Water-Mediated On-Demand Detachable Solid-State Adhesive of Porous Hydroxyapatite for Internal Organ Retractions.

Novel adhesives for biological tissues offer an advanced surgical approach. Here, the authors report the development and application of solid-state adhesives consisting of porous hydroxyapatite (HAp) biocompatible ceramics as novel internal organ retractors. The operational principles of the porous solid-state adhesives are experimentally established in terms of water migration from biological soft tissues into the pores of the adhesives, and their performance is evaluated on several soft tissues with different hydration states. As an example of practical medical utility, HAp adhesive devices demonstrate the holding ability of porcine livers and on-demand detachability in vivo, showing great potential as internal organ retractors in laparoscopic surgery.

Surgical interpretation of the WHO subclassification of intrahepatic cholangiocarcinoma: a narrative review.

Intrahepatic cholangiocarcinoma (iCCA) has been subclassified by its gross morphology into the mass-forming (MF), periductal-infiltrating (PI), and intraductal growth (IG) types and their combinations. This classification correlates well with clinical features; for example, MF-iCCA has less lymph-node metastasis and a better prognosis than PI-iCCA. According to the recently accumulated evidence from histological investigations, the WHO classification endorsed a subclassification scheme in which iCCA cases are classified into small- and large-duct types. Small-duct iCCA is considered to originate from septal or smaller bile ducts and is characterized by less frequent lymph-node metastasis, a favorable prognosis, and an MF appearance. Large-duct iCCA arises around the second branch of the biliary tree and has more aggressive biology and distinct genetic abnormalities. According to the practice guidelines for iCCA from the Liver Cancer Study Group of Japan and the National Comprehensive Cancer Network, upfront surgery is recommended for iCCA without distant metastasis regardless of the morphological subtype, based on clinical experience. In consideration of the biological heterogeneity of iCCA, the treatment strategy for iCCA needs to be reconsidered based on the WHO subtypes.

Current Roles of Ramucirumab in the Sequential Treatment of Unresectable Hepatocellular Carcinoma.

BACKGROUND/AIM: The treatment algorithm for systemic therapies for advanced hepatocellular carcinoma (HCC) has changed dramatically; however, the therapeutic landscape for sequential second-line or later-line treatments, including ramucirumab, remains controversial. This study aimed to investigate the role of ramucirumab for treating HCC. PATIENTS AND METHODS: We retrospectively analyzed data from 17 patients with advanced HCC who received ramucirumab, and 8 of them who received lenvatinib re-administration after ramucirumab treatment failure. RESULTS: The median overall survival of 17 patients treated with ramucirumab was 11.5 months. The median ratios of the 1-month post-treatment α-fetoprotein (AFP) levels and albumin-bilirubin (ALBI) scores to the pre-treatment AFP levels and ALBI scores following ramucirumab treatment were 0.880 and 0.965, respectively. The median ratios of the 1-month post-treatment AFP and ALBI levels to the pre-treatment levels were 1.587 and 0.970 for mALBI grade 1/2a, and 1.313 and 0.936 for mALBI grade 2b/3, respectively. Six of the eight patients who received lenvatinib rechallenge treatment exhibited a decrease in AFP levels one month post-lenvatinib treatment. Deterioration of liver function 3 months post-lenvatinib treatment was noted in five of the eight patients who received lenvatinib rechallenge treatment after ramucirumab. CONCLUSION: Ramucirumab may be equally useful in patients with unresectable HCC who have poor liver function or whose liver function is aggravated by other therapies. Rechallenge treatment with lenvatinib after ramucirumab may be a valid treatment option for HCC.

The Albumin-bilirubin Grade as Prognostic Indicator for Recurrent Hepatocellular Carcinoma Needing Repeat Liver Resection.

BACKGROUND/AIM: This study aimed to evaluate the utility of the albumin-bilirubin grade for predicting the prognosis after repeat liver resection for patients with recurrent hepatocellular carcinoma. PATIENTS AND METHODS: Ninety patients with intrahepatic recurrent hepatocellular carcinoma who underwent repeat liver resection at our institution between 2005 and 2019 were retrospectively analyzed. Cox proportional-hazards regression models evaluated independent preoperative prognostic factors, including the albumin-bilirubin grade. Prognosis differences between patients with albumin-bilirubin grades 1 and 2 were analyzed using the Kaplan-Meier method. RESULTS: Cox proportional-hazards regression analysis revealed that albumin-bilirubin grade 2 (p=0.003) and early recurrence within one year from the initial surgery (p=0.001) were independently associated with poor recurrence-free survival, and albumin-bilirubin grade 2 (p=0.020) was independently associated with poor overall survival. The five-year recurrence-free (31% and 17%, respectively) and overall (86% and 60%, respectively) survival rates after repeat liver resection for patients with albumin-bilirubin grades 1 and 2 were significantly different between groups (both p=0.003). CONCLUSION: The albumin-bilirubin grade is useful for preoperatively predicting favorable survival rates after repeat liver resection for patients with recurrent hepatocellular carcinoma. Patients with an albumin-bilirubin grade 1 are better candidates for surgical treatment of recurrent hepatocellular carcinoma.

Novel concept of "sequential particle radiotherapy" with atezolizumab plus bevacizumab for hepatocellular carcinoma with portal vein tumor thrombus.

Owing to the high objective response rate of atezolizumab plus bevacizumab (Atez/Bev) for hepatocellular carcinoma (HCC), the concept of sequential conversion to local treatment has recently become mainstream. The conversion concept is mainly applied to Barcelona Clinic for Liver Cancer (BCLC) stage B cases, and radiotherapy is rarely considered as a conversion local treatment. We herein report three patients who were treated with the novel concept of "sequential particle radiotherapy," consisting of Atez/Bev therapy followed by particle radiotherapy (PRT) for HCC with advanced portal vein tumor thrombus (Vp3/4 PVTT). All patients achieved partial response radiologically and were switched to PRT. All patients were recurrence free at 1 year after the introduction of Atez/Bev therapy without any additional treatment. This upcoming combination strategy includes the advocacy of sequential concepts for BCLC stage C cases and the introduction of PRT as a local treatment after Atez/Bev.

Optimal cutoff values of drain amylase for predicting pancreatic fistula are different between open and laparoscopic distal pancreatectomy.

BACKGROUND: Drainage fluid amylase (DFA) is useful for predicting clinically relevant postoperative pancreatic fistula (CR-POPF) after distal pancreatectomy (DP). However, difference in optimal cutoff value of DFA for predicting CR-POPF between open DP (ODP) and laparoscopic DP (LDP) has not been investigated. This study aimed to identify the optimal cutoff values of DFA for predicting CR-POPF after ODP and LDP. METHODS: Data for 294 patients (ODP, n = 127; LDP, n = 167) undergoing DP at Kobe University Hospital between 2010 and 2021 were reviewed. Propensity score matching was performed to minimize treatment selection bias. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff values of DFA for predicting CR-POPF for ODP and LDP. Logistic regression analysis for CR-POPF was performed to investigate the diagnostic value of DFA on postoperative day (POD) three with identified cutoff value. RESULTS: In the matched cohort, CR-POPF rates were 24.7% and 7.9% after ODP and LDP, respectively. DFA on POD one was significantly lower after ODP than after LDP (2263 U/L vs 4243 U/L, p < 0.001), while the difference was not significant on POD three (543 U/L vs 1221 U/L, p = 0.171). ROC analysis revealed that the optimal cutoff value of DFA on POD one and three for predicting CR-POPF were different between ODP and LDP (ODP, 3697 U/L on POD one, 1114 U/L on POD three; LDP, 10564 U/L on POD one, 6020 U/L on POD three). Multivariate analysis showed that DFA on POD three with identified cutoff value was the independent predictor for CR-POPF both for ODP and LDP. CONCLUSIONS: DFA on POD three is an independent predictor for CR-POPF after both ODP and LDP. However, the optimal cutoff value for it is significantly higher after LDP than after ODP. Optimal threshold of DFA for drain removal may be different between ODP and LDP.

Spontaneous rupture of splenic hilar lymph node metastasis from hepatocellular carcinoma.

Spontaneous rupture of a primary hepatocellular carcinoma (HCC) is a frequently observed and fatal complication. However, the rupture of lymph node (LN) metastases from HCC is rare. A 79 year-old male with hepatitis B underwent three liver resections for HCC. Two years and 6 months after the last liver resection, enhanced computed tomography (CT) revealed a nodule with a diameter of 3 cm in the lower pole of the spleen. Splenic metastasis of HCC was suspected, and splenectomy was scheduled. During our hospital stay for a urinary tract infection before the scheduled operation, he complained of acute left-sided abdominal pain, and CT showed intra-abdominal hemorrhage due to rupture of the splenic tumor. Emergency splenectomy was performed, and the postoperative course was uneventful. Histopathological examination revealed a poorly differentiated HCC in the lower splenic pole lesion, which contained LN structures. The ruptured lesion was diagnosed as splenic hilar LN metastasis of HCC. Although laparoscopic partial liver resection was performed for intrahepatic recurrence, and atezolizumab plus bevacizumab therapy was administered for peritoneal metastases, the patient was alive 25 months after the splenectomy. Our case suggests that emergency surgery for LN metastatic rupture can achieve hemostasis and lead to improved survival outcomes.

Utility of plasma D-dimer for diagnosis of venous thromboembolism after hepatectomy.

BACKGROUND: Venous thromboembolism (VTE) is a potentially fatal complication of hepatectomy. The use of postoperative prophylactic anticoagulation in patients who have undergone hepatectomy is controversial because of the risk of postoperative bleeding. Therefore, we hypothesized that monitoring plasma D-dimer could be useful in the early diagnosis of VTE after hepatectomy. AIM: To evaluate the utility of monitoring plasma D-dimer levels in the early diagnosis of VTE after hepatectomy. METHODS: The medical records of patients who underwent hepatectomy at our institution between January 2017 and December 2020 were retrospectively analyzed. Patients were divided into two groups according to whether or not they developed VTE after hepatectomy, as diagnosed by contrast-enhanced computed tomography and/or ultrasonography of the lower extremities. Clinicopathological factors, including demographic data and perioperative D-dimer values, were compared between the two groups. Receiver operating characteristic curve analysis was performed to determine the D-dimer cutoff value. Univariate and multivariate analyses were performed using logistic regression analysis to identify significant predictors. RESULTS: In total, 234 patients who underwent hepatectomy were, of whom (5.6%) were diagnosed with VTE following hepatectomy. A comparison between the two groups showed significant differences in operative time (529 vs 403 min, P = 0.0274) and blood loss (530 vs 138 mL, P = 0.0067). The D-dimer levels on postoperative days (POD) 1, 3, 5, 7 were significantly higher in the VTE group than in the non-VTE group. In the multivariate analysis, intraoperative blood loss of > 275 mL [odds ratio (OR) = 5.32, 95% confidence interval (CI): 1.05-27.0, P = 0.044] and plasma D-dimer levels on POD 5 ≥ 21 µg/mL (OR = 10.1, 95%CI: 2.04-50.1, P = 0.0046) were independent risk factors for VTE after hepatectomy. CONCLUSION: Monitoring of plasma D-dimer levels after hepatectomy is useful for early diagnosis of VTE and may avoid routine prophylactic anticoagulation in the postoperative period.

Association between tumor morphology and efficacy of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma.

AIM: The IMbrave150 trial revealed that atezolizumab plus bevacizumab (AtezoBv) showed a higher objective response rate (ORR) in patients with advanced hepatocellular carcinoma (HCC). Although conversion therapy after AtezoBv has been recently reported, markers predictive of its efficacy, particularly radiological imaging markers, have not yet been identified. The present study focused on tumor morphological appearance on radiological imaging and evaluated whether it could be associated with AtezoBv efficacy. METHODS: Ninety-five intrahepatic lesions in 74 patients who were given AtezoBv for advanced HCC were recruited for evaluation. The lesions were divided into two groups, simple nodular (SN group) and non-simple nodular (non-SN group), based on the gross morphology on pretreatment imaging, and retrospectively evaluated for treatment response and other relevant clinical outcomes. RESULTS: Assessing the size of individual tumors after treatment, waterfall plots showed that tumor shrinkage in the non-SN group including 56 lesions was higher than that in the SN group comprising 39 lesions. The ORR was significantly higher in the non-SN group (39.3% vs. 15.4%, p = 0.012). Additionally, the median time to nodular progression was longer in the non-SN group (21.0 months vs. 8.1 months, p = 0.119) compared to the SN group. Six patients with non-SN lesions underwent sequential local therapy. CONCLUSIONS: Atezolizumab plus bevacizumab may show increased therapeutic efficacy in patients with tumors with a higher potential for aggressive oncological behavior, such as non-SN lesions. Treatment strategies focusing on conversion therapy may be crucial in patients with non-SN lesions.

Efficacy of S-1 Adjuvant Chemotherapy for Resected Biliary Tract Cancer: A Retrospective Propensity-Matched Analysis.

INTRODUCTION: Surgical resection is considered an effective cure for biliary tract cancer (BTC); however, the prognosis is unsatisfactory despite improved surgical techniques and perioperative management. The recurrence rate remains high even after curative resection. The efficacy of adjuvant chemotherapy in pancreatic and gastric cancers has been previously reported, and the feasibility of adjuvant therapy with S-1 has recently been reported in patients with resected BTC. We aimed to retrospectively investigate the effects of adjuvant chemotherapy with S-1 on resected advanced BTC. METHODS: We included data from 438 BTC patients who underwent resection between 2001 and 2020. After excluding patients with pTis-pT1 (n = 112) and other exclusion criteria, 266 patients were included in the analysis. RESULTS: After propensity score matching, 48 patients received S-1 adjuvant chemotherapy (S-1 group), and 48 patients received non-S1 adjuvant chemotherapy or underwent surgery alone (Non-S-1 group). The patients in the S-1 group had significantly better overall survival (OS) than those in the non-S-1 group (MST 51 vs 37 months, hazard ratio [HR]:.54, 95% confidence interval [CI]:.30-.98, P = .04). The S-1 group had a significantly better recurrence-free survival (RFS) than the non-S-1 group (94 vs 21 months, HR: .57, 95% CI: .33-.97, P = .03). Subgroup analyses for OS and RFS exhibited the benefits of S-1 in patients aged <75 years and in patients with primary sites of extrahepatic and perineural invasion and curability of R0. DISCUSSION: S-1 adjuvant therapy is promising for improving the postoperative survival of patients with resected advanced BTC, positive nerve invasion, and R0 resection.

A Novel Method Using Gadolinium-Ethoxybenzyl Diethylenetriamine Pentaacetate Acid-Enhanced Magnetic Resonance Imaging for Predicting Post-Hepatectomy Liver Failure in Hepatocellular Carcinoma Patients with a Major Portal Vein Tumor Thrombus.

INTRODUCTION: The usefulness of gadolinium-ethoxybenzyl diethylenetriamine pentaacetate acid-enhanced magnetic resonance imaging (EOB-MRI) in assessing the functional future remnant liver volume (fFRLV) to predict post-hepatectomy liver failure (PHLF) has been previously reported. Herein, we evaluated the efficacy of this technique in patients with hepatocellular carcinoma (HCC) with a major portal vein tumor thrombus (PVTT). METHODS: This study included 21 patients with PVTT in the ipsilateral first-order branch (Vp3) and 30 patients with PVTT in the main trunk/contralateral branch (Vp4). To evaluate fFRLV, the signal intensity (SI) of the remnant liver was determined on T1-weighted images, using both conventional and newly developed methods. The fFRLV was calculated using the SI of the remnant liver and muscle, remnant liver volume, and body surface area. Preoperative factors predicting PHLF (≥grade B) in HCC patients with Vp3/4 PVTT were evaluated. RESULTS: In the Vp3 group, we found fFRLV area under the receiver-operating characteristic curves (AUCs) above 0.70 (AUC = 0.875, 0.750) using EOB-MRI results calculated using either the plot or whole method. None of the parameters in the Vp4 group had an AUC greater than 0.70. CONCLUSION: The fFRLV calculated by EOB-MRI using the whole method can be as useful as the conventional method in predicting PHLF (≥grade B) for HCC patients with Vp3 PVTT.

Impact of intratumoral microbiome on tumor immunity and prognosis in human pancreatic ductal adenocarcinoma.

BACKGROUND: Recent evidence suggests that the presence of microbiome within human pancreatic ductal adenocarcinoma (PDAC) tissue potentially influences cancer progression and prognosis. However, the significance of tumor-resident microbiome remains unclear. We aimed to elucidate the impact of intratumoral bacteria on the pathophysiology and prognosis of human PDAC. METHODS: The presence of intratumoral bacteria was assessed in 162 surgically resected PDACs using quantitative polymerase chain reaction (qPCR) and in situ hybridization (ISH) targeting 16S rRNA. The intratumoral microbiome was explored by 16S metagenome sequencing using DNA extracted from formalin-fixed paraffin-embedded tissues. The profile of intratumoral bacteria was compared with clinical information, pathological findings including tumor-infiltrating T cells, tumor-associated macrophage, fibrosis, and alterations in four main driver genes (KRAS, TP53, CDKN2A/p16, SMAD4) in tumor genomes. RESULTS: The presence of intratumoral bacteria was confirmed in 52 tumors (32%) using both qPCR and ISH. The 16S metagenome sequencing revealed characteristic bacterial profiles within these tumors, including phyla such as Proteobacteria and Firmicutes. Comparison of bacterial profiles between cases with good and poor prognosis revealed a significant positive correlation between a shorter survival time and the presence of anaerobic bacteria such as Bacteroides, Lactobacillus, and Peptoniphilus. The abundance of these bacteria was correlated with a decrease in the number of tumor-infiltrating T cells positive for CD4, CD8, and CD45RO. CONCLUSIONS: Intratumoral infection of anaerobic bacteria such as Bacteroides, Lactobacillus, and Peptoniphilus is correlated with the suppressed anti-PDAC immunity and poor prognosis.

Innovative Combination Treatment to Expand the Indications of Particle Therapy: Spacer Placement Surgery Using Bio-Absorbable Polyglycolic Acid Spacer.

BACKGROUND: Particle therapy has favorable dose distribution and high curability. However, radiotherapy for malignant tumors adjacent to the gastrointestinal tract is contraindicated owing to its low tolerance. To overcome this, combination treatment with surgery to make a space between the tumor and adjacent gastrointestinal tract followed by particle therapy has been developed. Several materials have been used for the spacer and recently, we developed the absorbable polyglycolic acid (PGA) spacer, which has been used since 2019. This study is the first report of consecutive case series of spacer placement surgery using the PGA spacer. STUDY DESIGN: Fifty consecutive patients undergoing spacer placement surgery with the PGA spacer were evaluated. Postoperative laboratory data, morbidity related to the treatment, and spacer volume after treatment were evaluated. RESULTS: There were no treatment-related deaths, and all but 2 patients completed combination treatment. The median ratios of postoperative PGA spacer volume to the pretreatment volume were 96.9%, 87.7%, and 74.6% at weeks 2, 4, and 8, respectively. The spacer volume was maintained at 80% at 7 weeks and was predicted to be 50% at 15 weeks and 20% in 24 weeks. CONCLUSIONS: Spacer placement surgery using the PGA spacer was feasible and tolerable. The PGA spacers maintained sufficient thickness during the duration of subsequent particle therapy. Combination treatment using the PGA spacer is innovative and has the potential to become a new standard curative local treatment.

An Analysis of 10,000 Cases of Living Donor Liver Transplantation in Japan: Special Reference to the Graft-Versus-Recipient Weight Ratio and Donor Age.

OBJECTIVE: To analyze 10,000 cases of living donor liver transplantation (LDLT) recipient data to elucidate outcomes with special reference to the graft-versus-recipient weight ratio (GRWR), based on the Japanese Liver Transplantation Society (JLTS) registry. BACKGROUND: The JLTS registry has been accurate and complete in characterizing and following trends in patient characteristics and survival of all patients with LDLT. METHODS: Between November 1989 and August 2021, 10,000 patients underwent LDLT in Japan. The procedures performed during the study period included pediatric liver transplantation (age <18 years, n = 3572) and adult liver transplantation (age ≥18 years, n=6428). Factors related to patient survival (PS) and graft survival (GS) were also analyzed. RESULTS: The GRWR was <0.7, 0.7 to <0.8, 0.8 to <3, 3 to <5, and ≥5 in 0.2%, 2.0%, 61.8%, 31.8%, and 2.6% of pediatric patients and <0.6, 0.6 to <0.7, 0.7 to <0.8, and ≥0.8 in 8.0%, 12.7%, 17.7%, and 61.5% of adult patients, respectively. Among pediatric recipients, the PS rate up to 5 years was significantly better in cases with a GRWR ≤5 than in those with a GRWR >5. When the GRWR and donor age were combined, among adult recipients 50 to 60 years old, the early PS and GS up to 5 years were significantly better in cases with a GRWR ≥0.7, than in those with a GRWR <0.7. (P = 0.02). In adults, a multivariate analysis showed that GRWR <0.6, transplant era (<2011), donor age (>60 years), recipient age (>60 years), model for end-stage liver disease score (≥20), and center volume (<10) were significant prognostic factors for long-term PS. CONCLUSION: Although a satisfactory long-term PS and GS, especially in the recent era (2011-2021), was achieved in the JLTS series, a GRWR ≥5 in pediatric cases and relatively old donors with a GRWR <0.7 in adult cases should be managed with caution.

Clinical impact of spacer placement surgery with expanded polytetrafluoroethylene sheet for particle therapy.

BACKGROUND: Spacer placement surgery is useful in particle therapy (PT) for patients with abdominopelvic malignant tumors located adjacent to the gastrointestinal tract. This study aimed to assess the safety, efficacy, and long-term outcomes of spacer placement surgery using an expanded polytetrafluoroethylene (ePTFE) spacer. METHODS: This study included 131 patients who underwent ePTFE spacer placement surgery and subsequent PT between September 2006 and June 2019. The overall survival (OS) and local control (LC) rates were calculated using Kaplan-Meier method. Spacer-related complications were classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). RESULTS: The median follow-up period after spacer placement surgery was 36.8 months. The 3-year estimated OS and LC rates were 60.5% and 76.5%, respectively. A total of 130 patients (99.2%) were able to complete PT. Spacer-related complications of ≥ grade 3 were observed in four patients (3.1%) in the acute phase and 13 patients (9.9%) in the late phase. Ten patients (7.6%) required removal of the ePTFE spacer. CONCLUSIONS: Spacer placement surgery using an ePTFE spacer for abdominopelvic malignant tumors is technically feasible and acceptable for subsequent PT. However, severe spacer-related late complications were observed in some patients. Since long-term placement of a non-absorbable ePTFE spacer is associated with risks for morbidity and infection, careful long-term follow-up and prompt therapeutic intervention are essential when complications associated with the ePTFE spacer occur. TRIAL REGISTRATION: retrospectively registered.

Histological diagnosis of polyploidy discriminates an aggressive subset of hepatocellular carcinomas with poor prognosis.

BACKGROUND: Although genome duplication, or polyploidization, is believed to drive cancer evolution and affect tumor features, its significance in hepatocellular carcinoma (HCC) is unclear. We aimed to determine the characteristics of polyploid HCCs by evaluating chromosome duplication and to discover surrogate markers to discriminate polyploid HCCs. METHODS: The ploidy in human HCC was assessed by fluorescence in situ hybridization for multiple chromosomes. Clinicopathological and expression features were compared between polyploid and near-diploid HCCs. Markers indicating polyploid HCC were explored by transcriptome analysis of cultured HCC cells. RESULTS: Polyploidy was detected in 36% (20/56) of HCCs and discriminated an aggressive subset of HCC that typically showed high serum alpha-fetoprotein, poor differentiation, and poor prognosis compared to near-diploid HCCs. Molecular subtyping revealed that polyploid HCCs highly expressed alpha-fetoprotein but did not necessarily show progenitor features. Histological examination revealed abundant polyploid giant cancer cells (PGCCs) with a distinct appearance and frequent macrotrabecular-massive architecture in polyploid HCCs. Notably, the abundance of PGCCs and overexpression of ubiquitin-conjugating enzymes 2C indicated polyploidy in HCC and efficiently predicted poor prognosis in combination. CONCLUSIONS: Histological diagnosis of polyploidy using surrogate markers discriminates an aggressive subset of HCC, apart from known HCC subgroups, and predict poor prognosis in HCC.

Impact of GLIM criteria-based malnutrition diagnosis on outcomes following liver resection for hepatocellular carcinoma.

BACKGROUND: The Global Leadership Initiative on Malnutrition (GLIM), comprising several of the major global clinical nutrition societies, suggested the world's first criteria for diagnosis of the severity of malnutrition. However, the impact of the resulting diagnosis on patient outcomes for those with hepatocellular carcinoma (HCC) following liver resection (LR) has not been investigated. METHODS: A retrospective analysis of 293 patients with HCC who underwent LR between January 2011 and December 2018 was performed. We compared overall survival (OS) and recurrence-free survival (RFS) and evaluated prognostic factors after LR using Cox proportional hazards regression models. RESULTS: Preoperative patient nutritional status, n (%), was classified as follows: normal, 130 (44%), moderate malnutrition, 116 (40%), and severe malnutrition, 47 (16%). The median OS (129 vs. 43 months, p < 0.001) and median RFS (54 vs. 20 months, p = 0.001) were significantly greater in the normal group than in the severe malnutrition group. Multivariate analysis showed that severe malnutrition was a significant risk factor for OS (p = 0.006) and RFS (p = 0.010) after initial LR. CONCLUSION: Severe malnutrition, as diagnosed by the GLIM criteria, is a significant prognostic factor for survival and recurrence in patients with HCC after LR.

Report of the 23rd nationwide follow-up survey of primary liver cancer in Japan (2014-2015).

For the 23rd Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 20 889 newly registered patients and 42 274 previously registered follow-up patients were compiled from 516 institutions over a 2-year period from January 1, 2014 to December 31, 2015. Basic statistics compiled for patients newly registered in the 23rd survey were cause of death, past medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathological diagnosis, recurrence status, and autopsy findings. Compared with the previous 22nd survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, had more patients with non-B non-C HCC, had smaller tumor diameter, and was more frequently treated with hepatectomy. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 2004 and 2015 whose final outcome was survival or death. The median overall survival and cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter, Child-Pugh grade, or albumin-bilirubin grade) and by treatment type (hepatectomy, radiofrequency ablation therapy, transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy, and systemic therapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2015 into five time period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer in the world.

LC-1000 flow cytometry system complements intraoperative peritoneal cytology for pancreatic and biliary tract cancer.

BACKGROUND: The exfoliative cell analyzer, LC-1000, is medical device that utilizes the principles of flow cytometry, and might provide digital diagnostic information for cytology using a different approach from conventional cytomorphology. In this study, wae examined the usefulness of the LC-1000 as a diagnostic support system for intraoperative peritoneal lavage cytology and its prognostic impact for pancreatic (PC) and biliary tract cancer (BTC). METHODS: Patients with PC and BTC who underwent surgical treatment were included. First, we identified useful indicators of LC-1000 and established cutoff values to discriminate positive cytology. Next, we verified the validity of these cutoff values. RESULTS: In the test set (n = 48), of the LC-1000 indicators examined, only MR-CPIx was significantly different between the negative and positive cytology groups, yielding a cutoff value of 0.86. In the validation set (n = 52), the sensitivity, specificity, positive and negative predictive value of the LC-1000 for cytology results was 1.0, 0.49, 0.11 and 1.0, respectively. In patients who had undergone radical resection, recurrence-free survival rate was significantly higher in the LC-1000 negative group than in the positive group in PC, but not in BTC. CONCLUSION: The LC-1000 was useful as digital support system for peritoneal cytology, and it might have potential as a prognostic factor for PC.

Proton radiotherapy as a treatment strategy to increase survival in locally advanced pancreatic cancer in the body and tail: a retrospective study.

BACKGROUND: Long-term outcomes and prognostic factors of proton radiotherapy for locally advanced pancreatic cancer (LAPC) in the body and tail are still unknown. The aim of this study was to determine the prognostic factors after proton radiotherapy in a large group of patients with LAPC in the body and tail. METHODS: The medical records of 200 patients with LAPC in the body and tail who underwent proton radiotherapy between February 2009 and January 2021 at the Hyogo Ion Beam Medical Center were retrospectively reviewed to identify prognostic factors that contribute to long-term survival. RESULTS: The overall survival rate at 1- and 2-year after PT was 69.6% and 35.4% with a median overall survival of 18.4 months. The 1- and 2-year local progression-free, and progression-free survival rates were 84.3% and 68.0%, and 44.3% and 19.4%, respectively. In multivariate analysis, superior mesenteric artery (SMA) invasion (SMA only invasion vs. celiac artery only invasion; P = 0.049: SMA and celiac artery invasion vs. celiac artery only invasion; P = 0.017), carbohydrate antigen 19-9 (CA 19-9) level ≥ 231.9 U/mL (P = 0.001), anterior peripancreatic invasion (P = 0.006), and incomplete scheduled concurrent chemotherapy (P = 0.009) were statistically significant prognostic factors for overall survival. There was no significant difference in local progression-free survival; however, distant metastasis-free survival was statistically worse in patients with prognostic factors than in those without. CONCLUSIONS: Proton radiotherapy for LAPC in the body and tail may be a valuable multidisciplinary treatment option. Patients with SMA invasion, higher pre-proton radiotherapy serum CA 19-9 level, anterior peripancreatic invasion, or incomplete scheduled concurrent chemotherapy had worse overall survival because of worse distant metastasis-free survival, suggesting that distant metastases have a significant impact on overall survival in such patients. TRIAL REGISTRATION: Retrospectively registered.