Quality indicators for integrating oncology and home palliative care in Japan: modified Delphi study.

CONTEXT: Home palliative care service increases the chance of dying at home, particularly for patients with advanced cancer, but late referrals to home palliative care services still exist. Indicators for evaluating programs that can facilitate the integration of oncology and home palliative care have not been defined. OBJECTIVES: This study developed quality indicators for the integration of oncology and home palliative care in Japan. METHODS: We conducted a systematic literature review (Databases included CENTRAL, MEDLINE, EMBASE, and Emcare) and a modified Delphi study to develop the quality indicators. Panelists rated a potential list of indicators using a 9-point scale over three rounds according to two criteria: appropriateness and feasibility. The criterion for the adoption of candidate indicators was set at a total mean score of 7 or more. Final quality indicators with no disagreement were included. RESULTS: Of the 973 publications in our initial search, 12 studies were included. The preliminary list of quality indicators by systematic literature review comprised 50 items. In total, 37 panelists participated in the modified Delphi study. Ultimately, 18 indicators were identified from the following domains: structure in cancer hospitals, structure in home palliative care services, the process of home palliative care service delivery, less aggressive end-of-life care, patient's psychological comfort, caregiver's psychological comfort, and patient's satisfaction with home palliative care service. CONCLUSION: Comprehensive quality indicators for the integration of oncology and home palliative care were identified. These indicators may facilitate interdisciplinary collaboration between professional healthcare providers in both cancer hospitals and home palliative care services.

Safety of cannabidiol products as a social issue: A case series.

Background: Cannabidiol (CBD) products have increased in popularity in Japan in recent years, particularly among young people. Some CBD products contain tetrahydrocannabinol (THC), the main ingredient of cannabis, and its analogs, which are illegal in Japan and have become a social issue. This report discusses the safety of CBD products. Case Presentation: Five patients with symptoms of CBD ingestion, including nausea, presented to our hospital. Three of the products these patients ingested contained THC. Metabolites of THC were detected in the blood and urine of all three patients, although there were some discrepancies in the urine drug screening test (DS10®). These examination results differed even when the same product was consumed. Conclusion: CBD products are unsafe and may unintentionally contain THC. It is also important to understand that CBD can turn into THC, and the effective time needed to conduct urine drug screening.

Surgical resection of double advanced pancreatic neuroendocrine tumors with multiple renal cell carcinoma associated with von Hippel-Lindau disease.

Von Hippel-Lindau (VHL) disease, an autosomal dominant genetic disorder caused by a germline mutation, is associated with non-functional and slow-growing pancreatic neuroendocrine tumor (PNET) and kidney cancer. We describe the case of a 46 year-old man with a 35 mm mass in the pancreatic head causing stricture of the bile duct and main pancreatic duct, a 55 mm mass in the pancreatic tail causing obstruction of the splenic vein (SV), and multiple masses of > 36 mm on both kidneys. We performed a two-stage resection. First, a total pancreatectomy with superior mesenteric vein (SMV) resection and reconstruction and retroperitoneoscopic right partial nephrectomy (NP) for five lesions was performed, followed by retroperitoneoscopic left partial NP of the five lesions 6 months later. Postoperative histopathological examination revealed NET G2 in the pancreatic head with SMV invasion and somatostatin receptor type 2A (SSTR2A) positivity, NET G2 in the pancreatic tail showed SV invasion and negative SSTR2A, and multiple clear cell renal cell carcinomas (RCC) were also noted. Multiple liver recurrences occurred 22 months after primary surgery. The patient remains alive 41 months after primary surgery. Kidney cancer generally determines VHL prognosis; however, we experienced dual-advanced PNETs with a more defined prognosis than multiple RCC associated with VHL.

Sphingosine-1-phosphate receptor 1/5 selective agonist alleviates ocular vascular pathologies.

Ocular abnormal angiogenesis and edema are featured in several ocular diseases. S1P signaling via S1P1 likely is part of the negative feedback mechanism necessary to maintain vascular health. In this study, we conducted pharmacological experiments to determine whether ASP4058, a sphingosine 1-phosphate receptor 1/5 (S1P1/5) agonist, is useful in abnormal vascular pathology in the eye. First, human retinal microvascular endothelial cells (HRMECs) were examined using vascular endothelial growth factor (VEGF)-induced cell proliferation and hyperpermeability. ASP4058 showed high affinity and inhibited VEGF-induced proliferation and hyperpermeability of HRMECs. Furthermore, S1P1 expression and localization changes were examined in the murine laser-induced choroidal neovascularization (CNV) model, a mouse model of exudative age-related macular degeneration, and the efficacy of ASP4058 was verified. In the CNV model mice, S1P1 tended to decrease in expression immediately after laser irradiation and colocalized with endothelial cells and Müller glial cells. Oral administration of ASP4058 also suppressed vascular hyperpermeability and CNV, and the effect was comparable to that of the intravitreal administration of aflibercept, an anti-VEGF drug. Next, efficacy was also examined in a retinal vein occlusion (RVO) model in which retinal vascular permeability was increased. ASP4058 dose-dependently suppressed the intraretinal edema. In addition, it suppressed the expansion of the perfusion area observed in the RVO model. ASP4058 also suppressed the production of VEGF in the eye. Collectively, ASP4058 can be a potential therapeutic agent that normalizes abnormal vascular pathology, such as age-related macular degeneration and RVO, through its direct action on endothelial cells.

A rare case of synchronous double primary hepatocellular carcinoma and intrahepatic cholangiocarcinoma: A case report.

INTRODUCTION: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are two primary liver cancers. Synchronous occurrence of both types is rare. Here, we present a case of synchronous, double primary liver cancer in a patient who underwent successful surgical resection. PRESENTATION OF A CASE: A 77-year-old woman presented with two suspected liver tumors. Dynamic computed tomography (CT) and ethoxybenzyl-magnetic resonance imaging revealed two lesions, one in hepatic segments S8/4 and another in S5. Positron emission tomography (PET)/CT scans revealed an elevated maximum standardized uptake value (SUVmax) of 5.7 in the S8/4 tumor, and no elevation in the S5 tumor. The S8/4 tumor was diagnosed as either ICC or mixed-type liver cancer, while the S5 tumor was confirmed HCC. Surgical resection confirmed the diagnosis, while pathology identified the S8/4 tumor as ICC and the S5 tumor as HCC. Two months post-operation, the patient received adjuvant chemotherapy and completed eight courses with no recurrence one year later. DISCUSSION: Synchronous double-primary HCC and ICC is uncommon and exhibits diagnostic and therapeutic challenges. Notably, PET-CT scans can differentiate between the two cancers, with HCC typically showing similar uptake to the background liver tissue, whereas ICC is often found with higher accumulation. This highlights the potential utility of PET/CT in preoperative diagnoses and the potential benefit of postoperative adjuvant chemotherapy in patients with double primary HCC and ICC. CONCLUSION: We report a successful case of synchronous double primary liver cancer, emphasizing the potential role of PET/CT in preoperative differentiation, and the efficacy of postoperative adjuvant chemotherapy.

A Case of Mesangial Proliferative Nephritis Caused by Slow Cryoglobulin.

The patient was a woman in her 60s. She was found to have proteinuria on a health checkup. She did not have any particular subjective symptoms, and no definitive diagnosis was made, despite serological findings indicative of immune abnormalities. A renal biopsy was performed. Light microscopy of renal tissue section revealed mesangial proliferative nephritis. Electron microscopic findings included electron-dense deposits and fibrillar/tubular structures with a diameter of 20-30 nm. These findings suggested the presence of cryoglobulin (CG), but CG was not detected in qualitative or quantitative hematologic tests. Thus, the serum samples were stored at 37°C for a long period of time and then cooled to 4°C. When the obtained precipitates were examined, CG was successfully detected. CG that precipitates only after a long period of time is referred to as slow cryoglobulin (sCG), and sCG is extremely rare. The present case is the first documented case, to our knowledge, of renal disorders caused by sCG. It should be noted that there are some cases in which it takes much time for CG to precipitate. Thus, when CG cannot be detected, it is necessary to spend much time to determine whether CG precipitates.

Acute acrylamide poisoning with severe symptoms in a short time: a case report.

BACKGROUND: Acrylamide poisoning is often reported as chronic poisoning presenting with peripheral neuropathy or carcinogenic action due to long-term exposure to low concentrations. However, there have been few reports of acute poisoning due to oral ingestion of acrylamide, where the symptoms appear a few hours after ingestion. Here, we report a case of acute acrylamide poisoning where a high concentration was ingested in a short time, resulting in a fatal outcome due to the rapid course of events. CASE PRESENTATION: The patient was an adolescent female who ingested 150 ml (148 g) of acrylamide with suicidal intent. A disorder of consciousness was observed when the emergency medical team arrived 36 min later. An hour later, tracheal intubation and intravenous access were performed at a hospital, and 2 h after that, she was transported to our hospital. After she arrived at the hospital, circulatory dynamics could not be maintained despite vasopressor and colloid osmotic infusion, and hemodialysis could not be introduced. Subsequently, cardiopulmonary arrest occurred, and the patient passed away 7 h after ingestion. In the present case, severe symptoms appeared shortly after acrylamide ingestion, unlike other reported cases. In previous report summarizing animal studies, there was a relationship among the symptoms of acute poisoning, the dose, and onset time. The data from this case were compared to those from previous reports, and we were able to predict the early appearance of severe symptoms based on this comparison. CONCLUSION: The severity of acute acrylamide poisoning by oral ingestion was primarily dependent on the amount and rate of ingestion.

Successful Preoperative QUAD SHOT for Bulky Parotid Carcinoma: Potential Preoperative Ultra-Hypofractionated Radiotherapy for Conversion Surgery.

QUAD SHOT is an ultra-hypofractionated radiotherapy (RT) technique that prescribes 14.0-14.8 Gy over 2 days. Although this technique has already gained some status as an effective palliative treatment for inoperable head and neck cancer (HNC), its application in other situations has not been given much consideration. Herein, we report a case of a 62-year-old woman who received preoperative QUAD SHOT therapy for poorly differentiated parotid carcinoma. In this case, after two courses of QUAD SHOT plus a standard chemotherapy regimen with pembrolizumab, the patient's inoperable, bulky tumor shrank dramatically and became operable. Best of all, while adequate therapeutic effects were achieved, the patient's time commitment and physical exertion were limited. RT during this period consisted of only eight fractions over 4 days. According to previous reports, the response rate for QUAD SHOT is sufficiently high, and the rate of serious adverse events is quite low. This case asks the question of whether the indications for QUAD SHOT irradiation can be expanded as one of the preoperative interventions undertaken by HNC surgeons to achieve conversion surgery.

PGE2-EP2/EP4 signaling elicits immunosuppression by driving the mregDC-Treg axis in inflammatory tumor microenvironment.

Active inflammation generally promotes immune activation. However, in the tumor microenvironment (TME), active inflammation occurs in parallel with immunosuppression, and both contribute to tumor growth. Why inflammation does not lead to immune activation in TME remains unclear. In this study, using the immune checkpoint inhibitor-insensitive mouse cancer model and single-cell RNA sequencing, we show that PGE2-EP2/EP4 signaling simultaneously promotes active inflammation by inducing expression of the NF-κB genes in myeloid cells and elicits immunosuppression by driving the mregDC (mature DC enriched in immunoregulatory molecules)-Treg (regulatory T cell) axis for Treg recruitment and activation in the tumor. Importantly, the EP2/EP4 expression level is strongly correlated with the gene signatures of both active inflammation and the mregDC-Treg axis and has significant prognosis value in various human cancers. Thus, PGE2-EP2/EP4 signaling functions as the key regulatory node linking active inflammation and immunosuppression in TME, which can be targeted by EP2 and EP4 antagonists for cancer therapeutics.

Mixed neuroendocrine non-neuroendocrine neoplasm: a case report and review.

Mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) of the pancreas is a rare entity, and obtaining a preoperative diagnosis is difficult. We present a 70-year-old man in whom the possibility of MiNEN was successfully discovered preoperatively by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Immunostaining revealed positive results for the neuroendocrine markers chromogranin A and synaptophysin. We considered the possibility for MiNEN before surgery. He underwent distal pancreatectomy with splenectomy. Immunohistochemical examination of the tumor cells showed a wide range of positivity for trypsin as well as for chromogranin A and synaptophysin. Considering that ≥ 30% tumors ware positive for both acinar and neuroendocrine markers, the patient was diagnosed with MiNEN. MiNEN is a malignant tumor that requires early detection and treatment but is a rare disease for which no method has been established. We found that EUS-FNA and immunostaining are effective diagnostic methods for MiNEN.

Comparison of administration of single- and triple-course steroid pulse therapy combined with tonsillectomy for immunoglobulin A nephropathy.

ABSTRACT: Immunoglobulin A nephropathy (IgAN) is a form of chronic glomerulonephritis that can cause end-stage renal disease. Recently, tonsillectomy combined with corticosteroid pulse (TSP) has been shown to be effective for achieving clinical remission and favorable renal outcome in patients with IgAN. However, the standard regimen of corticosteroid use in TSP has not been established. Herein, we compared the effect of single- or triple-course steroid pulse therapy combined with tonsillectomy in patients with IgAN.This retrospective, observational cohort study included 122 patients with IgAN enrolled from January 2004 to December 2018 at 2 independent institutions. We divided the patients into 2 groups; single-course (TSP1: n = 70) and triple-course (TSP3: n = 52) of corticosteroid pulse therapy (1 course comprised 3 consecutive days' infusion of 0.5 g methylprednisolone) combined with tonsillectomy. The primary outcome for renal survival was defined as the first occurrence of ≧30% decrease in estimated glomerular filtration rate from baseline. Secondary outcomes included the incidence of clinical remission and recurrence of the disease.Regarding clinical parameters and findings at baseline, there were no significant differences between the 2 groups. The 8-years renal survival in the 2 groups was not significantly different according to Kaplan-Meier curves (TSP1; 82.5% vs TSP3; 69.2%, log-rank test P = .39). The cumulative incidence rates of remission of hematuria (94.4% vs 85.4%, P = .56) and clinical remission (85.0% vs 64.8%, P = .07) were comparable in both groups, while those of proteinuria showed higher rates in TSP1 than TSP3 (88.4% vs 65.4%, P = .02). The cumulative incidence of relapse of hematuria (5.6% vs 2.3%, P = .42) and proteinuria (7.1% vs 3.3%, P = .41) showed no significant differences in the 2 groups. Cox regression analyses showed that the number of courses of corticosteroid pulse therapy was not significantly associated with renal outcome (TSP1 vs TSP3; Hazard ratios 0.69, 95% confidence intervals 0.29-1.64, P = .39).The effect of single-course corticosteroid pulse therapy is not statistically, significantly different from triple-course in TSP protocol for improving renal outcome and preventing relapse in patients with IgAN. Single-course corticosteroid pulse therapy may become a treatment option for patients with IgAN.

A lymphoepithelial cyst in the pancreatic accessory spleen: A case report.

We present the first report of a lymphoepithelial cyst. As additional cases will likely be encountered in the future, our study sets the precedent for future research.

Intussusception caused by small intestine metastasis of malignant pleural mesothelioma: a case report.

Malignant pleural mesothelioma (MPM) is an aggressive form of malignant tumor that originates in the pleural mesothelioma and presents as a local disease in the affected hemithorax. Small intestine metastasis is a rare complication. Herein, the case of a patient with jejunal intussusception caused by small intestine metastasis of MPM has been reported. A 72-year-old man with MPM was admitted to our hospital for abdominal pain. Computed tomography revealed small intestine intussusception. An emergency surgery was performed, and the tumor and intussusception were located in the upper jejunum. Histopathological examination of the resected jejunum revealed that the tumor was a small intestinal metastasis of the MPM from the chest wall. This case showed that MPM may metastasize to the small intestine, and metastatic tumors may cause intussusception.

[A Case of Extranodal NK/T-Cell Lymphoma with Perforation of the Small Intestine].

A rare case of extranodal NK/T-cell lymphoma(ENKL)with small intestinal perforation is reported. A 92-year-old man was admitted for a loss of consciousness. Computed tomography(CT)scan revealed the presence of an intraperitoneal abscess that was drained. Two days later, the drained fluid changed to intestinal juice, and intestinal perforation was suspected. The patient underwent surgery which revealed a 1 cm perforation site in the ileum. A high fever continued after surgery, and malignant lymphoma was diagnosed from pathological findings; however, further treatment could not be performed. He died 24 days after the operation. Pathological dissection revealed metastasis of ENKL at the systemic lymph nodes.

Glucocorticoid treatment is associated with ICU-acquired hypernatremia: a nested case-control study.

BACKGROUND: Hypernatremia is a major electrolyte disorder associated with death among critically ill patients. Glucocorticoid therapy may cause hypernatremia in refractory septic shock patients, but the association between glucocorticoid and intensive care unit (ICU)-acquired hypernatremia (IAH) remains unclear. The aim of this study was to clarify whether glucocorticoid administration was associated with IAH. METHODS: This was a nested case-control study using data from an established cohort including 121 IAH cases identified from 1756 patients who were admitted to ICU in a tertiary care facility in Japan. We included patients who were admitted with a normal range of serum sodium concentrations (130-149 mEq/L) from January 1, 2013 to December 31, 2015 and remained in ICU for ≥ 2 days. Hypernatremia was defined as serum sodium concentration ≥ 150 mEq/L. Each case was matched to one control. RESULTS: Multivariable conditional logistic regression revealed high-dose glucocorticoid {odds ratio (OR), 4.15 [95% confidence interval (CI) 1.29-13.4]}, acute kidney injury (AKI) [OR, 2.72 (95% CI 1.31-5.62)], and osmotic diuretics [OR, 3.44 (95% CI 1.41-8.39)] to be significantly associated with IAH. The contents and amounts of fluid infusion were not significantly associated with IAH. There were also significant duration-response effects between duration of glucocorticoid use and IAH; however, pulse glucocorticoid administration was not associated with IAH. CONCLUSION: In this nested case-control study, we demonstrated a significant association between IAH and high-dose glucocorticoid with significant duration-response effects. Serum sodium concentrations should be monitored carefully in critically ill patients administered prolonged high-dose glucocorticoid.

Comparison of bioelectrical impedance analysis in healthy pregnant women and patient on hemodialysis.

Pregnant woman undergoing dialysis face challenges such as miscarriage and stillbirth when carrying a baby to term. A complication of prenatal care is the difficulty in properly managing body fluids. We compare fluid volumes between healthy pregnant women and two pregnant women undergoing dialysis using bioelectrical impedance analysis (BIA). Data of 52 healthy pregnant women at various stages of their pregnancy were analyzed for the study. We included these many cases so as to collect sufficient data to compare them with our two cases of women undergoing dialysis who successfully completed their term deliveries. Fluid volumes were measured every week before and after dialysis using BIA. We also measured the levels of human atrial natriuretic peptide after dialysis. During dialysis, the dry weight (DW) of pregnant patients is altered based on the state of the amniotic fluid and fetus. However, evaluating body fluid and DW using radiography is difficult in pregnant women. BIA offers a mostly harmless alternative for such measurements. Using BIA, we were able to easily measure body fluid volume and change the setting of DW for dialysis. Thus, our successful example can serve as a reference for future cases of pregnant women undergoing dialysis. Nevertheless, given that the state of the fetus and amniotic fluid affect the results of dialysis, it is important that we use not only BIA but also a comprehensive evaluation to determine dialysis settings in pregnant women.

ASP1126, a Novel Sphingosine-1-Phosphate-Selective Agonist With a Favorable Safety Profile, Prolongs Allograft Survival in Rats and Nonhuman Primates in Combination With Tacrolimus With a Broad Safety Margin for Bradycardia.

Sphingosine-1-phosphate (S1P) is a biologically active sphingolipid that acts through the members of a family of 5 G protein-coupled receptors (S1P1 to S1P5). Among these, S1P1 is a major regulator of lymphocyte trafficking. Fingolimod, whose active metabolite, fingolimod phosphate, acts as a nonselective S1P-receptor agonist, exerts its immunomodulatory effect, at least in part, by regulating lymphocyte trafficking via downregulation of S1P1 expression on lymphocytes. Here, we describe the pharmacologic profile of a novel S1P1 agonist, ASP1126. ASP1126 preferentially activated S1P1 compared to S1P3 in rat and human guanosine-5'-(γ-thio)-triphosphate (GTPγS) assays. Oral single administration of ASP1126 decreased the number of peripheral lymphocytes and repeated dosing showed a cumulative effect on lymphopenia in both rats and monkeys. ASP1126 prolonged allograft survival in a rat heterotopic heart transplantation model in combination with a subtherapeutic dose of tacrolimus that was independent of drug-drug interactions. In addition, in nonhuman primate (NHP) renal transplantation, pretreatment with ASP1126 reduced not only the number of naive T cells and central memory T cells but also effector memory T cells in the peripheral blood, all of which could contribute to acute graft rejection and prolonged allograft survival in combination with tacrolimus. Further, we confirmed that ASP1126 has a broad ranging safety margin with respect to its effect on lung weight in rats and bradycardia in NHPs, which were the adverse events found in clinical studies of fingolimod. ASP1126 with improved safety profile has the potential to be an adjunct therapy in combination with tacrolimus in clinical transplantation.

Spontaneous remission of giant cell arteritis: possible association with a preceding acute respiratory infection and seropositivity to Chlamydia pneumoniae antibodies.

Recent epidemiological or immunopathological studies demonstrate the possible association between giant cell arteritis and infectious agents including Chlamydia pneumoniae. A 62-year-old Japanese man with type 1 diabetes mellitus developed biopsy-proven giant cell arteritis after acute upper respiratory infection. Serological examination indicated concurrent re-infection with C. pneumoniae. Clinical manifestations of the vasculitis subsided within a month without any immunosuppressive therapy, and no relapse was observed for the following 12 months. The natural history of this disease is unclear and spontaneous remission is rarely reported. The self-limiting nature of the infection could contribute to this phenomenon.

A Case of Chronic Calcium Oxalate Nephropathy due to Short Bowel Syndrome and Cholecystectomy.

BACKGROUND: Oxalate nephropathy is a rare disease. Especially chronic oxalate nephropathy still has many unknown aspects as compared to acute oxalate nephropathy with relatively well-known causality. CASE PRESENTATION: The patient was a 70-year-old woman who had a history of small bowel resection 25 years before, cholecystectomy 10 years before, and renal stones (calcium oxalate stones) 7 years before. She had been suffering from chronic diarrhea and had been treated by a local physician. The patient was found to have renal dysfunction (creatinine 3.09 mg/dL, eGFR 12.3 mL/min/1.73 m2, hemoglobin 7.8 g/dL) and was referred to our department. The patient was admitted to our hospital for further investigation. Renal ultrasound showed hepatorenal echo contrast in an opposite manner and clear contrast between the renal cortex and medullary pyramid. Renal biopsy was performed, and histological examination showed tubulointerstitial disorder due to deposition of calcium oxalate. Daily urinary excretion of calcium oxalate was significantly increased. The patient was encouraged to drink water and administered vitamin B6, citric acid, K and Na hydrate. Thereafter, her symptoms improved. CONCLUSION: Case reports of chronic oxalate neuropathy are rare in the literature, and its underlying mechanism has not been understood. Our patient had a history of small bowel resection and cholecystectomy. We considered that her short bowel syndrome had influenced the development of calcium oxalate nephropathy.