Mannitol versus furosemide in patients with thoracic malignancies who received cisplatin-based chemotherapy using short hydration: A randomized phase II trial.

BACKGROUND: Mannitol is exclusively recommended in the National Comprehensive Cancer Network guidelines for diuresis in cisplatin (CDDP)-based chemotherapy. The utility of furosemide, a widely used and convenient diuretic, thus requires clarification. METHODS: This is a prospective, single-centered, open-label, noninferiority phase II study. Patients with thoracic malignancies who planned to receive CDDP-based chemotherapy were randomly assigned to receive either mannitol (arm A) or furosemide (arm B). The primary end point was set as the proportion of patients who experienced any grade of "creatinine (Cr) increased" based on the upper limit of the normal range (ULN) during the first cycle as assessed by Common Terminology Criteria for Adverse Events Version 4.0. Secondary end points were Cr increased based on the baseline value during the first cycle, Cr increased after the completion of CDDP, and the proportion of patients with phlebitis. RESULTS: Between April 2018 and March 2022, 115 patients were enrolled and 106 were analyzed. Any grade of Cr increased based on the ULN during the first cycle was 17.3% (arm A) and 24.1% (arm B), respectively (p = 0.34). Therefore, the primary end point was not met. After completion of chemotherapy, any grade of Cr increased was observed in 23.1% (arm A) and 31.5% (arm B), respectively. However, the actual serum Cr level and Cr clearance during the courses were not different between the arms. Phlebitis occurred more frequently in arm A (28.8%) than arm B (16.7%). CONCLUSIONS: Mannitol should remain the standard diuresis in CDDP-based chemotherapy assessed by conventional CTCAE grading, but furosemide can be room for consideration when assessed by actual serum Cr level and Cr clearance.

A Phase II Study of High-Flow Nasal Cannula for Relieving Dyspnea in Advanced Cancer Patients.

CONTEXT: The efficacy and tolerability of high-flow nasal cannula (HFNC) for relieving dyspnea in advanced cancer patients with limited prognosis requires elucidation. OBJECTIVES: The primary aim of this trial was to assess the efficacy and tolerability of HFNC regarding dyspnea including severe as well as moderate for longer durations in patients under palliative care. METHODS: In this prospective study, hospitalized patients with advanced cancer who had dyspnea at rest (numeric rating scale, NRS≥3) and hypoxemia were enrolled. They were treated with HFNC for five days in the respiratory unit. Primary endpoint was mean change of modified Borg scale at 24 hours. Key secondary endpoints consisted of mean changes in modified Borg scale during the study period and feasibility (Trial Identifier, UMIN000035738). RESULTS: Between February 2019 and February 2022, 25 patients were enrolled and 21 were analyzed. Twenty patients used inspired oxygen and the mean fraction of inspired oxygen (FiO2) was 0.34 (range, 0.21-1.0). At baseline, mean NRS (dyspnea) was 5.9 (range, 3-10). Median survival time was 19 days (range, 3-657). The mean change of modified Borg scale was 1.4 (80% confidence interval [CI]: 0.8-1.9) at 24 hours, 12 patients (57%) showed 1.0 points improvement of modified Borg scale. Within two hours, 15 patients showed 1.0 points improvement of modified Borg scale and such early responders were likely to maintain dyspnea improvement for 24 hours. Nineteen patients could continue HFNC for 24 hours and 11 patients completed five days of HFNC. CONCLUSION: To our knowledge, this trial is the first prospective study to assess the five-day efficacy and tolerability of HFNC for dyspnea in patients under palliative care. Although this did not reach the prespecified endpoint, about half of the patients showed 1.0 point improvement, a minimally clinically important difference (MCID) in the chronic lung disease. HFNC can be a palliative treatment option in advanced cancer patients with dyspnea.

Validation of Simple Prediction Equations for Step Count in Japanese Patients with Chronic Obstructive Pulmonary Disease.

Physical activity is decreased in patients with chronic obstructive pulmonary disease, and decreased physical activity leads to a poor prognosis. To determine an individual's target step count from the measured step counts and predicted step counts, simple and detailed prediction equations for step count were developed. To verify the validity of the simple prediction equation, the validity of the simple equation was evaluated in a different cohort and the correlation between the step counts calculated by the simple equation and those by the detailed prediction equation were evaluated. When the step counts calculated by the simple prediction equation for all participants were compared with the measured step counts, a significant correlation was obtained among them, and the calculated values were found to be reproducible with the measured values in patients with a measured step count of <6500 by Bland−Altman plots. Furthermore, the values calculated by the simple prediction equation and those calculated by the detailed prediction equation showed a significant correlation. In conclusion, the simple prediction equation was considered reasonable.

Radiographic findings useful for diagnosis of primary chest wall lymphoma without preceding pleural disease: A case report.

A 70-year-old man with no history of pleural diseases had a dumbbell-shaped chest wall mass extending from the thoracic cavity to the spinal canal at the intervertebral foramen without bone destruction. Computed tomography revealed a positive a 'pleural sandwich sign', where the intercostal artery was enveloped by the mass. A high maximum standard uptake value was noted on fluorodeoxyglucose-positron emission tomography. No lesions were found in areas other than the chest wall. CT-guided biopsy was performed and he was diagnosed with primary chest wall lymphoma. This case report suggests that these radiographic findings may be helpful for diagnosing chest wall lymphomas even in patients without prior pleural disease.

The validation and reliability of a Japanese version of the Problematic Online Gaming Questionnaire (POGQ-J).

BACKGROUND: The Problematic Online Gaming Questionnaire (POGQ) is an 18-item self-rated measure designed to assess the degree of problematic online gaming. This study translated the POGQ into Japanese (POGQ-J) and examined the POGQ-J's factor structure, validity, and reliability for a Japanese population. METHOD: A total of 285 undergraduate students (128 males, 157 females, Mage = 19.66, SD = 1.36) participated in this study. RESULTS: A confirmatory factor analysis indicated the appropriateness of the POGQ-J's six-factor structure, χ2(129) = 106.027, p < .931; CFI = .957; RMSEA = .040; SRMR = .054. Regarding convergent validity, the POGQ-J was found to be related to the time spent on online gaming (r = .309), the Game Addiction Scale for Adolescents (r = .824), and Young's Internet Addiction Test (r = .581). Finally, the POGQ-J was found to have a high test-retest reliability. CONCLUSIONS: The POGQ-J is valid and reliable for assessing problematic online gaming in a Japanese population.

Psychosocial Adjustment and Mental Distress Associated With In-Game Purchases Among Japanese Junior High School Students.

In-game purchases, including microtransactions and loot box spending, are the monetization systems of free-to-play online games. Although some studies have suggested that excessive in-game purchases increase the risk of psychosocial maladjustment and mental distress as well as predict future problematic gaming and gambling practices, empirical studies on problematic behavioral patterns related to in-game purchasing among adolescents are lacking. This study sought to explore whether knowing the style of in-game purchases (non-purchase, planned purchase, or unplanned purchase) could be useful when characterizing maladaptive behavior among adolescents from the perspective of psychosocial adjustment and mental distress. A total of 335 junior high school students (aged 12-15 years) participated in the survey and completed a questionnaire assessing daily online gaming usage, in-game purchases, psychosocial adjustment, and mental distress. The results showed that (1) 30.7% of students had previously made in-game purchases, and at least 14.0% had made unplanned in-game purchases; (2) 19.2% of the users who had made unplanned purchases had spent greater than or equal to their actual monthly allowance within the past month, and (3) unplanned purchase gamers exhibited more behavioral problems and peer problems regarding psychosocial adjustment compared to planned purchase gamers, and more overall difficulties compared to non-purchasers. Meanwhile, more hyperactivity/inattention was seen among in-game purchasers compared to non-purchasers, regardless of whether the purchase was planned or unplanned. These findings support that understanding whether adolescents make unplanned in-game purchases could be a useful approach to describing the characteristics of online gamers with maladaptive tendencies.

Characteristics of Gamers who Purchase Loot Box: a Systematic Literature Review.

PURPOSE OF REVIEW: Research has indicated that loot boxes are risky gaming components that could exacerbate Internet gaming disorder due to a link between loot box purchasing and gambling. We conducted a systematic review to identify the characteristics of people who purchase loot boxes with real money, focusing on the relationships (a) between loot boxes and gaming, (b) between loot boxes and gambling, and (c) between loot boxes and other variables. RECENT FINDINGS: Of the 201 studies examined for eligibility, we reviewed 20 studies that met the predefined criteria, which were extracted by searching electronic databases (PsycINFO, PubMed, Ovid, EBSCO, and Web of Science) and the reference lists of included studies, and that were published up to March 27, 2021. Overall, this review identified positive relationships among Internet gaming disorder-related symptoms, disordered gambling symptoms, and engagement with, or investment in, loot boxes. In addition to gaming and gambling, the relationships among some variables, such as mood, gender, physiological state, motivation, and loot box engagement, were examined. SUMMARY: The present review clarified relationships between loot box engagement, gaming, gambling, and other variables, such as mood, gender, physiological state, and motivation, and partially identified the characteristics of people who purchase loot boxes using real money. Specifically, those who spend more money in-game on loot boxes exhibit Internet gaming-related and/or disordered gambling symptoms and behaviors. Finally, we discussed future directions for clinical psychological studies on loot boxes.

Discontinuation of infliximab in patients with ulcerative colitis in remission (HAYABUSA): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Anti-tumour necrosis factor (TNF) agents are the mainstay of long-term treatment for refractory ulcerative colitis. However, long-term use of anti-TNF therapy might lead to an increased risk of malignancy or infection. To date, no randomised controlled trial has evaluated whether anti-TNF agents can be safely discontinued in patients with ulcerative colitis in remission. We therefore aimed to compare outcomes in these patients who continued infliximab with those who discontinued infliximab. METHODS: We did a multicentre, open-label randomised controlled trial at 24 specialist centres in Japan. We enrolled patients with ulcerative colitis who were in remission, had been treated with intravenous infliximab (5 mg/kg) every 8 weeks, and had started infliximab at least 14 weeks before study enrolment. No restrictions regarding age and comorbidities were used to exclude participation. Patients who were confirmed to be in remission for more than 6 months, to be corticosteroid-free, and to have a Mayo Endoscopic Subscore (MES) of 0 or 1 were centrally randomised. An independent organisation randomly assigned patients (1:1) into either the infliximab-continued group or infliximab-discontinued group, using a computer-generated stratified randomisation procedure. The stratified factors were the use of immunomodulators (yes or no) and MES (0 or 1). Neither patients nor health-care providers were masked to the randomisation. The primary endpoint was the remission rate at week 48 in the full analysis set, which was based on the intention-to-treat principle and excluded participants with no efficacy data after randomisation. This study was registered with the University Hospital Medical Information Network Center Trials registry, UMIN000012092. FINDINGS: Between June 16, 2014, and July 28, 2017, 122 patients were eligible for screening and a total of 95 patients were randomly assigned to the infliximab-continued group (n=48) or the infliximab-discontinued group (n=47). 92 patients (n=46 for both groups) were included in the full analysis set. 37 (80·4% [95% CI 66·1-90·6]) of 46 patients in the infliximab-continued group and 25 (54·3% [39·0-69·1]) of 46 patients in the infliximab-discontinued group were in remission at week 48. The between-group difference was 26·1% (95% CI 7·7-44·5; p=0·0076) before adjustment and 27·3% (95% CI 8·0-44·1; p=0·0059) after adjustment for stratification factors. Eight (17%) of 48 patients in the infliximab-continued group and six (13%) of 47 in the infliximab-discontinued group developed adverse events (between-group difference 3·9% [95% CI -10·3 to 18·1]; p=0·59). In the infliximab-continued group, one patient had an infusion reaction and two patients had psoriatic skin lesions. Eight (66·7%, 95% CI 34·9-90·1) of the 12 patients in the infliximab-discontinuation group who were re-treated with infliximab after relapsing were in remission within 8 weeks of re-treatment; none had infusion reactions. INTERPRETATION: Maintenance of remission was significantly more common in patients who continued infliximab than in those who discontinued. Discontinuing infliximab should therefore be discussed with caution, taking both risk of relapse and efficacy of re-treatment into account. FUNDING: Mitsubishi Tanabe Pharma Corporation and the Intractable Disease Project of the Ministry of Health, Labour and Welfare of Japan. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.

Chemotherapy plus atezolizumab for a patient with small cell lung cancer undergoing haemodialysis: a case report and review of literature.

Little is known about the safety of chemotherapy plus atezolizumab for patients with extensive-stage small cell lung cancer (ES-SCLC) undergoing haemodialysis (HD). An 80-year-old male received carboplatin [area under the concentration-time curve (AUC) = 5 on day 1], etoposide (40 mg/m2 on days 1, 2, and 3), and atezolizumab (1200 mg/body on day 1) as the first-line therapy for ES-SCLC. He was undergoing HD thrice a week for seven years. HD was provided 16 h after carboplatin administration. During the first cycle, grade 4 neutropenia (neutrophil count: 74/µL) and leukopenia (white blood cell count: 680/µL) occurred. Therefore, chemotherapy was administered with a reduced dose of carboplatin (AUC = 4) and etoposide (30 mg/m2) from the second to fourth cycles. After four cycles, no severe non-haematological adverse events occurred, showing a remarkable response. We conclude that the carboplatin, etoposide, and atezolizumab combination can be safely administered to cancer patients undergoing HD.

Interformat Reliability of Web-Based Parent-Rated Questionnaires for Assessing Neurodevelopmental Disorders Among Preschoolers: Cross-sectional Community Study.

BACKGROUND: Early detection and intervention for neurodevelopmental disorders are effective. Several types of paper questionnaires have been developed to assess these conditions in early childhood; however, the psychometric equivalence between the web-based and the paper versions of these questionnaires is unknown. OBJECTIVE: This study examined the interformat reliability of the web-based parent-rated version of the Autism Spectrum Screening Questionnaire (ASSQ), Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS), Developmental Coordination Disorder Questionnaire 2007 (DCDQ), and Strengths and Difficulties Questionnaire (SDQ) among Japanese preschoolers in a community developmental health check-up setting. METHODS: A set of paper-based questionnaires were distributed for voluntary completion to parents of children aged 5 years. The package of the paper format questionnaires included the ASSQ, ADHD-RS, DCDQ, parent-reported SDQ (P-SDQ), and several additional demographic questions. Responses were received from 508 parents of children who agreed to participate in the study. After 3 months, 300 parents, who were among the initial responders, were randomly selected and asked to complete the web-based versions of these questionnaires. A total of 140 parents replied to the web-based format and were included as a final sample in this study. RESULTS: We obtained the McDonald ω coefficients for both the web-based and paper formats of the ASSQ (web-based: ω=.90; paper: ω=.86), ADHD-RS total and subscales (web-based: ω=.88-.94; paper: ω=.87-.93), DCDQ total and subscales (web-based: ω=.82-.94; paper: ω=.74-.92), and P-SDQ total and subscales (web-based: ω=.55-.81; paper: ω=.52-.80). The intraclass correlation coefficients between the web-based and paper formats were all significant at the 99.9% confidence level: ASSQ (r=0.66, P<.001); ADHD-RS total and subscales (r=0.66-0.74, P<.001); DCDQ total and subscales (r=0.66-0.71, P<.001); P-SDQ Total Difficulties and subscales (r=0.55-0.73, P<.001). There were no significant differences between the web-based and paper formats for total mean score of the ASSQ (P=.76), total (P=.12) and subscale (P=.11-.47) mean scores of DCDQ, and the P-SDQ Total Difficulties mean score (P=.20) and mean subscale scores (P=.28-.79). Although significant differences were found between the web-based and paper formats for mean ADHD-RS scores (total: t132=2.83, P=.005; Inattention subscale: t133=2.15, P=.03; Hyperactivity/Impulsivity subscale: t133=3.21, P=.002), the effect sizes were small (Cohen d=0.18-0.22). CONCLUSIONS: These results suggest that the web-based versions of the ASSQ, ADHD-RS, DCDQ, and P-SDQ were equivalent, with the same level of internal consistency and intrarater reliability as the paper versions, indicating the applicability of the web-based versions of these questionnaires for assessing neurodevelopmental disorders.

CD24, not CD47, negatively impacts upon response to PD-1/L1 inhibitors in non-small-cell lung cancer with PD-L1 tumor proportion score < 50.

CD24, a heavily glycosylated glycosylphosphatidylinositol-anchored surface protein, inhibits phagocytosis as potently as CD47. The relationship between such anti-phagocytic factors and the immune response with immune-checkpoint inhibitors (ICI) remains unexplored. We evaluated CD24 and CD47 tumor proportion scores (TPS) in 68 of the 106 patients with advanced non-small-cell lung cancer who participated in a prospective observational study of ICI treatment. We also explored the impact of CD24 TPS and CD47 TPS on ICI efficacy and serum cytokine changes. CD24 positivity (TPS ≥ 1) was negatively associated with progression-free survival (PFS) of ICI when PD-L1 TPS was < 50 (median PFS; 37 vs 127 d, P = .033), but there was no association when PD-L1 TPS was ≥ 50 (median PFS; 494 vs 144 d, P = .168). CD24 positivity was also related to significantly higher increase of CCL2 from baseline to 4-6 wk later, and such increase was notably observed only when PD-L1 TPS < 50 (P = .0004). CCL2 increase after ICI initiation was negatively predictive for survival after initiation of ICI (median survival time; not reached vs 233 d; P = .028). CD47 TPS high (≥60) significantly suppressed the increase in vascular endothelial growth factor (VEGF)-A, D and PDGF-AB/BB after ICI initiation. There was no association, however, between CD47 tumor expression and the efficacy of ICI. In conclusion, CD24, not CD47, is a candidate negative predictive marker of ICI in advanced, non-small-cell lung cancer with PD-L1 TPS < 50. Tumor expression of both CD24 and CD47 was associated with changes in factors related to monocytes and angiogenesis after ICI initiation (UMIN000024414).

Comprehensive Targeted Sequencing Identifies Monogenic Disorders in Patients With Early-onset Refractory Diarrhea.

OBJECTIVES: Causes of early-onset refractory diarrhea include exudative diarrhea associated with very early-onset inflammatory bowel diseases, osmotic or secretory diarrhea, and protein-losing enteropathy. Monogenic disorders are included in these diseases, yet a comprehensive genetic analysis has not been fully established. METHODS: We established targeted gene panels covering all responsible genes for early-onset diarrhea. In total, 108 patients from 15 institutions were enrolled in this study. We collected clinical data from all patients. Seventy-three patients with exudative diarrhea, 4 with osmotic or secretory diarrhea and 8 with protein-losing enteropathy were subjected to genetic analysis. RESULTS: A total of 15 out of the 108 enrolled patients (13.9%) were identified as monogenic. We identified 1 patient with RELA, 2 with TNFAIP3, 1 with CTLA4, 1 with SLCO2A1, 4 with XIAP, 3 with IL10RA, 1 with HPS1, 1 with FOXP3, and 1 with CYBB gene mutations. We also identified 1 patient with NFKB2 and 1 with TERT mutations from the gene panel for primary immunodeficiency syndromes. The patient with refractory diarrhea caused by heterozygous truncated RelA protein expression is the first case identified worldwide, and functional analysis revealed that the mutation affected nuclear factor kappa B signaling. Genotypes were significantly associated with the clinical and pathological findings in each patient. CONCLUSIONS: We identified variable monogenic diseases in the patients and found that genes responsible for primary immunodeficiency diseases were frequently involved in molecular pathogenesis. Comprehensive genetic analysis was useful for accurate molecular diagnosis, understanding of underlying pathogenesis, and selecting the optimal treatment for patients with early-onset refractory diarrhea.An infographic for this article is available at: http://links.lww.com/MPG/B853.

Immune-Related Adverse Events by Immune Checkpoint Inhibitors Significantly Predict Durable Efficacy Even in Responders with Advanced Non-Small Cell Lung Cancer.

BACKGROUND: Although predictive value of immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) have been suggested by several studies, their assessments were insufficient because patients were categorized only by the occurrence of irAEs. It has not been elucidated whether irAEs also play a significant role even in responders. MATERIALS AND METHODS: Between December 2015 and September 2018, 106 patients with advanced non-small cell lung cancer treated with ICIs were enrolled in our prospective biomarker study. Twenty-three of these were responders, defined as those with complete or partial response. We investigated the proportion of irAEs among overall and responders. For responders, progression-free survival (PFS) and overall survival of ICIs were compared between those with and without irAEs. As an exploratory analysis, we measured 41 proteins from peripheral blood before and after ICI treatment. RESULTS: The proportion of irAEs was significantly higher in responders than nonresponders (65.2% vs. 19.3%, p < .01). Among responders, clinical characteristics did not differ regardless of the occurrence of irAEs. However, there was a significant difference in PFS among responders (irAE group 19.1 months vs. non-irAE group 5.6 months; hazard ratio: 0.30 [95% confidence interval: 0.10-0.85]; p = .02). Of 41 protein analyses, fibroblast growth factor-2 at baseline and monocyte chemoattractant protein fold change showed significant differences between them (p < .04). CONCLUSION: Although this is a small sample-sized study, irAE might be a predictive factor of durable efficacy, even in patients who responded to ICIs. Investigation into the significance of irAEs in responders will contribute to the establishment of optimal administration of ICI. IMPLICATIONS FOR PRACTICE: Although the predictive value of immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) has been suggested by several studies, it has not been elucidated whether irAEs also play a significant role even in responders. This study showed that more than 60% of responders had irAEs. It demonstrated the strong correlation between irAEs and efficacy even in responders. Investigation into the significance of irAEs in responders will contribute to the establishment of optimal administration of ICI.

Long-term maintenance of the mucosal healing induced by azacitidine therapy in a patient with intestinal Behçet's-like disease accompanied with myelodysplastic syndrome involving trisomy 8.

Myelodysplastic syndromes (MDSs) are a group of myeloid neoplasms characterized by blood cell deformation and dysfunction, and MDS with trisomy 8 is closely linked with intestinal Behçet's-like diseases. Intestinal Behçet's-like disease is refractory to conventional therapies, including prednisolone, immunomodulators, and anti-tumor necrosis factor α agents. Here, we describe a 56-year-old woman with intestinal Behçet's-like disease ascribed to MDS with trisomy 8 who had multiple intractable intestinal ulcers. She presented with periodic fever and abdominal pain. The genetic analysis showed a heterozygous E148Q mutation in the Mediterranean fever gene. The patient did not tolerate treatment with colchicine because of diarrhea; therefore, azacitidine therapy was initiated. One cycle of azacitidine therapy improved the multiple intestinal ulcers, and the periodic fever and abdominal pain gradually disappeared. After eight cycles of azacitidine therapy, ileocolonoscopy, histological assessment and capsule endoscopy revealed mucosal healing. Azacitidine therapy was continued, and mucosal healing was maintained for more than 2 years. This case suggests that azacitidine therapy which has immunoregulatory effects and epigenetic modulations, might control intestinal Behçet's-like disease associated with MDS involving trisomy 8.

A case of celiac disease with type I enteropathy-associated T-cell lymphoma in a Japanese male patient.

A 45-year-old Japanese male patient who was diagnosed with celiac disease (CeD) developed type I enteropathy-associated T-cell lymphoma (EATL). In 2013, the patient was admitted to our hospital with worsening of diarrhea and weight loss. Pathological examination of biopsy specimens from the duodenum and ileum led to a diagnosis of suspected EATL. A previous total colonoscopy (TCS) indicated villous atrophy in the terminal ileum. The patient was changed to a gluten-free diet, and the nutritional status gradually improved. In September 2014, he experienced acute right lower abdominal pain. He underwent urgent surgery, and a perforation was identified in the ileum. A diagnosis of type I EATL was made following histopathological examination. After eight courses of CHOP therapy, the patient entered complete remission. TCS and esophagogastroduodenoscopy with magnifying narrow-band imaging performed in 2015 identified villous regrowth in the distal ileum and duodenum. Capsule endoscopy also found villous regrowth in the entire small intestine. To our knowledge, this is the first case of type I EATL following CeD with villous atrophy before EATL occurrence in a Japanese HLA-DQ2 carrier. The possibility of type I EATL occurring after CeD should be recognized, although CeD is quite rare in Japan.

ALK-positive anaplastic large cell lymphoma presenting multiple lymphomatous polyposis: A case report and literature review.

BACKGROUND: Anaplastic large cell lymphoma (ALCL) is a type of T-cell lymphoma that can be divided into two categories: anaplastic lymphoma kinase-positive (ALK+) and ALK-negative. Gastrointestinal ALK+ ALCL is rare. Multiple lymphomatous polyposis (MLP) is thought to be a representative form of gastrointestinal lesion in mantle cell lymphoma, and T-cell lymphomas seldom show this feature. Here, we report the first known case of ALK+ ALCL with gastroduodenal involvement to present with MLP. CASE SUMMARY: The patient was a 43-year-old man who was complained of a mass in the left inguinal area and was performed open biopsy. ALK+ ALCL was diagnosed pathologically. Computed tomography scan demonstrated multiple lymph node lesions in the abdomen - pelvis/inguinal region, and scattered nodular lesions in both lung fields. He did not complain of gastrointestinal symptoms. While, esophagogastroduodenoscopy identified MLP lesions from the antrum of the stomach to the descending portion of the duodenum and mild thickened folds on the corpus of the stomach, and biopsy showed invasion of ALK+ ALCL. We treated this patient with six cycles of CHOEP (Cyclophosphamide, Doxorubicin, Vincristine, Etoposide, and Prednisone) chemotherapy. At the conclusion of treatment, there was complete remission. Numerous white scars were found on the stomach, endoscopically consistent with a remission image of lymphoma. The endoscopic features of this case were thought to be similar to those of MCL. CONCLUSION: The macroscopic/endoscopic features of gastrointestinal ALK+ ALCL may be more similar to those of B-cell lymphomas rather than T-cell lymphomas.

Successful Treatment of Gastrosplenic Fistula Arising from Diffuse Large B-Cell Lymphoma with Chemotherapy: Two Case Reports.

Gastrosplenic fistula (GSF) is a rare condition arising from gastric or splenic lymphomas. Surgical resection is the most common treatment, as described in previous reports. We report two cases of GSF in diffuse large B-cell lymphoma (DLBCL) patients that were successfully treated with chemotherapy and irradiation without surgical resection. Case 1 was of a 63-year-old man who had primary gastric DLBCL with a large lesion outside the stomach wall, leading to a spontaneous fistula in the spleen. Case 2 was of a 59-year-old man who had primary splenic DLBCL, which proliferated and infiltrated directly into the stomach. In both cases, chemotherapy comprising rituximab + dose-adjusted EPOCH regimen (etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) was administered. Case 1 had significant bleeding from the lesion of the stomach during the treatment cycle; however, endoscopic hemostasis was achieved. Case 2 developed a fistula between the stomach and the spleen following therapeutic chemotherapy; however, no complications related to the fistula were observed thereafter. In both cases, irradiation was administered, and complete remission was achieved.

A case of nivolumab-associated colitis, which relapsed after mucosal healing and was then successfully treated with mesalazine.

Currently, the number of patients treated with immune-checkpoint inhibitor involving nivolumab is increasing. Nevertheless, it causes various immune-related adverse events (irAEs). Here, we report the case of a patient who underwent long-term follow-up after suffering from nivolumab-associated colitis. The patient was a 57-year-old man who underwent resection of a bladder tumor. Following surgery, lymph node metastasis was detected, and he was treated by nivolumab. Two months after treatment with nivolumab, the patient complained of bloody diarrhea. Colonoscopy revealed pancolitis with erosions, loss of vascular pattern and erythema. Pathological findings indicated a disease state of pan-ulcerative colitis. As an irAE by nivolumab, the patient was started with 30 mg of prednisolone. Prednisolone treatment successfully induced clinical remission and mucosal healing. Nevertheless, eight months after stopping the steroid treatment, the colitis relapsed with diarrhea following elevation of fecal immunochemical test (FIT) and fecal calprotectin (CPT). The relapsed colitis was treated by mesalazine, and then diarrhea was improved. Nivolumab-associated colitis relapsed following mucosal healing suggesting that it is necessary to consider maintenance therapy as well as remission induction for long-term survivor. The present case also demonstrates that the FIT and CPT would be effective biomarker to assess the disease activity of nivolumab-associated colitis.

Usefulness of Cytological Scoring Method by Breast Fine Needle Aspiration Cytology on Breast Duct Dilatation and Cystic Lesions.

AIM: The objective of this study was to apply a scoring method to fine needle aspiration cytology on breast duct dilatation and cystic lesions, to set an optimum cut-off value to differentiate between benign and malignant cases, and to identify features useful for cell judgment. MATERIALS AND METHODS: Samples were 23 preparations of specimens (12 benign and 11 malignant cases) suspected with intraductal lesions or cystic change by ultrasonography or mammography and cytology. The scoring system comprised the following 10 items, and each item was scored 1-3, with a total score of 10-30. Three items were concerning structural atypia: 1, scattered epithelial cells; 2, uneven irregular cluster edge; and 3, overlapping nuclei of epithelial cells, and seven items were concerning cellular atypia: 4, irregular nuclear size; 5, irregular nuclear morphology; 6, deep dyeing chromatin; 7, chromatin granularity; 8, chromatin distribution; 9, nucleolus; and 10, absence of myoepithelial cells. RESULTS: (1) Scoring cut-off value: malignancy is to be suspected when the score is 20.75 or higher (diagnostic accuracy: 95.7%). (2) Findings useful for cancer judgment: the sensitivity of the following four findings was high: uneven irregular cluster edge, irregular nuclear overlapping, chromatin granularity, and absence of myoepithelial cells. (3) Correlation among the findings: the findings correlated with malignancy were as follows: scattered epithelial cells versus uneven irregular cluster edge (rs = 0.8). CONCLUSION: Cytological evaluation by scoring lesions accompanied by intraductal dilatation and cystic change was a useful method capable of differentiating between benign and malignant cases at a high accuracy.

Serum level of soluble interleukin-2 receptor is positively correlated with metabolic tumor volume on 18 F-FDG PET/CT in newly diagnosed patients with diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most frequent subtype of non-Hodgkin lymphoma. High total metabolic tumor volume (TMTV) calculated using 18 F-FDG PET/CT images at diagnosis predicts poor prognosis of patients with DLBCL. However, high cost and poor access to the imaging facilities hamper wider use of 18 F-FDG PET/CT. In order to explore a surrogate marker for TMTV, we evaluated the correlation between the serum levels of soluble interleukin-2 receptor (sIL-2R) and TMTV in 64 patients with DLBCL, and the results were verified in an independent validation cohort of 86 patients. Serum levels of sIL-2R were significantly correlated with TMTV. ROC analysis revealed that the cutoff value of TMTV ≥150 cm3 or sIL-2R ≥ 1300 U/mL could predict failure to achieve EFS24 with areas under the curve (AUC) 0.706 and 0.758, respectively. Each of TMTV ≥150 cm3 and sIL-2R ≥1300 U/mL was significantly associated with worse 5-year overall survival and event-free survival. Importantly, each of sIL-2R <1300 U/mL or TMTV <150 cm3 identified patients with favorable prognosis among NCCN-IPI high-intermediate and high-risk group. Serum level of sIL-2R represents a convenient surrogate marker to estimate metabolic tumor burden measured by 18 F-FDG PET/CT that can predict treatment outcomes of patients with DLBCL.