Profilin 2 isoform expression is associated with lung metastasis of colorectal cancer according to a comprehensive gene expression study using a mouse model.

Lung metastasis is the second most common type of metastasis in colorectal cancer. Specific treatments for lung metastasis have not been developed since the underlying mechanisms are poorly understood. The present study aimed to elucidate the molecular basis of lung metastasis in colorectal cancer. In a mouse model, cell lines that were highly metastatic to the lungs were established by injecting colorectal cancer cells through the tail vein and removing them from the lungs. Differential gene expression comparing the transfected cells with their parental cells was investigated using DNA microarrays. The results were functionally interpreted using gene enrichment analysis and validated using reverse transcription-quantitative PCR (RT-qPCR). The isoforms of the identified genes were examined by melting curve analysis. The present study established colorectal cancer cell lines that were highly metastatic to the lungs. DNA microarray experiments revealed that genes (N-cadherin, VE-cadherin, Six4, Akt and VCAM1) involved in motility, proliferation and adhesion were upregulated, and genes (tissue inhibitor of metalloproteinase-3 and PAX6) with tumor-suppressive functions were downregulated in metastatic cells. Profilin 2 (PFN2) expression was upregulated in multiple metastatic cell lines using RT-qPCR. Two PFN2 isoforms were overexpressed in metastatic cells. In vitro and in vivo models were established and genes associated with lung metastasis were identified to overcome the heterogeneity of the disease. Overall, aberrant PFN2 expression is unreported in lung metastasis in colorectal cancer. In the present study, two PFN2 isoforms with differential tissue distribution were upregulated in metastatic cells, suggesting that they promote lung metastasis in colorectal cancer.

Combined Comprehensive Risk Score of the Estimation of Physiologic Ability and Surgical Stress and C-Reactive Protein-to-Albumin Ratio Is a Strong Prognostic Indicator of Long-term Outcomes in Colorectal Cancer.

BACKGROUND: In patients with colorectal cancer, both C-reactive protein-to-albumin ratio and comprehensive risk score of the estimation of physiologic ability and surgical stress have demonstrated prognostic significance. OBJECTIVE: To assess the clinical value of the combined use of C-reactive protein-to-albumin ratio and comprehensive risk score for predicting prognosis in patients with colorectal cancer. DESIGN: Multicenter retrospective study. SETTINGS: The cohort was divided into 3 groups based on a combined score derived from the value of C-reactive protein-to-albumin ratio and comprehensive risk score (low/mid /high). PATIENTS: Patients who underwent curative resection between 2010 and 2019 at multiple institutions were enrolled in this study. MAIN OUTCOME MEASURES: Overall and recurrence-free survival. RESULTS: A total of 2207 patients (801 in low cohort, 817 in mid cohort, and 589 in high cohort) were included in this study. Multivariate analysis revealed that combined score was an independent prognostic factor for both overall and recurrence-free survival, irrespective of disease stage (p < 0.05). Furthermore, Harrell's C-Index indicated that the predictive power of combined score was significantly superior to that of C-reactive protein-to-albumin ratio or comprehensive risk score (p < 0.001). LIMITATIONS: This study had a retrospective design, and data on genetic markers were not included. CONCLUSION: The synergistic combination of C-reactive protein-to-albumin ratio and comprehensive risk score contributes to the robust definition of combined score, a potent prognostic factor, regardless of disease stage. This finding has the potential to provide novel insights into the management of patients with CRC who have undergone curative resection. See Video Abstract.

Correlation Analysis of Clinician- and Patient-Reported Outcomes Among Japanese Adults with Atopic Dermatitis.

INTRODUCTION: Atopic dermatitis (AD) is a chronic relapsing condition with high disease burden and impact on health-related quality of life (HRQoL). Correlations between clinician- and patient-reported outcomes tend to be poor, and limited data in Asian patients are available. METHODS: ADDRESS-J was a prospective, non-interventional, longitudinal study that evaluated the real-world effectiveness and safety of AD treatment in Japanese adults (aged 20-59 years) with moderate-to-severe AD. Three clinician-reported AD severity outcomes (Investigator's Global Assessment, Eczema Area and Severity Index, and body surface area affected), three dermatological patient-reported outcomes (Patient-Oriented Eczema Measure, Dermatology Life Quality Index, and Worst Itch Numerical Rating Scale), and two general HRQoL patient-reported outcomes (5-dimension EuroQoL questionnaire and EuroQol Visual Analog Scale) were collected at baseline and every 3 months throughout the 24-month observation period. Four biomarkers were also analyzed when available (thymus and activation-regulated chemokine [TARC], lactate dehydrogenase [LDH], total immunoglobulin E [IgE], and peripheral blood eosinophil counts [PB EOS]). Spearman's correlation coefficients were calculated using all available pooled data from baseline through 24 months. RESULTS: Correlations between the three clinician-reported outcomes were high/very high (Spearman's correlation coefficients 0.76-0.92); those between the three dermatological patient-reported outcomes were moderate (0.53-0.64), and those between the clinician-reported and dermatological patient-reported outcomes were low/moderate (0.37-0.51). Correlations between the general HRQoL patient-reported outcomes and the clinician-reported and dermatological patient-reported outcomes were negligible-moderate (0.26-0.60). Biomarker correlations with the clinician-reported and dermatological patient-reported outcomes were low/moderate for TARC and LDH (0.44-0.63), but negligible/low for PB EOS and total IgE (0.01-0.41). CONCLUSIONS: These results show that clinician- and patient-reported outcomes do not necessarily correlate well in Japanese adults with AD. This highlights the importance of including patient-reported outcomes when assessing disease severity/impact, planning treatment, and assessing response to treatment. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR) Identifier UMIN000022623.

Atopic dermatitis (AD) is a long-term recurring skin disease that needs monitoring over time. Various measures (outcomes) are used to assess the severity of AD and its effect on patients. Some outcomes are based on examinations used by clinicians (doctors). Others are based on questionnaires used by patients themselves to report how severe they feel their AD is, and how it affects their lives. It is not known how well these different measures correlate with one another (how a severity score given by one outcome agrees with that given by another outcome), especially in Asian patients. This analysis used information from ADDRESS-J, a study that followed Japanese adults with moderate-to-severe AD who were treated for AD in the real world for a period of 2 years. It used a statistical method to compare three clinician-reported severity outcomes, three dermatological (skin-related) patient-reported outcomes, and two general health-related quality of life patient-reported outcomes. Agreement between the three clinician-reported outcomes was high or very high. Agreement between the three dermatological patient-reported outcomes was moderate. However, importantly, agreement between the clinician-reported outcomes and the dermatological patient-reported outcomes was low or moderate. Agreement between the general health-related quality of life outcomes and all other dermatological outcomes (whether clinician- or patient-reported) was low or moderate. The study showed that clinician-reported and patient-reported AD outcomes do not necessarily agree well in Japanese adults with AD. This highlights the importance of including patient-reported outcomes when evaluating AD, planning treatment, or judging how well patients are responding to treatment.

Stratification of Stage II Colon Cancer Using Recurrence Prediction Value: A Multi-institutional International Retrospective Study.

OBJECTIVE: To create a recurrence prediction value (RPV) of high-risk factor and identify the patients with high risk of cancer recurrence. SUMMARY BACKGROUND DATA: There are several high-risk factors known to lead to poor outcomes. Weighting each high-risk factor based on their association with increased risk of cancer recurrence can provide a more precise understanding of risk of recurrence. METHODS: We performed a multi-institutional international retrospective analysis of patients with Stage II colon cancer patients who underwent surgery from 2010 to 2020. Patient data from a multi-institutional database were used as the Training data, and data from a completely separate international database from two countries were used as the Validation data. The primary endpoint was recurrence-free survival (RFS). RESULTS: A total of 739 patients were included from Training data. To validate the feasibility of RPV, 467 patients were included from Validation data. Training data patients were divided into RPV low (n = 564) and RPV high (n = 175). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (Hazard ratio (HR) 2.628; 95% confidence interval (CI) 1.887-3.660; P < 0.001). Validation data patients were divided into two groups (RPV low, n = 420) and RPV high (n = 47). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (HR 3.053; 95% CI 1.962-4.750; P < 0.001). CONCLUSIONS: RPV can identify Stage II colon cancer patients with high risk of cancer recurrence world-wide.

Development of a unilateral porcine emphysema model induced by porcine pancreatic elastase.

Emphysema is one of the pathological hallmarks of chronic obstructive pulmonary disease. We have recently reported that radiofrequency therapy improves lung function in rodent models of emphysema. However, preclinical data using large animals is necessary for clinical translation. Here, we describe the work performed to establish a unilateral porcine emphysema model. Different doses of porcine pancreatic elastase (PPE) were instilled into the left lung of 10 Yucatan pigs. Three additional pigs were used as controls. Six weeks after instillation, lungs were harvested. Lung compliance was measured by a water displacement method and plethysmography. Systematic uniform random sampling of the left and right lungs was performed independently to measure alveolar surface area using micro-computed tomography (micro-CT) and histology. In pigs instilled with 725-750 U/kg of PPE (PPE group, n = 6), the compliance of the left lung was significantly higher by 37.6% than that of the right lung (P = 0.03) using the water displacement method. With plethysmography, the volume of the left lung was significantly larger than that of the right lung at 3, 5, and 10 cmH2O. Measurements from either micro-CT or histology images showed a significant decrease in alveolar surface area by 14.2% or 14.5% (P = 0.031) in the left lung compared with the right lung of the PPE group. A unilateral model for mild emphysema in Yucatan pigs has been established, which can now be used for evaluating novel therapeutics and interventional strategies.NEW & NOTEWORTHY For clinical translation, preclinical data using large animal models is necessary. However, papers describing an emphysema model in pigs, which are anatomically and physiologically similar to humans, are lacking. Here, we report success in creating a unilateral mild-emphysema model in pigs with only one single dose of porcine pancreatic elastase. This model will be useful in bringing novel technologies and therapies from small animals to humans with emphysema.

Prognostic Impact of Main Lymph Node Metastasis in Patients with Colon Cancer.

BACKGROUND: Although extended lymph node dissection during colon cancer surgery is recommended in both Western and Eastern countries, the perception and clinical significance of main lymph node metastasis (MLNM) remains controversial. METHODS: In total, 1557 patients with colon cancer who underwent curative resection with D3 dissection were retrospectively analyzed. Clinicopathological factors associated with MLNM were analyzed. Kaplan-Meier survival analysis and log-rank tests were used to compare the prognosis between the MLNM and non-MLNM groups. RESULTS: Multivariate analysis showed that overall survival (OS) [hazard ratio, 2.117 (0.939-4.774), p = 0.071] and recurrence-free survival (RFS) [hazard ratio, 2.183 (1.182-4.031), p = 0.013] were affected by the MLNM status independent of the TNM stage. Survival analysis demonstrated that among patients with stage III disease, the OS and RFS rates were significantly different between patients with and without MLNM (OS: p = 0.0147, RFS: p = 0.0001). However, the OS and RFS rates were not significantly different between patients who had stage III disease with MLNM and patients who had stage IV disease (OS: p = 0.5901, RFS: p = 0.9610). CONCLUSIONS: MLNM is an independent prognostic factor for patients with colon cancer. The addition of the MLNM status to the current TNM classification may enhance the prognostic value of the TNM staging system and the clinical efficacy of adjuvant therapy in patients with colon cancer.

MEdical Database AnaLysIS of Japanese multiple myeloma patienTs with apheresis #2 (MEDALIST-2): the impact of plerixafor use on costs and healthcare resources during mobilization and stem cell transplantation.

Treatment for multiple myeloma (MM) can involve apheresis to mobilize hematopoietic stem cells for later autologous stem cell transplantation (ASCT), which can become costly over time. This retrospective claims database study examined healthcare resource use and medical costs associated with plerixafor, a selective CXCR4 inhibitor that mobilizes hematopoietic stem cells and minimizes apheresis times. Medical data were sampled from Japanese MM patients between April 2017 and September 2019, after the Japanese launch of plerixafor. The study population (190 plerixafor users and 180 non-users) was identified from the Medical Data Vision database, and further stratified into those using granulocyte-colony stimulating factor in monotherapy or in combination with cyclophosphamide to trigger apheresis. A descriptive comparison of patient characteristics, healthcare resource use, and medical costs across the mobilization and ASCT phases indicated plerixafor is associated with higher average total medical costs. However, plerixafor-treated patients received fewer concomitant medications and spent less time in apheresis than non-users. A comparison of non-users with a similar analysis conducted pre-plerixafor launch (2013-2017) showed general improvements to treatment independent of plerixafor. The results of this research can inform guidelines for the role of plerixafor in balancing cost-effectiveness and drug efficacy in MM treatment.

Comprehensive analysis of the associations between clinical factors and outcomes by machine learning, using post marketing surveillance data of cabazitaxel in patients with castration-resistant prostate cancer.

BACKGROUND: We aimed to evaluate relationships between clinical outcomes and explanatory variables by network clustering analysis using data from a post marketing surveillance (PMS) study of castration-resistant prostate cancer (CRPC) patients. METHODS: The PMS was a prospective, multicenter, observational study of patients with metastatic, docetaxel-refractory CRPC treated with cabazitaxel in Japan after its launch in 2014. Graphical Markov (GM) model-based simulations and network clustering in 'R' package were conducted to identify correlations between clinical factors and outcomes. Factors shown to be associated with overall survival (OS) in the machine learning analysis were confirmed according to the clinical outcomes observed in the PMS. RESULTS: Among the 660 patients analyzed, median patient age was 70.0 years, and median OS and time-to-treatment failure (TTF) were 319 and 116 days, respectively. In GM-based simulations, factors associated with OS were liver metastases, performance status (PS), TTF, and neutropenia (threshold 0.05), and liver metastases, PS, and TTF (threshold 0.01). Factors associated with TTF were OS and relative dose intensity (threshold 0.05), and OS (threshold 0.01). In network clustering in 'R' package, factors associated with OS were number of treatment cycles, discontinuation due to disease progression, and TTF (threshold 0.05), and liver and lung metastases, PS, discontinuation due to adverse events, and febrile neutropenia (threshold 0.01). Kaplan-Meier analysis of patient subgroups demonstrated that visceral metastases and poor PS at baseline were associated with worse OS, while neutropenia or febrile neutropenia and higher number of cabazitaxel cycles were associated with better OS. CONCLUSIONS: Neutropenia may be a predictive factor for treatment efficacy in terms of survival. Poor PS and distant metastases to the liver and lungs were shown to be associated with worse outcomes, while factors related to treatment duration were shown to positively correlate with better OS.

Comprehensive risk score of the E-PASS as a prognostic indicator for patients after elective and emergency curative colorectal cancer surgery: A multicenter retrospective study.

OBJECTIVE: To evaluate the prognostic value of the comprehensive risk score (CRS) of the Estimation of Physiologic Ability and Surgical Stress for managing patients with colorectal cancer (CRC) who underwent elective and emergency colorectal cancer surgery with curative intent. SUMMARY BACKGROUND DATA: CRS, which is calculated based on both clinical and surgical factors, is a good predictor of postoperative complications and mortality. However, the impact of CRS in CRC prognosis remains unclear. METHODS: Patients with CRC who underwent curative resection between 2010 and 2019 were retrospectively enrolled in this study. The cohort was divided into the low and high CRS groups. The prognostic value of CRS was evaluated via Cox regression and Kaplan-Meier analyses. The CRS cutoff value was obtained using the Youden index applied to OS curves and have not been validated by any validation cohorts. RESULTS: In total, 2407 patients, including 1359 and 1048 patients with low and high CRS, respectively, were enrolled in this study. Multivariate analysis revealed that a CRS was an independent prognostic factor of overall and recurrence-free survival regardless of disease stage. Furthermore, adjuvant chemotherapy was beneficial for the survival of patients with stage III CRC in both high and low CRS groups; however, the survival benefit was limited in elderly high CRS patients. CONCLUSIONS: CRS was a strong prognostic factor for CRC regardless of disease stage and might be considered as a biomarker for selecting elderly patients who are eligible for adjuvant chemotherapy.

Metastatic intradural extramedullary spinal cord tumor from ovarian cancer: A case report with a literature review.

Context: Metastatic intradural extramedullary spinal cord tumors are extremely rare.Findings: A 76-year-old woman presented with intractable neck pain. Three years earlier, she had been treated for ovarian cancer with bilateral salpingo-oophorectomy. A year later, she underwent resection of a brain metastasis. Magnetic resonance imaging (MRI) showed an encapsulated intradural extramedullary mass at C4-C5. C4-C5 hemilaminectomy, tumor resection, and biopsy were performed. Histological examination of the resection revealed an adenocarcinoma. After surgery, her intolerable neck-shoulder pain was fully resolved, and she had no difficulties with daily living activities. However, two months later, she underwent gamma knife radiosurgery for the recurrent metastatic brain tumor, and four months later, she died from cachexia.Conclusion: Although cases of metastatic intradural extramedullary spinal tumors from ovarian cancer are extremely rare, their possibility should be considered in the differential diagnosis. A history of brain metastases and enhancement on T1-weighted MRI were helpful for making an accurate diagnosis.

Unresectable esophageal cancer treated with multiple chemotherapies in combination with chemoradiotherapy: A case report.

BACKGROUND: Definitive chemoradiotherapy (dCRT) using cisplatin plus 5fluorouracil (CF) with radiation is considered the standard treatment for unresectable locally advanced T4 esophageal squamous cell carcinoma (ESCC). Recently, induction chemotherapy has received attention as an effective treatment strategy. CASE SUMMARY: We report a successful case of a 59-year-old female with unresectable locally advanced T4 ESCC treated by two additional courses of chemotherapy with CF after induction chemotherapy with docetaxel, cisplatin and fluorouracil (DCF) followed by dCRT. Initial esophagogastroduodenoscopy (EGD) detected a type 2 advanced lesion located on the middle part of the esophagus, with stenosis. Computed tomography detected the primary tumor with suspected invasion of the left bronchus and 90° of direct contact with the aorta, and upper mediastinal lymph node metastasis. Pathological findings from biopsy revealed squamous cell carcinoma. We initially performed induction chemotherapy using three courses of DCF, but the lesion was still evaluated unresectable after DCF chemotherapy. Therefore, we subsequently performed dCRT treatment (CF and radiation). After dCRT, prominent reduction of the primary tumor was recognized but a residual tumor with ulceration was detected by EGD. Since the patient had some surgical risk, we performed two additional courses of CF and achieved a clinically complete response. After 14 mo from last administration of CF chemotherapy, recurrence has not been detected by computed tomography and EGD, and biopsy from the scar formation has revealed no cancer cells. CONCLUSION: We report successful case with tumor remnants even after DCF and subsequent dCRT, for whom a complete response was finally achieved with two additional courses of CF chemotherapy. Additional CF chemotherapy could be one radical treatment option for residual ESCC after treatment with induction DCF followed by dCRT to avoid salvage surgery, especially for high-risk patients.

Pancreaticoduodenectomy after neoadjuvant chemotherapy for gastric cancer invading the pancreatic head: A case report.

BACKGROUND: Pancreaticoduodenectomy (PD) for advanced gastric cancer is rarely performed because of the high morbidity and mortality rates and low survival rate. However, neoadjuvant chemotherapy for advanced gastric cancer has improved, and chemotherapy combined with trastuzumab may have a preoperative tumor-reducing effect, especially for human epidermal growth factor receptor 2 (HER2)-positive cases. CASE SUMMARY: We report a case of successful radical resection with PD after neoadjuvant S-1 plus oxaliplatin (SOX) and trastuzumab in a patient (66-year-old male) with advanced gastric cancer invading the pancreatic head. Initial esophagogastroduodenoscopy detected a type 3 advanced lesion located on the lower part of the stomach obstructing the pyloric ring. Computed tomography detected lymph node metastasis and tumor invasion to the pancreatic head without distant metastasis. Pathological findings revealed adenocarcinoma and HER2 positivity (immunohistochemical score of 3 +). We performed staging laparoscopy and confirmed no liver metastasis, no dissemination, negative lavage cytological findings, and immobility of the distal side of the stomach due to invasion to the pancreas. Laparoscopic gastrojejunostomy was performed at that time. One course of SOX and three courses of SOX plus trastuzumab were administered. Preoperative computed tomography showed partial response; therefore, PD was performed after neoadjuvant chemotherapy, and pathological radical resection was achieved. CONCLUSION: We suggest that radical resection with PD after neoadjuvant chemotherapy plus trastuzumab is an option for locally advanced HER2-positive gastric cancer invading the pancreatic head in the absence of non-curative factors.

Indirect inguinal hernia containing portosystemic shunt vessel: A case report.

BACKGROUND: Inguinal hernia repair is one of the most common general surgical operations worldwide. We present a case of indirect inguinal hernia containing an expanded portosystemic shunt vessel. CASE SUMMARY: We report a 72-year-old man who had a 4 cm × 4 cm swelling in the right inguinal region, which disappeared with light manual pressure. Abdominal-pelvic computed tomography (CT) revealed a right inguinal hernia containing an expanded portosystemic shunt vessel, which had been noted for 7 years due to liver cirrhosis. We performed Lichtenstein's herniorrhaphy and identified the hernia sac as being indirect and the shunt vessel existing in the extraperitoneal cavity through the internal inguinal ring. Then, we found two short branches between the expanded shunt vessel and testicular vein in the middle part of the inguinal canal and cut these branches to allow the shunt vessel to return to the extraperitoneal cavity of the abdomen. The hernia sac was returned as well. We encountered no intraoperative complications. After discharge, groin seroma requiring puncture at the outpatient clinic was observed. CONCLUSION: If an inguinal hernia patient has portal hypertension, ultrasound should be used to determine the contents of the hernia. When atypical vessels are visualized, they may be shunt vessels and additional CT is recommended to ensure the selection of an adequate approach for safe hernia repair.

Distal gastric tube resection with vascular preservation for gastric tube cancer: A case report and review of literature.

BACKGROUND: Survival rates in patients with esophageal cancer undergoing esophagectomy have improved, but the prevalence of gastric tube cancer (GTC) has also increased. Total resection of the gastric tube with lymph node dissection is considered a radical treatment, but GTC surgery is more invasive and involves a higher risk of severe complications or death, particularly in elderly patients. CASE SUMMARY: We report an elderly patient with early GTC that had invaded the duodenum who was successfully treated with resection of the distal gastric tube and Roux-en-Y (R-Y) reconstruction. The tumor was a type 0-IIc lesion with ulcer scars surrounding the pyloric ring. Endoscopic submucosal resection was not indicated because the primary lesion was submucosally invasive, was undifferentiated type, surrounded the pyloric ring, and had invaded the duodenum. Resection of distal gastric tube with R-Y reconstruction was safely performed, with preservation of the right gastroepiploic artery (RGEA) and right gastric artery (RGA). CONCLUSION: Distal resection of the gastric tube with preservation of the RGEA and RGA is a good treatment option for elderly patients with cT1bN0 GTC in the lower part of the gastric tube.

Association of surfactant protein D with pulmonary metastases from colon cancer.

Surfactant protein D (SP-D) is a member of the collectin family of proteins, which is secreted by airway epithelial cells. SP-D serves an important role in the immune system and in the inflammatory regulation of the lung. SP-D was recently found to suppress lung cancer progression by downregulating epidermal growth factor signaling. However, the relationship between SP-D and pulmonary metastases from colon cancer remains unknown. The present study aimed to determine whether SP-D may suppress the development of the mouse rectal carcinoma cell line, CMT93, in vitro. The present study investigated the effect of SP-D on pulmonary metastases from colon cancer in vivo using SP-D knockout mice. A wound healing assay and cell invasion assay revealed that SP-D suppressed the proliferation, migration and invasion of CMT-93 cells. After injection of CMT-93 cells into the tail vein, SP-D knockout mice were significantly more susceptible to developing pulmonary metastases than C57/BL6 mice (control). Moreover, a novel cell line (CMT-93 pulmonary metastasis; CMT-93 PM) was established from the lesions of pulmonary metastases in C57/BL6 mice following injection of CMT93 into the tail vein. CMT-93 PM exhibited more robust invasion and proliferation compared to CMT93, which was unaffected by exposure to SP-D. A higher incidence of pulmonary metastases was detected following injection of CMT93 PM into the tail vein of C57/BL6 mice compared with CMT-93. Consequently, SP-D may be involved in the pathogenesis of pulmonary metastases from colon cancer.

[A Case of Small Bowel Perforation Caused by Malignant Lymphoma after Methotrexate Therapy for Rheumatoid Arthritis].

A 73-year-old woman had a history of medication, including methotrexate for rheumatoid arthritis, for 5 years. She had chronic epigastralgia for 2 weeks and found to have multiple submucosal tumors on upper gastrointestinal endoscopy in another hospital. She had a strong abdominal pain thereafter and diagnosed as having gastrointestinal perforation on the basis of CT scans. Abdominal examination revealed disseminated peritonitis, and emergency laparoscopic surgery was performed on the day of admission. A 1 cm perforation of the ileum was identified, and a 5 cm mass of the mesentery near the perforation was also identified. Small bowel partial resection, including both lesions, was performed. From the intraoperative findings, methotrexate-associated lymphoproliferative disorders(MTX-LPD)was suspected, and methotrexate was discontinued after the surgery. At a later date, the pathological result from both the surgical specimen and upper gastrointestinal endoscopy was diffuse large B cell lymphoma(DLBCL). CT scan, PET-CT scan, and upper gastrointestinal endoscopy were performed 1-2 months after surgery, and no tumor was identified. Currently, 6 months after the surgery, the patient is still alive without any progression of the lymphoma.

Identification of subgroups of patients with type 2 diabetes with differences in renal function preservation, comparing patients receiving sodium-glucose co-transporter-2 inhibitors with those receiving dipeptidyl peptidase-4 inhibitors, using a supervised machine-learning algorithm (PROFILE study): A retrospective analysis of a Japanese commercial medical database.

AIMS: To investigate the effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors vs. dipeptidyl peptidase-4 (DPP-4) inhibitors on renal function preservation (RFP) using real-world data of patients with type 2 diabetes in Japan, and to identify which subgroups of patients obtained greater RFP benefits with SGLT2 inhibitors vs. DPP-4 inhibitors. METHODS: We retrospectively analysed claims data recorded in the Medical Data Vision database in Japan of patients with type 2 diabetes (aged ≥18 years) prescribed any SGLT2 inhibitor or any DPP-4 inhibitor between May 2014 and September 2016 (identification period), in whom estimated glomerular filtration rate (eGFR) was measured at least twice (baseline, up to 6 months before the index date; follow-up, 9 to 15 months after the index date) with continuous treatment until the follow-up eGFR. The endpoint was the percentage of patients with RFP, defined as no change or an increase in eGFR from baseline to follow-up. A proprietary supervised learning algorithm (Q-Finder; Quinten, Paris, France) was used to identify the profiles of patients with an additional RFP benefit of SGLT2 inhibitors vs. DPP-4 inhibitors. RESULTS: Data were available for 990 patients prescribed SGLT2 inhibitors and 4257 prescribed DPP-4 inhibitors. The proportion of patients with RFP was significantly greater in the SGLT2 inhibitor group (odds ratio 1.27; P = 0.01). The Q-Finder algorithm identified four clinically relevant subgroups showing superior RFP with SGLT2 inhibitors (P < 0.1): no hyperlipidaemia and eGFR ≥79 mL/min/1.73 m2 ; eGFR ≥79 mL/min/1.73 m2 and diabetes duration ≤1.2 years; eGFR ≥75 mL/min/1.73 m2 and use of antithrombotic agents; and haemoglobin ≤13.4 g/dL and LDL cholesterol ≥95.1 mg/dL. In each profile, glycaemic control was similar in the two groups. CONCLUSION: SGLT2 inhibitors were associated with more favourable RFP vs. DPP-4 inhibitors in patients with certain profiles in real-world settings in Japan.

Atopic dermatitis disease registry in Japanese adult patients with moderate to severe atopic dermatitis (ADDRESS-J): Baseline characteristics, treatment history and disease burden.

Moderate to severe atopic dermatitis (AD) has a high disease burden and a significant effect on quality of life. Observational studies are necessary to determine the patient disease burden and long-term disease control in the Japanese population. ADDRESS-J is a non-interventional, observational registry of adult Japanese patients with moderate to severe AD. Herein, we report baseline data from the ADDRESS-J study describing disease characteristics and current treatment practices. At baseline, 300 adult AD patients with Investigator's Global Assessment (IGA) scores (range, 0-4) of 3 (moderate) or 4 (severe) whose treatments for AD were intensified, were assessed for clinical and patient-reported outcomes and current AD treatments. The registry patients' median age was 34.0 years; 60.7% were male and 71.7% had had AD for more than 20 years. At baseline, 220 study patients had an IGA score of 3 and 80 had an IGA score of 4. The median Eczema Area and Severity Index score was 21.7 (range, 0-72), the median body surface area involvement was 46.25%, and the median pruritus numerical rating scale score was 7.0 (range, 0-10); for each of these measures, higher scores represent greater severity. Most registry patients (86.7%) had recently used topical corticosteroids or topical calcineurin inhibitors as treatment for AD. This registry cohort represents a population of Japanese patients with moderate to severe AD and provides an important resource for characterizing the disease burden and evaluating the safety and effectiveness of various AD treatments.

[Trastuzumab Combination Chemotherapy Followed by R0 Resection for Locally Advanced Human Epidermal Growth Factor Receptor 2-Positive Gastric Cancer-A Case Report].

A man in the 60s visited our hospital with the complaints of epigastralgia and weight loss. Following an investigation, he was diagnosed with human epidermal growth factor receptor 2(HER2)-positive gastric cancer with invasion to the pancreas (T4b[pancreas], N2, M0, Stage ⅣA[Union for International Cancer Control 8th edition]). Preoperatively, he was administered a chemotherapeutic regimen of S-1 and cisplatin plus trastuzumab. After 2 courses of chemotherapy, computed tomography revealed invasion to the abdominal wall and pyloric stenosis; however, invasion to the pancreas was obscured, and the lymph node metastases had shrunk. He underwent laparoscopic gastro-jejunostomy. After 4 courses of chemotherapy, his condition was considered stable. A laparoscopic distal gastrectomy was performed together with resection of the abdominal wall invasion. The pathological stage was pT4b(abdominal wall), pN0, M0, Stage ⅢA, and R0 resection was achieved. The patient was administered 4 courses of adjuvant capecitabine plus oxaliplatin therapy and 4 courses of capecitabine monotherapy. He has been followed-up for 1.5 years since the curative resection and has not developed recurrences. This case suggests the usefulness of multimodal therapy for locally advanced gastric cancer.