Tocilizumab suppresses NF-kappa B activation via toll-like receptor 9 signaling by reducing cell-free DNA in rheumatoid arthritis.

Endogenous DNA is released into the bloodstream as cell-free DNA (cfDNA) following cell death and is associated with various pathological conditions. However, their association with therapeutic drugs against rheumatoid arthritis (RA) remains unknown. Therefore, we investigated the significance of cfDNA in RA treated with tocilizumab and tumour necrosis factor inhibitor (TNF-I). Biological DMARDs (bDMARDs), including tocilizumab and TNF-I, were administered to 77 and 59 RA patients, respectively. Plasma cfDNA levels were measured at weeks 0, 4, and 12 by quantitative polymerase chain reaction. Disease activity was evaluated at the same time point using DAS28ESR. cfDNA levels from RA synovial cells treated with tocilizumab or etanercept for 24 h were measured. Human toll-like receptor 9 (hTLR9)-expressing HEK293 cells, which release secreted embryonic alkaline phosphatase (SEAP) upon NF-κB activation, were stimulated by cfDNA from RA patients, and subsequently, SEAP levels were determined. NF-κB translocation was evaluated by immunofluorescence staining with or without tocilizumab. The DAS28ESR significantly improved in both bDMARD groups at week 12. However, plasma cfDNA levels significantly decreased in the tocilizumab group at week 12 compared to that in week 0. cfDNA levels correlated with DAS28ESR in biological treatment-naïve patients administered tocilizumab. cfDNA levels in synovial cells were significantly suppressed by tocilizumab treatment and unaltered with etanercept. HEK293 cells released SEAP upon cfDNA stimulation, and the observed NF-κB nuclear translocation was suppressed by tocilizumab. Tocilizumab suppressed inflammation via the TLR9 pathway by decreasing cfDNA levels. Regulation of cfDNA may be a therapeutic target for RA.

Distinct role of tumor-infiltrating lymphocytes between synchronous and metachronous colorectal cancer.

PURPOSE: Tumor-infiltrating lymphocytes (TILs) may influence the prognosis of colorectal liver metastasis (CRLM). We assessed the prognostic value of evaluating TILs in the primary and metastatic sites of synchronous CRLM as well as metachronous CRLM. METHODS: We examined 90 patients who underwent curative primary and liver metastasis resection for colorectal cancer. CD8+ TILs (cytotoxic T cells) or CD45RO+ TILs (memory T cells) in both primary and metastatic sites were simultaneously evaluated by immunohistochemistry. RESULTS: Fifty-one patients had synchronous CRLM, and 39 patients had metachronous CRLM. In synchronous cases, the overall survival (OS) was significantly worse in patients with low CD8+ or CD45RO+ TILs in a metastatic site than in those with high CD8+ or CD45RO+ TILs (P = 0.017 and P = 0.005, respectively). Multivariate analysis showed that age ≥ 65 years (P = 0.043), maximum tumor size ≥ 30 mm (P = 0.003), primary N2-3 (P = 0.019), and low CD8+ TILs in metastatic site (P = 0.046) were independent poor prognostic factors. In contrast, in metachronous cases, OS was significantly worse in patients with low CD45RO+ TILs in a primary site than in those with high CD45RO+ TILs (P = 0.021). CD45RO+ TILs in a primary site (P = 0.044) were determined to be independent prognostic factor on multivariate analysis. CONCLUSIONS: The immune microenvironment between synchronous and metachronous CRLM might be different, and these differences may affect its prognosis.

The effect of tetrastarch on the endothelial glycocalyx layer in early hemorrhagic shock using fluorescence intravital microscopy: a mouse model.

PURPOSE: To investigate vascular endothelial dysfunction based on glycocalyx impairment in massive hemorrhage and to evaluate fluid therapy. METHODS: In this randomized controlled animal study, we withdrew 1.5 mL blood and administered 1.5 mL resuscitation fluid. Mice were divided into six groups according to the infusion type and administration timing: NS-NS (normal saline), NS-HES ([hydroxyethyl starch]130), HES-NS, NS-ALB (albumin), ALB-NS, and C (control) groups. RESULTS: The glycocalyx index (GCXI) of a 40-µm artery was significantly larger in group C than in other groups (P < 0.01). Similarly, the GCXI for a 60-µm artery was significantly higher in group C than in NS-NS (P ≤ 0.05), NS-HES (P ≤ 0.01), and NS-ALB groups (P ≤ 0.05). The plasma syndecan-1 concentration, at 7.70 ± 5.71 ng/mL, was significantly lower in group C than in group NS-NS (P ≤ 0.01). The tetramethylrhodamine-labeled dextran (TMR-DEX40) fluorescence intensity in ALB-NS and HES-NS groups and the fluorescein isothiocyanate-labeled hydroxyethyl starch (FITC-HES130) fluorescence intensity in NS-HES and HES-NS groups were not significantly different from those of group C at any time point. FITC-HES130 was localized on the inner vessel wall in groups without HES130 infusion but uniformly distributed in HES130-treated groups in intravital microscopy. FITC-FITC-HES130 was localized remarkably in the inner vessel walls in group HES-NS in electron microscopy. CONCLUSIONS: In an acute massive hemorrhage mouse model, initial fluid resuscitation therapy with saline administration impaired glycocalyx and increased vascular permeability. Prior colloid-fluid administration prevented the progression of glycocalyx damage and improve prognosis. Prior HES130 administration may protect endothelial cell function.

Sodium-glucose cotransporter 2 inhibitor-associated perioperative ketoacidosis: a systematic review of case reports.

Although the recommended preoperative cessation period for sodium-glucose cotransporter 2 inhibitors (SGLT2is) changed in 2020 (from 24 h to 3-4 days preoperatively) to reduce the risk of SGLT2i-associated perioperative ketoacidosis (SAPKA), the validity of the new recommendation has not been verified. Using case reports, we assessed the new recommendation effectiveness and extrapolated precipitating factors for SAPKA. We searched electronic databases up to June 1, 2022 to assess SAPKA (blood pH < 7.3 and blood or urine ketone positivity within 30 days postoperatively in patients taking SGLT2i). We included 76 publications with 99 cases. The preoperative SGLT2i cessation duration was reported for 59 patients (59.6%). In all cases with available cessation periods, the SGLT2is were interrupted < 3 days preoperatively. No SAPKA cases with > 2-day preoperative cessation periods were found. Many case reports lack important information for estimating precipitating factors, including preoperative SGLT2i cessation period, body mass index, baseline hemoglobin A1c level, details of perioperative fluid management, and type of anesthesia. Our study suggested that preoperative SGLT2i cessation for at least 3 days could prevent SAPKA. Large prospective epidemiologic studies are needed to identify risk factors for SAPKA.

[COMPONENT ANALYSIS OF THREE ANISAKIASIS ALLERGY CASES IN OUR DEPARTMENT].

Reactivity to an anisakis allergen component was examined in three patients with a history of an anisakiasis anaphylaxis. Case 1, a 38-year-old man, allergic symptoms appeared 0.5 hours after ingestion, and the component Ani s 1 and 3 were positive. Case 2, a 44-year-old woman, allergic symptoms appeared 4 hours after ingestion, and components Ani s 3 and 12 were positive. Case 3, a 36-year-old woman, developed allergic symptoms 7 hours after ingestion of fish and shellfish, and tested positive for Ani s 1, 4, and 12. Case 3 reacted strongly to both heated and unheated Anisakis extract, while cases 1 and 2 reacted weakly to heated Anisakis extract. The most common allergen was Ani s 12, followed by Ani s 1, when analyzed in conjunction with existing reports on 10 cases. Anisakis IgE was class 3 or higher in all cases. Analysis of 13 cases showed 2 cases sensitized to Ani s 4 and moderate or higher anaphylaxis, while Ani s 4-sensitized patients were reported to be more likely to develop severe disease. It is possible that the patients sensitized to Ani s 4 need to be careful about the severity of their allergic symptoms.

Neural effects of viewing children's faces on mental fatigue: a magnetoencephalography study.

We examined whether the recovery from fatigue could be facilitated by viewing the children's faces. Seventeen healthy mothers with child or children over 6 years old participated in our experiment. After performing a 2-back task for 40 min, they viewed the pictures of children's and adult's faces in the target and control conditions, respectively. The target and control conditions were performed on the separate days in a two-crossover design. Neural activity caused by viewing the children's faces was recorded using magnetoencephalography and electrocardiography was performed to assess the index of heart rate variability (low-frequency component power/high-frequency component power ratio, LF/HF) reflecting fatigue. The subjective level of mental fatigue sensation and LF/HF ratio was decreased after viewing the children's faces and the overactivation of the visual cortex caused by performing the 2-back task, assessed by the alteration of alpha band power in the visual cortex, was attenuated by viewing the children's faces, suggesting that viewing the children's faces affected the time course of mental fatigue after performing the 2-back task.

Neural mechanism by which physical fatigue sensation suppresses physical performance: a magnetoencephalography study.

The right dorsolateral prefrontal cortex (DLPFC) has been proposed to be the brain region regulating performance through fatigue sensation in fatigue, but direct evidence has been lacking for right DLPFC activation when physical performance is suppressed in the presence of fatigue sensation. We examined whether the right DLPFC is activated when physical performance is suppressed by remembering a physical fatigue sensation. Eighteen healthy male volunteers participated. They performed a rest session followed by a handgrip session to induce physical fatigue sensation. Then, they were instructed to remember the state of the right hand with (i.e., the target condition) and without (i.e., the control condition) fatigue sensation as experienced in the handgrip and rest sessions, respectively while performing motor imagery of maximum handgrip of the right hand. Neural activity during both conditions was recorded using magnetoencephalography. The level of fatigue sensation was higher in the target condition than in the control condition. Decreases of handgrip strength and beta band power in the right Brodmann's area 46 were observed in the target condition, suggesting that the right DLPFC is involved in the regulation of physical performance through fatigue sensation. These findings may help elucidate the neural mechanisms regulating performance under fatigue conditions.

Impact of laparoscopic liver resection on liver regeneration.

BACKGROUND: Liver regeneration after liver resection plays an important role in preventing posthepatectomy liver failure. In this study, we aimed to evaluate and compare the impact of laparoscopic liver resection (LLR) and open liver resection (OLR) on liver regeneration. METHODS: Patients who underwent curative anatomical liver resection for hepatocellular carcinoma, cholangiocellular carcinoma, and colorectal liver metastases at our institution between January 2010 and December 2018 were included in this study. The patients were divided into the OLR and LLR groups. Preoperative liver volume (PLV), future remnant liver volume, resected liver volume (RLV), liver volume at 1 month after the surgery, and liver volume at 6 months after the surgery were calculated. The liver regeneration rate was defined as the increase in the rate of RLV, and the liver recovery rate was defined as the rate of return to the PLV. RESULTS: The study included 72 patients. Among them, 43 were included in the OLR group and 29 were included in the LLR group. No differences were observed in the baseline characteristics and surgical procedures between the two groups. Moreover, no significant difference was observed in the liver regeneration rate at 1 month after the surgery (OLR vs. LLR: 68.9% vs. 69.0%, p = 0.875) and at 6 months after the surgery (91.8% vs. 93.2%, p = 0.995). Furthermore, the liver recovery rates were not significantly different between the two groups at 1 month after the surgery (90.3% vs. 90.6%, p = 0.893) and at 6 months after the surgery (96.9% vs. 98.8%, p = 0.986). CONCLUSION: Liver regeneration after liver resection is not affected by the type of surgical procedure and both laparoscopic and open procedures yield similar regeneration and recovery rates.

Advantages of skin closure with subcuticular suture for liver resection on postoperative and cosmetic outcomes: a propensity matched analysis.

PURPOSE: The effects of subcuticular sutures on postoperative and cosmetic outcomes in patients who underwent liver resection have not been well studied. Here, we investigated the advantages of subcuticular suture compared to skin stapler regarding open liver resection. METHODS: We assessed 342 patients who underwent liver resection at Nara Medical University between 2008 and 2015. They were divided into two groups: subcuticular suture and staple groups. Baseline characteristics and perioperative outcomes were retrospectively compared using one-to-one propensity score matching analysis. RESULTS: In this period, 179 patients underwent skin closure with subcuticular sutures and 163 patients underwent skin closure with staples. After propensity matching, 85 pairs of cases were matched. The incidence of wound infection was similar in the two groups (3.5% in the subcuticular suture group and 9.4% in the staple group; p = 0.119). The length of hospital stay was significantly shorter in the subcuticular suture group than in the staple group (10 days vs 15 days; p < 0.001). In addition, the rate of patients who were discharged within 7 days after surgery was statistically higher in the subcuticular group (21.1% vs 3.5%, p = 0.001). Hypertrophic scar 6 months after surgery was significantly less frequent in the subcuticular group (9.4% vs 25.9%, p = 0.010). CONCLUSION: Subcuticular sutures might be advantageous for liver surgery reducing length of hospital stay and proportion of hypertrophic scar.

Acute tubulointerstitial nephritis in a patient with early bronchial tuberculosis.

Patients with chronic kidney disease (CKD) are commonly at high risk of tuberculosis (TB). Conversely, TB rarely causes tubulointerstitial nephritis. A 75-year-old Japanese man who was undergoing periodic follow-ups for CKD stage G3aA3 with membranous nephropathy was diagnosed with acute kidney injury (AKI) (estimated glomerular filtration rate [eGFR]: 15 mL/min/1.73 m2) without prerenal AKI. He reported developing recent-onset cough 3 weeks prior to presenting to us. Renal biopsy revealed acute tubulointerstitial nephritis along with known membranous nephropathy. CD4+ helper T cells comprised most lymphocytes in the tubulointerstitium. Results of the interferon-gamma release assay, sputum smear test, polymerase chain reaction (PCR), and culture test were positive for TB. Chest computed tomography revealed thickening of the left bronchial wall; therefore, a diagnosis of early bronchial TB was made; his urine culture and PCR were negative for TB. At four months after TB treatment with no immunosuppressive therapy, his eGFR improved to 50 mL/min/1.73 m2, and based on this progress, the AKI was diagnosed as tuberculosis-associated tubulointerstitial nephritis (TATIN). Although TATIN typically occurs with chronic or miliary tuberculosis, it is very rare in early bronchial TB. Identification of TATIN is important in kidney diseases of unknown etiology, and treatment with anti-TB drugs is necessary.

Clamp-Crush Technique for Laparoscopic Liver Resection.

Liver parenchymal transection is the most important process in laparoscopic liver resection (LLR). Various surgical methods and devices for LLR have been applied including the cavitron ultrasonic surgical aspirator, ultrasonic scalpel, and staplers. Very few reports have investigated the clamp--crush technique for LLR.1,2 Current study shows a clamp-crush technique for LLR and evaluates its perioperative outcomes. The clamp-crush technique was performed using simple forceps and the Pringle maneuver under a low central venous pressure. The vessels that remained after crushing were clipped if they were thick; or removed with an ultrasonic cutting-coagulation system if they were thin. Sixty-one LLRs were performed using the clamp-crush technique. Pathological cirrhosis was observed in 22 patients (36.0%). The types of resection were as follows: 31 wedge resections (50.8%), 11 segmentectomies (19.0%), 9 sectionectomies (14.8%), and 10 hemihepatectomies (16.4%). The intraoperative blood loss was 62 ml; the surgical duration was 272 min. The postoperative major complication (Clavien-Dindo ≥ IIIa) rate was 4.9%. The median hospital stay was 8 days (range = 4-53 days). A 76-year-old female underwent right LLR for a 9-cm HCC. The right hepatic artery and portal vein were dissected separately. After mobilizing the liver, parenchymal transection was performed using the clamp-crush technique. The middle hepatic vein was totally exposed. Intraoperative blood loss was 32 ml and the surgical duration was 5 h 32 min with no postoperative complications. The clamp-crush technique is safe and feasible for LLR and could contribute to quick parenchymal transection and flattening of the transection plane.

Clinical Importance of CD200 Expression in Colorectal Liver Metastasis.

BACKGROUND: Approximately 30% of patients diagnosed with colorectal cancer (CRC) develop liver metastases. We evaluated the role of CD200, a potent immunosuppressive molecule, in colorectal liver metastases (CRLM). METHODS: We examined 110 patients who underwent curative liver resection for CRLM at our institution between 2000 and 2016. Based on the results of immunohistochemical analysis, the patients were divided into high-CD200 (n = 47) and low-CD200 (n = 63) expression groups. The relationships between CD200 expression and various clinicopathological outcomes were investigated. RESULTS: The overall survival (OS) of patients in the high-CD200 group was significantly worse than that in the low-CD200 group (p = 0.009). Multivariate analysis showed that the independent prognostic factors in CRLM were maximum tumor size > 30 mm (p = 0.002), preoperative carcinoembryonic antigen level > 20 ng/mL (p < 0.001), primary CRC N2-3 (p = 0.049), and high-CD200 expression (p = 0.004). Furthermore, CD4+, CD8+, and CD45RO+ tumor-infiltrating lymphocytes in CRLM were significantly higher in the low-CD200 group than in the high-CD200 group (p = 0.005, p = 0.001, and p < 0.001, respectively). In addition, patients who had received preoperative chemotherapy had higher CD200 expression than those who had not received preoperative chemotherapy, and OS was significantly worse in patients in the high-CD200 group who had received preoperative chemotherapy. CONCLUSIONS: CD200 expression was an independent prognostic factor in CRLM. CD200 may play a critical role in tumor immunity in CRLM, and can therefore be used as a potential therapeutic target in CRLM.

Selective formation of a phenathridine derivative by photodegradation of azilsartan.

Photodegradation of azilsartan produces a phenanthridine derivative, with its molecular structure determined by 1H and 13C NMR spectroscopy. This structure is confirmed by single-crystal X-ray diffraction and alternative synthesis. The phenanthridine ring formation is explained through the ring closure of an imidoylnitrene intermediate produced by decarboxylation of the 5-oxo-1,2,4-oxadiazole ring (oxadiazolone).

Pulmonary complications after laparoscopic liver resection.

BACKGROUND: Although postoperative pulmonary complications (PPCs) are one of the common complications after liver surgery and might be avoided with the use of a laparoscopic approach, few reports have focused on the comparison of PPCs between laparoscopic liver resection (LLR) and open liver resection (OLR). The aim of this study was to clarify the effect of LLR on PPCs. METHODS: The study included 307 patients who underwent liver resection, excluding biliary reconstruction, at our institution between 2014 and 2018. Patients were divided into the OLR and LLR groups. The perioperative outcomes and PPCs were compared between the two groups using propensity score matching. On day 3 after liver surgery, all patients had chest radiography to confirm the presence of pleural effusion, including cases that required thoracentesis, and pneumonia. RESULTS: Of the 307 patients, 172 and 135 patients were included in OLR and LLR groups, respectively. After propensity score matching, 65 patients were included in each group. Compared with the matched OLR group, the matched LLR group had significantly lower intraoperative blood loss (P < 0.001); rate of intraoperative blood transfusion (P = 0.011); overall PPCs (P = 0.032); and number of cases with chest radiography-confirmed pleural effusion (P = 0.048), pleural effusion requiring thoracentesis (P = 0.029), and pneumonia (P = 0.012). Moreover, postoperative hospital stay was significantly shorter in the matched LLR group than in the matched OLR group. CONCLUSIONS: Compared with OLR, LLR might be a better surgical approach to avoid PPCs.

Outcomes in Patients with Chronic Kidney Disease After Liver Resection for Hepatocellular Carcinoma.

BACKGROUND: The aim of this study was to clarify the feasibility of liver resection in hepatocellular carcinoma (HCC) patients with chronic kidney disease (CKD). METHODS: In all, 204 patients who underwent primary liver resection for HCC between 2011 and 2019 were analyzed. Short-term and long-term outcomes were compared between the CKD and control groups. The CKD group was defined by a preoperative estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 and chronic kidney disease Stage 3B or higher. RESULTS: Twenty-eight patients (13.7%) had CKD. No significant differences were observed in the overall complication rates between the groups (46.4% vs. 34.7% p = 0.229). The incidence of bile leakage was significantly higher in the CKD group than in the control group (14.3% vs. 4.0% p = 0.048), and the median postoperative hospital stay was significantly longer in the CKD group (11 vs. 9 days p = 0.031). No significant differences were found in the disease-free survival between the two groups (p = 0.763), but overall survival (OS) was significantly worse in the CKD group than in the control group (p = 0.022). In the multivariable analysis, a CKD diagnosis (hazard ratio, 2.261; 95% confidence interval (CI), 1.139-4.486 p = 0.020) was identified as an independent poor prognostic factor for OS. The percentage of patients who died from cardiovascular disease was significantly higher in the CKD group (27.3% vs. 2.3% p = 0.023). CONCLUSIONS: Liver resection for HCC in CKD patients is associated with acceptable perioperative outcomes. However, cardiovascular disease may negatively affect the OS of CKD patients after liver resection.

Anti-neutrophil cytoplasmic antibody-associated vasculitis accompanied by type II heparin-induced thrombocytopenia resulting in asymptomatic cerebral infarction: a case report.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) involves platelet activation and aggregation caused by heparin or HIT antibodies associated with poor survival outcomes. We report a case of HIT that occurred after hemodialysis was started for rapidly progressive glomerulonephritis (RPGN), which was caused by anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), and ultimately resulted in asymptomatic cerebral infarction. CASE PRESENTATION: A 76-year-old Japanese man was urgently admitted to our hospital for weight loss and acute kidney injury (serum creatinine: 12 mg/dL). Hemodialysis therapy was started using heparin for anticoagulation. Blood testing revealed elevated titers of myeloperoxidase anti-neutrophil cytoplasmic antibodies, and renal biopsy revealed crescentic glomerulonephritis with broad hyalinization of most of the glomeruli and a pauci-immune staining pattern. These findings fulfilled the diagnostic criteria for microscopic polyangiitis, and the patient was diagnosed with RPGN caused by AAV. Steroid pulse therapy, intermittent pulse intravenous cyclophosphamide, and oral steroid therapy failed to improve the patient's renal function, and maintenance dialysis was started. However, on day 15, his platelet count had decreased to 47,000/µL, with clotting observed in the hemodialysis catheter. Magnetic resonance imaging of the head identified acute asymptomatic brain infarction in the left occipital lobe, and a positive HIT antibody test result supported a diagnosis of type II HIT. During hemodialysis, the anticoagulant treatment was changed from heparin to argatroban. Platelet counts subsequently normalized, and the patient was discharged. A negative HIT antibody test result was observed on day 622. CONCLUSIONS: There have been several similar reports of AAV and HIT co-existence. However, this is a rare case report on cerebral infarction with AAV and HIT co-existence. Autoimmune diseases are considered risk factors for HIT, and AAV may overlap with other systemic autoimmune diseases. To confirm the relationship between these two diseases, it is necessary to accumulate more information from future cases with AAV and HIT co-existence. If acute thrombocytopenia and clotting events are observed when heparin is used as an anticoagulant, type II HIT should always be considered in any patient due to its potentially fatal thrombotic complications.

Evaluation of changes in oral health-related quality of life over time in patients with Sjögren's syndrome.

OBJECTIVES: To assess oral health-related quality of life (OHRQoL) and changes in OHRQoL in 3 years of patients with Sjögren's symdrome (SS). METHODS: Thirty-five SS patients and 23 non-SS individuals were enrolled. OHRQoL were quantitatively evaluated using the shortened Oral Health Impact Profile (OHIP-14). After 3 years, 22 patients and 14 controls tool the OHIP-14 survey again. RESULTS: The SS group had a significantly higher OHIP-14 score, which indicated a lower OHRQoL, than the non-SS group. Among individual questions in the OHIP-14, scores for 'trouble pronouncing words', 'uncomfortable to eat foods', 'self-conscious', and 'diet unsatisfactory' were markedly higher in the SS group than in the non-SS group. The OHIP-14 score significantly increased in 3 years in the SS group. Furthermore, there was an inverse correlation between the change rate of salivary flow rate and change of OHIP-14 scores in 3 years in patients with SS whose OHIP-14 score increased. Scores for 'irritable with other people', 'difficulty doing usual jobs', 'felt life less satisfying', and 'unable to function' significantly increased in 3 years. CONCLUSION: In SS, OHRQoL decreased in 3 years, which was associated with a decrease in saliva secretion. Moreover, troubles related to psychosocial aspects in SS patients were found to intensify over time.

Influence of the Glissonean Pedicle Transection Approach in Spiegel Lobe-Preserving Left Hepatectomy on Spiegel Lobe Volume and Remnant Liver Functions.

BACKGROUND: The extrahepatic surgical technique in liver resection can be divided into glissonean pedicle transection and glissonean separated transection approaches. In this study, we compared remnant liver function and liver regeneration involving the Spiegel lobe between these two approaches regarding Spiegel lobe-preserving left hepatectomy. METHODS: We enrolled 31 patients who underwent Spiegel lobe-preserving left hepatectomy for malignant hepatobiliary diseases between April 2008 and January 2020. The postoperative Spiegel lobe volume was measured using a volume analyzer at 3 and 6 months postoperatively. RESULTS: Of the 31 patients, 22 and 9 were included in the glissonean separated transection and glissonean pedicle transection groups, respectively. There was no significant between-group difference in the preoperative Spiegel lobe volume. However, the volumes at 3 and 6 months postoperatively were significantly larger in the glissonean pedicle transection group than in the glissonean transection group (29.92 mL vs. 13.00 mL; P < 0.001 and 28.43 mL vs. 15.01 mL; P < 0.001, respectively). There was no significant between-group difference in postoperative remnant liver function. CONCLUSIONS: The postoperative Spiegel lobe volume was larger, and liver regeneration was better with the glissonean pedicle transection approach because of transection for Spiegel branch of the portal vein. It is desirable to preserve Spiegel branch in possible cases when surgeons select the glissonean separated transection approach based on the location and size of the tumors.

Significance of Herpesvirus Entry Mediator Expression in Human Colorectal Liver Metastasis.

BACKGROUND: Herpesvirus entry mediator (HVEM) has been suggested to play various roles in cancer biology. The authors report that HVEM expression in tumor cells is associated with a reduction in the number of tumor-infiltrating lymphocytes and a poor prognosis after surgical resection in various human gastrointestinal cancers. This study aimed to clarify the clinical significance of HVEM expression in human colorectal liver metastasis (CRLM). METHODS: This study examined the cases of 104 patients with CRLM who underwent curative liver resection at Nara Medical University between 2000 and 2014. The median follow-up period was 50.2 months. Immunohistochemical staining was performed using antibodies against HVEM, CD4, CD8, and CD45RO. RESULTS: High HVEM expression was observed in 49 patients (47.1%) with CRLM. Expression of HVEM was not associated with age, gender, administration of preoperative chemotherapy, tumor size, number of tumors, or histologic differentiation. The high-HVEM group exhibited significantly worse overall survival (OS) than the low-HVEM group (P = 0.002). Multivariate analysis showed that high HVEM expression in CRLM, age of 70 years or older, and having five or more tumors are independent poor prognostic factors for OS (hazard ratio [HR], 3.35; 95% confidence interval [CI], 1.41-7.93; P = 0.006). The number of tumor-infiltrating CD8+ and CD45RO+ T cells was significantly lower in the high-HVEM group than in the low-HVEM group. High HVEM expression in primary colorectal cancer was significantly associated with synchronous CRLM, but not with metachronous CRLM. CONCLUSIONS: Tumor HVEM expression might play a critical role in CRLM.

Serum neopterin as well as ferritin, soluble interleukin-2 receptor, KL-6 and anti-MDA5 antibody titer provide markers of the response to therapy in patients with interstitial lung disease complicating anti-MDA5 antibody-positive dermatomyositis.

Objective: This study identified biomarkers that can be used to assess disease activity and response to therapy in patients with interstitial lung disease complicating anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab)-positive clinically amyopathic dermatomyositis (CADM). Methods: In 15 patients with interstitial lung disease complicating anti-MDA5 Ab-positive CADM, anti-MDA5 Ab, neopterin, interleukin (IL)-18, ferritin, and soluble interleukin 2 receptor (sIL-2R) levels were measured in cryopreserved serum specimens before and at multiple times after remission induction therapy, and their correlations were assessed. Results: Anti-MDA5 Ab, neopterin, IL-18, ferritin, and sIL-2R levels did not differ significantly between patients who survived and those who succumbed to the disease. In many cases, serum anti-MDA5 Ab titers were over the upper limit (over 150 index value) before treatment in the usual measuring method, and gradually decreased to the normal range at stable phase. Meanwhile, serum neopterin levels (21.6 [15.3-48.3] nmol/L) were significantly elevated in newly diagnosed patients and fell to 6.8 (5-11.4) nmol/L at 6 months after treatment introduction. Conclusions: Elevated serum neopterin as well as ferritin, sIL-2R, KL-6, and anti-MDA5 Ab titer might help identify patients with interstitial lung disease complicated with DM and might be useful in monitoring response to therapy.