Autophagy is a self-digestive process that is conserved in eukaryotic cells and responsible for maintaining cellular homeostasis through proteolysis. By this process, cells break down their own components in lysosomes. Autophagy can be classified into three categories: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Macroautophagy involves membrane elongation and microautophagy involves membrane internalization, and both pathways undergo selective or non-selective processes that transport cytoplasmic components into lysosomes to be degraded. CMA, however, involves selective incorporation of cytosolic materials into lysosomes without membrane deformation. All three categories of autophagy have attracted much attention due to their involvement in various biological phenomena and their relevance to human diseases, such as neurodegenerative diseases and cancer. Clarification of the molecular mechanisms behind these processes is key to understanding autophagy and recent studies have made major progress in this regard, especially for the mechanisms of initiation and membrane elongation in macroautophagy and substrate recognition in microautophagy and CMA. Furthermore, it is becoming evident that the three categories of autophagy are related to each other despite their implementation by different sets of proteins and the involvement of completely different membrane dynamics. In this review, recent progress in macroautophagy, microautophagy, and CMA are summarized.

Laparoscopic surgery is performed worldwide and has clear economic and social benefits in terms of patient recovery time. It is used for most gastrointestinal surgical procedures, but laparoscopic surgery for more complex procedures in the esophageal, hepatobiliary, and pancreatic regions remains challenging. Minimally invasive surgery that results in accurate tumor dissection is vital in surgical oncology, and development of surgical systems and instruments plays a key role in assisting surgeons to achieve this. A notable advance in the latter half of the 1990s was the da Vinci Surgical System, which involves master-slave surgical support robots. Featuring high-resolution three-dimensional (3D) imaging with magnification capabilities and forceps with multi-joint function, anti-shake function, and motion scaling, the system compensates for the drawbacks of conventional laparoscopic surgery. It is expected to be particularly useful in the field of hepato-biliary-pancreatic surgery, which requires delicate reconstruction involving complex liver anatomy with diverse vascular and biliary systems and anastomosis of the biliary tract, pancreas, and intestines. The learning curve is said to be short, and it is hoped that robotic surgery will be standardized in the near future. There is also a need for a standardized robotic surgery training system for young surgeons that can later be adapted to a wider range of surgeries. This systematic review describes trends and future prospects for robotic surgery in the hepatobiliary-pancreatic region.

Smoking-related interstitial lung diseases (SRILDs) are a group of heterogeneous diffuse pulmonary parenchymal diseases associated with tobacco exposure. Smoking-related interstitial fibrosis (SRIF) is relatively recent, a pathologically defined form of SRILDs. SRIF is characterized by the accumulation of macrophages in the alveolar spaces, which is associated with interstitial inflammation and fibrosis. The macrophages frequently contain light brown pigment and are called 'smoker's macrophages'. Patients with SRIF who have clinical evidence of interstitial lung disease are most commonly relatively young, heavy smokers with abnormalities on chest computed tomography showing ground-glass opacities, peripheral consolidation, and reticulation. Although SRIF is caused by cigarette smoking, the exact pathophysiological mechanisms by which smoking causes this type of interstitial fibrosis remain unknown. The degree of fibrosis and appearance of macrophage aggregates are important points of distinction when evaluating and diagnosing SRIF. Macrophage heterogeneity, particularly the activation and function of monocyte-derived alveolar macrophages (Mo-AMs) and interstitial macrophages (IMs), has important implications for the pathogenesis of SRIF and developing treatments. Further researches focused on smoker's macrophages are needed to understand of the pathogenesis of SRIF.

Purpose: To quantify and compare the severity of metamorphopsia in patients undergoing vitrectomy for vitreoretinal disorders. Methods: Data were collected evaluated from 319 patients with vitreoretinal disorders, including epiretinal membrane (ERM), macular hole (MH), cystoid macular edema with branch retinal vein occlusion (BRVO-CME), CME with central retinal vein occlusion (CRVO), diabetic macular edema (DME), macula-off rhegmatogenous retinal detachment (M-off RD), and macula-on RD (M-on RD). Metamorphopsia was recorded with the M-CHARTS preoperatively and at 3 and 6 months postoperatively. Results: Preoperative and 6-month postoperative metamorphopsia scores were 0.69 ± 0.50 and 0.50 ± 0.52, respectively. Before surgery, 94% of patients presented with metamorphopsia (score ≥0.2). Preoperative metamorphopsia scores were significantly correlated with postoperative metamorphopsia scores (r = 0.378, p < 0.0001). Preoperative metamorphopsia score was significantly higher for ERM (0.89) than for DME (0.51). Vitrectomy significantly improved metamorphopsia in ERM and MH but not in the other disorders. In contrast, treatment improved visual acuity for all disorders except CRVO-CME and M-on RD. Conclusion: This quantitative study indicated that metamorphopsia is present in most patients undergoing surgery for vitreoretinal diseases and is most severe in ERM. In these patients, vitrectomy improved visual acuity but not metamorphopsia.

Background: Perioperative factors are useful for predicting postoperative infectious complications (PIC) in gastric cancer. Specifically, postoperative inflammatory response indicators (PIRI), [C-reactive protein (CRP) level, body temperature (BT), and white blood cell (WBC) count], are widely used in clinical practice. We investigated predictive factors for PIC, including PIRI, to establish a simple and practical indicator of postoperative complications after gastrectomy. Methods: We retrospectively collected clinical data from 200 patients with fStage I-III gastric cancer. Univariate/multivariate analysis was performed to evaluate the relationship of predictive factors [host factors, clinicopathological factors, and PIRI (BT, WBC count, and CRP level on postoperative day (POD) 1 and 3) ]. Cut-off values of the predictive factors were analyzed using receiver operating characteristic (ROC) curve modulated by the presence/absence of PIC Grade II, III (Clavien-Dindo classification). Results: Age [Odds ratio (OR): 5.67], smoking history (OR: 3.51), and CRP level (OR: 5.65), WBC count (OR: 8.96), and BT (OR: 3.37) on POD3 were selected as independent factors from multivariate analysis. Cut-off values were 77 years, 14.8 mg/dL, 116.0×10²/μL, and 37.4°C, respectively. Conclusions: Predictive factors relative to PIC in gastric cancer were CRP level ≥ 14.8 mg/dL, WBC count ≥ 116.0×10²/μL, and BT ≥ 37.4°C all on POD3. Age ≥ 77 years, and history of smoking were relative to PIC, suggesting a simple and practical indicator applicable in clinical practice.

Background: This study examined the appropriateness of the current paradigm for differential diagnosis of painless thyroiditis and Graves' disease (GD) in patients with thyrotoxicosis. Methods: We retrospectively evaluated the clinical course of 343 consecutive patients with hyperthyroidism diagnosed by Tc-99m pertechnetate thyroid uptake (TcTU) testing at our hospital from January 2011 to December 2017. Results: Of the 263 patients with normal or high TcTU levels (≥1.0%), 255 (97%) had unequivocal GD and 5 had spontaneous remission GD or atypical GD. Of the 10 patients with low TcTU levels (<1.0% and ≥0.5%), 7 had GD, while others had subclinical GD, spontaneous remission GD with later relapse, and painless thyroiditis. Of those with very low TcTU levels (<0.5%), most had thyroiditis (painless thyroiditis, 33/67 [49%]; subacute thyroiditis, 29/67 [43%]), and some were positive for anti-TSH receptor antibodies. Conclusion: Given that atypical GD may confound the diagnosis of thyrotoxicosis, it is essential to follow the patient as a tentative diagnosis, whatever the diagnosis. This is the first report clearly demonstrating that so far there is no gold standard for the diagnosis of GD. It is therefore urgent to establish a consensus on the definition of GD so that the specificity and sensitivity of future diagnostic tests can be determined.

Background: The Japanese Society for Pharmaceutical Palliative Care and Sciences specializes in pharmacology in the field of palliative medicine. More than 700 board-certified pharmacists in palliative pharmacy (BCPPP) are actively involved in palliative pharmacotherapy at various hospitals and pharmacies. The purpose of this study was to determine the economic effect of pharmaceutical interventions by BCPPPs. Methods: This multicenter retrospective study included 27 medical centers and analyzed the medical economic effect of interventions by BCPPPs (17 pharmacists) and non-BCPPPs (24 pharmacists) on patients using medical narcotics for cancer pain in September 2021. Results: The percentage of patients who received a pharmaceutical intervention and whose drug costs were reduced by pharmacist intervention was significantly higher in the BCPPP group than in the non-BCPPP group. Although there was no significant difference between the two groups in drug cost reduction per patient per month (BCPPP group: $0.89 [−$64.91 to $106.76] vs. non-BCPPP group $0.00 [−$1,828.95 to $25.82]; P = 0.730), the medical economic benefit of pharmacist intervention in avoiding or reducing adverse drug reactions was higher in the BCPPP group ($103.18 [$0.00 to $628.03]) than in the non-BCPPP group ($0.00 [$0.00 to $628.03]) (P = 0.070). The total medical economic benefit-the sum of these-was significantly higher in the BCPPP group ($88.82 [−$14.62 to $705.37]) than in the non-BCPPP group ($0.66 [−$1,200.93 to $269.61]) (P = 0.006). Conclusion: Pharmacological intervention for patients with cancer using medical narcotics may have a greater medical economic benefit when managed by BCPPPs than by non-certified pharmacists in Japan.

Background: Lower extremity artery disease is strongly associated with morbidity and is typically addressed through revascularization interventions. We assessed the clinical outcomes of patients with chronic limb-threatening ischemia (CLTI) without revascularization who did and did not undergo repetitive hyperbaric oxygen therapy (HBOT). Methods: Between April 2002 and March 2017, the records of 58 patients with CLTI (Rutherford classification 4 in 19% and 5 in 81%) were evaluated retrospectively. HBOT was performed at 2.8 atm of oxygen (HBOT group). The control group included those who could not continue HBOT and historical controls. Patients in poor general health or with an indication for revascularization therapy were excluded. We examined major adverse events (MAEs) and limb salvage rates. Independent predictors and risk stratification were analyzed using a multivariate regression analysis. Results: The mean age was 71±13 years. Of all patients, 67% had diabetes and 43% were undergoing hemodialysis. The mean follow-up period was 4.3±0.8 years. The overall survival rate was 84.5% and 81.0% at 1 and 3 years, respectively. The Cox regression analysis indicated that high body mass index (odds ratio [OR]: 0.86; 95% confidence interval [CI]: 0.76-0.97; p=0.01), well-nourished (OR: 1.21; 95% CI: 1.01-1.45), and HBOT (OR: 0.05; 95% CI: 0.01-0.26; p<0.001) independently predicted absence of MAEs. For major limb amputation, the ankle-brachial index (OR: 0.2; 95% CI: 0.05-0.86; p=0.03) and HBOT (OR: 0.04; 95% CI: 0.004-0.32; p=0.003) were independent predictors. Conclusions: Repetitive, stand-alone HBOT was associated with MAE-free survival and limb salvage in patients with CLTI.

Background: No accurate prognostic tool is available for patients with cancer who spend their final days at home. In this study, we examined whether performance status (PS) and the palliative prognostic index (PPI), a well-known prognostic tool in palliative care units, could be used to predict prognosis in the home care setting at the time of intervention by home physicians. Subjects and Methods: Using medical records, we conducted a retrospective analysis of 132 patients who were referred to the Home Clinic Naginoki for home care for terminal stages of carcinoma in situ. Based on the status at the time of the first visit, the PPI-Low group was defined as those scoring six or below and the PPI-High group as those scoring greater than six. Results: The PPI-high group had a significantly poorer prognosis within 21 days than the PPI-low group (21-day-OS; Low 71.4% vs. High 13.2%; p<0.001). The Eastern Cooperative Oncology Group (ECOG) PS alone predicted better prognosis in the group with PS of one or two (21-day survival 90.1%), and the PPI score further significantly stratified the prognosis for patients with PS three or four, with a trend toward poor prognosis (p ≤ 0.005). Conclusion: ECOG PS 1 or 2 has a favorable prognosis and that using PPI in ECOG PS 3 or 4 leads to a more accurate prognosis prediction. PPI evaluated during the hospital-based treatment of patients with terminal cancer can also be used to predict prognosis if the patient is transitioned to a home care environment.

Introduction: The spleen is a lymphatic organ that manages immune surveillance of the blood, produces blood cells, and helps filter the blood, remove old blood cells, and fight infection. The normal splenic weight is approximately 65-265 g. This study evaluated spleen volume and segmental volume. Methods: 121 patients who underwent enhanced CT at our center were analyzed. The spleen was divided into upper, middle, and lower segments according to arterial flow area, and the volume of each segment was measured. Patients were classified into two groups as those with and without liver cirrhosis, and differences in the distribution of the segments in these groups was evaluated. Results: The mean upper, middle, and lower spleen segmental volume ratios were 35.4%, 37.0%, and 27.6%, respectively. In the liver cirrhosis group, the segmental splenic volume ratios for the upper, middle, and lower segments were 34.5%, 38.5%, and 28.0%, respectively, indicating that these ratios remain similar regardless of liver cirrhosis status. Conclusion: The present findings on segmental spleen volume are useful for estimating infarction volume in cases of partial splenic arterial embolization.

Background: This study used finite element analysis (FEA) to investigate the effect of varus and valgus angle on the lateral compartment in unicompartmental knee arthroplasty (UKA). Methods: One patient who underwent UKA was enrolled as the subject. Thirteen working conditions of the femoral prosthesis were simulated at varus and valgus angles of 0°, 2°, 4°, 6°, 8°, 10°, and 12°. A load of 1,000 N was applied downward along the mechanical axis of the femur, and the highest stress values on the surface of the polyethylene liner, cancellous bone under the tibial prosthesis, cartilage of femur lateral condyle, lateral meniscus, and tibial lateral plateau cartilage in each model were recorded. The six highest points were used to calculate the mean value. Results: The highest stress values on the surface of the polyethylene liner, cancellous bone under the tibial prosthesis, cartilage of femur lateral condyle, lateral meniscus, and tibial lateral plateau cartilage increased with an increase in the femoral prosthesis varus/valgus angle. As compared with the standard position of the femoral prosthesis, there was no significant difference in the surface stress values of the polyethylene liner, cancellous bone under the tibial prosthesis, cartilage of femur lateral condyle, lateral meniscus and tibial lateral plateau cartilage when the femoral prosthesis varus/valgus angle was less than 4° (p > 0.05). In addition, the stress magnitude on the polyethylene liner, cancellous bone under the tibial prosthesis, cartilage of femur lateral condyle, lateral meniscus, and tibial lateral plateau cartilage significantly increased when the femoral prosthesis varus/valgus angle was greater than 4° (p < 0.001). Conclusions: The optimal femoral prosthesis varus/valgus angle in UKA was less than 4°.

Background: Repeated triage training is necessary to maintain and improve the accuracy of simple triage and rapid treatment (START), a popular triage method. Virtual reality (VR) may be more effective than conventional training methods. This study aimed to verify the educational usefulness of START using VR originally developed for students. Methods: A VR was initially developed with a function that allowed students to select the triage procedure and its evaluation. Triage was performed using a simple modified START method, and eight scenarios were developed. The participants included 70 paramedic students classified into VR and live lecture groups. They took a 20-question written test that evaluated their academic ability before the course. After the course, a practical test and a 20-question written test were conducted. The total score of the practical test was 43 points. Triage procedure (1 point), observation and evaluation (1-5 points), and triage categories (1 point) were evaluated in this test. Results: The VR and live lecture groups consisted of 33 and 29 participants, respectively. No significant differences were observed pre- and post-test. In the practical test, the median (interquartile range) score was 29 (26-32) and 25 (23-29) for the VR and live lecture groups, respectively, with the VR group scoring significantly higher (P=0.03). Conclusion: Our results confirmed the educational usefulness of selective VR for active learning of START. Therefore, VR combined with live lectures and simulations would be an optimal educational technique.

Background: Various energy devices are available for resection of the liver parenchyma during laparoscopic liver resection (LLR). We have historically performed liver resections using the Cavitron Ultrasonic Surgical Aspirator (CUSA). More recently, we have used new bipolar forceps (BiSect; Erbe Elektromedizin GmbH, Tübingen, Germany) to perform clamp-crush dissection with good results. The BiSect is a reusable bipolar forceps with a laparoscopic dissecting forceps tip and both an incision mode and coagulation mode. We evaluated the perioperative clinical course of patients who underwent LLR using the clamp-crush method with the BiSect compared with the CUSA. Methods: This single-center case control study involved patients with liver metastasis from colorectal cancer who underwent LLR using either the BiSect or CUSA at our hospital from January 2019 to December 2022. We performed the LLR using CUSA from January 2019 to early October 2020. After introduction of the BiSect in late October 2020, we used BiSect for the LLR. Before surgery, the three-dimensional liver was constructed based on computed tomography images, and a preoperative simulation was performed. We evaluated the results of LLR using the BiSect versus the CUSA and assessed the short-term results of LLR. Results: During the study period, we performed partial liver resection using the BiSect in 26 patients and the CUSA in 16 patients. In the BiSect group, the median bleeding volume was 55 mL, the median operation time was 227 minutes, and the median postoperative length of hospital stay was 9 days. In the CUSA group, the median bleeding volume was 87 mL, the median operation time was 305 minutes, and the median postoperative length of hospital stay was 10 days. There were no statistically significant differences in the clinical course including bile leakage, bile duct stenosis, and post operative hospital stay between the two groups. Conclusions: Compared with LLR using the CUSA, the clamp-crush method using the BiSect in LLR is a safe and useful liver transection technique. Further study should be conducted to clarify whether BiSect is safe and useful in LLR for patients with other tumor types and patients who undergo other procedures.

Background: Tarsal tunnel syndrome (TTS) is a common entrapment neuropathy that is sometimes elicited by ganglia in the tarsal tunnel. Methods: Between August 2020 and July 2022, we operated on 117 sides with TTS. This retrospective study examined data from 8 consecutive patients (8 sides: 5 men, 3 women; average age 67.8 years) with an extraneural ganglion in the tarsal tunnel. We investigated the clinical characteristics and surgical outcomes for these patients. Results: The mass was palpable through the skin in 1 patient, detected intraoperatively in 1 patient, and visualized on MRI scanning in the other 6 patients. Symptoms involved the medial plantar nerve area (n = 5), lateral plantar nerve area (n = 1), and medial and lateral plantar nerve areas (n = 2). The interval between symptom onset and surgery ranged from 4 to 168 months. Adhesion between large (≥20 mm) ganglia and surrounding tissue and nerves was observed intraoperatively in 4 patients. Of the 8 patients, 7 underwent total ganglion resection. There were no surgery-related complications. On their last postoperative visit, 3 patients with a duration of symptoms not exceeding 10 months reported favorable outcomes. Conclusions: Because ganglia eliciting TTS are often undetectable by skin palpation, imaging studies may be necessary. Early surgical intervention appears to yield favorable outcomes.

A Japanese man in his 20s was referred to our hospital with a two-month history of abdominal fullness and leg edema. Abdominal computed tomography revealing massive ascites and ostial blockage of the main hepatic veins, and angiographic evaluation demonstrating obstruction of the main hepatic veins yielded a diagnosis of Budd-Chiari syndrome (BCS). Diuretic agents were prescribed for the ascites but failed to provide relief. The patient was referred to our department for further evaluation and treatment. Angiography showed ostial obstruction of the main hepatic veins, with most of the portal hepatic flow draining from an inferior right hepatic vein (IRHV) into the inferior vena cava (IVC) thorough an intrahepatic portal venous and venovenous shunt. Access between the main hepatic veins and IVC was impossible, but cannulation between the IRHV and IVC was achieved. Because of the venovenous connection between the main hepatic vein and the IRHV, metallic stents were placed into two IRHVs to decrease congestion in the hepatic venous outflow. After stent placement followed by balloon expansion, the gradient pressure between the hepatic vein and IVC improved remarkably. The ascites and lower leg edema improved postoperatively, and long-term stent patency (6 years) was achieved.

Coronavirus disease 2019 (COVID-19) is associated with cardiovascular complications; however, Takotsubo cardiomyopathy (TCM) with QT prolongation and Torsade de pointes has been reported only rarely. We present a case of TCM after QT prolongation and Torsade de pointes. A 58-year-old woman was admitted because of COVID-19-related pneumonia. Seven days after admission, she developed sudden loss of consciousness without any indication of cardiovascular disease. A monitoring electrocardiogram indicated Torsade de pointes and a prolonged QT interval. Emergency cardiac catheterization revealed TCM. She was treated with favipiravir and steroids, followed by rehabilitation, and her condition improved. To detect asymptomatic TCM, routine electrocardiography screening should be considered for patients with COVID-19.

Infarction of the posterior inferior cerebellar artery (PICA) can lead to ischemic stroke in the lateral medullary oblongata. PICA dissection can also elicit an ischemic event in this region, but its detection on radiological images is difficult because of the small diameter of the vessel. We report a case of Wallenberg syndrome due to PICA dissection in a 48-year-old man, which was difficult to diagnose on first admission. He reported sudden onset of sensory disturbance on the right side of his face, ataxic gait, and headache. Brain magnetic resonance imaging (MRI) revealed a fresh cerebral infarct in the right lateral medulla oblongata. Magnetic resonance angiography (MRA) performed at the time of his admission showed no cerebral vessel abnormalities. An MRI study 18 months after the event revealed a fusiform aneurysm on the lateral medullary segment of the PICA, which was extremely close to the cerebral infarct. We concluded that the infarct was due to PICA dissection because of the sudden onset of symptoms and because the infarcted territory of the occluded penetrating branch of the dissecting aneurysm was consistent with Wallenberg syndrome. The aneurysm was trapped and an occipital artery-PICA bypass was placed. At the latest follow-up, 1 year after the procedure, he had no neurological symptoms. Imaging findings at the time of his first admission indicated that the PICA was intact. However, 18 months later, MRI revealed enlargement of an aneurysm at the site of the dissection. A cerebral infarct with headache may indicate PICA dissection.