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.

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.

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.

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.

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.

An Alternatively Spliced Sirtuin 2 Isoform 5 Inhibits Hepatitis B Virus Replication from cccDNA by Repressing Epigenetic Modifications Made by Histone Lysine Methyltransferases.

Sirtuin 2 (Sirt2), an NAD+-dependent protein deacetylase, deacetylates tubulin, AKT, and other proteins. Previously, we showed that Sirt2 isoform 1 (Sirt2.1) increased replication of hepatitis B virus (HBV). Here, we show that HBV replication upregulates the expression of Sirt2 primary and alternatively spliced transcripts and their respective isoforms, 1, 2, and 5. Since Sirt2 isoform 5 (Sirt2.5) is a catalytically inactive nuclear protein with a spliced-out nuclear export signal (NES), we speculated that its different localization affects its activity. The overexpression of Sirt2.5 reduced expression of HBV mRNAs, replicative intermediate DNAs, and covalently closed circular DNA (cccDNA), an activity opposite that of Sirt2.1 and Sirt2.2. Unlike the Sirt2.1-AKT interaction, the Sirt2.5-AKT interaction was weakened by HBV replication. Unlike Sirt2.1, Sirt2.5 activated the AKT/GSK-3ß/ß-catenin signaling pathway very weakly and independently of HBV replication. When the NES and an N-terminal truncated catalytic domain were added to the Sirt2.5 construct, it localized in the cytoplasm and increased HBV replication (like Sirt2.1 and Sirt2.2). Chromatin immunoprecipitation assays revealed that more Sirt2.5 was recruited to cccDNA than Sirt2.1. The recruitment of histone lysine methyltransferases (HKMTs), such as SETDB1, SUV39H1, EZH2, and PR-Set7, and their respective transcriptional repressive markers, H3K9me3, H3K27me3, and H4K20me1, to cccDNA also increased in Sirt2.5-overexpressing cells. Among these, the Sirt2.5-PR-Set7 and -SETDB1 interactions increased upon HBV replication. These results demonstrate that Sirt2.5 reduces cccDNA levels and viral transcription through epigenetic modification of cccDNA via direct and/or indirect association with HKMTs, thereby exhibiting anti-HBV activity.IMPORTANCE Sirt2, a predominant cytoplasmic α-tubulin deacetylase, promotes the growth of hepatocellular carcinoma; indeed, HBV replication increases Sirt2 expression, and overexpression of Sirt2 is associated with hepatic fibrosis and epithelial-to-mesenchymal transition. Increased amounts of Sirt2 isoforms 1, 2, and 5 upon HBV replication might further upregulate HBV replication, leading to a vicious cycle of virus replication/disease progression. However, we show here that catalytically inactive nuclear Sirt2.5 antagonizes the effects of Sirt2.1 and Sirt2.2 on HBV replication, thereby inhibiting cccDNA level, transcription of cccDNA, and subsequent synthesis of replicative intermediate DNA. More Sirt2.5 was recruited to cccDNA than Sirt2.1, thereby increasing epigenetic modification by depositing transcriptional repressive markers, possibly through direct and/or indirect association with histone lysine methyltransferases, such as SETDB1, SUV39H1, EZH2, and/or PR-Set7, which represses HBV transcription. Thus, Sirt2.5 might provide a functional cure for HBV by silencing the transcription of HBV.

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.

Clinical outcomes of complete cytoreduction with concurrent liver resection followed by hyperthermic intraperitoneal chemotherapy for synchronous peritoneal and liver metastatic colorectal cancer.

BACKGROUND: This study aimed to evaluate the clinical outcomes of concurrent liver resection with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in colorectal cancer patients with synchronous liver and peritoneal metastases. METHODS: Patients with colorectal liver and peritoneal metastasis who underwent complete cytoreduction and hyperthermic intraperitoneal chemotherapy with concurrent liver surgery between September 2014 and July 2018 were included. Perioperative outcomes, overall survival, and progression-free survival were analyzed retrospectively. RESULTS: In total, 22 patients were included. The median peritoneal cancer index was 13 (range, 0-26), and the median number of liver metastases was 3 (range, 1-13). The mean total operative time was 11.4 ± 2.6 h. Minor postoperative complications (Clavien-Dindo grade I-II) were reported in 10 patients (45.5%), and major postoperative complications (grade III-V) were reported in five patients (22.7%), including one mortality patient. The median overall survival since diagnosis with metastasis was 27.4 months. The median overall survival since surgical intervention and the progression-free survival were 16.7 months and 7.1 months, respectively. CONCLUSIONS: This short-term follow-up study showed that, in an experienced center, combined resection with hyperthermic intraperitoneal chemotherapy for colorectal liver and peritoneal metastases was feasible and safe with acceptable oncologic outcomes.

Robotic cholecystectomy using Revo-i Model MSR-5000, the newly developed Korean robotic surgical system: a preclinical study.

BACKGROUND: Laparoscopic surgery has become the standard option for gastrointestinal surgeries. However, laparoscopic procedures require extended training times and are difficult for inexperienced surgeons. Robot-assisted laparoscopic surgery facilitates easy adaptation of laparoscopic procedures, but robotic surgical systems are expensive. In addition, their cost has remained high because there is currently only one manufacturer of commercially available systems. Recently, a new Korean robotic surgical system, Revo-i, has been developed. The aim of this study was to evaluate the feasibility and safety of Revo-i by performing robotic cholecystectomy in a porcine model. METHODS: After approval by the Institutional Animal Care and Use Committee of Yonsei University Health System, cholecystectomy was performed in four pigs using the Revo-i robotic surgical system. Operative time and perioperative complications were recorded, and all animals were observed for postoperative complications for 2 weeks after surgery RESULTS: Robotic cholecystectomy was completed successfully and without gallbladder perforation in all cases. The mean operative time was 78 ± 12 min, the mean docking time was 4.5 ± 2.52 min, and the mean console time was 49.8 ± 14.17 min. There were no perioperative complications, and none of the animal used for the in vivo models exhibited abnormal behavior during the postoperative observation period. CONCLUSIONS: These preliminary results verify the safety and efficacy of robotic cholecystectomy using the Revo-i robotic surgical system. Human trials are slated to begin accordingly.

Preoperative fecal elastase-1 is a useful prognostic marker following curative resection of pancreatic cancer.

BACKGROUND: The clinical relevance of fibrosis with regard to tumor progression is supported by the correlation between fibrosis and poor outcomes. Fecal elastase-1 (FE-1) level has been used to assess exocrine dysfunction of the pancreas and to predict pancreas fibrosis. The aim of this study was to assess the impact of FE-1 on the survival of pancreatic cancer patients. METHODS: Between January 2006 and December 2014, 136 patients with pancreatic adenocarcinoma underwent R0 resection at Gangnam Severance Hospital, Korea. Preoperative FE-1 levels were available in 94 patients who were enrolled in the study. Patients were classified into two groups according to preoperative FE-1: "normal" (≥200 µg/g) or "reduced" (<200 µg/g). RESULTS: Median preoperative FE-1 level was 130.1 µg/g (IQR 32.0; 238.3). 62 patients (66.0%) had reduced pancreatic function and 32 patients (34.0%) had normal pancreatic function. The two groups had significantly different disease-free survival (P < 0.001). On multivariate analysis, normal FE-1, no lymph node metastasis and completion of adjuvant chemotherapy were found to be independent prognostic factors for better DFS (P = 0.001, P = 0.017, P = 0.038, respectively). CONCLUSION: FE-1 is a simple and non-invasive predictive clinical marker for prognosis of pancreatic cancer after attempted curative resection.

Ventral segment-preserving right hepatectomy in patients with hepatocellular carcinoma.

BACKGROUND: Transection along the anterior fissure was proposed as a mechanism by which to open the third door of the liver. In this study, we investigated surgical outcomes of a ventral segment-preserving right hepatectomy (VSPRH) compared with those of conventional right hepatectomy in patients with hepatocellular carcinoma (HCC). METHODS: Between January 2007 and December 2010, 595 primary HCC patients underwent liver resection at the authors' institution. Among them, the 123 HCC patients who underwent a right hepatectomy were retrospectively analyzed. The patients were classified into two groups according to the type of resection: those who underwent a VSPRH (Group A; 27 cases) and those who underwent a conventional right hepatectomy (Group B; 96 cases). RESULTS: In Group A, expected remnant liver volume after a right hepatectomy was calculated to be 32.1 ± 7.2% of functional total liver volume (FTLV); remnant liver volume increased up to 54.7 ± 7.2% of FTLV after a VSPRH. Clinicopathologic characteristics and intraoperative data did not differ between the two groups. The liver-related complication rate was higher in Group B (P = 0.02). Overall survival and disease-free survival rates were similar (3-year disease-free survival (Group A: 67.8%; Group B: 71.7%; P = 0.65); 3-year overall survival (Group A: 91.7%; Group B: 87.4%; P = 0.26). In regard to long-term synthetic function, the 1-year postoperative serum albumin level was higher in Group A. CONCLUSIONS: A VSPRH yielded fewer liver-related complications and similar long-term oncologic outcomes, compared with conventional right hepatectomy in cirrhotic patients with a small left lobe volume. Therefore, VSPRH can be considered to be an alternative procedure for a right hepatectomy.

Postoperative distress and influencing factors in patients with pancreatobiliary cancer.

This study aimed to investigate distress levels, using the distress thermometer (DT), and the factors associated with distress in postoperative patients with pancreatobiliary cancer. This study retrospectively investigated 155 patients who underwent surgery for pancreatobiliary cancer between December 1, 2019 and September 30, 2021. The DT and problem list were used to measure distress. Descriptive statistics, t-test, and multivariate logistic regression analysis were used to analyze the data. Of the 155 patients, 16.8% (n = 26) and 83.2% (n = 129) were in the mild-distress and moderate-to-severe distress groups, respectively. The average DT score was 6.21; that for the mild-distress and moderate-to-severe distress groups was 2.46 and 6.97, respectively. More patients in the moderate-to-severe distress group reported having problems of "sadness" (χ2 = 4.538, P < 0.05), "indigestion" (χ2 = 10.128, P < 0.001), "eating" (χ2 = 6.147, P < 0.013), and "getting around" (χ2 = 4.275, P < 0.039) than in the mild-distress group. In addition, occupation status (odds ratio [OR] = 0.342, 95% confidence interval [CI] = 0.133-0.879, P = 0.026) and indigestion (OR = 5.897, 95% CI = 1.647-21.111, P = 0.006) were independent risk factors for the presence of severe distress. Patients with pancreatobiliary cancer demonstrated elevated levels of psychological distress. Healthcare providers should therefore be vigilant when evaluating patients for distress and providing appropriate referrals, particularly those who are unemployed or have indigestion.

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.

Liver resection for Bismuth type I and Type II hilar cholangiocarcinoma.

BACKGROUND: In patients with Bismuth type I and II hilar cholangiocarcinoma (HCCA), bile duct resection alone has been the conventional approach. However, many authors have reported that concomitant liver resection improved surgical outcomes. METHODS: Between January 2000 and January 2012, 52 patients underwent surgical resection for a Bismuth type I and II HCCA (type I: n = 22; type II: n = 30). Patients were classified into two groups: concomitant liver resection (n = 26) and bile duct resection alone (n = 26). RESULTS: Bile duct resection alone was performed in 26 patients. Concomitant liver resection was performed in 26 patients (right side hepatectomy [n = 13]; left-side hepatectomy [n = 6]; volume-preserving liver resection [n = 7]). All liver resections included a caudate lobectomy. Patient and tumor characteristics did not differ between the two groups. Although concomitant liver resection required longer operating time (P < 0.001), it had a similar postoperative complication rate (P = 0.764), high curability (P = 0.010), and low local recurrence rate (P = 0.006). Concomitant liver resection showed better overall survival (P = 0.047). CONCLUSIONS: Concomitant liver resection should be considered in patients with Bismuth type I and II HCCA.

Surgical outcomes of hepatocellular carcinoma with bile duct tumor thrombus: a Korean multicenter study.

BACKGROUND: The long-term outcomes after resection for hepatocellular carcinoma (HCC) with macroscopic bile duct tumor thrombus (BDTT) are unclear. This multicenter study was conducted to determine the prognosis of HCC patients with macroscopic BDTT who underwent resection with curative intent. METHODS: Of 4,308 patients with HCC from four Korean institutions, this single-arm retrospective study included 73 patients (1.7 %) who underwent resection for HCC with BDTT. RESULTS: Jaundice was also present in 34 patients (46.6 %). According to Ueda classification, BDTT was type 2 in 34 cases (46.6 %) and type 3 in 39 cases (53.4 %). Biliary decompression was performed in 33 patients (45.2 %), decreasing the median lowest bilirubin level to 1.4 mg/dL before surgery. Systematic hepatectomy was performed in 69 patients (94.5 %), and concurrent bile duct resection was performed in 31 patients (42.5 %). Surgical curability types were R0 (n = 57; 78.1 %), R1 (n = 11; 15.1 %), and R2 (n = 5; 6.8 %). Patient survival rates were 76.5 % at 1 year, 41.4 % at 3 years, 32.0 % at 5 years, and 17.0 % at 10 years. Recurrence rates were 42.9 % at 1 year, 70.6 % at 3 years, 77.3 % at 5 years, and 81.1 % at 10 years. Results of univariate survival analysis showed that maximal tumor size, bile duct resection, and surgical curability were significant risk factors for survival, and surgical curability was a significant risk factor for recurrence. Multivariate analysis did not reveal any independent risk factors. CONCLUSIONS: Hepatocellular carcinoma patients with BDTT achieved relatively favorable long-term results after resection; therefore extensive surgery should be recommended when complete resection is anticipated.

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.

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.

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.

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.

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.