Long-Term Complete Response to Trastuzumab Deruxtecan in a Case of Unresectable Gastric Cancer.

Introduction: Trastuzumab deruxtecan (T-Dxd) has been approved for the treatment of HER2-positive gastric cancer. However, there are only a limited number of cases of gastric cancer where a long-term complete response (CR) has been maintained. Consequently, we report a case of gastric cancer in which long-term CR was maintained. Case Presentation: A woman in her late 60s underwent a gastrointestinal endoscopy, which revealed a type 2 lesion with ulceration in the lesser curvature of the vestibule, and a biopsy, which revealed an adenocarcinoma. Computed tomography (CT) revealed wall thickening of the gastric antecubital region, metastatic liver tumor, and extra-regional lymph node metastasis; a diagnosis of T4a, N3a, M1 (H, LYN), and cStage IVB (HER2 3+) was confirmed. Trastuzumab, oxaliplatin, and S-1 were administered initially. After 9 months, ascites appeared, and progressive disease was diagnosed. Paclitaxel and ramucirumab were started as second-line treatments but discontinued owing to neutropenia and increasing ascites. Third-line treatment with T-Dxd was initiated, and 11 months later, CT showed the disappearance of metastases. Even after 31 months, the CR was maintained. Conclusion: To the best of our knowledge, this is one of the few cases in which long-term CR was maintained with third-line T-Dxd treatment. Treatment strategies for patients with gastric cancer to achieve long-term CR require careful consideration.

Cystoid Macular Edema following Treatment with Nanoparticle Albumin-Bound Paclitaxel and Atezolizumab for Metastatic Breast Cancer.

Cystoid macular edema (CME) is a rare side effect associated with chemotherapy. Although the development of CME has been reported to occur following treatment with taxane drugs, such as nanoparticle albumin-bound paclitaxel (Nab-PTX), the occurrence of CME with treatment with atezolizumab has not yet been reported. Here, we report the case of a 49-year-old woman who developed CME 19 months into chemotherapy with Nab-PTX and atezolizumab. Improvement was not achieved with steroid injections into the Tenon's sac, and Nab-PTX and atezolizumab treatments were ceased. One month later, there was subjective improvement in her symptoms. Although many reports have indicated that cessation of chemotherapy has successfully improved CME, a specific treatment for CME has not yet been established. Clinicians should be aware of the ophthalmologic side effects and offer immediate treatment if symptoms develop.

An Adolescent Patient with Sick Sinus Syndrome Complicated by Hypothyroidism Carrying an SCN5A Variant.

Previous studies have reported that hypothyroidism can lead to sick sinus syndrome (SSS) or other rhythm disturbances. Variants in the alpha subunit of the cardiac sodium channel (SCN5A) are known to be among the genetic causes of SSS. We encountered an adolescent patient with SSS and hypothyroidism who also harbored an SCN5A variant. The patient was a 13-year-old girl who was referred to our hospital because of bradycardia identified during a school electrocardiography screening. Clinical examination revealed severe hypothyroidism due to Hashimoto thyroiditis and SSS. After levothyroxine supplementation, her symptoms of hypothyroidism improved; however, the SSS did not. Genetic testing revealed a heterozygous variant (c.1066 G>A, p.Asp356Asn) in SCN5A. This is the first report of the coexistence of SSS due to an SCN5A variant and severe hypothyroidism in an adolescent patient. While patients with SCN5A variants exhibit phenotypic heterogeneity due to the presence of various modifiers, the presence of severe hypothyroidism may affect the development of SSS. This case highlights the importance of genetic analysis, including testing for SCN5A variants, in patients with hypothyroidism complicated by SSS or cardiac conduction disorders.

Polymorphisms in CTLA-4 predict de novo donor specific antibody formation after kidney transplantation.

The post-transplant development of donor-specific antibodies (DSAs) initiates the antibody-mediated rejection, which is associated with an increased rate of graft loss. Therefore, risk prediction of de novo DSA (dnDSA) is important for understanding long-term prognostic implications for kidney transplantation outcomes. Cytotoxic T lymphocyte antigen-4 (CTLA-4), a cell surface molecule, suppresses T cell responses. Single-nucleotide polymorphisms (SNPs) in CTLA-4 are known to be associated with acute rejection; however, their association with dnDSA formation is not established. In the present study, we investigated the impact of CTLA-4 SNPs on dnDSA formation after kidney transplantation (KT) by analyzing three CTLA-4 SNPs (rs231775, rs3087243, and rs5742909) in 88 recipients. Patients with the GG genotype of CTLA-4 SNPs rs231775 and rs3087243 had higher rates of dnDSA formation than patients with the AA genotype or heterozygous genotypes. In conclusion, our findings indicate that CTLA-4 SNPs are predisposing factors for dnDSA formation after KT.

Molecular Mismatch Predicts T Cell-Mediated Rejection and De Novo Donor-Specific Antibody Formation After Living Donor Liver Transplantation.

Human leukocyte antigen (HLA) molecular mismatch (MM) analysis improves the prediction of clinical outcomes in kidney transplantation compared with prediction via traditional antigen MM. However, it remains unclear whether the level of MM can be used for risk stratification among liver transplantation (LT) recipients. A retrospective observational study of 45 living donor LTs was performed to evaluate eplet MM as a risk factor for both T cell-mediated rejection (TCMR) in the first month and de novo donor-specific antibody (dnDSA) formation. A total of 9 (20%) patients displayed TCMR. HLA-A, HLA-B, HLA-C, and HLA-DRB1 eplet MM numbers were not associated with TCMR. By contrast, HLA-DQB1 eplet MM (DQB1-EpMM) number was significantly high in patients with TCMR. The predicted indirectly recognizable HLA epitopes (PIRCHE-II) score for the HLA-DQB1 locus (DQB1-PIRCHE-II) was also significantly higher in the TCMR group than in the no-TCMR group. There was a high probability for TCMR to occur with either a DQB1-EpMM ≥7 or a DQB1-PIRCHE-II ≥13. Pretransplant mixed lymphocyte response analyses indicated that there were no significant differences between the antidonor T cell proliferation activities of patients with low-number (<7) and high-number (≥7) DQB1-EpMMs. However, the proportion of CD25 expression on proliferating antidonor CD8+ T cells, used as a cytotoxic activity marker, was high in DQB1-EpMMs ≥7. Moreover, both DQB1-EpMMs ≥9 and DQB1-PIRCHE-II ≥3 were predictors of dnDSA formation. Thus, MM analysis may be applied toward tailored immunosuppression based on individual risks.

Occurrence of Immunoglobulin G4-related Disease during Chemotherapy for Advanced Breast Cancer.

Immunoglobulin G4-related disease (IgG4-RD) is defined as an inflammatory lymphoproliferative disorder. The relationship between malignancies and IgG4-RD remains unclear. We herein present a case of IgG4-RD that occurred during chemotherapy for advanced breast cancer. In this case, it was challenging to determine which of these diseases was responsible for the patient's mediastinal lymphadenopathy. Lymphadenopathy with IgG4-RD was diagnosed by assessing the reactivity to corticosteroids, which were used as premedication in chemotherapy, over time. The administration of prednisolone, which was initiated to treat active IgG4-RD, led to stable systemic therapy for malignancy. It is imperative to assess the disease activity and consider each treatment.

Successful Treatment of Chronic Myeloid Leukemia With Dasatinib After Kidney Transplantation: A Case Report.

OBJECTIVE: Chronic myeloid leukemia (CML) is a rare malignancy in kidney transplant (KT) recipients. Although dasatinib is the first-line treatment for CML, it has inhibitory activity against CYP3A4; this might increase the blood concentration of tacrolimus (administered to KT patients for immune suppression). Furthermore, tacrolimus can also increase blood concentrations of dasatinib through P-glycoprotein inhibition. METHODS: Here, we report a case of sustained molecular remission of CML with prolonged first-line dasatinib therapy in a KT recipient being treated with tacrolimus. A 61-year-old woman developed CML-chronic phase (CML-CP) 38 months post KT. Her maintenance immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil, and methylprednisolone. Considering the potential drug interaction with tacrolimus, dasatinib was administered at a low dose of 50 mg/day. Her immune status was evaluated regularly by assessing the mixed lymphocyte reaction (MLR) using an intracellular carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeling technique; immunosuppressive therapy was adjusted accordingly. RESULTS: The patient achieved complete hematologic remission (CHR) after 1 month of dasatinib treatment. Six months after dasatinib treatment, she achieved a major molecular response. During the observation period, neither antibody-mediated nor acute cellular rejection were encountered in the patient. She remained in CHR with a major molecular response 12 months after the diagnosis of CML-CP. CONCLUSION: Data obtained from immune monitoring assays using CFSE-MLR helped us to successfully manage a KT recipient with CML-CP being treated with dasatinib. Drug-drug interactions are a key consideration while designing treatment regimens; such strategies would ensure that drug-drug interactions do not negatively affect the treatment outcomes.

Radiation myelitis after durvalumab administration following chemoradiotherapy for locally advanced non-small cell lung cancer: an illustrative case report and review of the literature.

A 69-year-old man with stage IIIB lung adenocarcinoma received durvalumab following chemoradiotherapy. The prescribed dose was 50 Gy in 2 Gy fractions, and the maximum spinal cord dose was 40 Gy. After three cycles of durvalumab, he experienced bladder and rectal disturbance, muscle weakness in the lower limbs, and sensory loss in the lower body. Magnetic resonance imaging revealed T2 signal hyperintensity involving the thoracic spinal cord. As the thoracic spinal cord with T2 signal hyperintensity matched with the irradiated site, the patient was diagnosed with radiation myelitis. This case report shows the clinical and radiographic features of a case of locally advanced non-small cell lung cancer that demonstrated radiation myelitis following durvalumab administration. The time of onset was very early and the influence of durvalumab was suspected as the cause of myelitis.

Advanced gastric cancer with features of a submucosal tumor diagnosed by endoscopic ultrasound-guided fine needle aspiration and boring biopsy preoperatively: A case report and literature review.

INTRODUCTION: Gastric cancer with features of a submucosal tumor (GCSMT) is rare, and the preoperative diagnosis is very difficult. We present a case of GCSMT diagnosed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and boring biopsy (deeper biopsy), successfully treated with distal gastrectomy and lymph node dissection. PRESENTATION OF CASE: An 81-year-old man with a history of myocardial infarction and type 2 diabetes mellitus was admitted to our hospital for further examination of a gastric submucosal tumor. Endoscopic examination of the gastrointestinal tract showed a 30-mm submucosal tumor at the lower gastric body. Enhanced computed tomography revealed a tumor located at the lower body of the stomach and pyloric lymph node swelling. EUS-FNA and boring biopsy from the tumor revealed adenocarcinoma. Accordingly, distal gastrectomy with lymph node dissection was performed. Histopathological examination showed a poorly differentiated adenocarcinoma. Postoperative diagnosis was GCSMT with lymph node metastasis (T2, N1, M0, stage IIA). CONCLUSION: We report a rare case of GCSMT with lymph node metastasis. Preoperative diagnosis of GCSMT is necessary to guide surgical management. EUS-FNA and boring biopsy could aid in obtaining adequate quantities of the specimens for histopathological and immunohistochemical diagnosis.

Visceral Adipose Tissue and Skeletal Muscle Index Distribution Predicts Severe Pancreatic Fistula Development After Pancreaticoduodenectomy.

BACKGROUND/AIM: In this study, we investigated the effect of body composition on pancreatic fistula (PF) development after pancreaticoduodenectomy (PD). MATERIALS AND METHODS: All consecutive patients with pancreatic and extrahepatic biliary malignancy following PD who were treated between 2006 and 2016 were enrolled. RESULTS: PF developed in 30.3% of cases (30/99 patients), including a grade B PF in 25.3% of cases (25/99 patients) and a grade C PF in 5.1% of cases (5/99 patients). Univariate analysis identified that body mass index ≥25 kg/m2, visceral adipose tissue area (VATA)/skeletal muscle index (SMI) ≥2.0, pancreatic duct diameter ≤3 mm, and drain amylase concentration (Amy) on postoperative day (POD) 1 ≥5000 U/L were significantly associated with PF (grade B, C) after PD. Multivariate analysis indicated that VATA/SMI ≥2.0 (p=0.009), pancreatic duct diameter ≤3 mm (p=0.003), and drain Amy on POD1 ≥5000 U/L (p=0.032) were independent risk factors for PF. CONCLUSION: Elevated VATA/SMI was the only preoperative key factor for PF after PD.

Effect of repeated adrenocorticotropic hormone administration on reproductive function and hair cortisol concentration during the estrous cycle in goats.

Measurement of the cortisol concentration in hair has been used as an index of chronic stress in several species including humans, wildlife and domestic animals. However, how accurately the cortisol concentration in hair reflects the changes in circulating cortisol concentrations has not been well documented. The objective of the present study was to examine the effect of repeated adrenocorticotropic hormone (ACTH) administration on the reproductive function during the estrous cycle and hair cortisol concentrations in goats. In experiment 1, goats were administered ACTH (0.625 IU/10 kg of body weight, n = 6) or saline (n = 6) intramuscularly once a day for 7 days on Day 11-17 of the estrous cycle (day 0 was the day of ovulation). In experiment 2, goats were administered ACTH (0.625 IU/10 kg of body weight, n = 6) or saline (n = 6) intramuscularly twice a day on Day 11-24 of the estrous cycle. Blood samples were collected 0, 0.5, and 6 h after first administration to determine the circulating cortisol concentrations. Hair was clipped at 0, 1, and 2 months after the start of administration. In both experiments, the plasma cortisol concentration increased at 0.5 h and returned to baseline at 6 h after ACTH administration. During the experiments, estrus was observed in most animals in ACTH and saline groups (6/6 and 4/6 in experiment 1 and 5/6 and 6/6 in experiment 2, respectively) and ovulation was observed in all goats examined. However, the number of ovulatory follicles was significantly different between the ACTH and saline groups, and the maximal diameter of ovulatory follicles tended to be different (P = .07) between the ACTH and saline groups. In experiment 1, the hair cortisol concentration was not influenced by the ACTH administration throughout the sampling period. In experiment 2, the hair cortisol concentration in the ACTH group was greater at 1 month after administration than the pre-administration value, but was not significantly different at 2 months. These results suggest that repeated ACTH administration affects the development and ovulatory process of ovarian follicles and analysis of the hair cortisol concentration can be used for assessing relatively long-term changes in cortisol concentration in the circulation.

A case of cholangiolocellular carcinoma featuring intratumoral hepatic artery penetration: A case report.

INTRODUCTION: Cholangiolocellular carcinoma (CoCC) is thought to originate from hepatic stem cells. Its clinical characteristics, including radiological and prognostic factors, remain unclear. PRESENTATION OF CASE: A 79-year-old woman with hypertension was admitted to our hospital after abnormal tumor marker levels were detected during an annual physical examination. Her laboratory data results were within normal range, and she was classified as Child-Pugh A. Enhanced computed tomography revealed a tumor located on the left side of the liver, with a maximum size of 60mm. The tumor showed heterogeneously enhancing edges in the arterial phase, while prolonged tumor enhancement was detected in the delayed phase. Tumor penetration by the left hepatic artery was evident, whereas the left portal vein was invaded by the tumor. The preoperative diagnosis was cholangiocellular carcinoma. Left hepatectomy and cholecystectomy were performed with no postoperative complications; the final diagnosis was CoCC. Multiple liver metastases appeared 6 months after surgery; the patient is now receiving systematic chemotherapy. DISCUSSION: While portal vein penetration into CoCCs has been reported, the same is not true of the hepatic artery; therefore, this case illustrates a unique tumor growth pattern. CONCLUSION: A unique growth pattern as well as a large primary tumor may contribute to earlier recurrence.