A Role in 15-Deacetylcalonectrin Acetylation in the Non-Enzymatic Cyclization of an Earlier Bicyclic Intermediate in Fusarium Trichothecene Biosynthesis.

The trichothecene biosynthesis in Fusarium begins with the cyclization of farnesyl pyrophosphate to trichodiene, followed by subsequent oxygenation to isotrichotriol. This initial bicyclic intermediate is further cyclized to isotrichodermol (ITDmol), a tricyclic precursor with a toxic trichothecene skeleton. Although the first cyclization and subsequent oxygenation are catalyzed by enzymes encoded by Tri5 and Tri4, the second cyclization occurs non-enzymatically. Following ITDmol formation, the enzymes encoded by Tri101, Tri11, Tri3, and Tri1 catalyze 3-O-acetylation, 15-hydroxylation, 15-O-acetylation, and A-ring oxygenation, respectively. In this study, we extensively analyzed the metabolites of the corresponding pathway-blocked mutants of Fusarium graminearum. The disruption of these Tri genes, except Tri3, led to the accumulation of tricyclic trichothecenes as the main products: ITDmol due to Tri101 disruption; a mixture of isotrichodermin (ITD), 7-hydroxyisotrichodermin (7-HIT), and 8-hydroxyisotrichodermin (8-HIT) due to Tri11 disruption; and a mixture of calonectrin and 3-deacetylcalonectrin due to Tri1 disruption. However, the ΔFgtri3 mutant accumulated substantial amounts of bicyclic metabolites, isotrichotriol and trichotriol, in addition to tricyclic 15-deacetylcalonectrin (15-deCAL). The ΔFgtri5ΔFgtri3 double gene disruptant transformed ITD into 7-HIT, 8-HIT, and 15-deCAL. The deletion of FgTri3 and overexpression of Tri6 and Tri10 trichothecene regulatory genes did not result in the accumulation of 15-deCAL in the transgenic strain. Thus, the absence of Tri3p and/or the presence of a small amount of 15-deCAL adversely affected the non-enzymatic second cyclization and C-15 hydroxylation steps.

Impact of Trinal Histological Glandular Differentiation Grade on the Prognosis of Patients with Intrahepatic Cholangiocarcinoma: a Multicenter Retrospective Study.

INTRODUCTION: It is unclear whether the histological glandular differentiation (HGD) score that evaluates the tumor grade of two dominant components is prognostic for survival in patients with intrahepatic cholangiocarcinoma (ICC). METHOD: We retrospectively analyzed the clinical and histopathologic data of 235 consecutive patients with histologically confirmed ICC following hepatectomy at 5 university hospitals in the Kansai region of Japan. RESULTS: Survival was statistically significantly stratified by trinal HGD grade (p < 0.05). Median disease-free survival (DFS) of patients with high HGD grade was significantly shorter compared with moderate HGD grade (13.0 vs 31.2 months, respectively; p = 0.004). By Cox proportional hazards regression analysis, HGD grade had the fifth-highest hazard ratio (HR = 1.77, p = 0.002) for DFS after vascular and/or biliary invasion, extrahepatic invasion, lymph node metastasis and multiple tumors. Multivariate logistic regression analysis revealed four predictors of early recurrence after hepatectomy (lymph node metastasis: odds ratio [OR] = 3.74, p = 0.001; tumor size > 50 mm: OR = 2.80, p = 0.002; HGD grade, high: OR = 2.11, p = 0.012; and vascular or biliary tract invasion: OR = 2.11, p = 0.048). CONCLUSION: Trinal HGD grade had a significant prognostic impact on the survival of patients with ICC after radical hepatectomy.

The Prognostic Impact of ABO Blood Group in Hepatocellular Carcinoma Following Hepatectomy.

BACKGROUND/PURPOSE: The effect of the ABO blood group on the survival of patients with hepatocellular carcinoma (HCC) is unclear. The aim of the present study is to determine the prognostic impact of ABO blood types on the survival of a Japanese population of patients with HCC who underwent surgical resection. METHODS: Patients with HCC (n = 480) who underwent an R0 resection between 2010 and 2020 were retrospectively analyzed. Survival outcomes were investigated according to ABO blood type (A, B, O, or AB). Outcomes for type A (n = 173) and non-type A (n = 173) groups after surgery were compared using 1-to-1 propensity score matching to control for variables. RESULTS: In the study cohort, 173 (36.0%), 133 (27.7%), 131 (27.3%), and 43 (9.0%) of participants had Type A, O, B, and AB, respectively. Type A and non-type A patients were successfully matched based on liver function and tumor characteristics. Recurrence-free survival (RFS; hazard ratio [HR] 0.75, 95% confidence interval [Cl] 0.58-0.98, p = 0.038) and overall survival (OS; HR: 0.67, 95% Cl: 0.48-0.95, p = 0.023) for patients with blood type A were both significantly decreased relative to non-type A patients. Cox proportional hazard analysis demonstrated that patients with HCC who have blood type A had a worse prognosis than those with non-type A blood. CONCLUSION: ABO blood type may have a prognostic impact on patients with HCC after hepatectomy. Blood type A is an independent unfavorable prognostic factor for recurrence-free and overall survival (RFS and OS) after hepatectomy.

Tumor budding may be a promising prognostic indicator in intrahepatic cholangiocarcinoma: A multicenter retrospective study.

Purpose: This retrospective study evaluated our hypothesis that high tumor budding (≥10 buds) may help determine the appropriate T category for more accurate staging of intrahepatic cholangiocarcinoma (ICC). Methods: We analyzed the clinical and histopathologic data of 235 consecutive patients with histologically confirmed ICC following hepatectomy at five university hospitals in the Kansai region of Japan between January 2009 and December 2020. ICC staging was based on the Liver Cancer Study Group of Japan (LCSGJ) staging system, 6th edition. Results: Patients with ICC with high budding showed significantly shorter disease-specific survival (DSS) and disease-free survival (DFS) than patients with low/intermediate budding. Cox proportional hazards regression analysis showed a hazard ratio of 2.2-2.3 (P < 0.05) for high budding. Based on these results, we modified the T category of ICC in the LCSGJ staging system by adding severity of tumor budding as a fourth determinant. This proposed staging system for ICC has significantly improved the prognostic accuracy for both DSS and DFS (both: P < 0.05). Conclusions: High tumor budding is a new candidate for an additional determinant of the T category in staging ICC. An LCSGJ staging system containing an additional evaluation of tumor budding may lead to improved staging accuracy.

Short- and long-term outcomes of laparoscopic versus open repeat liver resection for hepatocellular carcinoma: A multicenter study.

OBJECTIVE: This multicenter study aimed to compare the short- and long-term outcomes of laparoscopic (LRLR) versus open repeat liver resection (ORLR) for recurrent hepatocellular carcinoma (HCC) using propensity score matching (PSM). Despite the expanding indications for laparoscopic liver resection, limited data regarding the outcomes of LRLR have previously been reported. METHODS: This study included patients who underwent repeat liver resection for recurrent HCC. Patients were divided into the LRLR and ORLR groups, and their short- and long-term outcomes were compared via PSM. RESULTS: There were 256 and 130 patients in the ORLR and LRLR groups, respectively. After PSM, 64 patients were included in each group. Intraoperative blood loss was significantly less in LRLR than in ORLR (56 vs 208 ml, P < .001). Postoperative complications of Clavien-Dindo IIIa or more were significantly less in LRLR than in ORLR (3.1% vs 15.6%, P = .030). The length of hospital stay was notably shorter in LRLR than in ORLR (9 vs 12 days, P < .001). Survival rates after repeat liver resection at 1, 3, and 5 years, respectively, were comparable at 93.4%, 81.9%, and 63.5% for ORLR and at 94.8%, 80.7%, and 67.3% for LRLR (P = .623). Subgroup analysis of patients who underwent wedge resection in repeat liver resection revealed that the postoperative complication rate was notably lower in LRLR than in ORLR (7.2% vs 21.8%, P = .030). CONCLUSION: LRLR for recurrent HCC is a viable option due to its better short-term outcomes and comparable long-term outcomes compared to ORLR.

Modified Albumin-Bilirubin Grade and Alpha-Fetoprotein Score (mALF Score) for Predicting the Prognosis of Hepatocellular Carcinoma after Hepatectomy.

We developed and evaluated a modified albumin-bilirubin grade and α-fetoprotein (mALF) score, a nutritional and oncological assessment tool for patients with hepatocellular carcinoma (HCC) after surgical resection. Patients (n = 480) who underwent R0 resection between 2010 and 2020 were analyzed retrospectively. The mALF score assigned one point for a modified albumin-bilirubin (mALBI) grade 2b or 3 and one point for an α-fetoprotein (AFP) level ≥ 100 ng/mL. Patients were classified by mALF scores of 0 (mALBI grade 1/2a, AFP < 100 ng/mL), 1 (mALBI grade 2b/3 or AFP ≥ 100 ng/mL), or 2 (mALBI grade 2b/3, AFP ≥ 100 ng/mL) points. Liver reserve deteriorated and cancer progressed with increasing score. Postoperative complications (Clavien−Dindo classification ≥ 3) differed significantly among groups. The 5-year recurrence-free survival (RFS) rates were 34.8%, 11.2%, and 0.0% for 0, 1, and 2 points, respectively (1 or 2 versus 0 points, p < 0.001). The 5-year overall survival (OS) rates were 66.0%, 29.7%, and 17.8% for 0, 1, and 2 points, respectively (1 or 2 versus 0 points, p < 0.001). The mALF score was an independent prognostic predictor of RFS and OS. In HCC, the mALF score was effective for predicting postoperative complications and long-term survival.

Preoperative Serum Markers and Risk Classification in Intrahepatic Cholangiocarcinoma: A Multicenter Retrospective Study.

Accurate risk stratification selects patients who are expected to benefit most from surgery. This retrospective study enrolled 225 Japanese patients with intrahepatic cholangiocellular carcinoma (ICC) who underwent hepatectomy between January 2009 and December 2020 and identified preoperative blood test biomarkers to formulate a classification system that predicted prognosis. The optimal cut-off values of blood test parameters were determined by ROC curve analysis, with Cox univariate and multivariate analyses identifying prognostic factors. Risk classifications were established using classification and regression tree (CART) analysis. CART analysis revealed decision trees for recurrence-free survival (RFS) and overall survival (OS) and created three risk classifications based on machine learning of preoperative serum markers. Five-year rates differed significantly (p < 0.001) between groups: 60.4% (low-risk), 22.8% (moderate-risk), and 4.1% (high-risk) for RFS and 69.2% (low-risk), 32.3% (moderate-risk), and 9.2% (high-risk) for OS. No difference in OS was observed between patients in the low-risk group with or without postoperative adjuvant chemotherapy, although OS improved in the moderate group and was prolonged significantly in the high-risk group receiving chemotherapy. Stratification of patients with ICC who underwent hepatectomy into three risk groups for RFS and OS identified preoperative prognostic factors that predicted prognosis and were easy to understand and apply clinically.

Evaluation of a Triage Checklist for Mild COVID-19 Outpatients in Predicting Subsequent Emergency Department Visits and Hospitalization during the Isolation Period: A Single-Center Retrospective Study.

Managing mild illness in COVID-19 and predicting progression to severe disease are concerning issues. Here, we investigated the outcomes of Japanese patients with mild COVID-19, and identified triage risk factors for further hospitalization and emergency department (ED) visits at a single tertiary hospital. A triage checklist with 30 factors was used. Patients recommended for isolation were followed up for 10 days for subsequent ED visits or hospital admission. Overall, 338 patients (median age, 44.0; 45% women) visited the clinic 5.0 days (median) after symptom onset. Thirty-six patients were immediately hospitalized following triage; others were isolated. In total, 72 non-hospitalized patients visited the ED during their isolation, and 30 were hospitalized after evaluation for oxygen desaturation. The median ED visit and hospitalization durations after symptom onset were 5.0 and 8.0 days, respectively. The checklist factors associated with hospitalization during isolation were age > 50 years, body mass index > 25 kg/m2, hypertension, tachycardia with pulse rate > 100/min or blood pressure > 135 mmHg at triage, and >3-day delay in hospital visit after symptom onset. No patients died. Altogether, 80% of patients with mild COVID-19 could be safely isolated at home. Age, BMI, underlying hypertension, date after symptom onset, tachycardia, and systolic blood pressure at triage might be related to later hospitalization.

Theranostics Using Indocyanine Green Lactosomes.

Lactosomes™ are biocompatible nanoparticles that can be used for cancer tissue imaging and drug delivery. Lactosomes are polymeric micelles formed by the self-assembly of biodegradable amphiphilic block copolymers composed of hydrophilic polysarcosine and hydrophobic poly-L-lactic acid chains. The particle size can be controlled in the range of 20 to 100 nm. Lactosomes can also be loaded with hydrophobic imaging probes and photosensitizers, such as indocyanine green. Indocyanine green-loaded lactosomes are stable for long-term circulation in the blood, allowing for accumulation in cancer tissues. Such lactosomes function as a photosensitizer, which simultaneously enables fluorescence diagnosis and photodynamic therapy. This review provides an overview of lactosomes with respect to molecular design, accumulation in cancer tissue, and theranostics applications. The use of lactosomes can facilitate the treatment of cancers in unresectable tissues, such as glioblastoma and head and neck cancers, which can lead to improved quality of life for patients with recurrent and unresectable cancers. We conclude by describing some outstanding questions and future directions for cancer theranostics with respect to clinical applications.

Experience with Photodynamic Therapy Using Indocyanine Green Liposomes for Refractory Cancer.

We reported the development of an effective cancer treatment using a multidisciplinary treatment, including photodynamic therapy (PDT) with indocyanine green (ICG) liposomes and a combination of Lentinula edodes mycelia (LEM) and hydrogen gas inhalation therapy. ICG liposomes were prepared by adding 5 mg of ICG to 50 mL liposomes. Later, 25 mL of ICG liposomes were diluted with 250 mL of 5% glucose solution and administered intravenously to the patient. We selected the multi-laser delivery system (MLDS), a laser irradiator for performing PDT. Further, the patients received a combination of LEM and hydrogen gas inhalation therapy throughout the treatment. We reported two cases of PDT therapy, one with middle intrathoracic esophagus carcinoma and the other with hypopharyngeal cancer. In the first case, the MLDS laser was directly attached to the endoscope and directed to the cancer area with wavelengths of 810 nm. After the treatment, a biopsy demonstrated no tumor recurrence. In the second case, the patient was treated with endovascular PDT using ICG liposomes and MLDS fiber optics. Later, tumor shrinkage was demonstrated after the first round and disappeared after six months. In conclusion, the present findings suggest that the effect of PDT using ICG liposomes with LEM and hydrogen gas may eradicate cancer without burdening patients by enhancing tumor immunity.

Comparison of the New Neo-Glasgow Prognostic Score Based on the Albumin-Bilirubin Grade with Currently Used Nutritional Indices for Prognostic Prediction following Surgical Resection of Hepatocellular Carcinoma: A Multicenter Retrospective Study in Japan.

Nutritional assessment is important for predicting a prognosis in hepatocellular carcinoma (HCC). The authors examined the utility of the recently developed neo-Glasgow prognostic score (GPS) as a nutritional prognostic assessment in HCC in a multicenter retrospective study of 271 patients with HCC and Child-Pugh class A liver function who underwent R0 resection between 2011 and 2013. The median age was 72 years, 229 and 42 patients had Child-Pugh scores of 5 and 6, respectively, 223 patients had single tumors, the median tumor size was 3.6 cm, and open and laparoscopic resection were performed in 138 and 133 patients, respectively. We compared the prognostic predictive utility of the prognostic nutritional index, neutrophil/lymphocyte and platelet/lymphocyte ratios, controlling nutritional status score, GPS, and neo-GPS, which uses albumin-bilirubin grade (ALBI) instead of albumin. The c-indexes for the predictive prognostic value for overall survival (OS) and progression-free survival (PFS) were best for neo-GPS (OS: 0.571 vs. ≤0.555; PFS: 0.555 vs. ≤0.546). In multivariate analysis with the Cox proportional hazards model, elevated alpha-fetoprotein (AFP; ≥100 ng/mL; hazard ratio [HR] 2.190, 95% confidence interval [CI] 1.493−3.211, p < 0.001), multiple tumors (HR 1.784, 95%CI 1.178−2.703, p = 0.006), tumor size of ≥5 cm (HR 1.508, 95%CI 1.037−2.193, p = 0.032), and neo-GPS of ≥1 (HR 1.554, 95%CI 1.074−2.247, p = 0.019) were significant prognostic factors for OS, whereas elevated AFP (≥100 ng/mL) (HR 1.743, 95%CI 1.325−2.292, p < 0.001), multiple tumors (HR 1.537, 95%CI 1.148−2.057, p = 0.004), and neo-GPS of ≥1 (HR 1.522, 95%CI 1.186−1.954, p = 0.001) were significant prognostic factors for PFS. A neo-GPS of ≥1 was associated with a higher rate of high-grade (≥3) Clavien-Dindo complications than a neo-GPS of <1 (31.1% vs. 17.0%, p = 0.007). Neo-GPS was a good prognostic nutritional assessment tool for the prediction of postoperative complications and prognosis in patients undergoing surgical HCC resection.

Update on perioperative management of patients undergoing surgery for liver cancer.

Hepatocellular carcinoma is often accompanied by chronic hepatitis or cirrhosis. Preoperative evaluation of liver function and postoperative nutritional management are critical in patients with hepatocellular carcinoma who undergo liver surgery. Although the incidence of postoperative complications and death has declined in Japan over the last 10 years, postoperative complications have not been fully overcome. Therefore, surgical procedures and perioperative management must be improved. Accurate preoperative evaluations of liver function, nutrition, inflammation, and body skeletal muscle are required. Determination of the optimal surgical procedure should consider not only tumor characteristics but also the physical reserve of the patient. Nutritional management of chronic liver disorders, especially maintaining protein synthesis for postoperative protein/energy, is important. Prophylactic antibiotics are recommended for short-term use within 24 hours after surgery. Abdominal drainage is recommended for patients with cirrhosis who may develop large amounts of ascites, who are at risk of postoperative bleeding, or who may have bile leakage due to a large resection area. Postoperative exercise therapy may improve insulin resistance in patients with chronic liver damage. Implementation of an early/enhanced recovery after surgery program is recommended to reduce biological invasive responses and achieve early independence of physical activity and nutrition intake. We review the latest information on the perioperative management of patients undergoing liver resection for hepatocellular carcinoma.

Efficacy of Nanofiber Sheets Incorporating Lenvatinib in a Hepatocellular Carcinoma Xenograft Model.

Lenvatinib has a high response rate in unresectable advanced hepatocellular carcinoma (HCC). In this study, we investigated whether lenvatinib-incorporating poly(ε-caprolactone) sheets (lenvatinib sheets) as a drug delivery system (DDS) exerted antitumor effects in a murine HCC model. The lenvatinib sheets were designed for sustained release of approximately 1 mg lenvatinib for 14 days. For 14 days, 1 mg lenvatinib was orally administered to mice. Then, we compared the antitumor effects of lenvatinib sheets with those of oral lenvatinib. The tumor volume, body weight, and serum lenvatinib level were measured for 14 days. A peritoneal dissemination model was established to examine the survival prolongation effect of the lenvatinib sheets. Tumor growth was significantly inhibited in the lenvatinib sheet group compared with that in the no treatment and oral groups. The antitumor effect was significantly higher in the lenvatinib sheet group. Regardless of the insertion site, the serum lenvatinib levels were maintained and showed similar antitumor effects. The mitotic index was significantly inhibited in the lenvatinib sheet group compared with that in the control group. Furthermore, lenvatinib sheets improved the 30-day survival. Lenvatinib sheets showed sufficient antitumor effects and may serve as an effective novel DDS for advanced HCC.

The Impact of a Preoperative Staging System on Accurate Prediction of Prognosis in Intrahepatic Cholangiocarcinoma.

Background: Non-invasive biomarkers detected preoperatively are still inadequate for treatment decision making for patients with intrahepatic cholangiocarcinoma (ICC). In this study, we analyzed preoperative findings to establish a novel preoperative staging system (PRE-Stage) for patients with ICC. Methods: The clinical data of 227 consecutive patients with histologically confirmed ICC following hepatectomy at five university hospitals were analyzed. Results: Cox proportional hazards regression analysis of survival revealed that a CRP−albumin−lymphocyte index < 3, central tumor location, and CA19-9 level > 40 U/mL were prognostic factors among the preoperatively obtained clinical findings (hazard ratios (HRs) of all three factors for disease-specific survival (DSS) and disease-free survival (DFS: 2.4−3.3 and 1.7−2.9; all p < 0.05). The PRE-Stage was developed using these three prognostic factors, and it was able to significantly predict DSS and DFS when the patients were stratified into four stages (p < 0.05). In addition, the PRE-Stage resulted in similar HRs as those of the Liver Cancer Study Group of Japan (LCSGJ) stage (HRs for DSS: PRE-Stage, 1.985; LCSGJ stage, 1.923; HRs for DFS: LCSGJ stage, 1.909, and PRE-Stage, 1.623, all p < 0.05). Conclusion: The PRE-Stage demonstrated similar accuracy in predicting the prognosis of ICC as that of the LCSGJ stage, which is based on postoperative findings. The PRE-Stage may contribute to appropriate treatment decision making.

Predicting Complications following Surgical Resection of Hepatocellular Carcinoma Using Newly Developed Neo-Glasgow Prognostic Score with ALBI Grade: Comparison of Open and Laparoscopic Surgery Cases.

Background/Aim: Nutritional assessment is known to be important for predicting prognosis in patients with malignant diseases. This study examined the usefulness of a prognostic predictive nutritional assessment tool for hepatocellular carcinoma (HCC) patients treated with surgical resection. Materials/Methods: HCC patients (n = 429) classified as Child−Pugh A who underwent an R0 resection between 2010 and 2020 were retrospectively analyzed (median age 73 years, males 326 (76.0%), Child−Pugh score 5:6 = 326:103, single tumor 340 (79.2%), median tumor size 3.5 cm, open:laparoscopic = 304:125). Glasgow prognostic score (GPS) and the newly developed neo-GPS method, which uses albumin−bilirubin grade 1 instead of albumin, were evaluated to compare their usefulness for prognosis prediction. Results: Median survival time for patients with a GPS score of 0, 1, and 2 was 120, 51, and 20 months, respectively. As for neo-GPS, that for those with a score of 0, 1, and 2 was not applicable (NA), 53 months, and 35 months, respectively (each p < 0.001; c-index: 0.556 and 0.611, respectively). Furthermore, median progression-free survival was 33, 22, and 9 months, and 41, 24, and 15 months, respectively (each p < 0.001; c-index: 0.539 and 0.578, respectively). As compared to patients with a high GPS (≥1), those with a high neo-GPS (≥1) showed a greater rate of high Clavien−Dindo classification (≥3) (39.2% vs. 65.1%). A comparison of patients with a high GPS (≥1) with those with a high neo-GPS (≥1) showed no significant difference regarding frequency of open or laparoscopic hepatectomy (17.4% vs. 15.2%, p = 0.670; 44.7% vs. 43.2%, p = 0.831, respectively), while the frequency of high Clavien−Dindo classification (≥3) was lower in patients who underwent a laparoscopic hepatectomy (11.2% vs. 22.7%, p = 0.007). Conclusion: The present findings suggest that the newly developed neo-GPS based on ALBI grade is an effective prognostic nutritional assessment tool and can be used for prediction of postoperative complications.

Patients with polyclonal hepatocellular carcinoma are at a high risk of early recurrence and have a poor recurrence-free survival period.

BACKGROUND/PURPOSE OF THE STUDY: Tumor heterogeneity based on copy number variations is associated with the evolution of cancer and its clinical grade. Clonal composition (CC) represents the number of clones based on the distribution of B-allele frequency (BAF) obtained from a genome-wide single nucleotide polymorphism (SNP) array. A higher CC number represents a high degree of heterogeneity. We hypothesized and evaluated that the CC number in hepatocellular carcinoma (HCC) tissues might be associated with the clinical outcomes of patients. METHODS: Somatic mutation, whole transcriptome, and CC number based on copy number variations of 36 frozen tissue samples of operably resected HCC tissues were analyzed by targeted deep sequencing, transcriptome analysis, and SNP array. RESULTS: The samples were classified into the heterogeneous tumors as poly-CC (n = 26) and the homogeneous tumors as mono-CC (n = 8). The patients with poly-CC had a higher rate of early recurrence and a significantly shorter recurrence-free survival period than the mono-CC patients (7.0 months vs. not reached, p = 0.0084). No differences in pathogenic non-synonymous mutations, such as TP53, were observed between the two groups when targeted deep sequencing was applied. A transcriptome analysis showed that cell cycle-related pathways were enriched in the poly-CC tumors, compared to the mono-CC tumors. Poly-CC HCC is highly proliferative and has a high risk of early recurrence. CONCLUSION: CC is a possible candidate biomarker for predicting the risk of early postoperative recurrence and warrants further investigation.

Prospective Study to Evaluate the Safety and Efficacy of a New Surgical Tube Fixation Method: A Pilot Study.

BACKGROUND: Various tubes may be fixed to the skin by ligation using silk sutures after gastrointestinal surgery. We investigated the effects of a skin substitute, "Nonaht®," on pain and skin inflammation at the fixation sites of various tubes. METHODS: The effects of tubes (abdominal drains, small intestinal feeding tubes, and bile duct drainage tubes) fixed in place using either silk sutures or Nonaht were compared for 1-3 months. RESULTS: The median pain scores at the fixation site when abdominal drains were removed were 1.0 with silk sutures and 0 with Nonaht (p < 0.001). Scarring at the fixation site at postoperative month (POM) 1 occurred in 13 of 28 cases in the silk suture group and in no cases in the Nonaht group (p < 0.001). The median pain scores at the fixation site with long-term tubes on postoperative day (POD) 14 and POM 1 were 2.0 and 1.0, respectively, with silk sutures, and none at all time points with Nonaht (p < 0.001). Scarring at the fixation site at POM 3 occurred in all 10 cases in the silk suture group and in no cases in the Nonaht group (p < 0.001). CONCLUSIONS: Patients with conventional skin fixation of tubes using silk sutures were continuously aware of pain at the fixation site and developed skin damage and subsequent scar formation, especially for tubes inserted for ≥ 1 month. The use of Nonaht may reduce the incidence of dermatitis and wound infections at tube fixation sites, thereby promoting early postoperative recovery.

Superiority of CRP-albumin-lymphocyte index (CALLY index) as a non-invasive prognostic biomarker after hepatectomy for hepatocellular carcinoma.

BACKGROUND: We aimed to investigate whether a novel biomarker incorporating albumin, lymphocytes, and CRP can predict the prognosis for hepatocellular carcinoma (HCC) after hepatectomy. METHODS: Between January 2011 and December 2013, 384 patients who underwent hepatectomy in four university hospitals in Japan were investigated as a discovery cohort. The CRP-Albumin-Lymphocyte (CALLY index) was defined as (Albumin × Lymphocyte)/(CRP × 104). Patients with a CALLY index ≥5 (n = 200) were compared to those with an index <5 (n = 184). Next, validation was performed using 267 patients from three other university hospitals (external validation cohort). RESULTS: The number of TNM Stage III and IV patients was significantly higher in the CALLY <5 group than the ≥5 group (p = 0.003). There was a significant difference in the 5-year survival rate (CALLY ≥5: 71% vs. <5: 46%; p < 0.001). Multivariate analysis identified the CALLY index as an independent factor of overall survival. Similarly, there was a significant difference in the 5-year survival rate between the CALLY ≥5 (73%) and <5 (48%) groups (p < 0.001), and the CALLY index was identified as an independent prognostic factor in the external validation cohort. CONCLUSION: The CALLY index derived from CRP, albumin, and lymphocyte values is a promising predictive biomarker for postoperative prognosis of patients with HCC.

The Impact of Sorafenib in Combination with Intermittent Hepatic Arterial Infusion Chemotherapy for Unresectable Hepatocellular Carcinoma with Major Vascular Invasion.

The aim of the current study was to investigate the efficacy and safety of sorafenib and intermittent hepatic arterial infusion chemotherapy with cisplatin for unresectable hepatocellular carcinoma (HCC) with severe portal vein invasion. The antitumor effect was a complete response in 1 of 38 patients, a partial response in 12 patients, stable disease in 16 patients, and progressive disease in 9 patients, for a 34.2% response rate and a 76.3% disease control rate. This regimen had favorable efficacy and acceptable safety and may be feasible for unresectable HCC with severe portal vein invasion.

IgA Vasculitis in an Oldest-old Patient Successfully Treated with Glucocorticoid.

A 94-year-old man was diagnosed with immunoglobulin A vasculitis (IgAV), and losartan was initiated. His renal function rapidly deteriorated over a month; therefore, methylprednisolone was administered intravenously for three days followed by oral prednisolone. Renal function improvement and both proteinuria and hematuria remission were observed within six months. Prednisolone tapering was completed at eight months. In this case, we monitored the patient carefully and started glucocorticoids as soon as the patient's renal function deteriorated. We were thus able to treat the patient with a relatively small dose of glucocorticoids in a short treatment period without any adverse events due to glucocorticoids.