Journal of Nippon Medical School最新文献

Background: Postoperative bleeding is a potentially life-threatening complication following thyroidectomy, but the risk factors and timing remain insufficiently understood. The bleeding rate for endoscopic surgery, specifically video-assisted neck surgery (VANS), also remains unclear in Japan.

Methods: We conducted a retrospective case-control study of postoperative bleeding requiring readmission to the operating room.

Results: The overall postoperative bleeding rate was 1.85%. Multivariate analysis revealed that postoperative bleeding was independently associated with antithrombotic therapy (odds ratio 2.95; 95% confidence interval 1.15-7.59) and dialysis (odds ratio 6.53; 95% confidence interval 1.75-24.2). Among patients with postoperative bleeding, the complication developed within 6 h in 56.1% and within 24 h in 93.0%. The postoperative bleeding rate in endoscopic surgery was 1.6%. The most common site of bleeding was around the thyroid in conventional surgery and around the flap in endoscopic surgery.

Conclusions: Post-thyroidectomy bleeding is associated with antithrombotic therapy or dialysis. While the bleeding rate in endoscopic surgery is similar to that in conventional surgery, the bleeding site differs.

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: Although immunohistochemical techniques and proteomic analysis are widely used for typing diagnosis of amyloidosis, the diagnostic utility of immunohistochemical evaluation is not well understood.

Methods: We used immunohistochemical techniques to characterize staining patterns of in-house rabbit polyclonal anti-κ, anti-λ, anti-transthyretin antibodies, and commercial anti-amyloid A and anti-β₂-microglobulin antibodies in 40 autopsy cases.

Results: In thirty cases (75%), the subtype was determined by using the criterion that amyloid is strongly and diffusely positive for one antibody while negative for other antibodies. We then performed proteomic analysis of all 40 cases. In 39 cases, we identified only one amyloid protein and confirmed the immunohistochemically determined subtypes of the abovementioned 30 cases. In seven other cases, we could retrospectively determine subtypes with immunohistochemistry by using information from proteomic analysis, which increased the immunohistochemistry diagnosis rate to 92.5% (37/40). In one case, we identified double subtypes, both immunohistochemically and with proteomic analysis. In the remaining three cases, proteomic analysis was essential for typing diagnosis.

Conclusions: The present findings suggest that combined immunohistochemistry and proteomic analysis is more useful than immunohistochemistry alone. Our findings highlight the importance of carefully interpreting immunohistochemistry for anti-TTR and light chain and offer insights that can guide amyloid typing through immunohistochemistry.

Renal abscesses require prompt diagnosis and appropriate intervention, as they can be life-threatening. However, diagnosis based solely on clinical findings is often challenging. We present the case of a 69-year-old woman with left renal masses on follow-up computed tomography (CT) after surgery for pT2aN0M0 lung carcinosarcoma. The masses were localized only in the left kidney without suspected metastatic lesions at other sites. The patient was referred to our department for further evaluation and treatment under a diagnosis of suspected metastatic lung carcinosarcoma of the left kidney. On enhanced CT, the left renal masses, the largest of which had a diameter of 40×36 mm had thick irregular walls gradually enhanced by the contrast media and an internal low-attenuation area. The masses showed heterogeneous signal intensity with a pseudocapsule on T2-weighted magnetic resonance imaging. Clinical symptoms such as fever or costovertebral angle tenderness were absent, and blood and urine tests were not sufficiently inflammatory to suggest a renal abscess. Histopathological findings on CT-guided renal biopsy revealed only inflammatory tissue and no tumor cells. However, because lung carcinosarcoma metastatic nodules could not be ruled out, laparoscopic left nephrectomy was performed for a definitive diagnosis and curative intent. The pathological diagnosis was renal abscess without malignant lesions. Here, we present a case of renal abscess mimicking metastatic lesions in a patient with lung carcinosarcoma. Accurately differentiating renal abscesses from metastatic renal tumors before treatment is often difficult. Renal abscess diagnosis should be considered through a comprehensive evaluation of the clinical findings of individual cases.

Estrogen receptor α (ERα) regulates several physiological functions. In pathophysiological conditions, ERα is involved in the development and progression of estrogen-sensitive tumors. The ERα gene contains multiple 5'-untranslated exons and eight conventional coding exons and presents multiple isoforms generated by alternative promoter usage and alternative splicing. This gene also possesses non-conventional exons in the 3'- and intronic regions, and alternative use of cryptic exons contributes to further diversity of ERα mRNAs and proteins. Recently, the genomic organization of ERα genes and the splicing profiles of their transcripts were comparatively analyzed in humans, mice, and rats, and multiple ERα isoforms with distinct structures and functions were identified. These transcripts contain cryptic sequences that encode insertion-containing or truncated ERα proteins. In particular, alternative cryptic exons with in-frame stop codons yield transcripts encoding C-terminally-truncated ERα proteins. The C-terminally-truncated ERα isoforms lack part or all of the ligand-binding domain but possess an isoform-specific sequence. Some of these isoforms exhibit constitutive transactivation and resistance to estrogen receptor antagonists. Although numerous studies have reported conflicting results regarding their functions, the critical determinant for their gain-of-function has been identified structurally. Here we review recent progress in ERα variant research concerning the genomic organization of ERα genes, splicing profiles of ERα transcripts, and transactivation properties of ERα isoforms.

Background: No compatibility tests are available for remdesivir other than 0.9% sodium chloride. In this study, we aimed to evaluate the physical compatibility of remdesivir with drugs used in palliative care and COVID-19 treatment.

Methods: Remdesivir was tested for compatibility with 10 different drugs (fentanyl, morphine, hydromorphone, oxycodone, heparin, furosemide, octreotide, acetated Ringer's injection, 2-in-1 peripheral parenteral nutrition, and 2-in-1 total parenteral nutrition). Remdesivir was formulated to a final concentration of 1 mg/mL, and the other drugs were prepared at clinical concentrations. Three test solutions were used for compatibility testing, with remdesivir and the target drugs compounded in a 1:1 ratio. Appearance measurements, including Tyndall effect, turbidity, and pH, were performed immediately after mixing and at 1 h and 4 h after mixing. Changes in appearance, including the Tyndall effect, turbidity (turbidity change of ≥ 0.5 nephelometric turbidity unit [NTU] based on control solution for each test drug), and pH (a change of ≥ 10% based on the pH immediately after mixing) were used to determine physical compatibility.

Results: All the drugs tested were compatible with remdesivir. The combination of remdesivir and furosemide produced the highest turbidity (0.23 ± 0.03 NTU) 1 h after mixing. The lowest and highest pH values were observed at 4 h after mixing for the combinations of remdesivir and morphine (3.23 ± 0.02) and remdesivir and furosemide (8.81 ± 0.06).

Conclusions: The drugs tested in this study show Y-site physical compatibility with remdesivir.

Although necessary for hemodialysis (HD), arteriovenous grafts (AVG) frequently cause complications. Stenosis resulting in venous hypertension is a concern for physicians. Herein, we describe how venous hypertension was improved by using a Viabahn stent graft in an elderly HD patient. An 86-year-old woman started maintenance HD with a left-arm AVG. Two years later, she was referred to our hospital for treatment of juxta-graft-venous junction (GVJ) stenosis. Because of recurrence of stenosis at the juxta-GVJ, she underwent four percutaneous transluminal angioplasty (PTA) procedures during a period of 9 months. One month after the most recent PTA, the patient had redness, swelling, and pain in her left forearm. Venous hypertension was diagnosed on the basis of angiography findings showing regurgitation to the periphery of the basilic vein and juxta-GVJ stenosis. The stenosed juxta-GVJ was adequately expanded with a 7-mm balloon, and a 7-mm stent graft was inserted into the stenosis site. After successful treatment, there was no regurgitation to the periphery of the basilic vein and no symptoms. This complication should be considered when an AVG is created, because cutting off peripheral veins might prevent venous hypertension. Clinicians should perform regular postoperative monitoring.

Salivary gland carcinoma is a rare cancer and has more than 20 histopathological types. Although chemotherapy has been the mainstay of treatment for unresectable carcinomas such as multiple recurrence and distant metastasis, no standard regimen is available. In this article, we report a case of poorly differentiated salivary duct carcinoma of the submandibular gland with distant metastases that was successfully treated with pembrolizumab monotherapy. A 66-year-old man became aware of a left submandibular mass 2 months before his first visit to our department. A needle biopsy at a previous hospital revealed carcinoma, not otherwise specified. The combined positive score on a programmed death ligand-1 immunohistochemistry test was 1-10%. The patient was referred to our department for further treatment. Computed tomography revealed left level II and IV neck lymphadenopathy, bilateral lung shadowing, and osteolytic changes in the 12th thoracic vertebra. Needle biopsy showed poorly differentiated carcinoma, positive human epidermal growth factor receptor 2, and positive androgen receptor, which suggested salivary duct carcinoma. These findings indicated a diagnosis of submandibular carcinoma T4aN2bM1 stage IVC. Pembrolizumab monotherapy was started, and tumor shrinkage was observed after three courses of treatment. At 1 year, complete response was achieved without adverse events, and treatment is ongoing. Despite a lack of evidence for the efficacy of immune checkpoint inhibitors in salivary gland carcinoma, the present case suggests that some patients might respond to this treatment. Hence, clinical trials are warranted.

Intracranial tumors are rare in persons with Down syndrome. Although germ cell tumors and gliomas have been reported in Down syndrome, primary central nervous system lymphoma (PCNSL) has not. We report a case of PCNSL in a 48-year-old man with Down syndrome and no history of malignant tumors. He visited our hospital for evaluation of left hemiparesis and gait disturbance. A thorough examination revealed brain tumors, and analysis of a biopsy specimen of the tumor confirmed a diagnosis of PCNSL. The final pathological diagnosis was diffuse large B-cell lymphoma of the central nervous system. Chemotherapy with rituximab, methotrexate, procarbazine, and vincristine was administered, and whole-brain irradiation was planned in conjunction with chemotherapy. It is unclear whether chromosomal abnormalities related to Down syndrome were involved in the development of PCNSL. Further molecular biological analysis may clarify the mechanism of combined Down syndrome and PCNSL.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is essential for diagnosing and treating biliopancreatic disease. Because ERCP-related perforation can result in death, therapeutic decisions are important. The aim of this study was to determine the cause of ERCP-related perforation and suggest appropriate management.

Methods: Between January 1999 and August 2022, 7,896 ERCPs were performed in our hospital. We experienced 15 cases (0.18%) of ERCP-related perforation and conducted a retrospective review.

Results: Of the 15 patients, 6 were female and 9 were male, and the mean age was 77.1 years. According to Stapfer's classification, the 15 cases of ERCP-related perforation comprised 3 type I (duodenum), 3 type II (periampullary), 9 type III (distal bile duct or pancreatic duct), and no type IV cases. Fourteen of 15 (92.6%) were diagnosed during ERCP. The main cause of perforation was scope-induced damage, endoscopic sphincterotomy, and instrumentation penetration in type I, II, and III cases, respectively. Four patients with severe abdominal pain and extraluminal fluid collection underwent emergency surgery for repair and drainage. One type III patient with distal bile duct cancer underwent pancreaticoduodenectomy on day 6. Three type III patients with only retroperitoneal gas on computed tomography (CT) performed immediately after ERCP had no symptoms and needed no additional treatment. Seven of the 15 patents were treated by endoscopic nasobiliary drainage (n=5) or CT-guided drainage (n=2). There were no deaths, and all patients were discharged after treatment.

Conclusions: Early diagnosis and appropriate treatment are important in managing ERCP-related perforation.