A multicenter case-control study of self-expanding metallic stent versus trans-anal colorectal tube for stage II/III non-right-sided obstructive colon cancer.

BACKGROUND: Self-expanding metallic stent (SEMS) and trans-anal colorectal tube (TCT) are alternative treatments to conventional emergency surgery for non-right-sided obstructive colon cancer (NROCC). However, the one with better short- and long-term outcomes remains controversial. Thus, this multicenter case-control study aimed to analyze and compare SEMS and TCT for NROCC. METHODS: Patients with stage II/III NROCC who underwent surgery between January 2010 and December 2019 at either of the eight selected Japanese affiliate hospitals were, retrospectively, reviewed. Baseline characteristics between the SEMS and TCT groups were adjusted by propensity score (PS) matching. RESULTS: Among 239 reviewed patients (SEMS: 76, TCT: 163), 180 were finally included in two well-balanced cohorts through PS: SEMS group (65 patients) and TCT group (115 patients). Technical success, clinical success, morbidity, and short-term mortality were not significantly different between the two groups. SEMS placement achieved significantly higher rates for primary resection/anastomosis without stoma (SEMS: 90.8% vs. TCT: 77.4%, p < 0.001) and laparoscopic surgery (SEMS: 64.6% vs. TCT: 43.5%, p < 0.001) than TCT placement. However, 5-year overall survival (SEMS: 83.7% vs. TCT: 86.4%; p = 0.822) and 5-year relapse-free survival (SEMS: 64.7% vs. TCT: 66.4%; p = 0.854) showed no significant differences between these groups. CONCLUSIONS: Both SEMS and TCT revealed similar long-term outcomes, but SEMS placement was better in achieving primary resection/anastomosis and laparoscopic surgery in patients with stage II/III NROCC.

Severe Gastrointestinal Disorder Due to Capecitabine Associated with Dihydropyrimidine Dehydrogenase Deficiency: A Case Report and Literature Review.

Dihydropyrimidine dehydrogenase (DPD) deficiency induces severe adverse events in patients receiving fluoropyrimidines. We encountered a 64-year-old DPD-deficient man with a severe capecitabine-related gastrointestinal disorder. He received capecitabine-containing chemotherapy after rectal cancer resection. During the first course of chemotherapy, he developed severe diarrhea, a fever, and hematochezia. Endoscopy revealed mucosal shedding with bleeding throughout the gastrointestinal tract. DPD deficiency was suspected because he developed many severe adverse events of capecitabine early and was finally confirmed based on the finding of a low DPD activity level in peripheral blood mononuclear cells. After one month of intensive care, hemostasis and mucosal healing were noted, although his gastrointestinal function did not improve, and he had persistent nutritional management issues.

Long-term outcomes of nasogastric tube with Gastrografin for adhesive small bowel obstruction.

BACKGROUND: We had previously reported that the administration of Gastrografin through a nasogastric tube (NGT-G) followed by long tube (LT) strategy could be a novel standard treatment for adhesive small bowel obstruction (ASBO); however, the long-term outcomes after initial improvement remain unknown. This study aimed to analyze the long-term outcomes of first-line NGT-G. METHODS: Enrolled patients with ASBO were randomly assigned to receive LT or NGT-G between July 2016 and November 2018. Thereafter, the cumulative surgery rate, cumulative recurrence rate, and overall survival (OS) rate were analyzed. In addition, subset analysis was conducted to determine the cumulative recurrence rate according to colonic contrast with Gastrografin at 24 h. RESULTS: A total of 223 patients (LT group, n = 111; NGT-G group, n = 112) were analyzed over a median follow-up duration of 550 days. The cumulative 1-year surgery rates, cumulative 1-year recurrence rates, and 1-year OS rates in the LT and NGT-G groups were 18.8% and 18.1%, 30.0% and 31.7%, and 99.1% and 96.6%, respectively; no significant differences were observed between both groups. In the NGT-G group, a negative colonic contrast at 24 h demonstrated a higher tendency for future recurrence compared with a positive colonic contrast at 24 h (1-year recurrence rate: negative contrast, 46.9% vs positive contrast, 27.6%). CONCLUSIONS: Gastrografin through a nasogastric tube followed by LT can be a promising treatment strategy for ASBO, with long-term efficacies equivalent to initial LT placement.

Acute colonic pseudo-obstruction and rapid septic progression after transabdominal preperitoneal hernia repair: a case report.

BACKGROUND: Acute colonic pseudo-obstruction (ACPO) is a rare condition observed in patients with some underlying medical or surgical conditions. To the best of our knowledge, this is the first case report of a patient with ACPO development and rapid septic progression after laparoscopic inguinal hernia repair. CASE PRESENTATION: A 78-year-old man who underwent transabdominal preperitoneal hernia repair (TAPP) for right inguinal hernia presented with difficulty in defecation and abdominal distension. He visited our emergency department on the third postoperative day. Enhanced computed tomography (CT) detected marked enlargement from the cecum to the rectum. There was no evidence of mechanical obstruction, ischemia, or perforation. He was diagnosed with postoperative constipation and received conservative management. He gradually started to improve; however, he suddenly experienced cardiopulmonary arrest 30 h after admission and could not be resuscitated. CT imaging of the abdomen during autopsy did not show any significant change, such as perforation, from the time of admission. Based on the clinical course and examination results, postoperative ACPO was considered the fundamental cause of fulminant obstructive colitis leading to sepsis. CONCLUSIONS: ACPO following minimally invasive surgery is exceedingly rare. However, it is important to consider this disease as one of the differential diagnoses to avoid missing the chance for advanced therapy.

Adipose-derived mesenchymal stem cells differentiate into heterogeneous cancer-associated fibroblasts in a stroma-rich xenograft model.

Cancer-associated fibroblasts (CAFs) are the key components of the densely proliferated stroma in pancreatic ductal adenocarcinoma (PDAC) and contribute to tumor progression and drug resistance. CAFs comprise heterogeneous subpopulations playing unique and vital roles. However, the commonly used mouse models have not been able to fully reproduce the histological and functional characteristics of clinical human CAF. Here, we generated a human cell-derived stroma-rich CDX (Sr-CDX) model, to reproduce the clinical tumor microenvironment. By co-transplanting human adipose-derived mesenchymal stem cells (AD-MSCs) and a human PDAC cell line (Capan-1) into mice, the Sr-CDX model recapitulated the characteristics of clinical pancreatic cancer, such as accelerated tumor growth, abundant stromal proliferation, chemoresistance, and dense stroma formed from the heterogeneous CAFs. Global RNA sequencing, single-cell based RNA sequencing, and histological analysis of CAFs in the Sr-CDX model revealed that the CAFs of the Sr-CDX mice were derived from the transplanted AD-MSCs and composed of heterogeneous subpopulations of CAF, including known and unknown subtypes. These lines of evidences suggest that our new tumor-bearing mouse model has the potential to address an open question in CAF research, that is the mechanism of CAF differentiation.

The first management using intubation of a nasogastric tube with Gastrografin enterography or long tube for non-strangulated acute small bowel obstruction: a multicenter, randomized controlled trial.

BACKGROUND: Gastrointestinal decompression is generally applied to a non-strangulated acute small bowel obstruction (NSASBO). Although long tube (LT) placement and administration of Gastrografin through a nasogastric tube (NGT-G) have shown advantages over NGT alone in previous studies, no studies appear to have compared LT and NGT-G. METHODS: In this multicenter, randomized controlled trial, patients with NSASBO were randomly assigned to receive LT or NGT-G between July 2016 and November 2018 at 11 Japanese institutions. The primary endpoint was non-inferiority of NGT-G compared to LT for non-surgery rate, and the lower limit of the 95% confidence interval for the non-surgery rate (-15%) was set as the lower margin for inferiority of NGT-G compared to LT. RESULTS: In total, 223 patients (LT group, n = 111; NGT-G group, n = 112) were analyzed in the present trial. The non-surgery rate was 87.4% in the LT group and 91.1% in the NGT-G group, with a 3.7% difference between NGT-G and LT (95.3%CI - 5.55 to 12.91; non-inferiority P = 0.00002923). On the other hand, the non-surgery rate with pure NGT-G alone (76.8%) that represents non-cross-over NGT-G without subsequent LT was significantly lower than that with LT (P = 0.039). Median procedure time was significantly shorter with NGT-G (1 min) than with LT (25 min; P < 0.001), whereas no significant differences in mortality or hospital stay were noted between groups. CONCLUSION: NGT-G is an effective alternative to LT as a first-line treatment for NSASBO. A sequential strategy comprising NGT-G followed by LT might offer a new standard for NSASBO. CLINICAL TRIALS REGISTRATION: This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (umin.ac.jp/ctr Identifier: UMIN000022669) prior to the start of this trial.

Three-dimensional remnant pancreatic volume ratio indicates postoperative pancreatic exocrine insufficiency in pancreatic cancer patients after distal pancreatectomy.

BACKGROUND: Pancreatectomy may cause serious pancreatic exocrine insufficiency (PEI), which can lead to some nutritional problems, including new-onset diabetes mellitus (DM) or non-alcoholic fatty liver disease (NAFLD). Recent studies have reported that remnant pancreatic volume (RPV) significantly influences postoperative PEI. However, the specific correlation between RPV and postoperative PEI remains unclear. Here, we compare various pre-, peri-, and postoperative risk factors in a retrospective cohort to address whether preoperatively measured RPV is a predictor of postoperative PEI in pancreatic cancer patients after distal pancreatectomy (DP). METHODS: Sixty-one pancreatic cancer patients who underwent DP were retrospectively enrolled. Pancreatic volume was measured using preoperative 3D images, which simulated the actual intraoperative pancreatic parenchymal volume. We obtained the 3D-measured RPV and resected pancreatic volume. We calculated the ratio of the RPV to the total pancreatic volume and then divided the cohort into high- and low-RPV ratio groups based on a cut-off value (>0.35, n = 37 and ≤ 0.35, n = 24). Using multivariate analysis, the RPV ratio as well as pre-, peri- and postoperative PEI risk factors were independently assessed. RESULTS: The multivariate analysis revealed that a low RPV ratio (odds ratio [OR], 5.911; p = 0.001), a hard pancreatic texture (OR, 3.313; p = 0.023) and TNM stage III/IV (OR, 3.515; p = 0.031) were strong predictors of the incidence of PEI. CONCLUSIONS: The present study indicates that the RPV ratio is an additional useful predictor of postoperative nutrition status in pancreatic cancer patients.

Atypical femoral hernia called Laugier's hernia: clinical features, radiological findings, and management at a single center.

PURPOSE: Laugier's hernia is a rare clinical entity compared with a typical femoral hernia. Therefore, the clinical features, radiological findings, and appropriate treatment strategies remain largely unclear. In this study, we present 15 Laugier's hernia cases. Additionally, we review the relevant literature and discuss the clinical features, radiological findings, and appropriate treatment strategies pertaining to Laugier's hernia compared with a typical femoral hernia. METHODS: Among 1260 hernia patients, we retrospectively enrolled 15 Laugier's hernia patients (1.19%) and 89 femoral hernia patients (7.06%) who underwent herniorrhaphy and compared the demographic characteristics and radiological findings between the two groups. RESULTS: Regarding the patient characteristics, a significant difference was observed in the presence of pain (p < 0.001) and ileus symptoms (p = 0.001). Regarding the hernia characteristics, significant differences were observed in the size of the hernial sac (p = 0.001), contents of the hernial sac (p = 0.003), repositioning of the hernial sac (p < 0.001), and repair with polypropylene mesh (p < 0.001). The characteristic multi-detector computed tomography (MDCT) findings enabled the preoperative diagnosis of Laugier's hernia versus conventional femoral hernia. CONCLUSION: Surgeons should be alert to the possibility of atypical femoral hernias while examining femoral hernia or inguinal hernia patients. If Laugier's hernia is suspected, preoperative MDCT is recommended.

Red or Near-Infrared Light Operating Negative Photochromism of a Binaphthyl-Bridged Imidazole Dimer.

The development of red or near-infrared light (NIR) switchable photochromic molecules is required for an efficient utilization of sunlight and regulation of biological activities. While the photosensitization of photochromic molecules to red or NIR light has been achieved by a two-photon absorption process, the development of a molecule itself having sensitivity to red or NIR light has been now a challenging study. Herein, we developed an efficient molecular design for realizing red or NIR-light-responsive negative photochromism based on binaphthyl-bridged imidazole dimers. The introduction of electron-donating substituents shows the red shift of the absorption band at the visible-light region because of the contribution of a charge-transfer transition. Especially, the introduction of a di(4-methoxyphenyl)amino group (TPAOMe) and a perylenyl group largely shifts the absorption edge of the stable colored form to 900 nm. In addition, because the absorption band of one of the derivatives substituted with TPAOMe covers the whole visible-light region, the colored form shows a neutral gray color. Upon red (660 nm) or NIR-light (790 nm) irradiation, we observed the negative photochromic reaction from the stable colored form to the metastable colorless form. Therefore, the substituted binaphthyl-bridged imidazole dimers constitute the attractive photoswitches within a biological window.

Risk factors for histological progression of non-alcoholic steatohepatitis analyzed from repeated biopsy cases.

BACKGROUND AND AIM: The most important prognostic factor for non-alcoholic steatohepatitis (NASH) is liver fibrosis. The aim of this study is to examine clinical parameters involved in pathological progression in NASH patients who underwent repeated liver biopsy and to analyze the response to treatment with respect to NASH-related single nucleotide polymorphisms (SNPs). We performed longitudinal analysis of genetic and clinical factors associated with progression of NASH. METHODS: Eighty NASH patients who had undergone serial liver biopsies were enrolled in this retrospective cohort study. Histological exacerbation was determined based on non-alcoholic fatty liver disease activity score (NAS) and liver fibrosis. RESULTS: About 22.5% had progression of fibrosis, 22.5% had improvement of fibrosis, and 55.0% had no change. NAS increased in 12.5%, decreased in 61.3%, and remained stable in the remaining 26.3%. We examined factors associated with histological progression versus non-progression. Poor response of alanine aminotransferase (ALT) levels, increase in HbA1c levels, and presence of the tumor necrosis factor risk allele in the rs1799964 SNP were identified as independent risk factors contributing to histological progression in NASH patients. In addition, we found that the histological progression rate varies with ALT response, HbA1c levels, and rs1799964 genotype. CONCLUSIONS: In this study, we clarified the serum ALT level and the clinical significance of HbA1c to evaluate the progression of fibrosis in Japanese NASH patients. Furthermore, the tumor necrosis factor SNP was more likely to be involved in the response than PNPLA3 SNP. By simultaneously evaluating three factors, it is possible to estimate the risk of histological progression more accurately.

A Nationwide Survey of Hepatitis E Virus Infection and Chronic Hepatitis in Heart and Kidney Transplant Recipients in Japan.

BACKGROUND: Recently, chronic hepatitis E has been reported in solid organ transplant (SOT) recipients in European countries. Previously, we clarified the prevalence of hepatitis E virus (HEV) infection in Japanese liver transplant recipients and identified 2 chronic hepatitis E patients infected by blood transfusion. However, the rate of HEV infection in recipients of SOTs other than liver in Japan remains unclear, so we conducted a nationwide survey to clarify the prevalence of chronic HEV infection in Japanese heart and kidney transplant recipients. METHODS: A total of 99 heart and 2526 kidney transplant recipients in 17 hospitals in Japan were examined for the presence of the IgG class of anti-HEV antibodies as well as for serum HEV RNA. RESULTS: The prevalence of anti-HEV IgG among heart and kidney transplant recipients was 7.07% (7/99) and 4.08% (103/2526), respectively. One heart transplant patient (1.01%) and 11 kidney transplant patients (0.44%) were found to be positive for HEV RNA. The HEV isolates from all viremic patients were typed as genotype 3. Four patients developed chronic hepatitis E after transplantation. Three patients were treated with ribavirin; their liver enzymes normalized, and HEV RNA became negative immediately. Sustained virologic response was achieved in all cases. CONCLUSIONS: This is the first nationwide survey of HEV infection in Japanese heart and kidney transplant recipients. The prevalence of anti-HEV IgG and HEV RNA in heart and kidney transplant recipients in Japan was lower than that in European countries. Of note, 42% of viremic transplant patients developed chronic hepatitis.

Levocarnitine Use Is Associated With Improvement in Sarcopenia in Patients With Liver Cirrhosis.

Although the effect of levocarnitine (L-carnitine) on hyperammonemia has been reported in patients with liver cirrhosis (LC), its effect on sarcopenia remains to be elucidated. We assessed the effects of L-carnitine on sarcopenia in patients with LC. We retrospectively evaluated 52 patients with LC who were treated with L-carnitine for more than 3 months between February 2013 and June 2017. Computed tomography was used to measure the cross-sectional area of the skeletal muscles at the level of the third lumbar vertebra. The relative change in skeletal muscle index (SMI) per year (ΔSMI/year) was computed in each patient. We evaluated the relationship between ΔSMI/year and various parameters, such as age, sex, liver functional reserve, and dose of L-carnitine. The median ΔSMI/year for all patients was -0.22%. The ΔSMI/year values in Child-Pugh classes A, B, and C were not significantly different among the three groups. There was no significant relationship between ΔSMI/year and sex, age, body mass index, and sarcopenia. Multivariate analysis showed that only a high dose of L-carnitine (odds ratio [OR], 4.812; 95% confidence interval [CI], 1.233-18.784; P = 0.024) was associated with increased muscle mass. The L-carnitine high-dose group included a significantly larger number of patients with increased muscle mass compared with the low-dose group (OR, 3.568; 95% CI, 1.138-11.185; P = 0.027). Administration of L-carnitine led to a significant and gradual reduction in serum ammonia levels. Conclusion: L-carnitine seems to suppress the progression of sarcopenia dose dependently, and this was noted to be associated with the improvement of hyperammonemia in patients with LC.

On-Demand Control of the Photochromic Properties of Naphthopyrans.

Photofunctional compounds have emerged as critically important materials for both fundamental studies and industrial applications. Control of the thermal decoloration speed to within several seconds while sustaining satisfactory photochromic colorability is an important challenge for the application of such materials to photochromic lenses and smart windows. Photochromic naphthopyran derivatives are utilized for photochromic lenses because of their high durability and easily controllable colorability. However, the residual color imparted by the long-lived transient species upon ceasing light irradiation remains a hindrance to practical applications. In this study, a strategy is demonstrated for on-demand control of the thermal decoloration speed of the transient colored species of naphthopyran derivatives. The increase in the ring-size of the alkylenedioxy moiety on the naphthopyrans accelerates the thermal back-reaction independently of the maximum-absorption wavelength of the colored isomer, leading to the realization of yellow-, red-, and blue-photochromic naphthopyrans with similar thermal fading speeds. This novel molecular design provides a strategy for the future development of advanced photoresponsive materials.

Early experience of seven hepatocellular carcinoma cases treated with regorafenib.

Regorafenib became second-line treatment for the patients with sorafenib refractory. In our study, two patients could not continue regorafenib for its adverse effects. It was suggested that appropriate use criteria of regorafenib should be observed and manage adverse effects earlier.

Comparison of hepatic arterial infusion chemotherapy between 5-fluorouracil-based continuous infusion chemotherapy and low-dose cisplatin monotherapy for advanced hepatocellular carcinoma.

AIM: The aim of this study is to compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) between 5-fluorouracil (5-FU)-based continuous infusion chemotherapy and low-dose cisplatin (CDDP) monotherapy in patients with advanced hepatocellular carcinoma (HCC). METHODS: Patients were grouped according to HAIC regimen (5-FU group, n = 317/CDDP group, n = 66). A two-to-one match was created using propensity score analysis (5-FU group, n = 102/CDDP group, n = 51). After matching, response rate (RR) and adverse events as primary end-points, and survival and progression-free survival as secondary end-points, were analyzed. RESULTS: In the analysis of primary end-points, the RR in the 5-FU group was significantly higher than in the CDDP group (32.4% vs. 15.7%, P = 0.033). In patients with a Child-Pugh (CP) score of 5-7, the RR in the 5-FU group was significantly higher than that in the CDDP group (36.1% vs. 15.4%, P = 0.020). In those with a CP score of 8-9, there was no significant difference in RR between the two groups (15.8% vs. 16.6%, P = 1.000). The reservoir system-related complications were 9.8% in the 5-FU group, and there was no significant difference in the incidence of grade 3/4 adverse events between the two matched groups (P > 0.05). In terms of secondary end-points, the median survival time was 9.1 and 8.7 months for the 5-FU and CDDP groups, respectively (P = 0.4917). Progression-free survival was 3.9 months for the 5-FU group and 4.9 months for the CDDP group (P = 0.4). CONCLUSIONS: 5-Fluorouracil-based continuous infusion chemotherapy could be suitable for advanced HCC patients with a CP score of 5-7 considering the treatment response.

Stepwise photochromism of bisnaphthopyrans exhibiting an excitation intensity-dependent color change.

Non-linear photoresponses against excitation light intensity are important for the development of attractive photofunctional materials exhibiting high spatial selective photoswitching that is not affected by weak background light. Biphotochromic systems composed of two fast photochromic units have the potential to show a stepwise two-photon absorption process in which the optical properties can be non-linearly controlled by changing the excitation light conditions. Herein, we designed and synthesized novel bisnaphthopyran derivatives containing fast photoswitchable naphthopyran units. The bisnaphthopyran derivatives show a stepwise two-photon-induced photochromic reaction upon UV light irradiation accompanied by a drastic color change due to a large change in the molecular structure between the one-photon product and the two-photon product. Consequently, the color of the bisnaphthopyran derivatives can be non-linearly controlled by changing the excitation intensity. This characteristic photochromic property of the biphotochromic system provides important insight into advanced photoresponsive materials.

Laparoscopic treatment of a vesicointestinal fistula due to a Meckel's diverticulum: a case report and review of the literature.

While there have been numerous reports about colovesical fistulas and ruptured intestinal diverticula, there have been far fewer reports about vesicointestinal fistulas caused by Meckel's diverticula. Most Meckel's diverticula are asymptomatic. Furthermore, they seldom cause vesicointestinal fistulas, and the associated complications are non-specific. Thus, their preoperative diagnosis is difficult. We experienced a case in which a vesicointestinal fistula was caused by a Meckel's diverticulum and was treated with laparoscopic surgery. A 46-year-old male was referred to our hospital after exhibiting hematuria. Cystoscopy revealed a fistula between the small intestine and bladder. Contrast-enhanced computed tomography and magnetic resonance imaging showed a diverticulum in the ileum and a fistula between the ileum and bladder, which passed through the diverticulum. A Meckel's diverticulum was suspected. We conducted a laparoscopic operation. We dissected the Meckel's diverticulum with an automatic suturing device and removed it together with part of the ileum. The patient's postoperative course was good. We experienced a case in which a vesicointestinal fistula was caused by a Meckel's diverticulum and was successfully treated with laparoscopic surgery. In selected cases of Meckel's diverticulum, the dissection of the diverticulum with an automatic suturing device is appropriate.

Hepatic arterial infusion chemotherapy followed by sorafenib in patients with advanced hepatocellular carcinoma (HICS 55): an open label, non-comparative, phase II trial.

BACKGROUND: In patients with advanced hepatocellular carcinoma (HCC), evidence is unclear as to whether hepatic arterial infusion chemotherapy (HAIC) or sorafenib is superior. We performed a prospective, open-label, non-comparative phase II study to assess survival with HAIC or HAIC converted to sorafenib. METHODS: Fifty-five patients were prospectively enrolled. Patients received HAIC as a second course if they had complete response, partial response, or stable disease (SD) with an alpha fetoprotein (AFP) ratio < 1 or a des-γ-carboxy prothrombin (DCP) ratio < 1. Patients were switched to sorafenib if they had SD with an AFP ratio > 1 and a DCP ratio > 1 or disease progression. The primary endpoint was the 1-year survival rate. Secondary endpoints were the 2-year survival rate, HAIC response, survival rate among HAIC responders, progression-free survival, and adverse events. RESULTS: Of the 55 patients in the intent-to-treat population, the 1-year and 2-year survival rates were 64.0 and 48.3%, respectively. After the first course of HAIC, one (1.8%) patient showed complete response, 13 (23.6%) showed partial response, 30 (54.5%) had SD, and 10 (18.1%) patients had progressive disease. Twenty-three patients (41.8%) had SD with AFP ratios < 1 or DCP ratios < 1, and 7 (12.7%) had SD with AFP ratios > 1 and DCP ratios > 1. Thirty-seven patients (68.5%) were responders and 17 (30.9%) were non-responders to HAIC. In responders, the 1-year and 2-year survival rates were 78 and 62%, respectively. CONCLUSION: Given the results of this study, this protocol deserves consideration for patients with advanced HCC. This trial was registered prospectively from December 12. 2012 to September 1. 2016.

Comparison of clinical outcome of hepatic arterial infusion chemotherapy and sorafenib for advanced hepatocellular carcinoma according to macrovascular invasion and transcatheter arterial chemoembolization refractory status.

BACKGROUND AND AIM: Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC) with distant metastasis, unresectable HCC, and HCC refractory to transcatheter arterial chemoembolization (TACE) or with macroscopic vascular invasion (MVI). Also, hepatic arterial infusion chemotherapy (HAIC) has been used for advanced HCC in Southeast and East Asian countries. However, clearer information is needed for choosing appropriately between these therapies. METHODS: The subjects were 391 HAIC and 431 sorafenibs administered at our hospital and related hospitals. In this case, cases that satisfy the following three conditions were targeted: (i) no extrahepatic metastasis, (ii) Child-Pugh A, and (ii) not having received treatment of both HAIC and sorafenib during the course. As a result, 150 cases of HAIC and 134 cases of sorafenib were analyzed this time. RESULTS: Univariate and multivariate analyses were performed for the HAIC and sorafenib groups. TACE refractory status and MVI were factors contributing to overall survival (OS). Therefore, this study divided all cases according to those variables. The median survival time of MVI-positive and non-TACE refractory cases was significantly better with HAIC (13 months) versus sorafenib (6 months). However, in MVI-negative and TACE refractory cases, the median survival time of HAIC (8 months) was significantly poorer than for sorafenib (20 months). CONCLUSION: Transcatheter arterial chemoembolization refractory status with HAIC and MVI with sorafenib were factors for poor prognosis. In particular, HAIC was significantly better than sorafenib as primary treatment in MVI and non-TACE refractory cases. It is necessary to consider these factors in treatment selection.

Evaluation of glycemic variability in chronic liver disease patients with type 2 diabetes mellitus using continuous glucose monitoring.

BACKGROUND AND AIMS: The feature of blood glucose dynamics in patients with chronic liver disease (CLD) is marked blood glucose fluctuations. However, the detail of blood glucose dynamics is not well known. The aim of the present study was to evaluate glycemic fluctuations by continuous glucose monitoring (CGM). MATERIALS AND METHODS: A total of 105 CLD patients with type 2 diabetes mellitus (T2DM) were enrolled in this study. Various parameters of glycemic variability were evaluated. The association of these parameters with liver functional reserve was examined. The parameters were also evaluated according to glycated hemoglobin A1c (HbA1c) levels. RESULTS AND DISCUSSION: Data of all patients showed that mean blood glucose (MBG) levels and the difference between highest and lowest blood glucose (ΔBG) increased significantly with worsening of liver functional reserve (P < 0.001 and P = 0.005, respectively). Although many of the cases were being treated for diabetes, postprandial hyperglycemia was seen in 92% of patients. Nocturnal hypoglycemia was seen in 22% of patients. In non-anemic patients with HbA1c levels of < 7.0%, the percentage of patients with mean amplitude of glycemic excursion (MAGE) of ≥ 77.4 mg/dL and that of MBG levels of > 145 mg/dL were higher in liver cirrhosis (LC) patients than in chronic hepatitis (CH) patients. In them, homeostasis model assessment for insulin resistance (HOMA-IR) of > 2.5 and LC were significantly associated with the increase in MAGE. LC was also significantly associated with increased MBG levels. CONCLUSION: The CGM systems were useful in finding hidden abnormalities of blood glucose fluctuations in CLD patients with T2DM, especially in non-anemic CLD patients with HbA1c levels of < 7.0%.