Development of a human herpesvirus 8-negative effusion-based lymphoma during treatment with dasatinib for chronic myeloid leukemia.

We present the case of an 85-year-old male patient diagnosed with human herpesvirus 8 (HHV8)-negative effusion-based lymphoma (EBL) that developed from long-lasting pleural effusion (PE) induced by dasatinib treatment for chronic myeloid leukemia (CML). After the onset of this disorder, dasatinib treatment was discontinued and drainage was performed to regress the effusion. The major molecular response (MMR) was thus lost. The patient did not tolerate nilotinib treatment, but bosutinib was successful in restoring MMR. During these clinical courses, the patient suffered from a recurrence of EBL, which was treated with rituximab-based chemotherapy. The PE sample just before the 3rd cycle of chemotherapy revealed the proliferation of CD57-positive T cells, along with the disappearance of lymphoma cells. Anti-tumor immunity may have been activated following the immunochemotherapy in the undisturbed immunological environment when both EBL and CML almost regressed. After four cycles of R-CVP therapy, the patient has been in remission for 16 months and no longer requires drainage.

Transient atelectasis due to hilar lymph node swelling affected by lenalidomide-induced tumor flare reaction.

Tumor flare reaction (TFR) is a unique immune-mediated tumor recognition phenomenon presenting as rapid enlargement of the tumor, which mimics disease progression, developing in the early stage of treatment using immunomodulatory drugs or immune checkpoint inhibitors. A 59-year-old man with follicular lymphoma had residual tumor burden in the left hilar lymph nodes after R-CHOP therapy, and received lenalidomide and rituximab (R2) therapy. He developed respiratory distress on day 11 of R2 therapy. Chest X-ray and CT demonstrated left lung atelectasis due to left hilar lymph node swelling. We performed transbronchial lung biopsy on day 20 of R2 therapy. The biopsied left bronchus tissue exhibited extensive necrosis, which had a B-cell phenotype consistent with that of follicular lymphoma. Neither NK cells nor cytotoxic T cells were detected. It was unclear whether the immune effector cells disappeared at the time of transbronchial lung biopsy. Atelectasis in our patient improved by continuing R2 therapy beyond TFR.

Acquired amegakaryocytic thrombocytopenia after durvalumab administration.

Immune checkpoint inhibitors (ICIs), despite their ability to potentiate antitumor T-cell responses, may cause various immune-related adverse events. Most cases of thrombocytopenia induced by ICIs have revealed a pathophysiologic mechanism of immune thrombocytopenia with increased platelet destruction and preserved megakaryocytes. Acquired amegakaryocytic thrombocytopenic purpura (AATP) is an unusual disorder characterized by thrombocytopenia with markedly diminished bone marrow megakaryocytes in the presence of otherwise normal hematopoiesis. AATP caused by ICIs has not been reported on. Herein, we present the case of a 79-year-old man diagnosed with squamous cell carcinoma of the lung who developed AATP after two courses of durvalumab, a drug targeting programmed death-ligand 1. Two weeks after the second cycle, his platelet count decreased to 2.1 × 104/µL. After the patient underwent platelet transfusion, his platelet count increased to 8.1 × 104/µL the next day but subsequently decreased repeatedly even after the ICI was discontinued. Six weeks after the second cycle, he developed interstitial pneumonia and was administered prednisolone (50 mg/day). However, thrombocytopenia did not improve. Bone marrow biopsy showed scarce megakaryocytes (< 1 megakaryocyte/10 high-power fields) with preservation of myeloid and erythroid series. Myelodysplasia, myelofibrosis, or metastatic lesions were not observed. Cytogenetic analysis showed a normal male karyotype of 46XY. Hence, the patient received eltrombopag, a thrombopoietin receptor agonist, and his platelet count subsequently improved. After recovery, bone marrow aspiration revealed a normal number of megakaryocytes. AATP is rarely the type of thrombocytopenia induced by ICIs and may be successfully treated with thrombopoietin receptor agonists.

Acceptability of endoscopic submucosal dissection for sessile serrated lesions: comparison with non-sessile serrated lesions.

Background and study aims Sessile serrated lesions (SSL) are major precursor lesions of serrated pathway cancers, and appropriate treatment may prevent interval colorectal cancer. Studies have reported the outcomes of endoscopic mucosal resection (EMR) for SSL; however, there are insufficient reports on endoscopic submucosal dissection (ESD). We examined the characteristics and outcomes of SSL and compared them to those of non-SSL in ESD. Patients and methods We reviewed 370 consecutive cases in 322 patients who underwent colorectal ESD between January 2016 and March 2020 at our hospital. There were 267 0-IIa lesions that were stratified into 41 SSL and 226 non-SSL (intramucosal cancer, adenoma) cases. We used propensity matching to adjust for the variances in the factors affecting treatment between the SSL and non-SSL groups. Results In the baseline cases, young women and proximal colon tumor location were significantly more common in the SSL group. There were no statistically significant differences between the SSL and non-SSL groups in terms of en bloc resection rate (97.6 % vs. 99.6 %; P  = 0.28), R0 resection rate (92.7 % vs. 93.4 %; P  = 0.74), perforation (0 % vs. 0.9 %; P  > 0.99), and postoperative bleeding (2.4 % vs. 1.8 %; P  = 0.56). Thirty-eight pairs were matched using propensity score, and the median dissection speed (12 vs. 7.7 cm 2 /h; P  = 0.0095) was significantly faster in the SSL than in the non-SSL group. Conclusions ESD for SSL was safely performed, and SSL was smoother to remove than non-SSL. ESD might be an acceptable endoscopic treatment option for SSL.

Prognostic Understanding at Diagnosis and Associated Factors in Patients with Advanced Lung Cancer and Their Caregivers.

BACKGROUND: Prognostic understanding in advanced cancer patients and their caregivers may have an impact on the delivery of effective care. The aims of this study were to explore prognostic understanding at diagnosis in both patients with advanced lung cancer and their caregivers and to investigate correlates of their understanding. SUBJECTS, MATERIALS, AND METHODS: A total of 193 patients with newly diagnosed advanced lung cancer and their 167 caregivers were enrolled at 16 hospitals in Japan. We assessed their perceptions of prognosis and goals of therapy and examined their associations with their sociodemographic characteristics, clinical status, quality of life, mood symptoms, and the status of disclosure of information by their treating physicians. RESULTS: One fifth of patients and caregivers (21.7% and 17.6%, respectively) mistakenly believed that the patients' cancer was "completely curable." Substantial proportions of them (16.9% and 10.3%, respectively) mistakenly believed that the primary goal of therapy was to remove all the cancer. Levels of anxiety and depression in both patients and caregivers were significantly higher among those who had accurate understanding of prognosis. In multivariate analyses, inaccurate perceptions of prognosis in patients were associated with sex, better emotional well-being, and lower lung cancer-specific symptom burden. Caregivers' inaccurate perceptions of patients' prognoses were associated with better performance status and better emotional well-being of patients. CONCLUSION: Substantial proportions of advanced lung cancer patients and their caregivers misunderstood their prognosis. Interventions to improve their accurate prognostic understanding should be developed with careful attention paid to its associated factors. IMPLICATIONS FOR PRACTICE: This study demonstrated that substantial proportions of patients with newly diagnosed advanced lung cancer and their caregivers had misunderstandings about their prognosis. Accurate perceptions of prognosis, which are indispensable in the delivery of effective care, were associated with elevated levels of anxiety and depression in both patients and caregivers, warranting psychosocial care and support for them immediately after diagnosis. Inaccurate perceptions of prognosis in patients were associated with better emotional well-being and lower lung cancer-specific symptom burden. Illness understanding in caregivers was associated with patients' physical and mental status. Those findings provide insight into how they obtain accurate illness understanding.

A large cohort study concerning age-dependent impacts of anthropometric variables on spirometric parameters in nonsmoking healthy adults.

BACKGROUNDS: Although height (H) has been considered the principal anthropometric variable governing lung function, the age-dependent differences in its influences on determining spirometric parameters (SPs) have not been conclusively investigated. Moreover, there has been no study centered on age-dependent effects of other anthropometric variables, including body weight (BW) and body fat mass (BFM) on SPs. In addition, the age-dependent influences of these anthropometric variables are anticipated to differ quantitatively between male and female participants. METHODS: A total of 16,919 nonsmoking healthy Japanese adults (men: 6,116, women: 10,803) were partitioned into six groups stratified by gender and age at intervals of 20-years: young-, middle-, and advanced-age groups of either gender. Using a model in which a SP was described by a logarithmic additive function of age, H, BW, and BFM, we determined the partial regression coefficients of the respective anthropometric variables to predict the reference means of SPs, including FVC, FEV1, FEV1/FVC, PEF, FEF50, and FEF75, in the six groups. RESULTS/DISCUSSION: Although the impact of H on FVC and FEV1 was relatively homogeneous irrespective of gender and age, its homogeneity faded for flow parameters, particularly in the female middle- and advanced-age groups, indicating that the age-dependent contribution of H to SPs was enhanced more in women. The impact of BW on SPs differed depending on age, and this effect was also more conspicuous for female participants. H and BW generally exerted positive effects on SPs, whereas BFM had negative effects. Opposite effects of BW and BFM were observed in the female middle-age group in particular. CONCLUSIONS: The effects of anthropometric variables on spirometric parameters are highly age-dependent, particularly in women, leading to the conclusion that the assumption of age-independent, constant partial regression coefficients of anthropometric variables while predicting the reference mean of a certain spirometric parameter may result in substantial errors.

[A case of Sjogren syndrome coexistent with MALT lymphoma occurring along the parotid gland and trachea].

A 62-year-old woman with Sjogren syndrome was admitted for computed tomographic (CT) evaluation of a thickened trachea and parotid tumor. She had been given a diagnosis of mucosa-associated lymphoid tissue (MALT) lymphoma 6 years previously, and had undergone surgical resection of the parotid tumor. Endoscopic examination revealed an annular tumor that had formed a stricture in the mid-trachea. Pathologic specimens were obtained by surgical resection of the parotid tumor and bronchoscopic biopsy of the tracheal tumor. Both histological examinations revealed MALT-type marginal zone B-cell lymphoma. Because CD20 immunostaining was positive, the patient received 6 cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) without any signs of major toxicity. All lesions disappeared after treatment, and this patient remained disease-free for 40 months.

Inhibition of c-Jun NH2-terminal kinase activity improves ischemia/reperfusion injury in rat lungs.

Although c-Jun NH(2)-terminal kinase (JNK) has been implicated in the pathogenesis of transplantation-induced ischemia/reperfusion (I/R) injury in various organs, its significance in lung transplantation has not been conclusively elucidated. We therefore attempted to measure the transitional changes in JNK and AP-1 activities in I/R-injured lungs. Subsequently, we assessed the effects of JNK inhibition by the three agents including SP600125 on the degree of lung injury assessed by means of various biological markers in bronchoalveolar lavage fluid and histological examination including detection of apoptosis. In addition, we evaluated the changes in p38, extracellular signal-regulated kinase, and NF-kappaB-DNA binding activity. I/R injury was established in the isolated rat lung preserved in modified Euro-Collins solution at 4 degrees C for 4 h followed by reperfusion at 37 degrees C for 3 h. We found that AP-1 was transiently activated during ischemia but showed sustained activation during reperfusion, leading to significant lung injury and apoptosis. The change in AP-1 was generally in parallel with that of JNK, which was activated in epithelial cells (bronchial and alveolar), alveolar macrophages, and smooth muscle cells (bronchial and vascular) on immunohistochemical examination. The change in NF-kappaB qualitatively differed from that of AP-1. Protein leakage, release of lactate dehydrogenase and TNF-alpha into bronchoalveolar lavage fluid, and lung injury were improved, and apoptosis was suppressed by JNK inhibition. In conclusion, JNK plays a pivotal role in mediating lung injury caused by I/R. Therefore, inhibition of JNK activity has potential as an effective therapeutic strategy for preventing I/R injury during lung transplantation.