Identification of TPI1 As a potential therapeutic target in pancreatic cancer with dependency of TP53 mutation using multi-omics analysis.

Mutations of KRAS, CDKN2A, TP53, and SMAD4 are the four major driver genes for pancreatic ductal adenocarcinoma (PDAC), of which mutations of KRAS and TP53 are the most frequently recognized. However, molecular-targeted therapies for mutations of KRAS and TP53 have not yet been developed. To identify novel molecular targets, we newly established organoids with the Kras mutation (KrasmuOR) and Trp53 loss of function using Cre transduction and CRISPR/Cas9 (Krasmu/p53muOR) from murine epithelia of the pancreatic duct in KrasLSL-G12D mice, and then analyzed the proteomic and metabolomic profiles in both organoids by mass spectrometry. Hyperfunction of the glycolysis pathway was recognized in Krasmu/p53muOR compared with KrasmuOR. Loss of function of triosephosphate isomerase (TPI1), which is involved in glycolysis, induced a reduction of cell proliferation in human PDAC cell lines with the TP53 mutation, but not in PDAC or in human fibroblasts without TP53 mutation. The TP53 mutation is clinically recognized in 70% of patients with PDAC. In the present study, protein expression of TPI1 and nuclear accumulation of p53 were recognized in the same patients with PDAC. TPI1 is a potential candidate therapeutic target for PDAC with the TP53 mutation.

Three Molecular Developmental Pathways of Remnant Pancreatic Cancer after Resection: A Nationwide Project Study of Japan Pancreas Society.

OBJECTIVE: This study aimed to clarify the molecular mechanism of remnant pancreatic cancer (PC) development after primary PC resection. SUMMARY BACKGROUND DATA: Molecular mechanisms of the development of remnant PCs following primary PC resection are largely unknown. METHODS: Forty-three patients undergoing remnant PC resection after primary PC resection between 2001 and 2017 at 26 institutes were retrospectively analyzed. Clinicopathological features and molecular alterations detected by targeted amplicon sequencing of 36 PC-associated genes were evaluated. RESULTS: These patients showed significantly lower body mass indices and higher hemoglobin A1c values at remnant PC resection than at primary PC resection. A comparison of the molecular features between primary and remnant PCs indicated that remnant PCs were likely to develop via three different molecular pathways: successional, showing identical and accumulated alterations (n=14); phylogenic, showing identical and distinct alterations (n=26); and distinct, showing independent distinctive alterations (n=3). The similarity of gene alterations was associated with time to the remnant PC development (r=－0.384, P=0.0173). Phylogenic pathways were significantly associated with the intraductal spread of carcinoma (P=0.007). Patient survival did not differ significantly depending on these molecular pathways. CONCLUSION: Molecular profiling uncovered three pathways for the development of remnant PCs, namely, successional, phylogenic, and distinct pathways. The vast majority of remnant PCs are likely to be molecularly associated with primary PCs either in the successional or phylogenic way. This information could impact the design of a strategy for monitoring and treating remnant PCs.

The Modifying of Functional Connectivity Induced by Peripheral Nerve Field Stimulation using Electroacupuncture for Migraine: A Prospective Clinical Study.

OBJECTIVE: We examined the functional connectivity (FC) in patients with migraine compared with healthy subjects before and after C2 peripheral nerve field stimulation with electroacupuncture (EA-C2-PNfS) to evaluate the effect of EA-C2-PNfS and elucidate the mechanism of migraine. METHODS: Twenty-six patients with migraine and 24 healthy controls were recruited. All patients underwent resting state functional magnetic resonance imaging before and after 3 months of EA-C2-PNfS. We evaluated a numerical rating scale, the Headache Impact Test, and the Self-Rating Depression Scale, which assesses depression. Healthy controls underwent magnetic resonance imaging twice at a 3-month interval without acupuncture. An analysis of FC in the region of interest in the pain matrix was performed. RESULTS: Twenty patients with migraine and 23 healthy controls (mean ± standard deviation: 44.9 ± 12.9 years of age) were included. Three patients had migraine with aura (55.0 ± 18.0 years of age), 11 patients had migraine without aura (MWoA) (45.6 ± 14.6 years of age), and six patients had chronic migraine (40.8 ± 13.9 years of age). The clinical assessments significantly improved after EA-C2-PNfS in the MWoA group only. In FC analysis, the MWoA group showed a significant decrease after EA-C2-PNfS in FC between the right hypothalamus and left insula. Right hypothalamus-related FC was lower before acupuncture in the chronic migraine group than in the MWoA group. CONCLUSION: After EA-C2-PNfS for MWoA, significant changes in FC were observed at the hypothalamus and insula. Our results indicate that EA-C2-PNfS could improve migraine headache by modifying pain-related FC.

Patient satisfaction and loyalty in Japanese primary care: a cross-sectional study.

BACKGROUND: This study aimed to explore associations between various elements of primary care, patient satisfaction, and loyalty. METHODS: This cross-sectional study used a modified version of the Primary Care Assessment Tool (PCAT), which was adapted for Japan. We distributed the PCAT questionnaire to patients aged 20 years or older at five rural primary care centres in Japan. We confirmed the validity and reliability of the measure for our study. Next, we examined which elements of primary care were related to patient satisfaction and loyalty using Spearman's correlation and structural equation modelling. RESULTS: Of 220 eligible patients, 206 participated in this study. We developed nine component scales: first contact (regular access), first contact (urgent access), longitudinality, coordination, comprehensiveness (variety of care), comprehensiveness (risk prevention), comprehensiveness (health promotion), family-centeredness, and community orientation. Longitudinality and first contact (urgent access) were related with patient satisfaction. Longitudinality, first contact (regular access), and family-centeredness were related to patient loyalty. In the structural equation modelling analysis, two variables were significantly related to loyalty, namely a combined variable including longitudinality and first contact (regular access), along with family-centeredness. CONCLUSIONS: While a patient satisfaction model could not be distilled from the data, longitudinality, first contact (urgent access), and family-centeredness were identified as important elements for the cultivation of patient loyalty. This implies that primary care providers need to develop a deep understanding of patients' contexts and concerns and pay attention to their level of access to cultivate greater patient loyalty.

Rapid stimulation of human dentate gyrus function with acute mild exercise.

Physical exercise has beneficial effects on neurocognitive function, including hippocampus-dependent episodic memory. Exercise intensity level can be assessed according to whether it induces a stress response; the most effective exercise for improving hippocampal function remains unclear. Our prior work using a special treadmill running model in animals has shown that stress-free mild exercise increases hippocampal neuronal activity and promotes adult neurogenesis in the dentate gyrus (DG) of the hippocampus, improving spatial memory performance. However, the rapid modification, from mild exercise, on hippocampal memory function and the exact mechanisms for these changes, in particular the impact on pattern separation acting in the DG and CA3 regions, are yet to be elucidated. To this end, we adopted an acute-exercise design in humans, coupled with high-resolution functional MRI techniques, capable of resolving hippocampal subfields. A single 10-min bout of very light-intensity exercise (30%[Formula: see text]) results in rapid enhancement in pattern separation and an increase in functional connectivity between hippocampal DG/CA3 and cortical regions (i.e., parahippocampal, angular, and fusiform gyri). Importantly, the magnitude of the enhanced functional connectivity predicted the extent of memory improvement at an individual subject level. These results suggest that brief, very light exercise rapidly enhances hippocampal memory function, possibly by increasing DG/CA3-neocortical functional connectivity.

Robotic rehabilitation of the paralyzed upper limb for a stroke patient using the single-joint hybrid assistive limb: a case study assessed by accelerometer on the wrist.

[Purpose] Recent studies have reported the effectiveness of robotic rehabilitation of paralyzed upper limbs in stroke patients. For example, the Single-Joint Hybrid Assistive Limb has been shown to improve upper limb impairments. However, limited data are available on the effectiveness of robotic rehabilitation of the upper limb with regards to daily living. In this case study, an accelerometer was adopted to examine whether rehabilitation using the Single-Joint Hybrid Assistive Limb improved upper limb activity during daily living in a stroke patient. [Participant and Methods] The participant was a 69-year-old male diagnosed with stroke and left hemiparesis. The Single-Joint Hybrid Assistive Limb was applied to the participant's elbow on the paralyzed side. The participant wore an accelerometer on each wrist to measure the activities of the upper limbs. Clinical tests of the paralyzed upper limb were also performed. [Results] The activity of the paralytic limb was significantly higher after Single-Joint Hybrid Assistive Limb intervention than before the intervention. On the other hand, none of the results of the clinical tests changed beyond a clinically important difference. [Conclusion] The Single-Joint Hybrid Assistive Limb could be useful for promoting active use of a paralyzed upper limb in daily living. In addition, an accelerometer could be especially useful for evaluating the effects of robotic rehabilitation.

Development of the Japanese version of the general practice assessment questionnaire: measurement of patient experience and testing of data quality.

BACKGROUND: Physicians' interpersonal performance is critical in medical practice, especially primary care practice. The General Practice Assessment Questionnaire (GPAQ) was developed in the United Kingdom to evaluate the quality of primary care from the viewpoint of patients. This questionnaire highlights the evaluation of interpersonal skills and interactions between physicians and patients. Though several other tools also exist to evaluate primary care quality, the GPAQ has several distinctive evaluation items, covering receptionists, access to primary care, and enablement (patients' understanding of self-care and of their own health after consultation). Our purpose was to develop and validate a Japanese version of the GPAQ. METHODS: This cross-sectional study tested the validity and reliability of the Japanese version of the questionnaire. We translated the original GPAQ into Japanese and assessed its reliability and validity among patients aged ≥20 years at five rural primary care centres located in Shimane and Okayama prefectures, Japan. We also examined its internal reliability using Cronbach's alpha coefficient and construct validity-including item-scale correlations, item-other scale correlations, and inter-scale correlations. Moreover, we examined correlations between each score and overall satisfaction using Spearman's correlation coefficient for criterion-related validity. RESULTS: The translated version of the GPAQ was administered, and we received 252 responses (mean age: 68 ± 12.3 years, male: 42.9%); all data were analysed. The translated questionnaire showed good reliability and validity, with Cronbach's alphas ranging from 0.79-0.92 for all scales, and satisfactory item-scale, item-other scale, and inter-scale correlations. Correlations with overall satisfaction were strong (Spearman's correlation coefficients: 0.31-0.38) for all scales except 'continuity of care'. CONCLUSIONS: The Japanese version of the GPAQ was acceptable, reliable, and valid. This could be a useful instrument to evaluate key areas of primary care performance in Japan, particularly physicians' communication skills. Further work is required to evaluate its utility in urban areas.

Clinical Effect of C2 Peripheral Nerve Field Stimulation Using Electroacupuncture for Primary Headache.

OBJECTIVE: We applied C2 peripheral nerve field stimulation using electroacupuncture (EA-C2-PNfS) for primary headache, and investigated its clinical effectiveness. MATERIALS AND METHODS: Fifty-four primary headache patients (10 men, 44 women) with a mean age of 48.6 ± 15.0 years underwent EA-C2-PNfS for three months. We used questionnaires to assess outcomes; pain intensity (11-point numerical rating scale [NRS]), quality of daily life (Headache Impact Test [HIT-6]), depression (Self-Rating Depression Scale [SDS]). Monthly headache days and acute headache medication days were obtained from diaries. RESULTS: The headache intensity significantly declined after the EA-C2-PNfS with reduction of NRS pain scale; 7.4 ± 1.9 at baseline, 4.9 ± 2.9 at three month (p < 0.001). Both HIT-6 and SDS showed significant improvement (p < 0.001). Some patients showed moderate depression in SDS before treatment, that was alleviated in patients with tension-type headache after the EA-C2-PNfS. Monthly headache days significantly decreased from 18.0 ± 9.0 at one month to 14.0 ± 10.2 at three months (p < 0.001), accompanied with reduction of the monthly acute headache medication days from 8.0 ± 6.7 to 6.4 ± 6.5 (p = 0.003). CONCLUSIONS: EA-C2-PNfS was successfully used for reducing severity and disability in primary headache patients. We conclude that EA-C2-PNfS is a favorable option for medically intractable primary headache as less-invasive neuromodulation.

Mitotic index and multipolar mitosis in routine histologic sections as prognostic markers of pancreatic cancers: A clinicopathological study.

OBJECTIVES: Pancreatic cancer is characterized by genomic complexity and chromosomal instability, and atypical mitotic figures are morphological features of this phenotype. In the present study, we determined the frequency and the clinicopathological and prognostic significance of mitotic figures in pancreatic cancers. METHODS: We surveyed the mitotic figures of the normal ductal epithelium, acinar cells, pancreatic intraepithelial neoplasias, and pancreatic cancers on hematoxylin-and-eosin-stained tissue specimens (n = 121). RESULTS: Pancreatic cancer cells showed significantly higher mitotic indices as compared with the ductal cells, acinar cells, and pancreatic intraepithelial neoplasias. Both normal and atypical mitosis were significantly elevated only in pancreatic cancers. In pancreatic cancers, approximately 30% of total mitosis was atypical including multipolar, lag-type, ring and asymmetrical mitosis, and anaphase bridges. The Kaplan-Meier curves in pancreatic cancers showed significant correlations between total mitosis and disease free survival. Furthermore, the cases with multipolar mitosis showed poorer prognosis than those without. Lymph node metastasis and multipolar mitosis were independent prognostic factors for overall survival of patients with pancreatic cancer. In addition, lymph node metastasis and total mitosis were independent factors for disease free survival. CONCLUSION: These findings suggest that routinely obtained pathological specimens, even small biopsy or cytological specimens, can provide valuable information concerning the prognosis of pancreatic cancers.

Low-volume, high-intensity, aerobic interval exercise for sedentary adults: VO2max, cardiac mass, and heart rate recovery.

PURPOSE: The aim of this study was to compare the effects of low-volume, high-intensity aerobic interval training (HAIT) on maximal oxygen consumption (VO2max), left ventricular (LV) mass, and heart rate recovery (HRR) with high-volume, moderate-intensity continuous aerobic training (CAT) in sedentary adults. METHODS: Twenty-four healthy but sedentary male adults (aged 29.2 ± 7.2 years) participated in an 8-week, 3-day a week, supervised exercise intervention. They were randomly assigned to either HAIT (18 min, 180 kcal per exercise session) or CAT (45 min, 360 kcal). VO2max, LV mass (3T-MRI), and HRR at 1 min (HRR-1) and 2 min (HRR-2) after maximal exercise were measured pre- and post-intervention. RESULTS: Changes in VO2max during the 8-week intervention were significant (P < 0.01) in both groups (HAIT, 8.7 ± 3.2 ml kg(-1) min(-1), 22.4 ± 8.9%; CAT, 5.5 ± 2.8 ml kg(-1) min(-1), 14.7 ± 9.5%), while the VO2max improvement in HAIT was greater (P = 0.02) than in CAT. LV mass in HAIT increased (5.1 ± 8.4 g, 5.7 ± 9.1%, P = 0.05), but not in CAT (0.9 ± 7.8 g, 1.1 ± 8.4%, P = 0.71). While changes in HRR-1 were not significant in either group, change in HRR-2 for HAIT (9.5 ± 6.4 bpm, 19.0 ± 16.0%, P < 0.01) was greater (P = 0.03) than for CAT (1.6 ± 10.9 bpm, 3.9 ± 16.2%, P = 0.42). CONCLUSIONS: This study suggests that HAIT has potential as a time-efficient training mode to improve cardiorespiratory capacity and autonomic nervous system function in sedentary adults.

[Radical resection of a locally advanced pancreatic tail adenosquamous carcinoma treated with S-1 and gemcitabine as neoadjuvant chemotherapy - a case report].

We report a case of locally advanced pancreatic tail adenosquamous carcinoma that was treated by performing R0 resection after neoadjuvant chemotherapy with S-1 and gemcitabine. A 75-year-old man visited our hospital because of left lateral abdominal pain. On the basis of computed tomography and endoscopic biopsy findings, an 80-mm locally advanced pancreatic tail carcinoma with direct invasion to the gastric upper body, splenic flexure of the colon, and left kidney was diagnosed. Combined chemotherapy with S-1 and gemcitabine was initiated for reduction in the tumor size. After 11 courses of treatment, computed tomography revealed a partial response in tumor size reduction. Grade 3 neutropenia was observed as an adverse event. Distal pancreatectomy, proximal gastrectomy, partial resection of the descending colon, resection of the left kidney and left adrenal gland, and D2 lymph node dissection were performed. The pathological diagnosis was adenosquamous carcinoma in the pancreatic tail, and an R0 resection was achieved. However, a month after surgery, multiple distant liver metastases were observed. Neoadjuvant chemotherapy with S-1 and gemcitabine may reduce the tumor size in locally advanced pancreatic tail adenosquamous carcinoma and increase the R0 resection rate. However, treatment for distant metastasis is warranted in cases of pancreatic adenosquamous carcinoma.

Improvement of Functional Mobility Using a Hip-Wearable Exoskeleton Robot in Guillain-Barré Syndrome With Residual Gait Disturbance: A Case Report.

Patients with Guillain-Barré syndrome (GBS) occasionally have residual gait disturbance one year after disease onset. We hypothesized that providing hip joint movement assistance can improve gait in patients with GBS and residual gait disturbance. A 78-year-old man with GBS showed improvement in gait following conventional rehabilitation and gait training using GAIT TRAINER HWA-01 (HWA-01; Honda Motor Co., Ltd., Tokyo, Japan), which is a hip-wearable exoskeleton robot. Initially, he presented with gastrointestinal symptoms, subsequently flaccid quadriplegia, and respiratory muscle paralysis. He was diagnosed with acute motor axonal neuropathy and was transferred to our hospital on day 185 after the disease onset. Seven months after rehabilitation, his walking ability plateaued. On day 382, a single-case study with ABABA design intervention, with conventional gait training in phase A and gait training using HWA-01 in phase B, was conducted. The primary outcomes included a comfortable walking speed, stride length, and cadence. Comfortable walking speed, stride length, and cadence statistically improved after gait training using HWA-01. Furthermore, improvement in exercise capacity and activities of daily living exceeded the minimal clinically important difference for the intervention. The use of the HWA-01 gait trainer potentially improves gait in patients with GBS who have residual gait disturbance.

Choledochal Cyst Diagnosed during Pregnancy and Treated by Postpartum Laparoscopic Choledochal Cyst Excision: Case Report.

We report a rare case of choledochal cyst with acute cholangitis that was diagnosed at 37 weeks' gestation and treated by laparoscopic choledochal resection and biliary reconstruction after delivery. A 31-year-old Japanese primigravida at 37 weeks' gestation presented with right upper quadrant pain. The patient was diagnosed as having acute cholangitis due to a type-Ia choledochal cyst, according to the Todani classification, with pancreaticobiliary maljunction. Acute cholangitis improved with conservative treatment, the fetus was delivered by Cesarean section at 38 weeks' gestation, and the patient was treated by laparoscopic choledochal cyst excision and biliary reconstruction at 47 days postpartum. Total operation time was 579 minutes and intraoperative body fluid loss was 100 mL. The patient is now healthy with normal liver function 7 years after the operation. To ensure good outcomes for the mother and fetus, treatment decisions for choledochal cyst diagnosed during pregnancy must be carefully considered.

Safety and Feasibility of Laparoscopic Liver Resection with the Clamp-Crush Method Using the BiSect.

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.

Stenting of Inferior Right Hepatic Vein in a Patient with Budd-Chiari Syndrome: A Case Report.

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.

Clinical features of extrahepatic portal vein obstruction: Myeloproliferative neoplasms eliminate hypersplenic hematologic changes in extrahepatic portal vein obstruction.

Extrahepatic portal vein obstruction (EHPVO) is a rare disease. Most EHPVO patients are usually referred to a gastroenterologist for intestinal bleeding and hypersplenic thrombocytopenia; however, hypercoagulative diseases may be occult in these patients and require anticoagulation. The purpose of this study was to elucidate the clinical characteristics of EHPVO. We conducted a retrospective analysis of the hospital database, evaluating the medical records of 15 patients (7 males, 8 females, mean age of onset 42.0 years, range 5-74 years). Thirteen of 15 EHPVO patients (86.7%) had intestinal varices. These included 10 esophageal (66.7%), 12 gastric (80.0%), and 6 ectopic varices (40.0%). Nine (60.0%) of 15 had a history of intestinal bleeding. Regarding comorbidities, 5 of 15 (33.3%) suffered from vascular diseases, including acute myocardial infarction, cerebral infarction, pulmonary embolism, Budd-Chiari syndrome, and mesenteric vein thrombosis. The former 3 vascular commodities manifested at less than 32 years of age. Four patients (26.7%) with JAK2V617F mutation were diagnosed as myeloproliferative neoplasm (MPN). 72.3% of EHPVO patients without MPN experienced thrombocytopenic state. No EHPVO patients with MPN experienced thrombo-leukocytopenia. The elevation of white blood cell and platelet counts, and decrease of protein S were seen in EHPVO with MPN, compared with EHPVO without MPN. EHPVO is frequently associated with underlying hypercoagulative factors, causing a dilemma between thrombotic complications and portal hypertensive bleeding. Most EHPVO patients experience an evident thrombocytopenic state due to severe hypersplenism; however, hypersplenic hematologic changes are eliminated in EHPVO with MPN. MPN should be suspected in EHPVO patients negative for thrombo-leukocytopenia.

Distribution of Splenic Arterial Flow and Segmental Spleen Volume for Partial Splenic Arterial Embolization.

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.

Clinicopathological Characteristics of Everolimus-Associated Interstitial Lung Disease: A Single-Center Consecutive Analysis.

BACKGROUND: Everolimus, a mammalian target of rapamycin inhibitor used as an antineoplastic drug, is associated with a remarkably high incidence of interstitial lung disease (ILD). The clinical and pathological characteristics of ILD caused by everolimus have not been thoroughly investigated; therefore, we aimed to elucidate the features of everolimus-associated ILD. METHODS: We retrospectively reviewed the medical records of patients who received everolimus for cancer treatment at our hospital. Patient backgrounds were compared between the ILD and non-ILD groups. Chest computed tomography (CT), changes in biomarkers, and lung histopathological features were analyzed for ILD cases. RESULTS: Sixty-six patients were reviewed, and ILD developed in 19. There were no differences in patient demographics between the ILD and non-ILD groups. The severity of ILD was grade 1 (G1) in 9 and grade 2 (G2) in 10 cases. Chest CT showed organizing pneumonia (OP) or a hypersensitive pneumonia pattern. The levels of lactate dehydrogenase, C-reactive protein, Krebs von den lungen-6, and surfactant protein-D (SP-D) at the onset of ILD were significantly higher than those at baseline. Analysis of G1 and G2 ILD subgroups showed a higher SP-D levels in the G2 subgroup. Five patients underwent lung biopsies; all specimens demonstrated alveolitis with lymphocytic infiltration and granulomatous lesions, and some had OP findings. CONCLUSIONS: Everolimus-associated ILD is mild and has a favorable prognosis. Patients with symptomatic ILD were more likely to have higher SP-D levels than those with asymptomatic ILD. Granulomatous lesions are an important pathological feature of everolimus-associated ILD.

Splenectomy unveils thrombocytosis in underlying myeloproliferative neoplasms with extrahepatic portal vein obstruction.

Extrahepatic portal vein obstruction (EHPVO) is a rare disease with myeloproliferative neoplasm (MPN) as the most common cause. We report that hypersplenic hematologic changes in EHPVO might be eliminated by MPN. Through experience with splenectomy for variceal control with EHPVO, we suspected that spleen might mask MPN-induced thrombocytosis, and that MPN might have a significant influence on excessive thrombocytosis after splenectomy. To clarify the influence of MPN and spleen on platelet trends, we conducted a retrospective hospital database analysis, evaluating 8 EHPVO patients with splenectomy (2 males, 6 females; from 17 years to 64 years, mean 38.3 years). Three (37.5%) of 8 were diagnosed as MPN by JAK2V617F mutation. The perioperative serum platelet counts in EHPVO without MPN were 10.5, 35.4, and 36.6 (x104/µL) preoperatively, after 1 week and 3 weeks, respectively. The platelet counts in EHPVO with MPN were 34.2, 86.4, and 137.0 (x104/µL), respectively. Splenectomy and MPN showed positive interaction on platelet increasing with statistical significance. We also examined the spleen volume index (SpVI: splenic volume (cm3) / body surface area (m2) and postoperative platelet elevations ratio (PER: 3-week postoperative platelet counts / preoperative platelet counts). However, both SpVI and PER showed no significant difference with or without MPN. Histological examination revealed splenic congestion in all 8 EHPVO cases, and splenic extramedullary hematopoiesis in 2 of 3 MPN. In EHPVO with MPN, hypersplenism causes feigned normalization of platelet count by masking MPN-induced thrombocytosis; however, splenectomy unveils postoperative thrombocytosis. Spleen in EHPVO with MPN also participates in extramedullary hematopoiesis.