Hyponatremia due to adrenal insufficiency after a Mamushi bite: a case report.

BACKGROUND: Mamushi bites are the most common venomous snake bites in Japan, with known complications including rhabdomyolysis and acute kidney injury; however, adrenal insufficiency as a result of snake bites has not been previously reported. We report a case of empty sella with transient adrenal insufficiency during hospitalization for a Mamushi bite. CASE PRESENTATION: An 84-year-old man was admitted to our hospital with a Mamushi bite on the right fifth finger. Serum sodium (Na) level remained in the normal range. On the ninth day of admission, he developed hyponatremia, with a serum Na level of 114 mEq/L and serum cortisol level of 4.0 µg/dL (reference value 4.5-21.1 µg/dL). His serum Na level was restored within the normal range after administration of corticosteroids with 3% NaCl solution. Both rapid adrenocorticotrophin and corticotropin-releasing hormone loading tests showed low cortisol response. Based on the results of the hormone loading tests, a diagnosis of pituitary adrenal insufficiency was made. Contrast-enhanced pituitary magnetic resonance imaging (MRI) showed primary empty sella. After discontinuation of corticosteroids, the hyponatremia did not recur, and the patient was discharged on the 24th day of hospitalization. After discharge, the patient visited an outpatient clinic, but hyponatremia recurrence was not observed. CONCLUSIONS: This is the first report of hyponatremia due to pituitary adrenal insufficiency during hospitalization for a Mamushi bite in a patient with empty sella. When hyponatremia occurs during hospitalization for a Mamushi bite, cortisol measurement, hormone loading test, and head MRI should be performed to search for pituitary lesions because of the possibility of adrenal insufficiency caused by snake venom.

Long-Term Outcomes of Endoscopic Submucosal Dissection for Early Remnant Gastric Cancer: A Retrospective Multicenter Study.

INTRODUCTION: Favorable long-term outcomes of endoscopic submucosal dissection (ESD) for early remnant gastric cancer (ERGC) have been reported in single-center studies from advanced institutions. However, no studies have examined the long-term outcomes using a multicenter database. This study aimed to investigate the long-term outcomes of the aforementioned approach using a large multicenter database. METHODS: This retrospective multicenter cohort study included 242 cases with 256 lesions that underwent ESD for ERGC between April 2009 and March 2019 across 12 centers. We investigated the long-term outcomes of these patients with the Kaplan-Meier method, and the relationship between curability, additional treatment, or hospital category, and the survival time was evaluated using the log-rank test. RESULTS: During the median follow-up period of 48.4 months, the 5-year overall survival rate was 81.3%, and the 5-year gastric cancer-specific survival rate was 98.1%. The survival time of patients of endoscopic curability (eCura) C-2 without additional surgery was significantly shorter than the corresponding of patients of eCura A/B/C-1 and eCura C-2 with additional surgery. There was no significant difference in either overall survival or gastric cancer-specific survival rate between the high-volume and non-high-volume hospitals. CONCLUSION: The gastric cancer-specific survival of ESD for ERGC using a multicenter database was favorable. ESD for ERGC is widely applicable regardless of the hospital case volume. Management in accordance with the latest guidelines will lead to long-term survival.

Assessment of predictive factors associated with the technical difficulty of endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma: Japanese multicenter retrospective study.

OBJECTIVES: Endoscopic submucosal dissection (ESD) for superficial esophageal squamous cell carcinoma (ESCC) is performed for the treatment of lesions with varied backgrounds and factors. However, the predictive factors associated with the technical difficulty of ESD remain unknown in patients with varied lesions. Therefore, this study aimed to identify the predictive factors associated with the technical difficulty of ESD for ESCC using a retrospective cohort. METHODS: This multicenter, retrospective study was conducted in 10 hospitals in Japan. Consecutive patients who underwent esophageal ESD between January 2013 and December 2019 were enrolled. Lesions of subepithelial tumors, adenocarcinoma, and adenoma were excluded. Difficult lesions were defined as ESD requiring a long procedure time (≥120 min), perforation development, piecemeal resection, or discontinued ESD. In the present study, the clinical factors were assessed to identify the technical difficulty of ESD using univariate and multivariate analyses. RESULTS: Among 1708 lesions treated with esophageal ESD, eight subepithelial tumors, 44 adenocarcinomas, and two adenomas were excluded. Finally, 1505 patients with 1654 lesions were analyzed, and 217 patients with 217 lesions (13.1%) were classified as patients with difficult lesions. In multivariate analysis, the predictive factors associated with the technical difficulty of ESD were as follows: tumors with varices, tumors with diverticulum, antiplatelet use (discontinued), circumference of tumor (≥1/2), preoperative tumor size ≥30 mm, trainee, and nonhigh-volume center. CONCLUSION: This multicenter retrospective study identified the predictive factors associated with the technical difficulty of ESD for ESCC with varied backgrounds and factors.

The risk scoring system for assessing the technical difficulty of endoscopic submucosal dissection in cases of remnant gastric cancer after distal gastrectomy.

BACKGROUND: Endoscopic submucosal dissection (ESD) for remnant gastric cancer (RGC) after distal gastrectomy (DG) is considered technically challenging due to the narrow working space, and severe fibrosis and staples from the previous surgery. Technical difficulties of ESD for RGC after DG have not been thoroughly investigated. This study aimed to develop and validate a risk-scoring system for assessing the technical difficulty of ESD for RGC after DG in a large multicenter cohort. METHODS: We investigated patients who underwent ESD for RGC after DG in 10 institutions between April 2008 and March 2018. A difficult case was defined as ESD lasting ≥ 120 min, involving piecemeal resection, or the occurrence of perforation during the procedure. A risk-scoring system for the technical difficulty of the procedure was developed based on multiple logistic regression analyses, and its performance was internally validated using bootstrapping. RESULTS: A total of 197 consecutive patients with 201 lesions were analyzed. There were 90 and 111 difficult and non-difficult cases, respectively. The scoring model consisted of four independent risk factors and points of risk scores were assigned for each as follows: tumor size > 20 mm: 2 points; anastomosis site: 2 points; suture line: 1 point; and non-expert endoscopist: 2 points. The C-statistics of the scoring system for technical difficulty was 0.72. CONCLUSIONS: We developed a validated risk-scoring model for predicting the technical difficulty of ESD for RGC after DG that can contribute to its safer and more reliable performance.

Multicenter phase II study of FOLFIRI plus bevacizumab after discontinuation of oxaliplatin-based regimen for advanced or recurrent colorectal cancer (CR0802).

BACKGROUND: To investigate the efficacy and safety of FOLFIRI plus bevacizumab regimen with irinotecan (180 mg/m(2)) in patients with advanced or recurrent colorectal cancer who were of the wild-type or heterozygous group for UGT1A1*28 and *6 polymorphisms and discontinued to oxaliplatin-based regimen, prospectively. METHODS: The study population consisted of patients who had discontinued oxaliplatin-based regimen for any reason. The primary endpoint was the response rate. FOLFIRI and bevacizumab regimen [irinotecan: 180 mg/m(2), 5-fluorouracil infusion: 2400 mg/m(2), 5-fluorouracil bolus: 400 mg/m(2), levofolinate calcium: 200 mg/m(2), bevacizumab: 5 mg/kg] was repeated every 2 weeks for up to 24 cycles. RESULTS: Ninety-four patients were enrolled; 93 patients were evaluated on safety, 94 patients on efficacy. The response rate was 10.1% (95% confidence interval (CI): 4.7-18.3%). The median time to treatment failure, progression-free survival, and overall survival were 4.1 months (95% CI: 2.8-4.8 months), 5.4 months (95% CI: 4.1-6.2 months), and 14.5 months (95% CI: 11.8-17.0 months), respectively. The treatment-related death was 1.1%, and the early death ≤30 days after the last study treatment was 1.1%. The incidence of grade 3 or higher adverse events was 60.2% for neutropenia, 23.7% for leukopenia, 9.7% for diarrhea, 6.5% for anorexia, and 5.4% for fatigue. All these adverse events and other adverse events were controllable. CONCLUSIONS: FOLFIRI plus bevacizumab regimen with an initial irinotecan dose of 180 mg/m(2) exhibited an adequate antitumor effect and was confirmed to be manageable and tolerable in Japanese patients with advanced or recurrent colorectal cancer, who had discontinued oxaliplatin-based regimen. TRIAL REGISTRATION: UMIN000001817 .

Polypoid leiomyosarcoma of the esophagus treated by endoscopic submucosal dissection.

We report a rare case of polypoid leiomyosarcoma of the esophagus that was treated by endoscopic submucosal dissection (ESD). A 63-year-old man with complaints of progressive dysphagia was referred to Hyogo Cancer Center for treatment of esophageal tumor. Esophagoscopy revealed a polypoid tumor 25 mm in diameter on the left side of the upper esophagus. Despite several biopsy specimens, the diagnosis could not be confirmed. Computed tomography showed a protruded, homogeneously enhancing mass in the upper esophagus, but no lymph node enlargement or metastasis. After 1.5 months, the esophagogram showed a filling defect 47 mm in diameter in the upper esophagus. Given this rapid tumor growth, en bloc resection was done by ESD for therapeutic diagnosis. After this treatment, the tumor seemed to grow larger, showing a short stalk and occupying the esophageal lumen. Histopathologically, the tumor comprised pleomorphic spindle cells with mitosis. Tumor invasion involved the lumina propria mucosae and contact with the muscularis mucosae, but not involving the submucosa. Immunohistochemical examination showed positive staining for smooth muscle actin and HHF35, but negative for desmin, caldesmon, CD34, c-kit, DOG1, ALK, S-100 protein and cytokeratin. These histopathological findings were compatible with a diagnosis of esophageal leiomyosarcoma derived from the muscularis mucosae.

Dengue Fever Complicated with Hemophagocytic Lymphohistiocytosis: A Case Report of Resolution with Steroid-Sparing Supportive Care.

Dengue fever (DF) can be complicated by hemophagocytic lymphohistiocytosis (HLH). Steroid administration is markedly effective for this hematologic complication, and for other viral infections. We present a rare case of DF-associated HLH that improved with steroid-sparing supportive care. A 47-year-old Japanese male with diabetes mellitus and no history of DF traveled to the Philippines 10 days before his hospitalization. Three days before emergency admission, he experienced fever and joint pain and was referred to our hospital for suspected DF, after blood tests indicated liver damage and thrombocytopenia. Erythema of the extremities and trunk appeared on day 2, and the next day neutrophils were 550 cells/µL, platelets 29,000 cells/µL, ferritin 9840 ng/mL, and fibrinogen 141 mg/dL. Bone marrow aspirate revealed hemophagocytic lymphohistiocytosis, and he was diagnosed with HLH. On day 4, the symptoms and findings improved; only supportive care without steroids was continued. He tested positive for dengue virus antigen on admission. He was discharged on day 9 of hospitalization in good general condition with no vascular leakage or bleeding and recovery of blood cells. Although steroid administration is markedly effective in cases of DF complicated by HLH, this case suggests that such cases can resolve with steroid-sparing supportive care.

Steroid initiation timing and outcome of coronavirus disease 2019 patients: A multicenter, retrospective, observational study.

Objectives: Dexamethasone's (DEXA) beneficial effect on survival when administered to critically ill patients with coronavirus disease 2019 (COVID-19) has been documented in randomized trials and meta-analyses. Here, we conducted this study to clarify the association between time from COVID-19 onset to steroid initiation and mortality and to examine the factors underlying these results.Methods: This was a multicenter, retrospective, observational study of patients enrolled in the Japanese COVID-19 Registry from January 1, 2020, to April 30, 2021. Demographic and clinical factors were extracted from patient records. Patients diagnosed with COVID-19 using polymerase chain reaction, loop-mediated isothermal amplification, or antigen tests were included. Patients aged <18 years, pregnant, with a history of chronic obstructive pulmonary disease or steroid or immunosuppressive drug use, transferred to another hospital, or with an unknown symptom onset were excluded.Results and Conclusion: The analysis included 3692 patients (men, 64.1%; median age, 68 years). Unadjusted comparisons of mortality groups showed significant differences in demographic and clinical characteristics; patients with early dexamethasone initiation had more risk factors for severe disease and significantly higher mortality than did patients with delayed initiation (13.3% vs 7.9%, p < .001). No significant differences were found in intubation rates or duration, length of hospitalization, or time from intubation to death. Multivariate analyses showed significant differences from symptom onset to steroid administration, with an adjusted odds ratio of 0.7 (p = .05) for patients who received steroids for ≥8 days. Early steroid administration to COVID-19 patients was associated with increased mortality, suggesting a subset with early severe disease and high mortality and/or adverse effects of early steroid administration.

Giant infected hepatic cyst causing exclusion pancreatitis: A case report.

BACKGROUND: An infected hepatic cyst causes clinical symptoms, such as fever and abdominal pain. A cyst with a diameter > 10 cm increases the likelihood of exclusion symptoms in adjacent organs. Herein, we report a case of pancreatitis caused by an infected hepatic cyst. CASE SUMMARY: The patient was an 88-year-old woman with a history of polycystic liver disease and a cyst > 10 cm in diameter. She was referred to our hospital for upper abdominal pain that persisted for four days before consultation. She had a fever of 37.4ºC, and a blood test showed a C-reactive protein level of 23 mg/dL. An infected hepatic cyst was diagnosed by abdominal ultrasonography, computed tomography, and magnetic resonance imaging. Antibacterial therapy and percutaneous cyst puncture did not elicit sufficient therapeutic effects. As the cyst growth continued, laparoscopic hepatic cyst fenestration was performed on hospitalization day 20. Thereafter, symptoms improved, and she was discharged on hospital day 31. CONCLUSION: To our knowledge, this is the second case report of pancreatitis associated with hepatic cyst growth. Percutaneous cyst puncture and drainage or surgical therapy can be considered if a slight improvement with antibiotic therapy alone or exclusion of surrounding organs is observed. Further, attention is needed to avoid potential recurrence.

Association between Adverse Reactions to the First and Second Doses of COVID-19 Vaccine.

This study investigated the frequency of adverse reactions to COVID-19 vaccines in Japan and the impact of first-dose adverse reactions on second-dose adverse reactions. Individuals who received an mRNA COVID-19 vaccine at our center in March or April 2021 were included. Data were collected using questionnaires. The main factors were age (<40, 40−59, and >60 years), sex, underlying disease, and first-dose adverse reaction. The primary outcomes were incidence of local and systemic adverse reactions (ARs) attributable to the vaccine. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Among 671 participants, 90% experienced local or systemic ARs. An AR to the first dose was associated with a significantly increased risk of an AR to the second dose (OR: 49.63, 95% CI: 21.96−112.16). ARs were less common among men than among women (OR: 0.36, 95% CI: 0.17−0.76). Local ARs were less common among those aged 60 years or older (OR: 0.35, 95% CI: 0.18−0.66), whereas systemic ARs were more common among those aged under 40 years. Information on ARs to the first dose is important for healthcare providers and recipients when making vaccination decisions.

A Ruptured Left Gastric Artery Aneurysm That Neoplasticized during the Course of Coronavirus Disease 2019: A Case Report.

Coronavirus disease 2019 (COVID-19) is an acute respiratory syndrome caused by SARS-CoV-2 and is known to cause respiratory and systemic symptoms. A SARS-CoV-2 infection is involved in aneurysm formation, enlargement, and rupture in medium-sized vessels, such as the cerebral and coronary arteries and the aorta. In contrast, its involvement in forming aneurysms in medium-sized vessels other than the cerebral and coronary arteries has not been reported. An 84-year-old Japanese man with COVID-19 was admitted to our hospital. The treatment course was favorable, and the COVID-19 treatment was completed by the 10th day. On day 14, pancreatic enzymes increased mildly. An abdominal computed tomography revealed a ruptured left gastric aneurysm after spontaneous hemostasis. Arterial embolization was performed. In this patient, a new left gastric aneurysm was suspected of having formed and ruptured during the course of the COVID-19 treatment. To the best of our knowledge, this is the first report of abdominal visceral aneurysm formation caused by COVID-19 in a medium-sized vessel, and it is necessary to remember that aneurysms can be formed at any site when treating this syndrome.

Primary gastrointestinal follicular lymphoma involving the duodenal second portion is a distinct entity: a multicenter, retrospective analysis in Japan.

We conducted a multicenter, retrospective study to determine the anatomical distribution and prognostic factors of gastrointestinal (GI) follicular lymphoma (FL). This study included 125 patients with stage I and II(1) GI-FL. Of the 125 patients, the small intestine was examined in 70 patients, with double-balloon endoscopy and/or capsule endoscopy. The most frequently involved GI-FL site was the duodenal second portion (DSP) (81%), followed by the jejunum (40%); 85% of patients with involvement of the DSP also had jejunal or ileal lesions. The absence of abdominal symptoms and macroscopic appearance of multiple nodules were significantly present in the DSP-positive group. During a median follow up of 40 months, six patients showed disease progression. Patients with involvement of the DSP had better progression-free survival (PFS) than those without such involvement (P = 0.001). A multivariate analysis revealed that male sex, the presence of abdominal symptoms, and negative involvement of the DSP were independently associated with poor PFS. In conclusion, most patients with GI-FL have duodenal lesions associated with multiple jejunal or ileal lesions. Gastrointestinal follicular lymphomas involving the DSP might be a distinct entity showing a favorable clinical course.

Concerns and Anxieties of Patients During Hospitalization for COVID-19.

Objective The objective of this study was to evaluate the concerns and anxieties of hospitalized coronavirus disease (COVID-19) patients. Methods A questionnaire was distributed to patients on discharge. The responses were analyzed once they were returned by mail. Results Responses were received from 27 of 39 patients (average age, 50 ± 17 years). Among the participants, 16 were male (59.3%), 19 were symptomatic (70.4%), and two required a ventilator (7.4%). Anxiety about symptom exacerbation was reported by 36.0% of participants. Quarantine-associated stress was experienced by 60.0% of participants, and 72.0% of participants supported the change in federal policy that allows asymptomatic patients and patients with mild conditions to isolate themselves at a hotel or their home. Following discharge, 44.0% of participants experienced anxieties regarding their lives after discharge, and 56.0% were anxious regarding discrimination and rumors. During hospitalization, 68.0% of participants re-evaluated their attitude toward health, 44.0% regretted the preventative measures they took before contracting COVID-19, and 44.0% felt guilty for becoming infected. Conclusions Participants experienced various kinds of stress related to hospitalization for COVID-19. There was a trend of people being more concerned about their relationships than their own health. Therefore, as asymptomatic participants and participants with mild symptoms also experienced psychological stresses, it is also necessary to consider the psychological and social effects of the disease.

Changes in patients' outlook, behaviors, and attitudes toward COVID-19 after hospitalization and their experiences of discrimination and harassment.

OBJECTIVE: This study aims to examine changes in patients' perspectives and outlooks regarding the disease and their health after hospitalization for COVID-19 and investigate their discrimination and harassment experiences. This prospective observational study surveyed discharged patients who had been admitted to Hyogo Prefectural Tamba Medical Center in Japan for COVID-19. Patient characteristics, changes in outlook and behaviors after discharge, and incidents of discrimination and harassment were examined. The study was conducted in two waves: March-June 2020 and July-September 2020. RESULTS: Responses were obtained from 27 patients aged 50 ± 17 years, including 16 men (59.3%). We found most patients feared infection before hospitalization (88.5%) and had taken some preventive measures (96.3%), however after discharge, all (100%) practiced social distancing and infection prevention. Twenty patients (80%) considered changing their lifestyles, and 19 (79.2%) decided to use sick leave when they felt ill; these trends were more prominent during the second wave. Six patients (23.1%) reported experiencing discrimination or harassment after discharge. While most patients with COVID-19 had a strong fear of infection before hospitalization, their views about health and health behaviors changed after hospitalization.

Humidifier Use and Prone Positioning in a Patient with Severe COVID-19 Pneumonia and Endotracheal Tube Impaction Due to Highly Viscous Sputum.

COVID-19 can lead to severe pneumonia, requiring mechanical ventilation. While increased sputum secretion could cause airway obstruction during mechanical ventilation, there are few reported cases in the literature. We report a case of a 65-year-old man with diabetes and severe COVID-19 pneumonia requiring mechanical ventilation and treated with hydroxychloroquine, azithromycin, nafamostat, and prone positioning. Initially, mechanical ventilation consisted of a heat moisture exchanger, endotracheal tube aspiration, and subglottic secretion drainage using a closed suction system. However, endotracheal tube impaction by highly viscous sputum occurred during this mechanical ventilation system. Replacing the endotracheal tube, the use of a humidifier instead of a heat moisture exchanger, and prone positioning contributed to the patient being weaned off mechanical ventilation. Although anti-aerosol measures are important for severe COVID-19 pneumonia, attention should be given to potential endotracheal tube impaction during mechanical ventilation.

[A case of CNS metastasis from gastric MALT lymphoma].

Recently, the incidence of primary CNS lymphoma (PCNSL) is increasing. Metastatic CNS lymphoma occurs much less than PCNSL. We report the case of a 53-year-old man who presented with CNS metastasis from gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The symptoms at the time of diagnosis were dizziness and aphasia. MRI revealed a left parietal lobe tumor with a large peritumoral edema. About 4 years ago, he had suffered from gastric MALT lymphoma with a high grade component. Eradication of Helicobacter pylori led to remission of the disease 18 months after the treatment. From his past history, the brain tumor was suspected of being a metastatic lymphoma. Stereotactic biopsy revealed diffuse large B-cell lymhoma. Histopathological findings including lymphocytic subsets were almost identical between the primary gastric MALT lymphoma and metastatic brain lymphoma. Complete remission was obtained by repeated high-dose methotrexate chemotherapy. There has been no recurrence for 5 years without additional therapy. This case is probably the first report of CNS metastasis from gastric MALT lymphoma.

[Retrospective analysis of uracil/tegafur, cyclophosphamide and gemcitabine compared with gemcitabine monotherapy in unresectable pancreatic cancer].

In a retrospective analysis, we compared the effectiveness and tolerability of gemcitabine (GEM) plus uracil/tegafur and cyclophosphamide with single-agent GEM as 1st-line chemotherapy for unresectable or recurrent pancreatic cancer. 33 patients received combination therapy and 25 patients were treated with GEM alone. Tumor response rate was 14.3% vs 8.7%, median progression-free survival was 3.2 vs 4 months, and median survival time was 6.5 vs 6.5 months in the combination and GEM groups, respectively. Complete response was observed just in 2 cases of the combination group, and 1 of them has been relapse-free for 3 years. In a subgroup of patients with good performance status, combination therapy prolonged median survival time significantly (9.4 vs 6.2 months). This combination therapy is well tolerated and may provide superior benefits to GEM monotherapy.

[5-FU based chemoradiotherapy for unresectable locally advanced pancreatic cancer].

Twenty-one patients with unresectable locally advanced pancreatic cancer were evaluated in this retrospective analysis. They received extra-beam radiotherapy(50.4-54 Gy/28-30 fractions)with concurrent continuous infusion of 5-FU(250 mg/m(2)day)between December 1999 and April 2007. The radiation field included primary tumor and adjacent lymph nodes. Twenty patients(95%)completed chemoradiotherapy, although one patient quit radiotherapy due to vomiting. No lethal side effects were observed. The response rate was 10%. One of the patients judged to have stable disease underwent resection after maintenance chemotherapy. The median progression free survival and the median overall survival were 6.4 and 12 months, respectively. In eleven patients(52%), the initial sites of disease progression were local or peritoneum without liver metastases, suggesting systemic effects of this treatment. In conclusion, 5-FU based chemoradiotherapyis well tolerated and provides definite benefits against unresectable locally advanced pancreatic cancer.