Novel prognostic predictor of haemoglobin-platelet index in diffuse large B-cell lymphoma, not otherwise specified: Anaemia and thrombocytopenia are associated with IL-6 production in lymphoma cells.

We previously reported that a novel haemoglobin-platelet index (HPI) based on anaemia and thrombocytopenia was useful to predict the prognosis of patients with diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS). Here, we analyse the utility of HPI in a new validation cohort with DLBCL NOS (n  = 94). As a result, we confirm that HPI was effective for differentiating progression-free survival (PFS) and overall survival in this validation cohort. So, we further compare the utility of HPI with previously reported prognostic markers such as the National Comprehensive Center Network-International Prognostic Index (NCCN-IPI), Glasgow prognostic score (GPS), and platelet-albumin (PA) score, using a larger number of 160 patients consisting of the derivation cohort (n  = 66) and a validation cohort (n  = 94). As a result, the patients with a higher HPI score had significantly worse outcomes, and HPI predicted the prognosis of DLBCL NOS independently of NCCN-IPI. HPI was more sensitive than GPS and almost the same as PA score in predicting PFS. Moreover, the patients whose lymphoma cells were positive for interleukin-6 (IL-6) (75/111 cases) judged by immunohistochemical staining had significantly lower haemoglobin levels and platelet counts than IL-6-negative cases (36/111 cases), suggesting the involvement of IL-6 produced by lymphoma cells in anaemia and thrombocytopenia in DLBCL NOS patients.

Treatment of trigeminal and glossopharyngeal neuralgia in an adolescent: a case report.

BACKGROUND: Hyperactive dysfunction syndrome (HDS) refers to a constellation of symptoms developing from cranial nerve overactivity caused by neurovascular compression at the root entry or exit zone near the brainstem. Although the combined features of HDS are seen in the elderly, there are no reports of such cases in adolescents, to date. CASE PRESENTATION: A 17-year-old male was diagnosed with right glossopharyngeal neuralgia and treated with microvascular decompression. He experienced new-onset right facial pain later and was diagnosed with right trigeminal neuralgia, which required prompt radiofrequency thermocoagulation of the right mandibular nerve. Follow-up in the third post-treatment year revealed the absence of symptom recurrence. DISCUSSION: We report the treatment of a rare case of adolescent-onset combined HDS presenting as trigeminal and glossopharyngeal neuralgia. This report highlights the possibility of combined hyperactive dysfunction syndrome in younger age groups. It is crucial to establish a diagnosis early on for prompt management.

1-kHz high-frequency spinal cord stimulation alleviates chronic refractory pain after spinal cord injury: a case report.

BACKGROUND: Patients with spinal cord injury (SCI) frequently complain of intractable pain that is resistant to conservative treatments. Here, we report the successful application of 1-kHz high-frequency spinal cord stimulation (SCS) in a patient with refractory neuropathic pain secondary to SCI. CASE PRESENTATION: A 69-year-old male diagnosed with SCI (C4 American Spinal Injury Association Impairment Scale A) presented with severe at-level bilateral upper extremity neuropathic pain. Temporary improvement in his symptoms with a nerve block implied peripheral component involvement. The patient received SCS, and though the tip of the leads could not reach the cervical vertebrae, a 1-kHz frequency stimulus relieved the intractable pain. CONCLUSIONS: SCI-related symptoms may include peripheral components; SCS may have a considerable effect on intractable pain. Even when the SCS electrode lead cannot be positioned in the target area, 1-kHz high-frequency SCS may still produce positive effects.

Intubation Technique in a Patient with Tracheobronchopathia Osteochondroplastica.

BACKGROUND Tracheobronchopathia osteochondroplastica (TO) is a rare disorder characterized by cartilaginous or ossified submucosal nodules of unknown etiology that project into the tracheobronchial lumen. TO is often accompanied by endotracheal stenosis from cartilage proliferation and is often detected by difficult endotracheal intubation incidence. CASE REPORT Here we report the case of a patient (67-year-old man) with TO scheduled to undergo robot-assisted total prostatectomy for prostate cancer. The tracheal lumen was especially narrow at an area 1 cm below the glottis, with the smallest lumen diameter being 9 mm. After rapid induction, the bronchoscope passed through the stenosed region, and a 6.5-mm spiral endotracheal tube (ETT) was inserted with bronchoscopic assistance. However, because of resistance, the spiral ETT could not pass through the stenosed area. After changing to a 6.5-mm normal ETT, intubation was successfully performed with gentle rotation. Owing to the rotation, the tip entered and gained access to the gap between nodules. With use of a bronchoscope, we confirmed that the tip of the ETT was advanced 10 cm from the glottis, where the site of maximum stenosis was not covered by the tube cuff, and where the tip did not cross the bifurcation. After surgery, no bleeding or edema was found on bronchoscopy. CONCLUSIONS In patients with TO, it is important to assess the airway condition and prepare for difficult intubation. In this case, tracheal intubation was performed with rotation using a bronchoscope and normal ETT.

Spinal cord stimulation alleviates intractable pain due to malignant pleural mesothelioma: a case report.

BACKGROUND: Patients with malignant pleural mesothelioma (MPM) frequently complain of intractable pain that is resistant to conservative treatments. Although spinal cord stimulation (SCS) may be promising in the alleviation of such devastating pain, the effects of SCS on MPM-associated pain and the appropriate timing of its application remain unknown. CASE PRESENTATION: A 66-year-old man diagnosed with MPM presented with severe neuropathic pain due to rapid progression of the tumor to the intercostal nerves. The patient immediately decided to receive SCS implantation and burst stimulus, which relieved the conservative therapy-resistant pain and improved his sleep and daily activities. CONCLUSION: This report suggests that the execution of SCS as soon as possible may help to alleviate MPM symptoms. Since MPM extends aggressively to the thorax and nerves that cause mixed nociceptive and/or neuropathic pain, appropriate pain management requires the proper assessment of the etiology by an expert in pain management.

Targeted therapy for medullary and extramedullary relapse of FLT3-ITD acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation.

We report a case with extramedullary tumors affecting the supraclavicular region that presented as a relapse of acute myeloid leukemia (AML) with FLT3-ITD mutation after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Treatment with gilteritinib resulted in remarkable response with disappearance of both the medullary and extramedullary tumors. Subsequently, a 2nd allo-HSCT was performed in an attempt to cure his AML and complete molecular response has been sustained with gilteritinib resumption without worsening GVHD. Targeted therapy with gilteritinib for medullary and extramedullary relapse of FLT3-ITD AML could be effective and suitable as a bridging therapy for allo-HSCT.

The Impact of Hemodialysis and Liver Cirrhosis on the Plasma Concentrations of Tyrosine Kinase Inhibitors in a Patient with Chronic Myeloid Leukemia.

We recently treated a chronic myeloid leukemia (CML) patient with liver and renal dysfunction, who was undergoing hemodialysis (HD). He was treated with 50 mg dasatinib (DAS) once daily just before HD. The maximum plasma concentration of DAS was 227 ng/mL on a non-HD day and 46.9 ng/mL on a HD day. He was subsequently treated with 200 mg bosutinib (BOS) once daily. The plasma concentration of BOS changed from 74.5 ng/mL before HD to 58.8 ng/mL after HD. Our results indicate that close monitoring of the plasma tyrosine kinase inhibitor concentrations should be considered in CML patients with organ impairment.

Anesthetic management of laparoscopy-assisted total proctocolectomy in a cardiac sarcoidosis patient with a cardiac resynchronization therapy-defibrillator: a case report.

BACKGROUND: Cardiac sarcoidosis (CS) causes severe conduction abnormalities and arrhythmias. CS patients are increasingly being treated with cardiac resynchronization therapy-defibrillators (CRT-Ds). For the first time, we report the anesthetic management of a CS patient with a CRT-D. CASE PRESENTATION: A 65-year-old male with an implanted CRT-D due to CS was scheduled for a laparoscopy-assisted total proctocolectomy for his transverse colon cancer. His left ventricular ejection fraction was 32.0%, and his physical status was a New York Heart Association class III. General and epidural anesthesia were performed while using standard monitors and a FloTracTM system. The dual-chamber pacing (DDD) modality of the CRT-D was unchanged, and its defibrillation function was deactivated before surgery. The surgery was successfully performed, and the patient was discharged without worsening of his cardiac condition. CONCLUSIONS: A detailed understanding of this patient's condition, as well as sarcoidosis, helped to facilitate successful anesthetic management of this patient.

Tumour-immune microenvironment in duodenal-type follicular lymphoma.

Despite duodenal-type follicular lymphoma (DTFL) being morphologically, immunophenotypically and genetically indistinguishable from nodal FL (nFL), this entity typically shows a significantly better prognosis. Here, we analysed the tumour immune microenvironments of diagnostic specimens from patients with DTFL (n = 30), limited-stage FL (LSFL; n = 19) and advanced-stage FL (ASFL; n = 31). The mean number of CD8+ tumour-infiltrating lymphocytes (TILs) in the neoplastic follicles was higher in DTFL (1,827/mm2 ) than in LSFL (1,150/mm2 ) and ASFL (1,188/mm2 ) (P = 0·002, P = 0·002, respectively). In addition, CD8+ PD1-  T cells with non-exhausting phenotype were more abundant in the peripheral blood (PB) of DTFL than in LSFL and ASFL, indicating that DTFL may exhibit a better and longer-lasting T cell-mediated immune response. Moreover, whereas FOXP3+ CTLA-4+ effector regulatory T cells (eTregs) were rarely observed in the neoplastic follicles of DTFL (mean: 12/mm2 ), they were more abundant in LSFL (78/mm2 ) and ASFL (109/mm2 ) (P = 2·80 × 10-5 , P = 4·74 × 10-8 , respectively), and the numbers of eTregs correlated inversely with those of CD8+ TILs (r = -0267; P = 0·018). Furthermore, DTFL showed significantly fewer circulating FOXP3hi CD45RA- CD25hi eTregs (0·146%) than ASFL (0·497%) and healthy controls (0·639%) (P = 0·0003, P = 6·79 × 10-7 , respectively). These results suggest that the augmented anti-tumour immune reactions may contribute to a better prognosis on DTFL.

Epstein-Barr Virus-Induced Post-Transplant Lymphoproliferative Disorder of the Central Nervous System Successfully Treated with Chemo-immunotherapy.

Aplastic anemia is a rare blood disease characterized by the destruction of the hematopoietic stem cells (HSC) in the bone marrow that, in the majority of cases, is caused by an autoimmune reaction. Patients with aplastic anemia are treated with immunosuppressive drugs and some of them, especially younger individuals with a donor available, can be successfully treated with hematopoietic stem cell transplantation (HSCT). We report here a rare case of post-transplant lymphoproliferative disorder (PTLD) associated with Epstein-Barr virus (EBV) reactivation in a 30-year-old female patient who underwent allogeneic HSCT for severe aplastic anemia. The PTLD, which was diagnosed 230 days after transplantation, was localized exclusively in the central nervous system (specifically in the choroid plexus) and manifested with obvious signs of intracranial hypertension. After receiving three cycles of high dose methotrexate (HD-MTX) combined with rituximab, the patient achieved a complete clinical recovery with normalization of blood cell counts, no evidence of EBV reactivation, and no associated neurotoxicity.

Novel prognostic index based on hemoglobin level and platelet count for diffuse large B-cell lymphoma, not otherwise specified in the R-CHOP era.

The international prognostic index (IPI) is a broadly utilized clinical tool to aid in predicting the prognosis of patients with aggressive non-Hodgkin's lymphomas (NHL). However, since this score was developed before the development of rituximab, and the introduction of combined rituximab plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) (R-CHOP) therapy for NHL has dramatically improved clinical outcomes, the IPI may be inadequate to assess prognosis in the R-CHOP era. In the present study, we assessed the utility of hemoglobin (Hb) level and platelet count to predict prognosis in diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), the largest category of aggressive NHL. A total of 89 patients newly diagnosed with nodal DLBCL, NOS and treated with R-CHOP therapy were included. The blood count results at diagnosis were statistically analyzed. Available biopsy specimens were immunostained for interleukin (IL)-6. Hb levels lower than 120 g/L (p = 0.0133) and platelet counts lower than 135 × 109/L (p = 0.0233) were associated with worse overall survival (OS). Based on those levels as cutoff values, a hemoglobin-platelet (HP) index was calculated by assigning 1 point for an Hb level or a platelet count lower than the cutoff. The patients were divided into three groups based on the HP index: high, with a score of 2 (n = 8); intermediate, with a score of 1 (n = 39); and low, with a score of 0 (n = 42). A higher HP index was associated with worse OS (p = 0.0055). Patients with IL-6-positive tumors had significantly lower Hb levels than those with IL-6-negative tumors (p = 0.0264), suggesting that abnormal production of IL-6 by lymphoma cells is associated with anemia. On the other hand, there was no association between the platelet counts and the IL-6 expression in the lymphoma cells. In a multivariate analysis, the HP index predicted OS rate independently of the IPI. Since the HP index is based on inexpensive and broadly available laboratory values, we believe that this index will have great utility in clinical practice, and the addition of this index to IPI could more precisely predict prognosis.

Tumor necrosis factor- and interleukin-6-producing high-grade B-cell lymphoma, not otherwise specified in the pleura.

A 65-year-old man was admitted to our hospital with left-sided chest and back pain and dyspnea. Computed tomography demonstrated a marked circumferential left pleural thickening. A thoracoscopic pleural biopsy led to a diagnosis of high-grade B-cell lymphoma, not otherwise specified (HGBL, NOS). Lymphoma cells were positive for tumor necrosis factor (TNF) and interleukin-6. This is the first case report of TNF- and IL-6-producing aggressive HGBL, NOS in the pleura, in which radiological findings mimicked pleural mesothelioma. The aggressive tumor progression in the present case may have been caused by abnormal cytokine production from lymphoma cells.

Transforming growth factor ß- and interleukin 13-producing mast cells are associated with fibrosis in bone marrow.

Although bone marrow fibrosis is a lethal condition, its underlying mechanism is not fully understood. This study aimed to investigate the pathogenesis of fibrosis in the bone marrow through histologic examination of mast cell infiltration and the expression of fibrosis-associated cytokines. We analyzed 22 bone marrows with fibrosis (8 primary myelofibrosis [PMF], 5 post-essential thrombocythemia [ET], myelofibrosis, and 9 myelodysplastic syndrome [MDS] with bone marrow fibrosis [BMF]). Immunohistochemical and immunofluorescence stainings were performed using anti-mast cell tryptase, interleukin (IL) 13, transforming growth factor ß (TGF-ß), CD34, and CD42b antibodies. The number of mast cells in bone marrows with fibrosis was significantly higher than that in controls (P<.0001 for all cases with fibrosis versus control, P=.0470 for PMF versus control, P<.0001 post-ET myelofibrosis versus control, and P=.0005 for MDS with BMF versus control). Moreover, bone marrows with higher fibrotic grades exhibited greater amounts of infiltrating mast cells. Mast cells were positive for TGF-ß and IL-13 in bone marrows with fibrosis of all 3 groups. Megakaryocytes were negative for TGF-ß in post-ET and MDS with BMF, but some megakaryocytes in PMF were weakly positive for TGF-ß. Megakaryocytes were negative for IL-13 in all 3 groups. Blasts were negative for both TGF-ß and IL-13 in all 3 groups. Thus, TGF-ß- and IL-13-producing mast cells might be key players in the development of BMF. Therefore, mast cells could be potential therapeutic targets for the treatment of BMF.