Safety and feasibility of liver resection including major hepatectomy for geriatric patients with hepatocellular carcinoma: a retrospective observational study.

BACKGROUND: It is unclear whether hepatectomy, which ranges in invasiveness from partial to major hepatectomy, is safe and feasible for older adult patients. Therefore, we compared its postoperative complications and long-term outcomes between younger and older adult patients. METHODS: Patients who underwent hepatectomies for hepatocellular carcinoma (N = 883) were evaluated. Patients were divided into two groups: aged < 75 years (N = 593) and ≥ 75 years (N = 290). Short-term outcomes and prognoses were compared between the groups in the entire cohort. The same analyses were performed for the major hepatectomy cohort. RESULTS: In the entire cohort, no significant differences were found in complications between patients aged < 75 and ≥ 75 years, and the multivariate analysis did not reveal age as a prognostic factor for postoperative complications. However, overall survival was significantly worse in older patients, although no significant differences were noted in time to recurrence or cancer-specific survival. In the multivariate analyses of time to recurrence, overall survival, and cancer-specific survival, although older age was an independent poor prognostic factor for overall survival, it was not a prognostic factor for time to recurrence and cancer-specific survival. In the major hepatectomy subgroup, short- and long-term outcomes, including time to recurrence, overall survival, and cancer-specific survival, did not differ significantly between the age groups. In the multivariate analysis, age was not a significant prognostic factor for complications, time to recurrence, overall survival, or cancer-specific survival. CONCLUSION: Hepatectomy, including minor and major hepatectomy, may be safe and oncologically feasible options for selected older adult patients with hepatocellular carcinoma.

Characterization of Porous ß-Type Tricalcium Phosphate Ceramics Formed via Physical Foaming with Freeze-Drying.

Porous ß-tricalcium phosphate (Ca3(PO4)2; ß-TCP) was prepared via freeze-drying and the effects of this process on pore shapes and sizes were investigated. Various samples were prepared by freezing ß-TCP slurries above a liquid nitrogen surface at -180 °C with subsequent immersion in liquid nitrogen at -196 °C. These materials were then dried under reduced pressure in a freeze-dryer, after which they were sintered with heating. Compared with conventional heat-based drying, the resulting pores were more spherical, which increased both the mechanical strength and porosity of the ß-TCP. These materials had a wide range of pore sizes from 50 to 200 µm, with the mean and median values both approximately 100 µm regardless of the freeze-drying conditions. Mercury porosimetry data showed that the samples contained small, interconnected pores with sizes of 1.24 ± 0.25 µm and macroscopic, interconnected pores of 25.8 ± 4.7 µm in size. The effects of nonionic surfactants having different hydrophilic/lipophilic balance (HLB) values on foaming and pore size were also investigated. Materials made with surfactants having lower HLB values exhibited smaller pores and lower porosity, whereas higher HLB surfactants gave higher porosity and slightly larger macropores. Even so, the pore diameter could not be readily controlled solely by adjusting the HLB value. The findings of this work indicated that high porosity (>75%) and good compressive strength (>2 MPa) can both be obtained in the same porous material and that foaming agents with HLB values between 12.0 and 13.5 were optimal.

Prognostic Significance of the Histopathological Growth Pattern and Tumor-Infiltrating Lymphocytes in Stratifying Survival After Hepatectomy for Colorectal Liver Metastases.

BACKGROUND: A histopathological growth pattern (HGP) occurs at the interface between tumor cells and the surrounding liver parenchyma. Desmoplastic HGP (dHGP) is associated with a favorable prognosis and shows denser infiltration of lymphocytes than other HGPs. Tumor-infiltrating lymphocytes (TILs) exert antitumor immunity, nonetheless, their prognostic significance in patients with dHGP is unknown. This study aimed to identify the prognostic significance of HGP and TILs in colorectal liver metastasis (CRLM). METHODS: The study analyzed 140 patients who underwent hepatectomy for CRLM. Depending on the type of HGP and TIL, the patients were categorized into four groups (dHGP/high TIL, dHGP/low TIL, non-dHGP/high TIL, and non-dHGP/low TIL) for a comparison of their recurrence-free survival (RFS) and overall survival (OS). Uni- and multivariate analyses were performed using a Cox proportional hazards model. RESULTS: The RFS and OS curves differed significantly between the groups. The multivariate analysis showed that a combination of HGP and TIL could stratify the recurrence and survival outcomes. CONCLUSION: This study indicated that a combination of HGP and TIL can stratify the risk of survival after hepatectomy in patients with CRLM.

[A Case of the Spontaneously Ruptured Recurrence Hepatic Angiosarcoma after Hepatic Resection].

A 67-year-old male was referred to our hospital in a state of shock. Transcatheter arterial embolization(TAE)was performed for the diagnosis of liver tumor rupture, followed by extended posterior area resection 18 days later. Histopathologically, he was diagnosed with hepatic angiosarcoma. The patient was discharged 18 days after the surgery, but readmitted on the 51st day due to bleeding shock caused by the rupture of a recurrent tumor in the liver. Although TAE was performed, the patient developed hepatic failure and died on postoperative day 81. Autopsy revealed multiple intrahepatic recurrence and peritoneal dissemination. Herein, we report a case of ruptured hepatic angiosarcoma that underwent hepatic resection after TAE and had a rapid outcome due to early postoperative rupture of recurrent lesion.

C-reactive protein/albumin ratio and Glasgow prognostic score are associated with prognosis and infiltration of Foxp3+ or CD3+ lymphocytes in colorectal liver metastasis.

BACKGROUND: Inflammatory indices and tumor-infiltrating lymphocytes (TILs) have prognostic value in many cancer types. This study aimed to assess the prognostic value of inflammatory indices and evaluate their correlation with survival and presence of TILs in patients with colorectal liver metastasis (CRLM). METHODS: Medical records of 117 patients who underwent hepatectomy for CRLM were retrospectively reviewed. We calculated inflammatory indices comprising the neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, C-reactive protein/albumin ratio (CAR), and Glasgow prognostic score (GPS). Furthermore, we evaluated the relationship between these ratios and the GPS and survival rates and immunohistochemical results of tumor-infiltrating CD3+, CD8+, and Foxp3+ lymphocytes. RESULTS: The patients with low CAR values and low GPS had significantly better overall survival as per the log-rank test (p = 0.025 and p = 0.012, respectively). According to the multivariate analysis using the Cox proportional hazard model, the CAR (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.33-0.99; p = 0.048) and GPS (HR, 0.40; 95% CI, 0.19-0.83; p = 0.013) were independent prognostic factors. Additionally, Foxp3+ lymphocytes were more common in samples from the patients with a low CAR (p = 0.041). Moreover, the number of CD3+ TILs was significantly higher in the patients with a low GPS (p = 0.015). CONCLUSIONS: The CAR and GPS are simple, inexpensive, and objective markers associated with predicting survival in patients with CRLM. Moreover, they can predict the presence of Foxp3+ and CD3+ lymphocytes in the invasive margin of a tumor. TRIAL REGISTRATION: Retrospectively registered. https://www.kurume-u.ac.jp/uploaded/attachment/14282.pdf .

[A Case of Small Cell Neuroendocrine Carcinoma of the Gallbladder].

A 76-year-old female was referred to our hospital with a tumor of the gallbladder using ultrasonography. CT and MRI of the abdomen and endoscopic ultrasonography revealed thickened walls of the body of her gallbladder. Endoscopic retrograde cholangiopancreatography was performed, adenocarcinoma was suspected based on bile cytology, and extended cholecystectomy with lymphadenectomy was performed. The postoperative pathological diagnosis was small cell neuroendcrine carcinoma. Three months after the surgery, CT revealed that she had multiple recurrences in the distant lymph node, and she died two months later. Gallbladder neuroendocrine carcinoma is rare and which is thought to have a poor prognosis, so effective multidisciplinary treatment must be required for this disease. In this case, it might need not to hesitate to perform preoperative endoscopic ultrasound guided fine needle aspiration(EUS-FNA).

[Laparoscopic Extirpation of Peritoneal Dissemination of Hepatocellular Carcinoma Using ICG Imaging].

A 71-year-old man who underwent laparoscopic partial liver resection for local recurrence hepatocellular carcinoma (HCC)in segment 4 one year after percutaneous radiofrequency ablation(RFA)for HCC. About 3 years after treatment, the patient showed elevation of serum level of tumor marker and a mass lesion in the round ligament on CT and EOB-MRI. We made a diagnosis of peritoneal dissemination of HCC. Laparoscopic extirpation of peritoneal dissemination using indocyanine green(ICG)imaging was performed and no other tumors were observed in the peritoneal cavity. A lesion was diagnosed as peritoneal dissemination of HCC, and postoperative course was uneventful. This patient underwent repeated RFA and partial resection for recurrence of HCC. The patient was died for intrahepatic multiple recurrence of HCC without peritoneal dissemination 25 months after extirpation of peritoneal dissemination. In the field of hepatobiliary surgery, ICG imaging can be used for the intraoperative real-time visualization of hepatic malignancies. The ICG imaging is restricted to detection of fluorescence for liver tumors 5-10 mm from the liver surface. In the detection of peritoneal dissemination, however, there are no such limitations. Laparoscopic extirpation using ICG imaging is useful for the detection of peritoneal dissemination of HCC and may improve the prognosis in selected patients.

Organ-specific development characterizes circadian clock gene Per2 expression in rats.

To explore developmental changes in circadian organization of central and peripheral oscillators, circadian rhythms in clock gene expression were examined in 12 organs in transgenic rats carrying a bioluminescence reporter for Per2. Organ slices were obtained from different developmental stages starting at postnatal day 5 and tissue was cultured for more than 6 days. In addition, four organs were examined from embryonic day 20. Robust circadian rhythms in bioluminescence were detected in all organs examined. The circadian period in vitro was specific to each organ and remained essentially the same during development. The circadian peak phase on the first day of culture was significantly different not only among organs but also in the same organ. Three patterns in circadian phase were detected during development. Thus, during development, circadian phase did not change in the suprachiasmatic nucleus, adrenal gland, and liver, whereas delay shifts were seen in the pineal, lung, heart, kidney, spleen, thymus, and testis. Finally, circadian phase advanced at postnatal day 10-15 and subsequently delayed in skeletal muscle and stomach.Circadian amplitude also showed developmental changes in several organs. These findings indicate that the temporal orders of physiological functions of various organs change during development. Such age-dependent and organ-specific changes in the phase relationship among circadian clocks most likely reflect entrainment to organ-specific time cues at different developmental stages.

Effect of Silicon Dioxide Nanoparticles on the Sintering Properties of Beta-Tricalcium Phosphate Composites.

Composite sintered bodies comprising silicon dioxide (SiO2) nanoparticles dispersed in ß-tricalcium phosphate (ß-TCP) were prepared. The addition of nano-sized colloidal SiO2 to the ß-TCP produced well-dispersed secondary phase nanoparticles that promoted densification by suppressing grain growth and increasing linear shrinkage of the sintered bodies. The SiO2 was found not to react with the ß-TCP at 1120 °C and the substitution of silicon for phosphorous to produce a solid solution did not occur. This lack of a reaction is ascribed to the absence of available calcium ions to compensate for the increase in charge associated with this substitution. The SiO2 nanoparticles were found to be present near the intersections of grain boundaries in the ß-TCP. ß-TCP composite sintered body containing 2.0 and 4.0 wt% SiO2 exhibited a bending strength comparable to that of cortical bone and hence could potentially be used as a bone filling material.

An operative case of gastric cancer with ectopic bile duct drainage in the lesser curvature of the stomach.

BACKGROUND: Among the various anomalies of the biliary system, a double common bile duct with ectopic drainage in the stomach is rare. Furthermore, ectopic bile ducts are extremely rare in gastric cancers. CASE PRESENTATION: A 67-year-old man was admitted to our hospital with gastric cancer and ectopic left extrahepatic bile duct drainage in the stomach. Pre-operative testing revealed no communication between the intrahepatic bile ducts. Distal gastrectomy and bile duct jejunostomy were performed. The post-operative course was uneventful, and the patient did not exhibit recurrence for 39 mo. CONCLUSIONS: Although it is uncertain whether sustained bile exposure from an ectopic bile duct is related to gastric cancer, short-term follow-up might be necessary because of the possibility of gastric cancer.

The Association of Central Sensitisation with Depression, Anxiety, and Somatic Symptoms: A Cross-Sectional Study of a Mental Health Outpatient Clinic in Japan.

For patients with chronic pain and persistent physical symptoms, understanding the mechanism of central sensitisation may help in understanding how symptoms persist. This cross-sectional study investigated the association of central sensitisation with depression, anxiety, and somatic symptoms. Four hundred and fifteen adults attending an outpatient psychosomatic clinic were evaluated. Participants completed the Hospital Anxiety and Depression Scale, Somatic Symptom Scale 8, and the Central Sensitisation Inventory. The relationships between these factors were examined using descriptive statistics and multiple logistic regression analyses. The mean age was 42.3 years, and 59% were female. The disorders included adjustment disorders (n = 70), anxiety disorders (n = 63), depressive disorders (n = 103), feeding and eating disorders (n = 30), sleep-wake disorders (n = 37), somatic symptoms and related disorders (n = 84), and others (n = 28). In multiple logistic regression analyses, higher central sensitisation was associated with more severe anxiety, depression, and somatic symptoms after controlling for potential confounders. In the disease-specific analysis, somatic symptoms correlated more positively with central sensitisation than with depression or anxiety. Central sensitisation and depression, anxiety, and somatic symptoms were associated with patients attending an outpatient clinic. These findings highlight the importance of evaluating depression, anxiety, and somatic symptoms when assessing central sensitisation.

Safety and Feasibility of Laparoscopic Anatomical Liver Resection for Hepatocellular Carcinoma: A Propensity Score-matched Study.

BACKGROUND/AIM: Laparoscopic anatomical liver resection (LAR) for hepatocellular carcinoma (HCC) is technically demanding. Therefore, this study aimed to compare the perioperative and long-term oncological outcomes of LAR and open anatomical liver resection (OAR) for HCC. PATIENTS AND METHODS: We retrospectively analyzed 460 consecutive patients who underwent anatomical liver resection as the initial treatment for primary HCC between January 2010 and February 2024. Patients were categorized into the LAR and OAR groups, and surgical outcomes between the groups were compared using 1:1 propensity score matching (PSM). RESULTS: After PSM, the LAR and OAR groups included 100 patients each. The LAR group exhibited significantly less blood loss (80 vs. 436 ml; p<0.0001), lower transfusion rates (0% vs. 12%; p=0.0002), shorter operative time (345 vs. 398 min; p=0.0009), lower postoperative morbidity rates (6% vs. 34%; p<0.0001), and shorter postoperative hospital stay (8 vs. 15 days; p<0.0001) than the OAR group. The 1-, 3-, and 5-year overall survival rates were 97.7%, 96.2%, and 89.7%, respectively, in the LAR group and 98.0%, 92.7%, and 88.4%, respectively, in the OAR group (p=0.5874). The 1-, 3-, and 5-year recurrence-free survival rates were 93.2%, 75.7%, and 60.7%, respectively, in the LAR group and 86.0%, 64.5%, and 59.1%, respectively, in the OAR group (p=0.2314). CONCLUSION: LAR showed improvements in perioperative complications, reduced postoperative hospital stay, and comparable recurrence-free and overall survival rates with those of OAR. Therefore, LAR for HCC is considered safe, feasible, and oncologically acceptable in selected patients.

Association Between Ego-Resilience and Social Isolation Among Urban Older People.

Social isolation among older adults affects their physical and mental health. Ego-resilience is associated with flexible adaptation to various environments and acceptable behaviors. However, its association with social isolation among older people is unclear. Therefore, a health survey was conducted with 510 adults aged 65 years or older to assess social isolation, its associated factors, and ego resilience. The results showed that the social isolation group had a lower median ego-resiliency scale score (42.0) compared to the non-social isolation group (38.0). The social isolation group were mostly males without spouses, took time to move, had more depressive moods, and poorer subjective health status. The non-social isolated group had faster maximum walking speed. Low ego-resilience was newly identified as a factor associated with social isolation among older people, as were being male, having no spouse, and depressive symptoms. Mediation analysis revealed that ego-resilience affected social isolation and was partially mediated by depressive symptoms.

Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) Score As a Predictor of Prognosis After Hepatectomy.

BACKGROUND/AIM: The hemoglobin, albumin, lymphocyte, and platelet (HALP) score is an immune-nutritional assessment score that is a prognostic indicator for several malignant tumors. This study aimed to investigate its prognostic value in patients who underwent hepatectomy for hepatocellular carcinoma. PATIENTS AND METHODS: Data of 685 patients with hepatocellular carcinoma who underwent hepatectomy at Kurume University between 2006 and 2021 were retrospectively analyzed. The patients were classified into high and low HALP score groups based on a cut-off HALP score determined using a receiver operating characteristic curve. To minimize bias, 1:1 propensity score matching was performed. Kaplan-Meier curves were used to estimate survival time, and data were evaluated using the log-rank test. Univariate and multivariate analyses were performed using Cox hazard or logistic regression models for assessing survival time and postoperative outcomes, respectively. RESULTS: Low HALP scores were significantly associated with poor overall survival (p=0.0066). Univariate and multivariate analyses revealed that the HALP score independently predicted overall survival (p=0.005). However, the HALP score was not significantly related to recurrence-free survival or postoperative outcomes. CONCLUSION: The HALP score is a simple inexpensive tool for predicting prognosis after hepatectomy for hepatocellular carcinoma.

A Multidisciplinary Therapeutic Approach Proposal for Huge Hepatocellular Carcinomas Exceeding 10 cm in Diameter.

BACKGROUND/AIM: The outcome of hepatectomy for a hepatocellular carcinoma (HCC) exceeding 10 cm (i.e., huge HCC) remains unfavorable. The aim of the current study was to evaluate the optimal therapeutic approach for huge HCCs. PATIENTS AND METHODS: Between 2008 and 2018, patients with a huge HCC who underwent treatment at our institution were enrolled. Cases not meeting the criteria (Child-Pugh grade A or performance status 0/1) and patients with distant metastases were excluded. Patients were stratified into three groups: a) upfront hepatectomy (Upfront); b) hepatectomy subsequent to hepatic arterial infusion chemotherapy (HAIC-Hr); and c) HAIC alone (HAIC). Survival rates, including overall survival (OS) and progression-free survival (PFS), were analyzed. The cancer-specific mortality attributed to recurrence within one year after surgery was defined as "futile surgery"; the rate of futile surgery was also assessed. RESULTS: A total of 70 cases were censored (Upfront/HAIC-Hr/HAIC: 28/13/29). The 5-year PFS and OS rates for Upfront, HAIC-Hr, and HAIC were 7.7%, 69.2%, and 6.9%, and 37.1%, 79.1%, and 19.7%, respectively. The number of futile surgeries was 6 (21.4%) in the Upfront group, whereas no such cases occurred in the HAIC-Hr group. CONCLUSION: Although hepatectomy was advocated in the Upfront group due to the potential resectability, the outcomes were comparable to those of the HAIC group. Conversely, the HAIC-Hr group had promising outcomes, marked by a decreased prevalence of futile surgeries. Huge HCCs should be regarded as borderline resectable, even when deemed potentially resectable. Therefore, a multidisciplinary therapeutic approach might be reasonable.

Clinicopathological Study of Resected and Recurrent Cases of Intrahepatic Intraductal Papillary Neoplasm of the Bile Duct.

BACKGROUND/AIM: This study aimed to characterize intraductal papillary neoplasm of the bile duct (IPNB) in patients undergoing initial and recurrent surgical resection and to evaluate the appropriateness of surgical treatment strategies. PATIENTS AND METHODS: This study included 14 patients who underwent liver resection for intrahepatic IPNB. We assessed intraoperative and postoperative clinicopathological factors in patients undergoing both initial and recurrent surgeries. RESULTS: Four patients experienced recurrence after initial surgery; all underwent pancreaticoduodenectomy. Postoperative complications were classified as Clavien-Dindo Grade 1-2 in three patients and Grade IIIb in one patient. There were no in-hospital deaths. CONCLUSION: Pancreaticoduodenectomy for recurrent cases following hepatectomy for IPNB is considered safe within an acceptable range and contributes to a favorable long-term prognosis.

Sex differences in the association between smoking and central sensitization: A cross-sectional study.

INTRODUCTION: Despite the acknowledged interconnection between smoking and pain, research on the relationship between smoking and central sensitization (CS) is scarce; this pain mechanism has attracted recent research attention. Considering potential sex differences, this cross-sectional study aimed to investigate the association between smoking and CS. METHODS: Overall, 415 adult participants from an outpatient clinic underwent evaluation. The analysis focused on determining the relationship between smoking status and CS by differentiating between sexes. Data were collected on smoking presence or absence (independent variable) and CS (dependent variable) for each sex, with age, education level, drinking history, depression, and anxiety as covariates. CS was evaluated using the Central Sensitization Inventory. Following a descriptive analysis of the study population's characteristics, logistic regression analysis was employed to assess the relationships. RESULTS: The average participant age was 42.3 years, with 59% being women. Among women, a significant association was found between smoking status and higher CS severity (AOR=3.21; 95% CI 1.29-7.99, p<0.01), after accounting for confounding variables. Conversely, no significant association was observed for men (AOR=1.50; 95% CI 0.63-3.60, p=0.36). Interaction by sex on the relationship between smoking and CS was not statistically significant (p=0.23). CONCLUSIONS: This study suggests a potential association between smoking and CS in women, whereas no conclusive relationship was observed among men. These findings indicate the necessity of considering CS when examining the relationship between smoking and pain.

Psychosomatic symptoms related to exacerbation of fatigue in patients with medically unexplained symptoms.

Background: Medically unexplained symptoms (MUS) are common conditions that cause various somatic complaints and are often avoided in primary care. Fatigue frequently occurs in patients with MUS. However, the somatic and psychiatric symptoms associated with fatigue in patients with MUS are unknown. This study aimed to clarify the intensity of fatigue and the related somatic and psychiatric symptoms in patients with MUS. Methods: A total of 120 patients with MUS aged 20-64 years who visited the Department of Psychosomatic Medicine, Toho University Medical Center Omori Hospital, between January and March 2021 were considered. The participants' medical conditions were assessed using the Chalder Fatigue Scale (CFS), Somatic Symptom Scale-8 (SSS-8), and Hospital Anxiety and Depression Scale (HADS). We estimated the relationship between CFS, SSS-8 and HADS by using Spearman's rank correlation. Additionally, linear multiple regression analysis with CFS as the objective variable was used to identify symptoms related to fatigue. Results: Fatigue was significantly associated with all symptoms observed (p < 0.01). Linear multiple regression analysis revealed that "dizziness," "headache," and "Sleep medication" were extracted as relevant somatic symptoms (p < 0.05), independent of anxiety and depression, which were already known to be associated with fatigue in MUS. Conclusion: The intensity of anxiety, depression, headache, and dizziness were all associated with the intensity of fatigue in MUS patients. On the contrary, sleeping medication was associated with lower levels of fatigue in MUS.

Prepancreatic postduodenal portal vein: a case report and literature review.

BACKGROUND: Among congenital anomalies of the portal venous system, prepancreatic postduodenal portal vein (PPPV) is very rare and has only been reported to date. Herein, we report a case of PPPV identified in preoperative examinations for hepatocellular carcinoma and a literature review. CASE PRESENTATION: A 63-year-old man was admitted to our hospital for treatment of a liver tumor. After examination, he was diagnosed with hepatocellular carcinoma with a diameter of 40 mm in segment 8. Contrast-enhanced computed tomography scan showed a portal vein passing between the duodenum and pancreas, hence called PPPV. At the hepatic hilus, the portal vein branched off in a complicated course with some porto-portal communications. We determined that anatomical resection with manipulation of the hepatic hilum in this case resulted in major vascular injury. Therefore, we performed partial liver resection, and the patient was discharged uneventfully on postoperative day 14. CONCLUSIONS: Although PPPV is an extremely rare congenital vascular variant, it is important to carefully identify vascular patterns preoperatively and to recognize the possibility of such an anomaly to avoid misidentification and inadvertent injuries during surgery.