[A Case of Interstitial Pneumonia Induced by Immune Checkpoint Inhibitors for Gastric Cancer During the COVID- 19 Pandemic].

BACKGROUND: The novel coronavirus disease(corona virus disease 2019: COVID-19)has calmed down worldwide, and the severity of the disease is decreasing. On the other hand, due to the emergence of strain mutations, the number of infected people shows a wavy course. I have experienced a case of gastric cancer that underwent chemotherapy including an immune checkpoint inhibitors(ICI) early after COVID-19, so I will report it including a discussion. CASE: A 71-year-old man. The patient visited our hospital with a chief complaint of stomach discomfort, and gastrointestinal endoscopy revealed advanced gastric cancer accompanied by narrowing of the gastric lumen. The histopathological examination showed a poorly differentiated adenocarcinoma. A CT scan of the chest and abdomen showed thickening of the entire gastric wall, indicating the presence of enlarged adjacent lymph nodes and infiltration into adjacent organs. No other obvious distant metastases were observed. Staging laparoscopy was performed, it revealed infiltration of the posterior wall of the stomach into the celiac artery and anterior surface of the pancreas. We determined that curative resection would be difficult. As a result of planning chemotherapy for locally advanced gastric cancer, the patient contracted COVID-19 due to a hospital- acquired infection. The patient's COVID-19 infection was managed with supportive care alone without severe complications, and they recovered within the course of treatment. Two weeks after the onset of the infection, chemotherapy(FOLFOX+ Nivo)was initiated. The patient completed up to 9 courses of chemotherapy, and the treatment response was determined to be stable disease(SD). Due to a tendency of stenosis in the gastric lumen, the possibility of future dilation procedures was considered. As a result, the patient underwent second-line chemotherapy with a combination of wPTX+RAM. After completing 1 course of treatment, the patient developed drug-induced interstitial pneumonia, which was managed with intensive care and steroid pulse therapy, resulting in improvement. There was progression of gastric lumen stenosis, and an endoscopic dilation procedure/stent placement was performed. Subsequently, there was a rapid increase in malignant ascites and a decline in activities of daily living(ADL), leading to palliative care. Unfortunately, the patient succumbed to cancer-related complications 10 months after the diagnosis. DISCUSSION: In this case, the serial antibody titers of COVID-19 also indicated the sustained effectiveness of the multi-drug combination chemotherapy. The treatment course suggests a suspicion of drug-induced interstitial pneumonia due to PTX/RAM, but the long-term imaging follow-up implies that ICI may be the cause. When using ICI, COVID-19 infection alone may pose a potential risk factor.

Tumor microenvironmental 15-PGDH depletion promotes fibrotic tumor formation and angiogenesis in pancreatic cancer.

The arachidonic acid cascade is a major inflammatory pathway that produces prostaglandin E2 (PGE2). Although inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is reported to lead to PGE2 accumulation, the role of 15-PGDH expression in the tumor microenvironment remains unclear. We utilized Panc02 murine pancreatic cancer cells for orthotopic transplantation into wild-type and 15-pgdh+/- mice and found that 15-pgdh depletion in the tumor microenvironment leads to enhanced tumorigenesis accompanied by an increase in cancer-associated fibroblasts (CAFs) and the promotion of fibrosis. The fibrotic tumor microenvironment is widely considered to be hypovascular; however, we found that the angiogenesis level is maintained in 15-pgdh+/- mice, and these changes were also observed in a genetically engineered PDAC mouse model. Further confirmation revealed that fibroblast growth factor 1 (FGF1) is secreted by pancreatic cancer cells after PGE2 stimulation, consequently promoting CAF proliferation and vascular endothelial growth factor A (VEGFA) expression in the tumor microenvironment. Finally, in 15-pgdh+/- Acta2-TK mice, depletion of fibroblasts inhibited angiogenesis and cancer cell viability in orthotopically transplanted tumors. These findings highlighted the role of 15-pgdh downregulation in enhancing PGE2 accumulation in the pancreatic tumor microenvironment and in subsequently maintaining the angiogenesis level in fibrotic tumors along with CAF expansion.

Association between Immunoglobulin G Levels and Adverse Effects Following Vaccination with the BNT162b2 Vaccine among Japanese Healthcare Workers.

The purpose of the study was to assess the association between the amount of immunoglobulin G (IgG) and the duration of adverse effects of COVID-19 vaccinations in the Japanese population. This cross-sectional study was conducted from April 2020 to August 2021 among workers at a community hospital. All participants received two doses of the BNT162b2 vaccine (Pfizer-BioNTech) in March and April 2021. Vaccine side effects were measured using a self-administered questionnaire. Serum anti-SARS-CoV-2 IgG was measured 3 months after vaccination. There was a total of 338 participants (mean age: 44.7 years). The incidence of adverse reactions after vaccination was higher in women. Adverse reactions associated with higher IgG levels included: erythema at the injection site after the first dose; induration and inflammation at the injection site; and systemic symptoms, e.g., fever and headache after the second dose. IgG levels were higher in younger participants. These findings could mitigate fears regarding the mild adverse effects of the COVID-19 vaccine and encourage uptake of the BNT162b2 vaccine.

Comprehensive Care through Family Medicine: Improving the Sustainability of Aging Societies.

Comprehensive care through family medicine can enhance the approach to multimorbidity, interprofessional collaboration, and community care, and make medical care more sustainable for older people. This study investigated the effect of implementing family medicine and the comprehensiveness of medical care in one of the most rural communities. This implementation research used medical care data from April 2015 to March 2020. Patients' diagnoses were categorized according to the 10th revision of the International Statistical Classification of Disease and Related Health Problems (ICD-10). In 2016, family medicine was implemented in only one general hospital in Unnan. The comprehensiveness rate improved in all ICD-10 disease categories during the study period, especially in the following categories-infections; neoplasms; endocrine, nutritional, and metabolic diseases; mental disorders; nervous system; circulatory system; respiratory system; digestive system; skin and subcutaneous tissue; musculoskeletal system and connective tissue; and the genitourinary system. Implementing family medicine in rural Japanese communities can improve the comprehensiveness of medical care and resolve the issue of fragmentation of care by improving interprofessional collaboration and community care. It can be a solution for the aging of both patient and healthcare professionals. Future research can investigate the relationship between family medicine and patient health outcomes for improved healthcare sustainability.

Strengths and Challenges for Medical Students and Residents in Rural Japan.

BACKGROUND AND OBJECTIVES: In Japan, family medicine training is driven by community-based medical education (CBME) and is often provided in rural community hospitals and clinics. Although CBME's positive relationship to family medicine in rural community hospitals is proven, the learning processes of medical students and residents in rural community hospitals needs investigating. The objective of this study was to reveal medical students' and residents' changing motivations and learning behaviors, as well as the factors underpinning their transition between medical schools or tertiary hospitals and rural community hospitals. METHODS: Over 2 years, the researchers conducted one-on-one interviews with 50 medical students and 30 residents participating in family medicine training at a rural community hospital, and analyzed the difficulties the participants encountered and how they overcame them. The interviews were audio recorded and transcribed verbatim. We used grounded theory in the data analysis to clarify the findings. RESULTS: Three key themes emerged: educational background, changing environment, and factors driving the learning cycle. Participants had difficulties in overcoming differences between their previous education and their CBME, particularly regarding expected roles and the variety of medical issues. They overcame their difficulties through cognitive apprenticeships and legitimate peripheral participation enhanced by daily reflection. CONCLUSIONS: In rural community hospitals, participants struggled to adapt to the wider practice range and the more interactive relationship with educators. Cognitive apprenticeships and legitimate peripheral participation, supported by constant reflection between learners and clinical teachers, can facilitate learning, leading to more effective learning and practice of family medicine in rural areas.

Visualization of Toyoura sand-grown plant roots by X-ray computer tomography.

Plants establish their root system as a three-dimensional structure, which is then used to explore the soil to absorb resources and provide mechanical anchorage. Simplified two-dimensional growth systems, such as agar plates, have been used to study various aspects of plant root biology. However, it remains challenging to study the more realistic three-dimensional structure and function of roots hidden in opaque soil. Here, we optimized X-ray computer tomography (CT)-based visualization of an intact root system by using Toyoura sand, a standard silica sand used in geotechnology research, as a growth substrate. Distinct X-ray attenuation densities of root tissue and Toyoura sand enabled clear image segmentation of the CT data. Sorghum grew especially vigorously in Toyoura sand and it could be used as a model for analyzing root structure optimization in response to mechanical obstacles. The use of Toyoura sand has the potential to link plant root biology and geotechnology applications.

Students' perceptions of general medicine following community-based medical education in rural Japan.

BACKGROUND: Japan's population is rapidly aging, and at the same time, the number of medical students interested in general or family medicine is declining. Community-based medical education (CBME) programs may be used to promote interest and competencies in general medicine among medical students. METHOD: This mixed-method study investigated the perceptions of fifth- and sixth year undergraduate medical students who completed a two week CBME course in Unnan, a small city in rural Japan. The participants completed two survey questionnaires: (a) The achievement questionnaire administered pre- and posttraining, and (b) the curriculum content questionnaire administered posttraining. To understand the students' perceptions about general medicine further, semistructured interviews were conducted with each participant post-CBME training. RESULTS: The participants' ratings on the achievement survey improved significantly from pre- to posttraining. The average ratings for the curriculum content survey indicated that the educational objectives were met in all but one area. A qualitative analysis of the interview data revealed that the participants had little exposure to general medicine at their university hospital, and there was a lack of understanding in other medical professionals regarding the roles of general medicine physicians. CONCLUSION: This study demonstrates that there are educational gaps between medical universities and community hospitals regarding general medicine. Increased exposure, early exposure, and a clarification of the competencies were noted as areas to improve the students' understanding of general medicine. Undergraduates should be exposed to general medicine more frequently and from early training stages through effective collaborations between universities and hospitals.

Percutaneous sonographically assisted endoscopic gastrostomy for difficult cases with interposed organs.

OBJECTIVES: The aim of this retrospective observational study was to clarify the usefulness and safety of percutaneous sonographically assisted endoscopic gastrostomy or duodenostomy (PSEGD) using the introduction method. METHODS: The information for the sequential 22 patients who could not undergo standard percutaneous endoscopic gastrostomy (PEG) and underwent PSEGD for 3 y was extracted and was reviewed. In standard PEG, we performed pushing out of the stomach from the mediastinum and full distention to adhere the gastric wall to the peritoneal wall without interposing of the intraperitoneal tissues by air inflation and a turning-over procedure of the endoscope, four-point square fixation of the stomach to the peritoneal wall by using a Funada-style gastric wall fixation kit under diaphanoscopy, extracorporeal thumb pushing, and in difficult cases extracorporeal ultrasound guidance, and if necessary confirmation of fixation of the gastric wall to the peritoneal wall and placement of the PEG tube without any interposed tissues by using ultrasound. RESULTS: Twenty-one patients (95.5%) successfully underwent PSEGD. Early complications (more than grade 2 in Clavien-Dindo classification) just after the procedure occurred in one case (active oozing). We did not encounter a case with mispuncture of the intraperitoneal organs and tissues. Delayed complications occurring within 1 mo were pneumonia in five patients, including death in three cases; bleeding from puncture site in two patients; and atrial fibrilation in one patient. CONCLUSION: PSEGD using the introduction method is a useful procedure for difficult patients in whom intraperitoneal organ or tissue is suspected to be interposed between the abdominal wall and stomach.

Evaluation of Collateral Source Characteristics With 3-Dimensional Analysis Using Micro-X-Ray Computed Tomography.

BACKGROUND: Collateral arteries provide an alternative blood supply and protect tissues from ischemic damage in patients with peripheral artery disease. However, the mechanism of collateral artery development is difficult to validate. METHODS AND RESULTS: Collateral arteries were visualized using micro-x-ray computed tomography. Developmental characteristics were assessed using confocal microscopy. We conducted a single-center, retrospective, observational study and assessed the dilatation of collateral arteries on ischemic sides. We quantified the vascular volume in both ischemic and nonischemic legs. A prominent increase in vascular volume was observed in the ischemic leg using a murine hind-limb ischemia model. We also performed qualitative assessment and confirmed that the inferior gluteal artery functioned as a major collateral source. Serial analysis of murine hind-limb vessel development revealed that the inferior gluteal artery was a remnant of the ischial artery, which emerged as a representative vessel on the dorsal side during hind-limb organogenesis. We retrospectively analyzed consecutive patients who were admitted for the diagnosis or treatment of peripheral artery disease. The diameter of the inferior gluteal artery on the ischemic side showed significant dilatation compared with that on the nonischemic side. CONCLUSIONS: Our findings indicate that an embryonic remnant artery can become a collateral source under ischemic conditions. Flow enhancement in the inferior gluteal artery might become a novel therapeutic approach for patients with peripheral artery disease.

Epigastric hernia contiguous with the laparoscopic port site after endoscopic robotic total prostatectomy.

Both laparoscopic and endoscopic robotic surgery are widely accepted for many abdominal surgeries. However, the port site for the laparoscope cannot be easily sutured without defect, particularly in the cranial end; this can result in a port-site incisional hernia and trigger the progressive thinning and stretching of the linea alba, leading to epigastric hernia. In the present case, we encountered an epigastric hernia contiguous with an incisional scar at the port site from a previous endoscopic robotic total prostatectomy. Abdominal ultrasound and CT revealed that the width of the linea alba was 30-48 mm. Previous CT images prepared before endoscopic robotic prostatectomy had shown a thinning of the linea alba. We should be aware of the possibility of epigastric hernia after laparoscopic and endoscopic robotic surgery. In laparoscopic and endoscopic robotic surgery for a high-risk patient for epigastric hernia, we should consider additional sutures cranial to the port-site incision to prevent of an epigastric hernia.

Unprotected left main intervention for surgery-ineligible patients with coronary artery disease-Usefulness of micro-CT images for stent.

BACKGROUND: Percutaneous coronary intervention (PCI) for unprotected left main truncus (LMT) lesions is controversial. Inoperable status with advanced age, renal dysfunction, frailty, or patient request may require an unprotected left main PCI. PCI for LMT is not recommended in the typical clinical situation; however, when it is the only feasible option, the performance is not bad. We demonstrated the result of a cobalt-chromium everolimus-eluting stent (CoCr-EES) in the LMT stenting and serial changes via micro-computed tomography (µCT). µCT is an established imaging technique used for high-resolution, non-destructive assessment of vascular samples. The technique has drawn increasing interest for investigations of atherosclerotic arteries in both humans and animal models. There are no reports regarding the linkage between clinical results and µCT images. METHODS AND RESULTS: Between January 2009 and December 2014, we recruited 118 consecutive, unprotected LMT stenting cases in our institution. We examined the clinical outcomes and angiographic results with a CoCr-EES compared with a first-generation drug-eluting stent. The primary endpoint of this registry was the rate of one-year major adverse cardiac events (MACE). The one-year MACE rate was 2.54%; this did not include the CoCr-EES. We established LMT bifurcation models (mini-crush and culotte) using a CoCr-EES and obtained µCT images of the CoCr-EES. The images showed no deformation or strut apposition. CONCLUSION: CoCr-EES performed well in LMT in our institution and according to µCT. µCT images may be useful for anatomical simulation in stent deployment.

Percutaneous transhepatic duodenostomy for a gastrectomy case with CT guidance and real-time visualization by an ultrasound and endoscopy.

After gastrectomy, the remnant stomach, a small stomach behind the lateral segment of the liver, is thought to be a relative contraindication to receiving a percutaneous endoscopy-guided gastrostomy (PEG). We successfully performed a percutaneous duodenostomy in a case with remnant stomach. We used a transhepatic pull method with computed tomography (CT) guidance and real-time visualization by using ultrasound (US) and an endoscopy. The procedure was as follows: 1. Full stretching of the remnant stomach; 2. Insertion of a fine injection needle into the duodenal lumen through the lateral segment of the liver without an intrahepatic vascular and biliary injury using real-time visualization through US; 3. Confirmation of the location of the fine needle using abdominal CT, which showed the fine needle penetrating through the lateral segment and the duodenal lumen; 4. Insertion of the thick needle of the PEG kit just laterally of the fine needle; 5. Confirmation of the location of the thick needle using a repeated CT; 6. Endoscopic confirmation of the location of the two needles; 7. Changing the direction of the thick needle using guidance with endoscopy, inserting the thick needle into the duodenal lumen, and removing the fine needle; 8. Insertion of the guide wire through the thick needle; and 9. Placement of the PEG tube using the pull method. Using a real-time US scan, we detected the puncture of the anterior wall of the duodenum or stomach and avoided intrahepatic major vascular and biliary injuries.

Successful nutritional support for a dysphagic patient with massive cirrhotic ascites and intrathoracic stomach using percutaneous endoscopic gastrostomy (PEG).

Although massive cirrhotic ascites is generally considered a contraindication for the placement of percutaneous endoscopic gastrostomy (PEG), such patients are usually poorly nourished. Preceding paracentesis of ascites is one method for controlling ascites and allowing the safe placement of PEG, but it often results in overuse of albumin. Preceding peritoneal-venous (P-V) shunting can avoid excessive use of albumin, but this introduces the risk of infectious contamination. We encountered an 88-y-old woman with massive cirrhotic ascites, a giant esophageal hernia with dislocation of the proximal stomach into the mediastinum, hypertrophy of the lateral segment of the liver, and malnutrition who had suffered from appetite loss and a swallowing disorder for 4 mo. She underwent PEG using a staged sequential introduction method using a Funada-style gastric wall fixation kit as follows: 1) full stretching and pushing out of the stomach from the mediastinum into the peritoneal cavity by deep insertion and a turning-over procedure of the endoscope, 2) full distention by air to adhere the gastric wall to the peritoneal wall without migration of the colon, 3) four-point square fixation under gastroenterological endoscopy without migration of the visceral organ, and 4) puncture of the needle introducer of the PEG tube in the center of the fixations under repeated gastroenterological endoscopy 3 d after the fixation. She underwent P-V shunting under local anesthesia on the 28th day after placement of PEG and enteral nutrition. Her case shows that we can achieve proper enteral nutritional support even for patients with massive cirrhotic ascites.

Contaminant migration in unsaturated porous media using X-ray computerized tomography (CT).

Landfills are usually located in unsaturated zones. Contaminant leaking can easily infiltrate groundwater through these porous media and contribute to groundwater pollution. The main objective of this work is to study the leachate migration in unsaturated porous media using X-ray computerized tomography (CT) and image-processing software. Silica sand and Yamazuna sand (collected from Japan) with different particle sizes are considered. Potassium iodide (KI) solution is used as a contaminant and injected into sand specimens at appropriate rates. The specimens are scanned at each cross section before and after contaminant injection by X-ray CT. Subsequently, all CT images are transformed into mean CT values by Image J software. VGStudio software is then used to reconstruct the subtracted images into three-dimensional images. The results indicate that vertical migration is dominant in uniform sand and horizontal migration is the main behavior in well-graded sand. Meanwhile, it is also confirmed that CT scanning is an effective technology to study contaminant migration in unsaturated porous media with different grain sizes.

Efficacy of half-solid nutrient for the elderly patients with percutaneous endoscopic gastrostomy.

Percutaneous endoscopic gastrostomy tube feeding is widely used for patients with swallowing dysfunction and a history of repeated aspiration pneumonitis. However, liquid nutrient feeding via percutaneous endoscopic gastrostomy is not effective enough to prevent aspiration pneumonitis and related inflammatory responses. We performed this prospective multi-centre study to clarify the efficacy of half-solidification of nutrients to prevent fever possibly caused by aspiration pneumonitis in elderly patients with percutaneous endoscopic gastrostomy. The study subjects were 42 elderly patients undergoing percutaneous endoscopic gastrostomy feeding (mean age 85.8 years). All subjects were fed half-solid as well as liquid nutrients for 8 weeks respectively in a cross over design. We counted the number of days with fever caused by pneumonitis and unidentified origin. Thirty-two of 42 patients were successfully observed in both nutrient periods. Fever was frequently observed in both nutrient periods, however, the percentage of observational days with fever during half-solid nutrient feeding was significantly lower than that during liquid nutrient feeding (15.3 ± 0.3 vs 19.8 ± 0.4%, p = 0.030). The percentage of observational days when patients had diarrhea was not significantly different (10.1 ± 3.8 vs 7.2 ± 3.2%, p = 0.357). In conclusion, half-solid nutrient feeding was determined to be effective for reducing fever in patients with percutaneous endoscopic gastrostomy feeding.