Background Several reports have suggested that hepatic resection provides a survival benefit in patients with hepatocellular carcinoma (HCC) at the intermediate stage of the Barcelona Clinic Liver ...Cancer classification (BCLC-B). The operative indications for multiple BCLC-B have not been established, however. The aim of this study was to clarify the survival benefit of hepatic resection for multinodular BCLC-B HCC. Methods We retrospectively analyzed 85 patients with BCLC-B HCC who underwent liver resection. To evaluate clinicopathologic factors and survival, we divided the patients into 3 types based on radiologic findings regarding tumor number and maximum tumor diameter: type 1, up to 3 lesions <5 cm; type 2, up to 3 lesions ≥5 cm or 4 nodules of any size; type 3, >4 nodules. Results Thirty-four patients were classified as type 1, 32 as type 2, and 19 as type 3. The 1-, 3-, and 5-year survival in type 1 were 97.1%, 87.4%, and 75.2%, respectively. Those in type 2 were 84.0%, 74.0%, and 63.0%, and those in type 3 were 64.9%, 55.7%, and 37.1%, respectively. The overall survival of type 1 patients was significantly better than that of type 3 patients. The prognosis of type 2 patients was worse than that of type 1 patients and better than that of type 3. Multivariate analysis identified radiologic tumor size and tumor number as independent prognostic factors. Conclusion Our findings suggest that hepatic resection should be considered a radical treatment for multinodular BCLC-B HCC. Our subclassification can be applied to select the initial treatment and when making decisions regarding hepatic resection of BCLC-B HCC with multiple nodules.
Background Smaller size grafts for living donor liver transplantation (LDLT) can enhance donor safety and expand donor availability. We previously reported that modulation of portal venous pressure ...(PVP) was key for successful LDLT with small grafts, and that it actively lowered graft-to-recipient weight ratio (GRWR) for adult-to-adult LDLT. This retrospective study investigated the outcome of LDLT using small grafts with PVP modulation. Method This study analyzed 221 adult LDLT patients between March 2008 and December 2013 and divided them into 3 groups based on GRWR: large (L), GRWR ≥ 0.8% ( n = 154), medium (M), ≥ 0.7% GRWR < 0.8% ( n = 38); and small (S) GRWR < 0.7% ( n = 29). Donor and recipient factors, PVP, pressure gradient between PVP and central venous pressure (CVP), occurrence of small for size syndrome (SFSS), ascites, and posttransplant laboratory data were compared across the 3 groups. Patient and graft survival were compared using Kaplan–Meier methods. Results There was no difference in patient or graft survival between the 3 groups. Amount of posttransplant ascites and posttransplant International Normalized Ratio were similar, but the S and M groups had more prolonged cholestasis. SFSS was identified in 17%, 13%, and 13% in the S, M, and L groups, respectively ( P = NS). Patients with a final PVP of ≤15 mmHg had better survival than patients with a final PVP of >15 mmHg ( P < .001). Multivariate analysis showed that donor age >40 years old, final PVP of >15 mmHg, and pressure gradient of PVP-CVP >5 mmHg were risk factors for inferior patient survival. Conclusion We achieved satisfactory outcomes in LDLT with GRWR as low as 0.6% using PVP modulation. Thus, we currently set a lower limit of GRWR at 0.6% while protecting donor safety and expanding donor availability.
Background Skeletal muscle depletion, referred to as sarcopenia, is predictive of mortality in patients undergoing digestive operations. The impact of muscle quality on outcomes, however, is unclear. ...This retrospective study investigated the impact of preoperative skeletal muscle quantity and quality on survival in patients undergoing resection of pancreatic cancer. Methods We investigated 230 patients who underwent resection of pancreatic cancer between 2004 and 2013. The quantity and quality of skeletal muscle, indicated by psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC), were measured in preoperative computed tomography images. Overall survival (OS) and recurrence-free survival (RFS) rates were compared according to PMI and IMAC, and prognostic factors after pancreatic resection were assessed. Results The OS and RFS rates in patients with low PMI were lesser than in those with normal/high PMI ( P < .001, P < .001), with a mean survival time of 17.7 and 33.2 months, respectively. The OS and RFS rates in patients with high IMAC also were less than in those with normal/low IMAC ( P < .001, P = .003) (mean survival time = 21.5 and 56.5 months, respectively). Low PMI (low muscle mass) and high IMAC (low muscle quality) were independent prognostic factors of poor OS (hazard ratio HR = 1.999, P < .001; HR = 2.527, P < .001) and RFS (HR = 1.607, P = .007; HR = 1.640, P = .004), respectively. Conclusion Preoperative sarcopenia, indicating low quality and quantity of skeletal muscle, is closely related to mortality after resection of pancreatic cancer.
In Japan, intravenous alteplase, a recombinant tissue-type plasminogen activator (rt-PA), was approved for an indication of ischemic stroke in 2005 on the basis of the results of a clinical trial ...with a unique dose of the drug (0.6 mg/kg). The Japan Stroke Society published the guidelines for intravenous application of rt-PA and organized training sessions for proper use all over Japan in an effort to promote the safe, widespread use of intravenous alteplase. Seven years following its approval, clinical experience with intravenous alteplase has accumulated, additional evidence of intravenous alteplase has been found in Japan and overseas, and the medical environment has substantially changed, including approvals for new drugs and medical devices. Notably, the use of alteplase in the extended therapeutic time window (within 4.5 hours of symptom onset) became covered by insurance in Japan in August 2012. To address these changing situations, we have decided to prepare the revised guidelines. In preparing the second edition, we took care to make its contents more practical by emphasizing information needed in clinical practice. While the first edition was developed with emphasis on safety in light of limited clinical experience with intravenous alteplase in Japan in 2005, this second edition is a substantial revision of the first edition mainly in terms of eligibility criteria, on the basis of accumulated evidence and the clinical experience.
Background There has been no report on risk stratification for hepatectomy using a nationwide surgical database in Japan. The objective of this study was to evaluate mortality and variables ...associated with surgical outcomes of hepatectomy at a national level. Study Design We analyzed records of 7,732 patients who underwent hepatectomy for more than 1 segment (MOS) during 2011 in 987 different hospitals, as identified in the National Clinical Database (NCD) of Japan. The NCD captured 30-day morbidity and mortality as well as 90-day in-hospital mortality outcomes, which were submitted through a web-based data entry system. Based on 80% of the population, independent predictors for 30-day mortality and 90-day in-hospital mortality were calculated using a logistic regression model. The risk factors were validated with the remaining 20% of the cohort. Results The median postoperative length of hospitalization was 16.0 days. The overall patient morbidity rate was 32.1%. Thirty-day mortality and 90-day in-hospital mortality rates were 2.0% and 4.0%, respectively. Totals of 14 and 23 risk factors were respectively identified for 30-day mortality and 90-day in-hospital mortality. Factors associated with risk for 90-day in-hospital mortality were preoperative condition and comorbidity, operative indication (emergency surgery, intrahepatic/perihilar cholangiocarcinoma, or gallbladder cancer), preoperative laboratory data, and extent and location of resected segments (segment 1, 7, or 8). As a performance metric, c-indices of 30-day mortality and 90-day in-hospital mortality were 0.714 and 0.761, respectively. Conclusions Here we report the first risk stratification analysis of hepatectomy using a Japanese nationwide surgical database. This system would predict surgical outcomes of hepatectomy and be useful to evaluate and benchmark performance.
Background Previously, we proposed expanded selection criteria for liver transplantation (LT) for hepatocellular carcinoma (HCC), the Kyoto criteria, involving a combination of tumor number ...≤10, maximal diameter of each tumor ≤5 cm, and serum des-gamma-carboxy prothrombin levels ≤400 mAU/mL, and we have used these criteria since January 2007. In the present study, the usefulness of the criteria was validated prospectively as well as retrospectively. Methods One hundred ninety-eight patients with HCC who underwent living donor LT (LDLT) from February 1999 through December 2011 were enrolled in this study. Overall survival and recurrence rates were investigated in patients classified according to the Kyoto criteria, the Milan criteria, or previous treatments for HCC. Tumor biological aggressiveness, including microvascular invasion and histologic differentiation, according to selection criteria was also examined. Results The 5-year overall survival for patients within the Kyoto criteria ( n = 147; 82%) was greater than that for the 49 patients exceeding them ( n = 49; 42%; P < .001). The 5-year recurrence rate for patients within the Kyoto criteria (4.4%) was less than that for patients exceeding them (51%; P < .001). Intention-to-treat analysis of the 62 patients who underwent LDLT after implementation of the Kyoto criteria showed that the 5-year overall survival rate and the recurrence rate were 82% and 7%, respectively. Tumor biology was significantly less aggressive in patients within the Kyoto criteria. Conclusion The Kyoto criteria are useful expanded criteria for LDLT for HCC and could help to achieve favorable outcomes.
IntroductionNecitumumab plus gemcitabine and cisplatin (GCN) is a standard therapy for patients with advanced lung squamous cell carcinoma (LSqCC). However, the efficacy and tolerability of GCN in ...second-line or later treatment for patients previously treated with immune checkpoint inhibitors (ICIs) remain unknown.MethodsThis multicenter, retrospective, cohort study assessed the efficacy and tolerability of GCN initiated between November 1, 2019 and March 31, 2022 as second-line to fourth-line treatment in patients with advanced LSqCC who had been pretreated with ICIs. The primary end point was progression-free survival (PFS).ResultsA total of 93 patients from 35 institutions in Japan were enrolled. The median PFS, median overall survival (OS), and objective response rate were 4.4 months (95% confidence interval CI: 3.8-5.3), 13.3 months (95% CI: 9.6-16.5), and 27.3% (95% CI: 18.3-37.8), respectively. The median PFS, median OS, and objective response rate for second-line, third-line, and fourth-line treatment groups were 4.8 months, 3.8 months, and 4.3 months (p = 0.24); 15.7 months, 11.6 months, and 10.1 months (p = 0.06); and 31.0%, 13.6%, and 37.5% (p = 0.22), respectively. The severity of GCN-related skin disorders was associated with longer PFS (p < 0.05) and OS (p < 0.05). The frequencies of grade ≥3 skin disorders, hypomagnesemia, pneumonitis, and febrile neutropenia were 16.1%, 7.5%, 1.1%, and 4.3%, respectively. There were no treatment-related deaths.ConclusionsGCN for ICI-pretreated patients with LSqCC seems tolerable and offers promising efficacy regardless of treatment line, and ICI pretreatment might enhance GCN efficacy.
Programmed cell death 1 (PD-1) inhibitors have become standard treatment for patients with advanced NSCLC. However, few studies have focused on the impact of cancer cachexia on the efficacy of PD-1 ...or programmed death-ligand 1 (PD-L1) inhibitors among patients with NSCLC.
We retrospectively reviewed medical records of patients with advanced NSCLC who received PD-1 or PD-L1 inhibitor monotherapy from May 2016 to December 2018. We defined cancer cachexia as unintentional weight loss greater than 5% over 6 months and high PD-L1 as greater than 50% expression on tumor cells. We evaluated the objective response rates (ORRs) and progression-free survival (PFS).
Among 108 patients, 52 had cancer cachexia. Patients with cachexia had a lower ORR (15% versus 57%, p < 0.001) and shorter PFS (2.3 mo versus 12.0 mo, p < 0.001) than those without cachexia. Patients with low PD-L1 expression had a lower ORR (14% versus 53%, p < 0.001) and shorter PFS (2.8 mo versus 10.8 mo, p = 0.002) than those with high PD-L1 expression. Multivariate analysis revealed cancer cachexia and low PD-L1 expression as independent negative predictors of PFS. Among patients with cachexia, there was no significant difference in the ORR (p = 0.514) or PFS (p = 0.992) on the basis of PD-L1 expression.
Our findings indicate that cancer cachexia might be a negative predictor of the efficacy of PD-1 or PD-L1 inhibitors and reduce the impact of PD-L1 expression on the effect of PD-1 or PD-L1 inhibitors in patients with advanced NSCLC. Further clinical and basic studies are needed.
This study aimed to clarify the characteristics of and evaluate the risk factors for radiation pneumonitis (RP) induced by chemoradiation therapy (CRT) using accelerated hyperfractionated (AHF) ...radiation therapy (RT) in patients with limited-stage small cell lung cancer (LS-SCLC).
Between September 2002 and February 2018, 125 patients with LS-SCLC were treated with early concurrent CRT using AHF-RT. Chemotherapy was comprised of carboplatin/cisplatin with etoposide. RT was administered twice daily (45 Gy/30 fractions). We collected data regarding onset and treatment outcomes for RP, and analyzed the relationship between RP and total lung dose–volume histogram findings. Uni- and multivariate analyses were performed to assess patient- and treatment-related factors for grade ≥2 RP.
The median age of patients was 65 years, and 73.6% of participants were men. In addition, 20% and 80.0% of participants presented with disease stage II and III, respectively. The median follow-up time was 73.1 months. Grades 1, 2, and 3 RP were observed in 69, 17, and 12 patients, respectively. Grades 4 to 5 RP were not observed. RP was treated with corticosteroids in patients with grade ≥2 RP, without recurrence. The median time from initiation of RT to onset of RP was 147 days. Three patients developed RP within 59 days, 6 within 60 to 89 days, 16 within 90 to 119 days, 29 within 120 to 149 days, 24 within 150 to 179 days, and 20 within ≥180 days. Among the dose–volume histogram parameters, the percentage of lung volume receiving >30 Gy (V30) was most strongly related to the incidence of grade ≥2 RP, and the optimal threshold to predict RP incidence was V30 ≥20%. On multivariate analysis, V30 ≥20% was an independent risk factor for grade ≥2 RP.
The incidence of grade ≥2 RP correlated strongly with a V30 of ≥20%. Contrarily, the onset of RP induced by concurrent CRT using AHF-RT may occur later. RP is manageable in patients with LS-SCLC.
Background Recent studies of hepatic regeneration have mainly focused on the growth of parenchymal cells. However, remodeling of liver vessels seems to be crucial during hepatic regeneration. In this ...study, we investigated the influence of antiangiogenesis on hepatic regeneration using sFlt-1, a soluble receptor for vascular endothelial growth factor that acts as a dominant negative receptor, and the hepatocyte growth factor antagonist NK4. Methods A sFlt-1–expressing adenoviral vector, an NK4-expressing adenoviral vector, or both combined were infected into C57BL6 mice via the tail vein. A 70% partial hepatectomy was performed on all of the mice 48 hours after infection. The remnants of the liver were removed after the partial hepatectomy, and hepatic regeneration was assessed by measuring the remnant liver weight and hepatocyte mitosis, bromodeoxyuridine staining, immunohistochemical staining with anti–platelet endothelial cell adhesion molecule-1 antibodies, and real-time polymerase chain reaction studies for angiogenic factors. Results The immunohistochemical staining for CD31 showed suppression of sinusoidal endothelial cells growth in sFlt-1–expressing adenoviral vector–and NK4-expressing adenoviral vector–infected mice. Increases in the remnant hepatic weight were significantly lower in the sFlt-1–expressing adenoviral vector–infected mice. The bromodeoxyuridine index and mitotic cell results revealed a significant decrease in hepatic regeneration in the sFlt-1–expressing adenoviral vector–and NK4-expressing adenoviral vector–infected mice. The suppressive effects on hepatic regeneration were significantly enhanced by combined sFlt-1–expressing adenoviral vector and NK4-expressing adenoviral vector infection. Real-time polymerase chain reaction results revealed the significant suppression of angiogenic growth factor receptors Tie-1 and Tie-2. Conclusion The angiogenesis inhibitor significantly suppressed hepatic regeneration. These results suggest that hepatic regeneration after hepatectomy closely correlates with angiogenesis.
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