Buruli ulcer: An epidemiological update from Japan.

Japan is one of the rare non-tropical countries with documented cases of Buruli ulcer (BU). Mycobacterium ulcerans subsp. shinshuense has been identified as the causative agent. The first report of BU in Japan dates back to 1982, with sporadic reports thereafter. Recently, the number of cases has been on the increase, and 50 cases (57.7%) are from the past decade alone, out of a total of 87 cases reported to date. Japan's well-developed healthcare facilities play a crucial role in enabling detailed investigations and providing appropriate treatment for patients, contributing to a favorable prognosis. However, the rarity of the disease results in lack of awareness among healthcare professionals, leading to frequent delays in diagnosis. This article aims to offer an updated overview of BU cases in Japan and to raise awareness of BU among dermatologists and other healthcare professionals in a non-endemic setting.

Gaming Disorders: Navigating the Fine Line between Entertainment and Addiction-Gaming History, Health Risks, Social Consequences, and Pathways to Prevention.

The number of people immersed in excessive gaming has increased in this age of rapid digitalization. The World Health Organization and American Psychiatric Association Organization recognize a gaming disorder as a condition that results in significant problems in daily life as a result of excessive gaming. Both organizations emphasize the similarities to behavioral addictions such as gambling. We examined the appropriate usage of video games from the perspectives of health and management in this study. For the general population, video games provide positive impacts such as stress alleviation and memory improvement. Game playing leads to a loss of time and money for the individual. It also has a negative impact on the individual's family and social life, evolving into a social problem. Gaming addiction is often accompanied by psychological disorders and other addictions, and long-term medical treatment, including approaches to the individual's psychological background and cognitive-behavioral therapy, is necessary. Therefore, the prevention of gaming disorder is essential. From a societal standpoint, action is required in three contexts: the government, game developers, and within the household as a whole. Simultaneously, the public needs to understand the positive potential of gaming, such as e-sports.

Esophageal dedifferentiated liposarcoma resected by the cervical approach: a case report.

BACKGROUND: While liposarcomas tend to mainly occur in the soft tissues of the extremities and retroperitoneum, esophageal liposarcoma is rare. Herein, we report a case of a patient who underwent complete resection of an esophageal dedifferentiated liposarcoma via the cervical approach, leading to the preservation of the esophagus. CASE PRESENTATION: A 69-year-old man underwent an upper gastrointestinal endoscopy, as a result of which a submucosal-like tumor was observed. Upper gastrointestinal imaging showed a 12-cm tumor with a stalk arising from the esophageal entrance, extending to the middle intrathoracic esophagus, with a normal surface mucosa. Endoscopic ultrasound-fine needle aspiration biopsy showed that the nuclei of tumors cells were positive for murine double minute (MDM) and weakly positive for cyclin-dependent kinase 4 (CDK4). We diagnosed the tumor as the esophageal dedifferentiated liposarcoma, and planed tumor resection via the cervical approach. The tumor was successfully resected and the postoperative course was uneventful. CONCLUSION: This case report highlights the use of tumor resection via the cervical approach as a good option for esophageal liposarcoma.

Locally advanced rectal cancer in a young adult affected with dyskeratosis congenita (Zinsser-Cole-Engman syndrome): a case report.

BACKGROUND: Dyskeratosis congenita (DKC), also known as Zinsser-Cole-Engman syndrome, is a progressive genetic disease with a triad of reticulate skin pigmentation, nail dystrophy, and leukoplakia. Approximately 8-10% of patients with DKC develop malignancies, and cases of colorectal cancer with DKC in young people have been reported previously. CASE PRESENTATION: A 25-year-old man with DKC since approximately 10 years of age developed fever and lower abdominal discomfort. Diagnostic imaging revealed locally advanced rectal cancer with lymph node metastasis, direct invasion of the prostate, and pelvic abscess due to tumor microperforation (cT4bN2M0 cStage IIIC). Biopsy showed well to moderately differentiated ductal adenocarcinoma. Genetic testing was negative for RAS and BRAF gene mutations, and microsatellite instability (MSI) testing was also negative. After sigmoid colostomy, the patient was treated with total neoadjuvant therapy (TNT) with systemic chemotherapy (six courses of FOLFOX + panitumumab) followed by chemoradiation therapy (50.4 Gy with capecitabine). After TNT, the primary tumor and metastatic lymph nodes shrank. According to the findings of colonoscopy and magnetic resonance image (MRI), we diagnosed near complete response (near-CR) and decided to follow the patient without surgery by every 3 months re-evaluation. However, 5 months after TNT, tumor regrowth was detected on colonoscopy and imaging, and the patient underwent total pelvic exenteration. He developed paralytic ileus as a postoperative complication, and was discharged on the 38th postoperative day. Pathological examination revealed a residual tumor with invasion of the periprostatic tissue. There was no metastasis in the pararectal and lateral pelvic lymph nodes, but one extramural non-contiguous cancerous extension (tumor deposit) was observed (ypT4bN1cM0 ypStage IIIC). The patient has been free of recurrence for one year after surgery. CONCLUSIONS: DKC often develops into various tumors in the digestive system at an early age; therefore, appropriate surveillance may be required. In addition, considering that cancers in patients with DKC occur at a young age, fertility preservation and survivorship are also important, and adequate explanations and care should be provided to patients before and after treatment.

Intracranial Subdural Empyema During Long-term Chemotherapy for Metastatic Colorectal Cancer: Case Report.

BACKGROUND/AIM: Although chemotherapy for colorectal cancer has advanced remarkably, long-term chemotherapy can lead to a variety of infections. However, if chemotherapy must be discontinued to control infection, there is a risk of progression of colorectal cancer. Intracranial subdural empyema is a life-threatening intracranial infection. The condition requires 6-8 weeks of antibiotic therapy, and the patient must discontinue chemotherapy during treatment. We herein present a case of intracranial subdural empyema during long-term chemotherapy for metastatic rectal cancer. CASE REPORT: A 69-year-old woman with unresectable metastatic rectal cancer had a convulsive seizure and was admitted to our hospital. The cause of the convulsive seizure was considered a metastatic brain tumor from rectal cancer. However, on the basis of contrast-enhanced computed tomography and contrast-enhanced magnetic resonance imaging, we diagnosed intracranial subdural empyema. The infection was controlled by antibiotics, but chemotherapy for rectal cancer was discontinued during antibiotic treatment. As a result, the rectal cancer progressed, and the patient died 65 days after admission to our hospital. CONCLUSION: Intracranial subdural empyema may develop rarely during chemotherapy. This condition requires long-term treatment with antibiotics; therefore, early detailed imaging and diagnosis may improve the prognosis.

Association of Acute Care Surgeon Involvement With Post-Surgery Complications.

INTRODUCTION: Acute care surgeons are experts in trauma treatment, emergency surgery, and critical surgical care. Here, we analyzed the association of acute care surgeons on postoperative outcomes of emergency general surgery. METHODS: This retrospective study included 92 patients who underwent emergency general surgery at our institution between January 2020 and September 2021. Propensity score matching was used to analyze postoperative outcomes. The primary outcome was postoperative complications, while secondary outcomes included perioperative management and surgery-related and postoperative complications. Logistic regression analysis was used to estimate the odds ratios for all complications. In this study, acute care surgeons were defined as acute care surgery (ACS)-certified surgeons by the Japanese Society for Acute Care Surgery. RESULTS: Overall, 30 patients were treated by an acute care surgeon and general surgeons (ACS group), and 62 patients were treated by general surgeons (non-ACS group), respectively. Propensity score matching identified 30 patients with balanced baseline covariates, in each group. The ACS group had lower complication rates (Clavien-Dindo classification ≥2) than the non-ACS group (17% versus 40%, P = 0.08). The ACS group had a significantly shorter surgery duration than the non-ACS group (75 min versus 96 min, P = 0.014). In the logistic analysis, acute care surgeon involvement was identified as an independent predictor for the decrease in all complications (odds ratio, 0.15; 95% confidence interval, 0.02-0.64). CONCLUSIONS: It was suggested that the involvement of acute care surgeons may reduce the overall complication rate in emergency general surgery.

Advanced Lung Cancer Inflammation Index: A Novel Comprehensive Biomarker of Host Status for Patients with Metastatic Colorectal Cancer.

Numerous biomarkers that reflect host status have been identified for patients with metastatic colorectal cancer (mCRC). However, there has been a paucity of biomarker studies that comprehensively indicate body composition, nutritional assessment, and systemic inflammation status. The advanced lung cancer inflammation index (ALI), initially introduced as a screening tool for patients with non-small-cell lung cancer in 2013, emerges as a holistic marker encompassing all body composition, nutritional status, and systemic inflammation status. The index is calculated by the simple formula: body mass index × albumin value / neutrophil-to-lymphocyte ratio. Given its accessibility in routine clinical practice, the ALI has exhibited promising clinical utility in prognosticating outcomes for patients with multiple types of cancer. In this review, we focus on the significance of host status and the clinical applicability of the ALI in the treatment and management of patients with malignancies, including mCRC. We also suggest its potential in guiding the formulation of treatment strategies against mCRC and outline future perspectives.

Pilot use of a mycolactone-specific lateral flow assay for Buruli ulcer: A case report from Japan.

Buruli ulcer, caused by Mycobacterium (M.) ulcerans, is a neglected tropical disease (NTD) characterized by necrosis of the cutaneous tissue, predominantly affecting the limbs. The pathogenesis of this disease is mainly attributed to mycolactone, a lipid toxin produced by M. ulcerans. Here, we report the case of a 7-year-old Japanese girl who presented with worsening ulceration on her left forearm, extending to the elbow, following antimicrobial treatment. To evaluate disease progression, we used a mycolactone-specific lateral flow assay. The test yielded positive results in the advancing necrotic area, aiding in determining the extent of necessary debridement. After undergoing two debridement surgeries and receiving 38 weeks of antimicrobial treatment followed by skin grafting, the patient achieved cure. Timely diagnosis is imperative in avoiding prolonged treatment, highlighting the importance of readily available diagnostic point-of-care tests for Buruli ulcer. Moreover, detection of mycolactone not only can serve as a diagnostic tool for Buruli ulcer but also enables prediction of lesion spread and assessment of cure.

BRAF-mutant mismatch repair deficient invasive colon cancer regressing to sessile serrated lesion.

A 69-year-old female was presented with a history of sigmoid colon cancer, uterine cancer, and intrahepatic carcinomas. After computed tomography revealed a disseminated nodule located in the peritoneum, colonoscopy demonstrated a rather flat-to-slightly elevated lesion with a depressed area located in the ascending colon. The flat component showed color similar to its surrounding area, and the depressed area showed redness and an expanded appearance. We obtained a biopsy specimen from the depressed area, and microscopic examination revealed well-differentiated adenocarcinoma, which was immunohistochemically positive for BRAF V600E-mutated and PMS2 proteins, and showed loss of MSH2 and MSH6 protein expressions. These findings suggested the lesion to have transformed from a sessile serrated lesion (SSL) to mismatch repair (MMR) deficient colon cancer. The patient underwent surgical removal of the nodule, which interpreted as metastasis of intrahepatic cholangiocarcinoma histopathologically. After postoperative chemotherapy, the follow-up colonoscopy revealed only the flat portion of the lesion without depressed area. Consequently, we performed an endoscopic resection, and microscopic examination confirmed the existence of BRAF V600E-mutated protein-positive and MMR protein-retained SSL without residual carcinoma. This is the first report of BRAF-mutant and MMR-deficient colon cancer, in association with SSL, showing regression.

Angiopoietin-Like Protein 2 Expression in Tumor Cells Supports Tumor-Associated Macrophage-Induced Tumor Progression in Esophageal Cancer.

BACKGROUND: Tumor-associated macrophages (TAM), a major component of the tumor microenvironment, play key roles in tumor formation and progression; however, mechanisms underlying TAM-induced tumor progression are complex and not well known. We previously reported that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) functions as a tumor promoter in some cancer contexts. METHODS: We examined ANGPTL2 expression in paraffin-embedded tumor samples from resected specimens of 221 patients with esophageal cancer. Patients were subdivided into four groups based on immunohistochemistry scores described above: ANGPTL2-low/TAM-low, ANGPTL2-low/TAM-high, ANGPTL2-high/TAM-low, and ANGPTL2-high/TAM-high groups. Gene expression datasets of esophageal cancer cell lines were obtained from the cancer cell line encyclopedia public database. RESULTS: In this study, we demonstrate that TAM infiltration is associated with poor prognosis in patients with esophageal cancer whose tumor cells show relatively higher ANGPTL2 expression levels; however, TAM infiltration did not affect prognosis in patients with ANGPTL2-low-expressing esophageal cancer, suggesting that ANGPTL2 expression in esophageal cancer cells is required for TAM-induced tumor progression. Our analysis of public datasets indicates a potential positive correlation of ANGPTL2 expression levels with that of transforming growth factor (TGF)-ß, a TAM-activating factor, in esophageal cancer cell lines. CONCLUSION: We conclude that ANGPTL2 signaling in tumor cells supports TAM-induced tumor progression and contributes to poor prognosis in patients with esophageal cancer. These findings overall provide novel insight into pro-tumor ANGPTL2 functions and illustrate the essential role of cancer cell/TAM crosstalk in cancer progression.

Presence of Fusobacterium nucleatum in relation to patient survival and an acidic environment in oesophagogastric junction and gastric cancers.

BACKGROUND: Fusobacterium nucleatum inhabits the oral cavity and affects the progression of gastrointestinal cancer. Our prior findings link F. nucleatum to poor prognosis in oesophageal squamous cell carcinoma via NF-κB pathway. However, its role in oesophagogastric junction and gastric adenocarcinoma remains unexplored. We investigated whether F. nucleatum influences these cancers, highlighting its potential impact. METHODS: Two cohorts of EGJ and gastric adenocarcinoma patients (438 from Japan, 380 from the USA) were studied. F. nucleatum presence was confirmed by qPCR, FISH, and staining. Patient overall survival (OS) was assessed based on F. nucleatum positivity. EGJ and gastric adenocarcinoma cell lines were exposed to F. nucleatum to study molecular and phenotypic effects, validated in xenograft mouse model. RESULTS: In both cohorts, F. nucleatum-positive EGJ or gastric adenocarcinoma patients had notably shorter OS. F. nucleatum positivity decreased in more acidic tumour environments. Cancer cell lines with F. nucleatum showed enhanced proliferation and NF-κB activation. The xenograft model indicated increased tumour growth and NF-κB activation in F. nucleatum-treated cells. Interestingly, co-occurrence of F. nucleatum and Helicobacter pylori, a known risk factor, was rare. CONCLUSIONS: F. nucleatum can induce the NF-κB pathway in EGJ and gastric adenocarcinomas, leading to tumour progression and poor prognosis.

Laparoscopic versus open abdominal lymph node dissection for esophageal squamous cell carcinoma: a propensity score matching analysis.

PURPOSE: To compare the short- and long-term outcomes of laparoscopic and open abdominal lymph node dissection using propensity score matching (PSM) analysis. METHODS: The subjects of this retrospective analysis were 459 patients who underwent curative resection for esophageal squamous cell carcinoma (ESCC) between May, 2005 and December, 2019, at our hospital. Patients were divided into two groups: the Laparoscopic (Lap group) and the Open (Open group). Post-PSM, 139 patients from each group were selected for the analysis to compare the short- and long-term outcomes between the groups. RESULTS: The Lap group experienced fewer Clavien-Dindo (CD) Grade ≥ 2 complications (28.1% vs. 40.3%, P = 0.04) and lower rates of abdominal surgical site infections (SSI) (2.9% vs. 7.9%, P = 0.02) than the Open group. The number of lymph nodes harvested was similar in the Lap and Open groups (14.8 ± 7.5 vs. 15.7 ± 8.6, P = 0.34). There was no significant difference in 3-year overall survival rates (81.2% vs. 69.5%, P = 0.12) or relapse-free survival rates (61.1% vs. 58.2%, P = 0.54) between the groups. CONCLUSIONS: Laparoscopic abdominal lymph node dissection for ESCC can be performed safely and appears to be beneficial.

Transcriptome analysis of long non-coding RNAs in Mycobacterium avium complex-infected macrophages.

Mycobacterium avium complex (MAC) is a non-tuberculous mycobacterium widely distributed in the environment. Even though MAC infection is increasing in older women and immunocompromised patients, to our knowledge there has been no comprehensive analysis of the MAC-infected host-cell transcriptome-and particularly of long non-coding RNAs (lncRNAs). By using in vitro-cultured primary mouse bone-marrow-derived macrophages (BMDMs) and Cap analysis of gene expression, we analyzed the transcriptional and kinetic landscape of macrophage genes, with a focus on lncRNAs, during MAC infection. MAC infection of macrophages induced the expression of immune/inflammatory response genes and other genes similar to those involved in M1 macrophage activation, consistent with previous reports, although Nos2 (M1 activation) and Arg1 (M2 activation) had distinct expression profiles. We identified 31 upregulated and 30 downregulated lncRNA promoters corresponding respectively to 18 and 26 lncRNAs. Upregulated lncRNAs were clustered into two groups-early and late upregulated-predicted to be associated with immune activation and the immune response to infection, respectively. Furthermore, an Ingenuity Pathway Analysis revealed canonical pathways and upstream transcription regulators associated with differentially expressed lncRNAs. Several differentially expressed lncRNAs reported elsewhere underwent expressional changes upon M1 or M2 preactivation and subsequent MAC infection. Finally, we showed that expressional change of lncRNAs in MAC-infected BMDMs was mediated by toll-like receptor 2, although there may be other mechanisms that sense MAC infection. We identified differentially expressed lncRNAs in MAC-infected BMDMs, revealing diverse features that imply the distinct roles of these lncRNAs in MAC infection and macrophage polarization.

Intractable Nocardial mycetoma with possible colonisation by Candida species.

A Japanese male in his 30s with no underlying medical condition presented with painless nodules after being bitten by a dog during a stay in Bali, Indonesia, 7 years earlier. He was referred to our department with multiple ulcers, nodules, and masses on the right leg. The final diagnosis was mycetoma caused by Nocardia vulneris, which may have been exacerbated by colonization of Candida parapsilosis and C. tropicalis as these yeasts were isolated by culture from the tissue. Treatment with minocycline hydrochloride and sulfamethoxazole trimethoprim showed partial efficacy, but the addition of posaconazole achieved significant efficacy. This suggests that the surmised coexistence of pathogenic yeasts of lower virulency may have made mycetoma in this case intractable.

The relationship between the treatment course and prognosis of oligometastasis after esophageal squamous cell carcinoma resection.

PURPOSE: The concept of oligometastasis, which represents limited metastatic disease, has recently gained interest, accompanied by a more detailed classification. This study aims to investigate the relationship between the treatment course and prognosis in patients with a recurrence of esophageal squamous cell carcinoma (ESCC) after curative esophagectomy. METHODS: 126 patients with ESCC recurrence after curative resection were enrolled in this study. Oligometastasis was defined as fewer than five recurrences in a single organ. Patients were classified as having oligometastatic recurrence (OLR) or polymetastatic recurrence (PLR). Patients were further classified into four subgroups according to lesion progression: persistent oligorecurrence (PER-OLR), converted polyrecurrence (CON-PLR), induced oligorecurrence (IND-OLR), and persistent polyrecurrence (PER-PLR). We analyzed the relationship between the recurrence patterns and prognosis according to the progression of oligometastatic lesions. RESULTS: OLR was identified in 58 (46%) of 126 patients with recurrence. Patients with OLR had a significantly better prognosis than those with PLR (P < 0.0001). A further subgroup analysis revealed that patients who underwent IND-OLR had a similar prognosis to those who underwent PER-OLR. CONCLUSIONS: This study suggests that OLR is a prognostic factor after recurrence following resection of ESCC and that PLR can be converted to OLR by therapeutic intervention to achieve a long-term survival.

Poorly differentiated mucinous carcinoma of the ascending colon complicated by bilateral ovarian mature cystic teratomas in a 17-year-old female patient: a case report.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide, and screening colonoscopy has led to a decreasing incidence rate. However, the incidence of CRC is increasing among young people, especially adolescents and young adults (AYAs) who are not routinely screened. Although CRC is the fourth most common cancer among AYAs, it is extremely rare. In younger patients, CRC is often diagnosed later, and the proportion of patients with advanced CRC is higher than that in older patients. We herein present a case of poorly differentiated mucinous carcinoma of the ascending colon complicated by bilateral ovarian mature cystic teratomas (MCTs) in an AYA. CASE PRESENTATION: A 17-year-old female patient presented with a chief complaint of abdominal pain and diarrhea that had persisted for more than 3 years. Colonoscopy revealed circumferential wall thickening of the ascending colon, and colonic biopsy revealed a mucous mass and findings of adenocarcinoma, predominantly signet ring cell carcinoma. Abdominal computed tomography (CT) and pelvic magnetic resonance imaging (MRI) showed bilateral ovarian tumors. Laparoscopic right hemicolectomy and enucleation of bilateral ovarian tumors were performed. Although the ascending colon cancer formed a large mass, there were no signs of peritoneal dissemination or direct invasion to the surrounding organs. Microscopically, the ascending colon was a poorly differentiated mucinous carcinoma with signet ring cell carcinoma and lymph node metastasis (9/42). The ovarian tumors were diagnosed as MCTs without any malignant components. The pathological diagnosis was ascending colon cancer (pT4aN2bM0, pStage IIIC) and bilateral ovarian MCTs. Microsatellite instability (MSI) testing was negative, and there were no gene mutations in either RAS or BRAF. Postoperative adjuvant chemotherapy with oxaliplatin and 5-FU was started. CONCLUSIONS: We presented a case of locally advanced ascending colon cancer in a 17-year-old female patient. CRC rarely occurs in AYAs. However, the incidence has gradually increased in recent years. It should be considered as a differential diagnosis for young patients with long-term abdominal symptoms of unknown cause.

Conversion surgery for stage IV gastric cancer with multiple liver metastases with a complete pathological response to S-1 plus oxaliplatin therapy.

Although patients with stage IV gastric cancer who respond well to systemic chemotherapy can be treated with gastrectomy, the prognosis of patients with multiple liver metastases is poor. We herein describe a patient with stage IV gastric cancer with multiple liver metastases who underwent conversion surgery after systemic treatment with S-1 plus oxaliplatin. The patient was a 62-year-old man. Upper gastrointestinal endoscopy revealed a 30-mm type 2 tumor in the greater curvature of the stomach at the anterior wall, and biopsy revealed a poorly differentiated adenocarcinoma. Imaging showed three suspected liver metastases in liver segment S8. The patient was judged to have gastric cancer, cStage IV (cT3N1M1(H)), and systemic chemotherapy was administered. He was treated with a total of six courses of chemotherapy. After re-evaluation, the primary tumor had shrunk significantly, and liver metastases could not be detected. Confirming no signs of seeding by laparoscopy, robot-assisted pylorus-preserving gastrectomy with D2 dissection and laparoscopic partial hepatic (S8) resection were performed. The patient was diagnosed with a complete pathological response. Conversion surgery is an option for stage IV gastric cancer when distant metastases are controlled with chemotherapy and when R0 resection is possible.

Age-associated reduction of sinus macrophages in human mesenteric lymph nodes.

There are numerous macrophages and dendritic cells in lymph nodes (LNs). Recent studies have highlighted that sinus macrophages (SMs) in LNs possess antigen-presenting capabilities and are related to anti-cancer immune responses. In this study, we assessed the distribution of SMs in mesenteric LNs removed during surgery for colorectal cancer. A marked reduction of SMs was noted in elderly patients, particularly those over 80 years old. We observed a disappearance of CD169-positive cells in LNs where SMs were reduced. In silico analysis of publicly available single-cell RNA sequencing data from LNs revealed that CD169-positive macrophages express numerous genes associated with antigen presentation and lymphocyte proliferation, similar to dendritic cells' functions. In conclusion, our study demonstrates that SMs, potentially crucial for immune activation, diminish in the LNs of elderly patients. This reduction of SMs may contribute to the immune dysfunction observed in the elderly.