Nagoya Journal of Medical Science

Endoscopic papillectomy is widely performed to treat duodenal papillary tumors, particularly at high-volume centers. It is indicated for adenomas without intraductal extension of the bile or pancreatic ducts. However, despite numerous reports of carcinomas that expand the indications to include well-differentiated adenocarcinomas that do not invade the sphincter of Oddi, the low agreement between biopsy and final pathological diagnosis, as well as the current inability of imaging modalities to diagnose sphincter of Oddi invasion, makes it difficult to consider expanding indications. Although complications can be prevented by certain methods, such as pancreatic duct stenting, and the frequency of severe complications has decreased, the safety of the procedure remains unconfirmed. In the future, this technology is expected to progress and enable wider applications, including those in tumors with extensive horizontal spread and those with intraductal extension of the bile and pancreatic ducts. Such technology may also improve the safety and accuracy of diagnosis.

This study aimed to investigate the effects of the coronavirus disease 2019 (COVID-19) pandemic on patients with diabetes mellitus using patient-rated outcome measures focusing on hand function and quality of life, as well as patients’ mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. It was a part of a longitudinal research involving patients with diabetes mellitus living in Sapporo, Japan. Among the 594 patients surveyed before the COVID-19 pandemic from March to June 2019, 417 patients who could be re-surveyed from March to June 2021 were included. We compared the patient-rated outcome measures, namely the Hand10 for hand function and EuroQol five-dimension questionnaire for assessing quality of life in the same population of patients with diabetes mellitus, before and during the COVID-19 pandemic. The results indicated no deterioration in the Hand10 (3.9 vs 3.6) and quality of life scores (0.89 vs 0.9), including mobility (1.25 vs 1.17), self-care (1.1 vs 1.08), pain/discomfort (1.43 vs 1.35), and anxiety/depression (1.21 vs 1.2), during the COVID-19 pandemic when compared with the pre-pandemic values. Usual activity values on the EuroQol five-dimension subscale significantly improved during the pandemic compared to those before the pandemic (1.21 vs 1.12, p<0.01). This study highlighted the effects of the COVID-19 pandemic on patients with diabetes mellitus by comparing patient-rated outcome measures in two different social situations. Patients with diabetes mellitus living in Sapporo, Japan maintained hand function and quality of life by continuing their usual activities during the COVID-19 pandemic.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for treating pain and inflammation. Spontaneous adverse drug reaction (ADR) reports represent a rich data source for the detection of unknown and rare ADRs. This cross-sectional study aimed to analyze the characteristics of ADRs due to NSAIDs in Thailand. All ADR reports of NSAIDs for systemic use from 2015 to 2019 were extracted from the national database in Thailand. Patient characteristics, drug use information, adverse event information, and source of senders in 32,857 reports were analyzed. The annual number of ADR reports due to NSAIDs decreased from 7,008 in 2015 to 5,922 in 2019. The most frequently reported drug was ibuprofen (n=12,645, 38.5%) followed by diclofenac (n=7,795, 23.7%), most patients were 40–59 years old, and the major adverse reaction was angioedema (n=7,513, 22.9%). Serious reactions were recorded in 20.7% (n=6,801) of the total ADRs. Most patients (n=20,593, 62.7%) recovered without sequelae, but there were 5,420 patients (16.5%) who could not recover and 3,109 patients (9.5%) who were recovering. Eight patients (0.02%) died of Stevens-Johnson syndrome (n=3), toxic epidermal necrolysis (n=4), and anaphylactic shock (n=1), which were possibly related to ADRs. The number of ADR reports due to NSAIDs decreased from 2015 to 2019 in Thailand. Serious ADRs and death cases accounted for 20.7% and 0.02%, respectively. Most fatal cases exhibited severe drug-induced skin reactions.

The use of mesenchymal stem/stromal cells (MSCs) has attracted attention in the field of regenerative medicine based on their anti-inflammatory and tissue repair-promoting effects. Bone marrow is widely used as a source of MSCs; however, the performance of bone marrow (BM)-MSCs deteriorates as the cells age along with cell passaging. Recently, it has been reported that MSCs can be generated from induced pluripotent stem cells (iPSCs), which is expected to represent a new source of MSCs. However, few studies have investigated aging in iPSC-derived MSCs (iMSCs) and their functions. In this study, we investigated whether iMSCs overcome cellular senescence compared to that in BM-MSCs. Cellular senescence was quantitatively evaluated by staining iMSCs and BM-MSCs with fluorescein di-β-D-galactopyranoside (FDG) and following flow cytometer analysis. The hepatocyte growth factor (HGF) concentration in the culture supernatant was also measured as a factor in the therapeutic efficacy of nephritis. The iMSCs did not reach their proliferation limit and their morphology did not change even after 10 passages. The FDG positivity of BM-MSCs increased with passaging, whereas that in iMSCs did not increase. The HGF concentration increased with passaging in iMSCs. In conclusion, our results suggest that iMSCs may be less susceptible to senescence than BM-MSCs and may be used in clinical applications.

We estimated the association between the age at smoking initiation and cessation and all-cause and cause-specific mortality among Japanese men (n = 41,711; age 40–79 years) by analyzing data from the Japan Collaborative Cohort Study for the Evaluation of Cancer Risks. From 1988 and 1990 to 2009, 13,429 all-cause deaths (cancers, n = 4999; cardiovascular diseases, n = 3682) occurred in this cohort. Fitted Cox proportional hazard models, with never smokers as the reference group, were created. Former smokers demonstrated a lower risk for all-cause and cause-specific mortality than current smokers, with a dose-dependent reduction in the risk based on smoking-initiation age. Among former smokers who quit smoking aged 50 years or more, the highest hazard ratios were detected for those who started smoking at <20 years of age (all-cause, cancer, and cardiovascular disease mortality, hazard ratio [95% confidence interval] 1.51 [1.29–1.77], 1.68 [1.27–2.23], and 1.48 [1.12–1.96], respectively). Former smokers who quit smoking at <50 years of age had negligible all-cause or cardiovascular disease mortality regardless of the smoking-initiation age, whereas the cancer mortality risk remained significantly high among those who quit smoking at 40–49 years of age. Thus, smoking cessation significantly reduces the all-cause mortality risk; however, early initiation and later cessation do not provide a huge benefit, which earlier cessation does. Therefore, all smokers should be encouraged to quit smoking earlier in life regardless of their age at smoking initiation.

In this study, we elucidate if synthetic contrast enhanced computed tomography images created from plain computed tomography images using deep neural networks could be used for screening, clinical diagnosis, and postoperative follow-up of small-diameter renal tumors. This retrospective, multicenter study included 155 patients (artificial intelligence training cohort [n = 99], validation cohort [n = 56]) who underwent surgery for small-diameter (≤40 mm) renal tumors, with the pathological diagnosis of renal cell carcinoma, during 2010–2020. We created a learned deep neural networks using pix2pix. We examined the quality of the synthetic enhanced computed tomography images created using this deep neural networks and compared them with real enhanced computed tomography images using the zero-mean normalized cross-correlation parameter. We assessed concordance rates between real and synthetic images and diagnoses according to 10 urologists by creating a receiver operating characteristic curve and calculating the area under the curve. The synthetic computed tomography images were highly concordant with the real computed tomography images, regardless of the existence or morphology of the renal tumor. Regarding the concordance rate, a greater area under the curve was obtained with synthetic computed tomography (area under the curve = 0.892) than with only computed tomography (area under the curve = 0.720; p < 0.001). In conclusions, this study is the first to use deep neural networks to create a high-quality synthetic computed tomography image that was highly concordant with a real computed tomography image. Our synthetic computed tomography images could be used for urological diagnoses and clinical screening.

We conducted a study to understand the characteristics of the finishing coils to select the appropriate coil for the final stage of embolization. Consequently, experimental embolization was performed on a 10 mm spherical silicone aneurysm filled with radiolucent coils, which simulated a volume embolization ratio of 20%. Nine different coils (i-ED complex ∞ SilkySoft, SilkySoft, ExtraSoft, V-Trak HyperSoft helical, Barricade 10 complex finishing, Optima complex 10 soft, Target 360 Ultra, Galaxy G3 mini, and Axium prime 3D ExtraSoft) were analyzed six times at random. After each coil insertion, indices that include area, Feret diameter, circularity, and centroid center of mass were calculated using biplane x-ray images. Furthermore, these data were analyzed using the spring constant k, which represents the stiffness of the coil. In multiple comparisons, a significant difference was observed in the area analysis. The i-ED complex ∞ SilkySoft was more widespread than Target 360 Ultra (p < 0.05). However, no significant differences were observed in the other indices. The spring constant k value of Target 360 Ultra was 2.5 times larger than that of the i-ED complex ∞ SilkySoft, and it negatively correlated with the area index rather than with the other indices. Notably, it was suggested that the smaller the spring constant k, the wider the distribution of the finishing coils. Although there was little difference between the coils, some coils had characteristics suggesting that good embolization could be expected using appropriate finishing coils.

The present research aimed to determine the clinical and pathohistological characteristics of thyroid gland diseases in adolescents who were previously surgically treated at the Endocrine Surgery Center of the University Medical Center of Serbia from 01/01/2001 to 01/01/2011. The study covered 170 patients of both sexes from the population of adolescents (aged 16 to 20 years) with various malignant and benign thyroid gland diseases. The data for this study were extracted from the medical histories of patients and the electronic database of the Center for Endocrine Surgery. Detailed data analysis included diagnosis, symptomatology, surgical intervention type, and disease stage. The following thyroid status parameters were analyzed from preoperative data: thyroxine (T4), thyroxine free fraction (FT4), triiodothyronine (T3), triiodothyronine free fraction (FT3), and thyroid stimulating hormone (TSH). In addition, the pathohistological features of diagnosed thyroid diseases were also determined, with a special focus on the presence of well-differentiated cancers. Papillary carcinomas were the most common of well-differentiated cancers in adolescents over the ten-year follow-up period. Based on the assessed data, total thyroidectomy was the most commonly used type of surgical intervention in these patients. The conducted research provides essential information related to both the biological characteristics and diagnostics of these cancers and their surgical treatment in such a sensitive population. Moreover, research showed that the clinical presentation of thyroid cancer in adolescents is almost identical to that in adults.

This study aimed to examine the validity and reliability of the expanded version of the Posttraumatic Growth Inventory-Japanese version (PTGI-X-J) among Japanese women who delivered by cesarean section. The study is a cross-sectional survey psychometric study. Participants were 517 Japanese women who were in the hospital after childbirth by cesarean section at six general hospitals and two obstetric clinics in Tokai Region, Japan. They completed a self-report questionnaire—which included sociodemographic and childbirth information and obstetric history, the PTGI-X-J, and the Postnatal Women Version of the Japanese-Language Version of the Impact of Event Scale-Revised (IES-R-J-PWV). We conducted an exploratory factor analysis to evaluate the factorial validity of the PTGI-X-J. We confirmed the internal consistency reliability of the Postpartum Women Version of PTGI-X-J (PTGI-X-J-PWV) using Cronbach’s α coefficients and examined Spearman’s correlation coefficients between the PTGI-X-J-PWV and the IES-R-J-PWV. The exploratory factor analysis resulted in a 22-item measure that comprised four factors: strength as mothers, spiritual change as mothers, new possibilities as mothers and appreciation of life, and relating to others as mothers. The PTGI-X-J-PWV exhibited good internal consistency reliability (Cronbach’s α = 0.94), and a weak significant positive correlation with the IES-R-J-PWV (rs = 0.18, p < 0.001) was evident. The results of this study indicated that the PTGI-X-J-PWV was a valid and reliable tool for measuring postpartum posttraumatic growth among Japanese women who have delivered by cesarean section. By accurately measuring mothers’ posttraumatic growth, midwives and nurses can provide the kind of care that encourages their growth as mothers.

We aimed to elucidate the distribution pattern of the positron emission tomography probe [18F]THK 5351, a marker for astrogliosis and tau accumulation, in healthy aging. We also assessed the relationship between THK5351 retention and resting state networks. We enrolled 62 healthy participants in this study. All participants underwent magnetic resonance imaging/positron emission tomography scanning consisting of T1-weighted images, resting state functional magnetic resonance imaging, Pittsburgh Compound-B and THK positron emission tomography. The preprocessed THK images were entered into a scaled subprofile modeling/principal component analysis to extract THK distribution patterns. Using the most significant THK pattern, we generated regions of interest, and performed seed-based functional connectivity analyses. We also evaluated the functional connectivity overlap ratio to identify regions with high between-network connectivity. The most significant THK distributions were observed in the medial prefrontal cortex and bilateral putamen. The seed regions of interest in the medial prefrontal cortex had a functional connectivity map that significantly overlapped with regions of the dorsal default mode network. The seed regions of interest in the putamen showed strong overlap with the basal ganglia and anterior salience networks. The functional connectivity overlap ratio also showed that three peak regions had the characteristics of connector hubs. We have identified an age-related spatial distribution of THK in the medial prefrontal cortex and basal ganglia in normal aging. Interestingly, the distribution’s peaks are located in regions of connector hubs that are strongly connected to large-scale resting state networks associated with higher cognitive function.

Microglial processes survey the brain parenchyma, but it is unknown whether this process is influenced by the cell activity of nearby microglia under physiological conditions. Herein, we showed that microglial process dynamics differ when facilitated by astrocytic activity and pre-synaptic activity. The results revealed distinct microglial process dynamics associated with the activity of other brain cells.

Human leukocyte antigen (HLA)-DPB1 antigens are mismatched in approximately 70% of allogeneic hematopoietic stem cell transplantations (allo-HSCT) from HLA 10/10 matched unrelated donors. HLA-DP-mismatched transplantation was shown to be associated with an increase in acute graft-versus-host disease (GVHD) and a decreased risk of leukemia relapse due to the graft-versus-leukemia (GVL) effect. Immunotherapy targeting mismatched HLA-DP is considered reasonable to treat leukemia following allo-HCT if performed under non-inflammatory conditions. Therefore, we isolated CD4⁺ T cell clones that recognize mismatched HLA-DPB1 from healthy volunteer donors and generated T cell receptor (TCR)-gene-modified T cells for future clinical applications. Detailed analysis of TCR-T cells expressing TCR from candidate clone #17 demonstrated specificity to myeloid and monocytic leukemia cell lines that even expressed low levels of targeted HLA-DP. However, they did not react to non-hematopoietic cell lines with a substantial level of targeted HLA-DP expression, suggesting that the TCR recognized antigenic peptide is only present in some hematopoietic cells. This study demonstrated that induction of T cells specific for HLA-DP, consisting of hematopoietic cell lineage-derived peptide and redirection of T cells with cloned TCR cDNA by gene transfer, is feasible when using careful specificity analysis.

This study aimed to confirm the reality of family-focused medical treatment of dementia in Japan and the US. It conducted a questionnaire survey on informed consent from patients with dementia among neurologists and psychiatrists in four prefectures in the Tokai Region (Aichi, Gifu, Mie, and Shizuoka) and dementia specialists in the US. Of the responses, 120 (39.7% response rate) and 20 (5.9% response rate) were obtained, respectively. In obtaining informed consent from patients with dementia, 75 Japanese specialists (62.5%) and 16 US specialists (80.0%) regularly assessed patients’ decision-making abilities. The majority of specialists in both Japan and the US used the Mini–Mental State Examination and Hierarchic Dementia Scale-Revised, which are widely used for cognitive function assessment. In the survey, 27 Japanese specialists (22.5%) and 10 US specialists (50.0%) had different considerations when obtaining informed consent for participation in research, compared to their medical practice. The majority of Japanese and US specialists obtained informed consent from both the patient and their family.

Oncological gastrectomy, despite remaining a mainstay of gastric cancer treatment, is reportedly associated with high morbidity and mortality in elderly patients. Less invasive modalities suitable for senior gastric cancer patients with insufficient surgical tolerance are thus needed. We adopted laparoscopic and endoscopic cooperative surgery as an alternative for elderly gastric cancer cases unsuitable for aggressive gastrectomy. To date, we have experienced three cases (80–86 years old) undergoing palliative laparoscopic and endoscopic cooperative surgery. Postoperative courses were uneventful in two cases, while sutural leakage occurred in the other, which was managed conservatively. Postoperative loss of body weight and skeletal muscle mass appeared to be minimal according to bioelectrical impedance analyses. No gastric cancer recurrence was detected in any of our three cases. As to the balance between radicality and safety, laparoscopic and endoscopic cooperative surgery is potentially a viable option for geriatric gastric cancer patients in whom conventional gastrectomy is contraindicated.

We experienced a relatively rare case of synchronous breast and ovarian cancer in a patient with hereditary breast and ovarian cancer syndrome (HBOC). Here, we report the usefulness of laparoscopic examination to determine the subsequent treatment strategy in cases of suspected concurrent multiple carcinomas. Our patient was diagnosed with breast cancer following detection of a right breast mass. She was diagnosed with HBOC as she was found to be harboring a germline pathogenic variant of breast cancer susceptibility gene 1 (BRCA1). Preoperative images suggested the presence of neoplastic masses in the abdominal cavity, and the possibility of metastatic peritoneal dissemination of breast cancer or concurrent overlapping of gynecological malignancies was considered. We decided to employ laparoscopic examination, and if simultaneous overlapping of cancers was suspected, we planned to further evaluate whether primary debulking surgery (PDS) for gynecological cancer was possible or not. Laparoscopy revealed the presence of ovarian cancer with neoplastic lesions on the bilateral ovaries and disseminations in the pelvic and abdominal cavities. The total predictive index was 0; therefore, PDS was considered feasible. We performed a total mastectomy, followed by laparotomy, and optimal surgery was achieved. The final diagnosis was simultaneous stage IIB invasive ductal breast carcinoma and stage IIIC high-grade serous ovarian carcinoma. In this case of suspected concurrent multiple carcinomas, laparoscopy was beneficial for decision-making regarding subsequent surgical treatment. We believe that the use of laparoscopy will enable simultaneous surgery for breast cancer and ovarian cancer to become one of the treatment strategies in the future.

A 21-year-old Japanese woman presented with sudden eye movement disorders. An ophthalmic examination revealed bilateral hypotropia and esotropia complex. Brain magnetic resonance imaging revealed abnormal signals in the posterior and medial part of the lower pontine tegmentum (including periventricular and subcortical white matter) that were suggestive of demyelination. A cerebrospinal fluid test was positive for oligoclonal bands. She was subsequently diagnosed with multiple sclerosis and was administered intravenous methylprednisolone and oral dimethyl fumarate, with complete recovery from hypotropia and esotropia after two months. Bilateral hypotropia and esotropia are important clinical signs for the accurate diagnosis of multiple sclerosis.

Gliosarcoma (GS), a morphological variant of glioblastoma, pathologically shows a biphasic pattern with gliomatous and sarcomatous components. It has been reported that GS has much higher metastatic capacity than glioblastoma. A few reports on the pathology of the extracranial metastasis of GS have shown that metastatic lesions had a sarcomatous component alone or a mixture of gliomatous and sarcomatous ones. Therefore, it is considered that GS tends to disseminate hematogenously due to its mesenchymal sarcomatous component. Herein, we report an autopsy case of GS with multiple extracranial metastases treated by craniotomy, radiotherapy, and bevacizumab. In this case, metastatic lesions at autopsy contained a gliomatous component alone, but no sarcomatous component. In addition, the sarcomatous component disappeared from the intracranial lesion at autopsy after the administration of bevacizumab. In this report, we discuss the clinical course and pathological findings at the initial state, recurrence, and autopsy, including the results of whole-genome analysis.

Ureteroenteric anastomotic strictures (UEAS) are typical complications after creating an ileal conduit for total pelvic exenteration (TPE) of rectal tumors. We report the ileal conduit for reconstruction in three patients, in the age-range of 47–73 years. Case 1 was when a left-sided UEAS had sufficient length of ureter for anastomosis, Case 2 was a right-sided UEAS with sufficient length of ureter for anastomosis, and Case 3 was a left-sided UEAS with insufficient length of ureter for anastomosis. There were no complications after operation and no recurrence of UEAS. It is important to learn the open surgical procedures for repair of a benign UEAS after TPE of rectal cancers. This has fewer complications and is safe in the long term.

Ultra-high-density mapping was used for potential-guided radiofrequency ablation for typical atrioventricular nodal reentrant tachycardia. The mapping detailed the spread of activation in the Koch’s triangle and identified target potentials and tachycardia circuits. This mapping provides additional information to the slow pathway conventionally used for safe and effective ablation.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) has been regarded as a long-term problem after silicone breast implantations. We report a case in which BIA-ALCL and breast cancer were not detected preoperatively, with subsequent removal of a ruptured breast implant. A 52-year-old woman had silicone breast implants on both sides for breast augmentation 15 years ago. Right axillary lymphadenopathy and intracapsular ruptures were noted by magnetic resonance imaging. Right axillary lymph node biopsy was performed at our department of breast surgery. Flow cytometry for BIA-ALCL was also performed using the exudate around the implant. The results were negative for breast cancer and BIA-ALCL. However, taking into consideration exacerbation of breast implant rupture and the patient’s anxiety about BIA-ALCL, ruptured bilateral implants were removed by total capsulectomy. The postoperative course was uneventful 1 year after the operation, and her anxiety was dispelled despite her breast deformity. Appropriate explantation and periodic examination may be required to prevent excessive anxiety.

Dupilumab-induced hypereosinophilia is mediated by blockade of the IL-4/IL-13 pathway, which reduces eosinophil migration from peripheral blood. The increase in peripheral blood eosinophils may lead to chronic eosinophilic pneumonia (CEP) and/or eosinophilic granulomatosis with polyangiitis, but a direct causal connection between dupilumab and eosinophilic lung diseases has not been established. A 33-year-old Japanese woman with bronchial asthma since age three was treated with fluticasone propionate plus salmeterol twice daily after several asthma exacerbations at age 17. Her course was complicated by CEP at age 33 which resolved without the need for systemic steroids. However, in the four months following resolution of her CEP, the patient had three asthma exacerbations, and a recurrence of CEP, with blood leukocytes of 8500/µL, of which 25.0% were eosinophils. She was treated with prednisolone 50 mg/day, but she could not continue this dose due to the onset of myalgia. Then she had relapsing CEP twice within three months. She was treated with prednisolone 15 mg/day for CEP, but she had persistent asthma for more than one month; dupilumab was added at 600 mg, followed by 300 mg every two weeks. In the first month of treatment with dupilumab, the patient’s asthma symptoms resolved completely, and she had only one relapse of CEP. In 12 months of follow-up, she had neither an asthma exacerbation nor another relapse of CEP. Dupilumab may be a promising treatment for patients with refractory asthma complicated by recurring CEP and undesirable steroid side effects.

Sporadic inclusion body myositis (s-IBM) is an acquired degenerative inflammatory myopathy that leads to slowly progressive muscle weakness and atrophy of the limbs, face, and pharynx. Owing to the slow progression of the disease, the indications for surgical intervention remain unclear. Herein, we retrospectively reviewed the records of four patients with s-IBM who had undergone cricopharyngeal myotomy for severe dysphagia at our institution between 2016 and 2021. Among these, one patient underwent transcervical cricopharyngeal myotomy and laryngeal suspension, as videofluoroscopic examination of swallowing revealed poor laryngeal elevation. The remaining three patients underwent endoscopic cricopharyngeal myotomy using a curved rigid laryngoscope. Preoperatively, the mean Hyodo score was 8 points (range: 6–10) using a flexible endoscope. The mean surgical duration was 104 min, and no severe complications were observed. Postoperatively, all patients achieved improvement in swallowing function and food intake. Moreover, swallowing function was maintained in all four patients even 6–12 months postoperatively. Cricopharyngeal myotomy may be a safe surgical procedure with the potential to improve swallowing function, and a Hyodo score of 6 may be considered a surgical indication for cricopharyngeal myotomy in patients with s-IBM.