (SERCA) as an essential factor for the survival of PTC cells refractory to the treatment with paclitaxel or sorafenib. We validated its use as a potential target for developing drugs against resistant PTC, by using patient-derived paclitaxel- or sorafenib-resistant PTC cells. We further discovered novel SERCA inhibitors, candidates 7 and 13, using the evolutionary chemical binding similarity method. These novel SERCA inhibitors determined a substantial reduction of tumors in a patient-derived xenograft tumor model developed using paclitaxel- or sorafenib-resistant PTC cells. These results could provide a basis for clinically meaningful progress in the treatment of refractory PTC by identifying a novel therapeutic strategy: using a combination therapy between sorafenib or paclitaxel and specific SERCA inhibitors for effectively and selectively targeting extremely malignant cells such as antineoplastic-resistant and carcinoma stem-like cells.

Discovery of Pharmaceutical Composition for Prevention and Treatment in Patient-Derived Metastatic Medullary Thyroid Carcinoma Model.

Medullary thyroid carcinoma (MTC) is a well-known neuroendocrine carcinoma, derived from C cells of the thyroid gland. Additionally, MTC is an uncommon aggressive carcinoma that metastasizes to lymph nodes, bones, lungs and liver. For MTC, the 10-year general survival ratio of patients with localized disease is about 95%, whereas that of patients with local phase disorder is around 75%. Only 20% of patients with distant metastasis to lung at diagnosis survive 10 years, which is notably lower than survival for well-differentiated thyroid carcinoma (WDTC). The management of MTC with distant metastasis to lung could be re-surgery or chemotherapy. In this research, we planned to assess the in vitro and in vivo combinational anticancer effect of a novel combination of low-dose cisplatin and sorafenib in patient-derived MTC. The patient-derived MTC cell lines YUMC-M1, M2, and M3 were isolated and treated with a combination of cisplatin and sorafenib or either agent alone. Cisplatin and sorafenib acted in combination to forward tumor restraint compared with each agent administered alone at a low dose. Therefore, a combination of cisplatin and sorafenib could be a new therapeutic approach for MTC.

Drug Discovery Using Evolutionary Similarities in Chemical Binding to Inhibit Patient-Derived Hepatocellular Carcinoma.

Drug resistance causes therapeutic failure in refractory cancer. Cancer drug resistance stems from various factors, such as patient heterogeneity and genetic alterations in somatic cancer cells, including those from identical tissues. Generally, resistance is intrinsic for cancers; however, cancer resistance becomes common owing to an increased drug treatment. Unfortunately, overcoming this issue is not yet possible. The present study aimed to evaluate a clinical approach using candidate compounds 19 and 23, which are sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) inhibitors, discovered using the evolutionary chemical binding similarity method. mRNA sequencing indicated SERCA as the dominant marker of patient-derived anti-cancer drug-resistant hepatocellular carcinoma (HCC), but not of patient-derived anti-cancer drug-sensitive HCC. Candidate compounds 19 and 23 led to significant tumor shrinkage in a tumor xenograft model of anti-cancer drug-resistant patient-derived HCC cells. Our results might be clinically significant for the development of novel combinatorial strategies that selectively and efficiently target highly malignant cells such as drug-resistant and cancer stem-like cells.

Comparison of pharmacologic therapies alone versus operative techniques in combination with pharmacologic therapies for postoperative analgesia in patients undergoing laparoscopic cholecystectomy: A randomized controlled trial.

BACKGROUND: Laparoscopic cholecystectomy (LC) causes moderate pain. Various operative analgesic techniques and pharmacologic treatments can reduce postoperative pain. This single-center, single-surgeon randomized controlled study aimed to assess the efficacy of combined operative analgesic techniques and pharmacologic analgesia in decreasing pain in patients undergoing LC. MATERIALS AND METHODS: Fifty-nine patients scheduled for LC were assigned into two groups. In the pharmacologic analgesia (P) group (n = 29), patients were treated with pharmacologic intervention, including preoperative celecoxib (200 mg), intraoperative acetaminophen (1 g), and dexamethasone (8 mg). In the operative analgesic treatments with pharmacologic analgesia (OP) group (n = 30), patients were treated with both operative analgesic techniques and pharmacologic analgesia, including low-pressure pneumoperitoneum, intraperitoneal normal saline irrigation, and aspiration of intraperitoneal carbon dioxide. The area under the curve (AUC) of pain score for postoperative 24 h was assessed at 0, 2, 6, and 24 h post-operation. The analgesic requirements and sleep quality at postoperative day 1 were assessed. RESULTS: The AUC/24 h of pain scores at rest and on cough were lower in the OP group (p < 0.001 and p = 0.001, respectively). The pain scores at rest were lower in the OP group at postoperative 2, 6, and 24 h (p = 0.001, p = 0.001, and p = 0.048, respectively). The pain scores on cough were lower in the OP group at postoperative 2 and 6 h (p = 0.004 and p = 0.008, respectively). Analgesic requirements were comparable. The sleep quality score at postoperative day 1 was higher in the OP group (56 ± 18 vs. 67 ± 15, absolute difference, 10; 95% confidence interval, 2 to 19; p = 0.017). CONCLUSIONS: Combined operative analgesic therapies and pharmacologic analgesia compared to pharmacologic analgesia alone decreased pain scores and increased sleep quality in patients undergoing LC.

Effect of early oral nutrition supplement using Encover in patients undergoing hepato-biliary-pancreatic surgery.

Backgrounds/Aims: Early recovery after surgery has become a popular trend. The aim of this study was to evaluate effect of nutritional intervention using Encover, an oral nutritional supplement, in patients undergoing hepato-biliary-pancreatic surgery. Methods: This single center, prospective case-control study was conducted in Gangnam Severance Hospital from September 2018 to April 2019. Through randomization, patients were divided into an experimental group (30 patients) and a control group (30 patients). At postoperative seven days, the experimental group was instructed to take two packs of Encover (JW Pharmaceutical, Seoul, Korea) daily for seven days. Body cell mass index was measured at seven days after surgery and 14 days after discharge and Patient-Generated Subjective Global Assessment (PG-SGA) was performed at 14 days after discharge. Results: Body cell mass index during outpatient follow-up was significantly decreased compared to that at discharge in both groups. However, the amount of body cell mass index showed no significant difference between postoperative seven days and outpatient follow- up in either group. During outpatient follow-up, the experimental group had a higher mean value of PG-SGA score than the control group (11.32 ± 3.46 vs. 9.48 ± 3.97; p = 0.037). Conclusions: Short-term Encover doses after surgery may not produce significant results in weight gain or other body cell mass index. Encover did not significantly affect other dietary conditions based on PG-SGA.

Ca2+/Calmodulin-Dependent Protein Kinase II Inhibits Hepatitis B Virus Replication from cccDNA via AMPK Activation and AKT/mTOR Suppression.

Ca2+/calmodulin-dependent protein kinase II (CaMKII), which is involved in the calcium signaling pathway, is an important regulator of cancer cell proliferation, motility, growth, and metastasis. The effects of CaMKII on hepatitis B virus (HBV) replication have never been evaluated. Here, we found that phosphorylated, active CaMKII is reduced during HBV replication. Similar to other members of the AMPK/AKT/mTOR signaling pathway associated with HBV replication, CaMKII, which is associated with this pathway, was found to be a novel regulator of HBV replication. Overexpression of CaMKII reduced the expression of covalently closed circular DNA (cccDNA), HBV RNAs, and replicative intermediate (RI) DNAs while activating AMPK and inhibiting the AKT/mTOR signaling pathway. Findings in HBx-deficient mutant-transfected HepG2 cells showed that the CaMKII-mediated AMPK/AKT/mTOR signaling pathway was independent of HBx. Moreover, AMPK overexpression reduced HBV cccDNA, RNAs, and RI DNAs through CaMKII activation. Although AMPK acts downstream of CaMKII, AMPK overexpression altered CaMKII phosphorylation, suggesting that CaMKII and AMPK form a positive feedback loop. These results demonstrate that HBV replication suppresses CaMKII activity, and that CaMKII upregulation suppresses HBV replication from cccDNA via AMPK and the AKT/mTOR signaling pathway. Thus, activation or overexpression of CaMKII may be a new therapeutic target against HBV infection.

Clinical effect of preoperative intravenous non-steroidal anti-inflammatory drugs on relief of postoperative pain in patients after laparoscopic cholecystectomy: Intravenous ibuprofen vs. intravenous ketorolac.

Backgrounds/Aims: Postoperative pain management is a key to enhanced recovery after surgery. The aim of this study was to evaluate clinical effect of preoperative intravenous (IV) non-steroidal anti-inflammatory drugs (NSAIDs) on relief of postoperative pain in patients after laparoscopic cholecystectomy. Methods: This single center, retrospective study was conducted between September 2019 and May 2020. A total of 163 patients were divided into two groups: Ibuprofen group (preoperative IV ibuprofen, n = 77) and Ketorolac group (preoperative IV ketorolac, n = 86). The primary outcome was postoperative pain score measured immediately in the recovery room. Results: There was no difference in demographic characteristics between the two groups of patients. Postoperative pain score measured immediately in the recovery room was significantly higher in the Ibuprofen group than in the Ketorolac group (mean value: 5.09 vs. 4.61; p = 0.027). The number of patients who needed analgesics immediately in the recovery room was also higher in the Ibuprofen group than in the Ketorolac group (28 [36.4%] vs. 18 [20.9%]; p = 0.036). Conclusions: In this study, preoperative IV injection with ketorolac reduced postoperative pain and analgesic requirement in the recovery room more effectively than that with ibuprofen. However, both showed similar effects on peak pain and pain at discharge. Numbers of patients requiring additional analgesics were also similar between the two groups.

Clinical application of protein-enhanced diet using mealworms in patients undergoing hepato-pancreato-biliary surgery.

OBJECTIVE: Patients with or without cancers who undergo major gastrointestinal surgery experience malnutrition owing to their catabolic status during the postoperative period. In this study, we evaluated the effect of the clinical application of protein-enhanced diet using mealworms in patients who underwent hepato-pancreato-biliary surgeries. METHODS: This study was designed as a prospective, two-armed, and double-blinded phase III study. The target number of enrolled patients was 216, and the patients were randomized on a 1:1 basis, either to the trial group (consuming mealworms) or to the control group (consuming grain powder). The primary endpoint was to examine the changes in body composition, including phase angle. For secondary outcomes, the activities of immune cells were evaluated using the patients' blood samples. RESULTS: No difference in the demographic characteristics of patients was observed. The ratio of the actual protein intake to the recommended daily intake in the trial group was significantly higher than that in the control group (110.03% vs. 98.80%, P = 0.023). In the data on body composition measured by InBody S-10 (Biospace, Seoul, South Korea), the ratios in body cell mass, fat free mass, muscle mass, and phase angle at the study endpoint compared with those at admission showed no statistically significant difference between the two groups. Immune cell analyses suggested that cytotoxic T cells in the trial group had higher activity than in the study group (1.192 vs. 0.974, P = 0.028). CONCLUSIONS: In this study, protein-enhanced diet using mealworms clinically improved the activity of immune cells. However, it did not significantly improve the patients' nutritional status after they experienced hepato-pancreato-biliary surgeries.

Long-term survival after CCRT and HAIC followed by ALPPS for hepatocellular carcinoma with portal vein invasion: a case report.

There are various methods for treating advanced hepatocellular carcinoma with portal vein invasion, such as systemic chemotherapy, transarterial chemoembolization, transarterial radioembolization, and concurrent chemoradiotherapy. These methods have similar clinical efficacy but are designed with a palliative aim. Herein, we report a case that experienced complete remission through "associating liver partition and portal vein ligation for staged hepatectomy (ALPPS)" after concurrent chemoradiotherapy and hepatic artery infusion chemotherapy. In this patient, concurrent chemoradiotherapy and hepatic artery infusion chemotherapy induced substantial tumor shrinkage, and hypertrophy of the nontumor liver was sufficiently induced by portal vein ligation (stage 1 surgery) followed by curative resection (stage 2 surgery). Using this approach, long-term survival with no evidence of recurrence was achieved at 16 months. Therefore, the optimal use of ALPPS requires sufficient consideration in cases of significant hepatocellular carcinoma shrinkage for curative purposes.

The HBV Core Protein and Core Particle Both Bind to the PPiase Par14 and Par17 to Enhance Their Stabilities and HBV Replication.

We recently reported that the PPIase Par14 and Par17 encoded by PIN4 upregulate HBV replication in an HBx-dependent manner by binding to conserved arginine-proline (RP) motifs of HBx. HBV core protein (HBc) has a conserved 133RP134 motif; therefore, we investigated whether Par14/Par17 bind to HBc and/or core particles. Native agarose gel electrophoresis (NAGE) and immunoblotting and co-immunoprecipitation were used. Chromatin immunoprecipitation from HBV-infected HepG2-hNTCP-C9 cells was performed. NAGE and immunoblotting revealed that Par14/Par17 bound to core particles and co-immunoprecipitation revealed that Par14/Par17 interacted with core particle assembly-defective, and dimer-positive HBc-Y132A. Thus, core particles and HBc interact with Par14/Par17. Par14/Par17 interacted with the HBc 133RP134 motif possibly via substrate-binding E46/D74 and E71/D99 motifs. Although Par14/Par17 dissociated from core particles upon heat treatment, they were detected in 0.2 N NaOH-treated opened-up core particles, demonstrating that Par14/Par17 bind outside and inside core particles. Furthermore, these interactions enhanced the stabilities of HBc and core particles. Like HBc-Y132A, HBc-R133D and HBc-R133E were core particle assembly-defective and dimer-positive, demonstrating that a negatively charged residue at position 133 cannot be tolerated for particle assembly. Although positively charged R133 is solely important for Par14/17 interactions, the 133RP134 motif is important for efficient HBV replication. Chromatin immunoprecipitation from HBV-infected cells revealed that the S19 and E46/D74 residues of Par14 and S44 and E71/D99 residues of Par17 were involved in recruitment of 133RP134 motif-containing HBc into cccDNA. Our results demonstrate that interactions of HBc, Par14/Par17, and cccDNA in the nucleus and core particle-Par14/Par17 interactions in the cytoplasm are important for HBV replication.

Comparison of outcomes of single incision robotic cholecystectomy and single incision laparoscopic cholecystectomy.

BACKGROUNDS/AIMS: Multiport laparoscopic cholecystectomy is the standard surgical procedure for symptomatic gallbladder diseases. However, as a result of the ongoing trend toward minimally invasive laparoscopy, single-incision laparoscopic cholecystectomy (SILC) has evolved. Single-incision robotic cholecystectomy (SIRC) can overcome several limitations of manual SILC. The purpose of this study is to evaluate and compare the safety and feasibility of SIRC and SILC. METHODS: This study retrospectively reviewed data for all patients who underwent SIRC or SILC from March 2018 to July 2019 in a single institution. The following variables were analyzed: age, sex, body mass index, pain scale, length of stay, and complications. The data were analyzed using the Independent two sample t-test or the Fisher's exact test. RESULTS: A total of 343 patients underwent SIRC or SILC during the study period. After excluding patients with acute cholecystitis, 197 SIRC and 103 SILC patients were analyzed in this study. The surgery time and postoperative hospital stay did not differ between SIRC and SILC. However, the SIRC patients experienced less bile spillage during the surgery than did the SILC patients (SIRC vs. SILC: 24 (23.3%) vs. 11 (5.6%) cases, respectively; p<0.001). Although there was no difference in the incidence of postoperative complications between procedures, additional pain control was administered more frequently in SILC patients (SILC 1.08±0.893, SIRC 0.58±0.795; p<0.001). CONCLUSIONS: While both SILC and SIRC are effective for single-incision cholecystectomy, SIRC was superior to SILC in terms of technical stability. Moreover, it has the advantage of postoperative pain control.

Cholecystectomy using the Revo-i robotic surgical system from Korea: the first clinical study.

This study evaluated the safety and efficacy of the newly developed Revo-i (Meerecompany, Yongin, Republic of Korea) robotic surgical system during robot-assisted cholecystectomy. This prospective, phase I clinical study involved 15 patients with gallbladder-related disease. The primary outcome evaluated was the intraoperative safety of the Revo-i; the secondary outcomes measured were the 30-day postoperative complications and patient satisfaction with the Revo-i's performance. Between August 17 and December 23, 2016, we performed 15 robot-assisted cholecystectomies. The operations were successfully completed, without any conversions to open or laparoscopic approaches. The mean patient age (53.07 years), mean operative time (115.3 ± 17.31 min [± standard deviation]), docking time (10.6 ± 3.16 min), console time (49.7 ± 15.41 min), actual dissection time (33.1 ± 10.53 min), and estimated blood loss (3.33 ± 6.17 mL) were determined. There were no intra- or postoperative complications, including gallbladder perforations. The mean hospital stay was 2.0 ± 1.00 days. Most patients reported satisfaction with the Revo-i's performance. Performing robot-assisted cholecystectomies using the Revo-i is feasible and safe. This report describes the first clinical study of the Revo-i robotic surgical system in human patients.

Obesity and the risk of primary liver cancer: A systematic review and meta-analysis.

BACKGROUND/AIMS: In this systematic review and meta-analysis, we aimed to clarify the effect of obesity on the occurrence of and mortality from primary liver cancer. METHODS: This study was conducted using a systematic literature search of MEDLINE, EMBASE, and the Cochrane Library until November 2018 using the primary keywords "obesity," "overweight," "body mass index (BMI)," "body weight," "liver," "cancer," "hepatocellular carcinoma," "liver cancer," "risk," and "mortality." Studies assessing the relationship between BMI and occurrence of or mortality from primary liver cancer in prospective cohorts and those reporting hazard ratios (HRs) or data that allow HR estimation were included. RESULTS: A total of 28 prospective cohort studies with 8,135,906 subjects were included in the final analysis. These included 22 studies with 6,059,561 subjects for cancer occurrence and seven studies with 2,077,425 subjects for cancerrelated mortality. In the meta-analysis, an increase in BMI was associated with the occurrence of primary liver cancer (HR, 1.69; 95% confidence interval, 1.50-1.90, I2=56%). A BMI-dependent increase in the risk of occurrence of primary liver cancer was reported. HRs were 1.36 (95% CI, 1.02-1.81), 1.77 (95% CI, 1.56-2.01), and 3.08 (95% CI, 1.21-7.86) for BMI >25 kg/m2, >30 kg/m2, and >35 kg/m2, respectively. Furthermore, increased BMI resulted in enhanced liver cancer-related mortality (HR, 1.61; 95% CI, 1.14-2.27, I2=80%). CONCLUSION: High BMI increases liver cancer mortality and occurrence of primary liver cancer. Obesity is an independent risk factor for the occurrence of and mortality from primary liver cancer.

Patient-Derived, Drug-Resistant Colon Cancer Cells Evade Chemotherapeutic Drug Effects via the Induction of Epithelial-Mesenchymal Transition-Mediated Angiogenesis.

Cancer cells can exhibit resistance to different anticancer drugs by acquiring enhanced anti-apoptotic potential, improved DNA injury resistance, diminished enzymatic inactivation, and enhanced permeability, allowing for cell survival. However, the genetic mechanisms for these effects are unknown. Therefore, in this study, we obtained drug-sensitive HT-29 cells (commercially) and drug-resistant cancer cells (derived from biochemically and histologically confirmed colon cancer patients) and performed microarray analysis to identify genetic differences. Cellular proliferation and other properties were determined after treatment with oxaliplatin, lenvatinib, or their combination. In vivo, tumor volume and other properties were examined using a mouse xenograft model. The oxaliplatin and lenvatinib cotreatment group showed more significant cell cycle arrest than the control group and groups treated with either agent alone. Oxaliplatin and lenvatinib cotreatment induced the most significant tumor shrinkage in the xenograft model. Drug-resistant and metastatic colon cancer cells evaded the anticancer drug effects via angiogenesis. These findings present a breakthrough strategy for treating drug-resistant cancer.

Phase I Radiation Dose-Escalation Study to Investigate the Dose-Limiting Toxicity of Concurrent Intra-Arterial Chemotherapy for Unresectable Hepatocellular Carcinoma.

Concurrent intra-arterial chemotherapy and radiotherapy (iA-CCRT) can increase the response rate in hepatocellular carcinoma (HCC), but may cause a higher toxicity. We conducted this Phase I study to investigate the dose-limiting toxicity of iA-CCRT for HCC. In total, 52.5 Gy in 25 fractions was prescribed as planning target volume (PTV) 1 at dose level 1. The dose escalation was 0.2 Gy per fraction and up to 2.5 Gy, with 62.5 Gy at level 3. Concurrent intra-arterial 5-fluorouracil was administered during the first and fifth weeks of radiotherapy (RT). Toxicities were graded using the Common Toxicity Criteria for Adverse Events, version 4.0. Results: Seventeen patients with HCC were analyzed: four at dose level 1, 6 at level 2, and 7 at level 3. The mean irradiated dose administered to the uninvolved liver at each dose level was 21.3, 21.6, and 18.2 Gy, respectively. There was no grade ≥3 gastrointestinal toxicity; two patients experienced grade 3 hyperbilirubinemia. All patients had Child-Pugh class A disease, but 3 patients developed class B disease after iA-CCRT. During a median follow-up of 13 months, the median progression-free survival (PFS) and overall survival (OS) were 10 and 22 months, respectively. Patients treated at dose level 3 showed improved PFS and OS. Conclusions: Radiation dose escalation of iA-CCRT did not cause any significant toxicities in patients with advanced HCC. Further large-scale studies with long-term follow-up are needed to determine the efficacy and feasibility of higher doses of iA-CCRT.