Case report and review of the literature of primary central nervous system lymphoma of the fourth ventricle.

Background: Primary central nervous system lymphoma of the fourth ventricle is very rare. We present a case of primary central nervous system lymphoma originating from the fourth ventricle and review cases reported in the literature. Case Description: A 54-year-old man with no previous medical history presented with headache and nausea. Magnetic resonance imaging showed a homogeneously enhancing tumor in the fourth ventricle and obstructive hydrocephalus. We performed biopsy of the tumor, which was diagnosed pathologically as diffuse large B-cell lymphoma. Although the tumor disappeared after 5 cycles of R-MPV regimen, the patient required repeated ventricular drainage and finally received a ventriculoperitoneal shunt. Complete response was achieved after 2 cycles of high-dose cytarabine chemotherapy with an autologous peripheral blood stem cell transplant. There was no sign of recurrence at 20 months after biopsy. Conclusion: Morbidity arising due to radical resection/radiotherapy of resistant primary central nervous system lymphoma originating from the fourth ventricle could be prevented by ventriculoperitoneal shunting with chemotherapy and autologous blood stem cell transplantation.

Association of thyroid transcription factor-1 with the efficacy of immune-checkpoint inhibitors in patients with advanced lung adenocarcinoma.

BACKGROUND: We aimed to identify the relationship between thyroid transcription factor-1 (TTF-1) expression of lung adenocarcinoma and the efficacy of immune-checkpoint inhibitor (ICI) therapy. METHODS: This retrospective multicenter study comprised patients with advanced lung adenocarcinoma treated with ICI monotherapy. We collected clinical medical records including data on TTF-1 expression and analyzed the relationship between TTF-1 expression and programmed death-ligand 1 tumor proportion score (PD-L1 TPS), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: In total, 108 patients with lung adenocarcinoma were analyzed. The rate of TPS ≥1% and ≥50% in patients with positive TTF-1 expression was significantly higher than that in patients with negative TTF-1 expression (88% vs. 60%, p < 0.001; 65% vs. 24%, p < 0.001). The ORR was significantly higher in TTF-1 positive patients than in TTF-1-negative patients (38% vs. 8%, p = 0.003). Among patients with TPS ≥50% and 1%-49%, the ORR in TTF-1 positive and negative patients was 48% (26/54) versus 17% (1/6) (p = 0.21), and 32% (6/19) versus 11% (1/9) (p = 0.37), respectively. The ORR for patients with TPS <1% was 0% in both the TTF-1 negative and positive cases. The median PFS and OS was significantly longer in TTF-1-positive patients than in TTF-1-negative patients (5.4 vs. 1.6 months, p < 0.001; 18.2 vs. 8.0 months, p = 0.041). Multivariate analysis revealed that TTF-1-negative status was an independent unfavorable prognostic factor for PFS. CONCLUSION: Patients with TTF-1-positive status receiving ICI monotherapy showed better outcomes than those with TTF-1-negative lung adenocarcinoma.

Vascular endothelial growth factor receptor 2 expression and immunotherapy efficacy in non-small cell lung cancer.

It is unclear whether tumor vascular endothelial growth factor receptor 2 expression affects the therapeutic efficacy of immune-checkpoint inhibitors and antiangiogenic agents. This retrospective, multicenter study included patients with advanced non-small cell lung cancer who were treated with immune-checkpoint inhibitors. We constructed tissue microarrays and performed immunohistochemistry with an anti-vascular endothelial growth factor receptor 2 antibody. We analyzed immune and tumor cell staining separately in order to determine their correlation with the objective response rate, progression-free survival, and overall survival in patients receiving immune-checkpoint inhibitors. Of 364 patients, 37 (10%) expressed vascular endothelial growth factor receptor 2 in immune cells and 165 (45%) in tumor cells. The objective response rate, progression-free survival, and overall survival were significantly worse in patients treated with immune checkpoint inhibitor monotherapy who expressed vascular endothelial growth factor receptor 2 in immune cells than those who did not (10% vs 30%, p = 0.028; median = 2.2 vs 3.6 months, p = 0.012; median = 7.9 vs 17.0 months, p = 0.049, respectively), while there was no significant difference based on tumor cell expression (24% vs 30%, p = 0.33; median = 3.1 vs 3.5 months, p = 0.55; median = 13.6 vs 16.8 months, p = 0.31). There was no significant difference in overall survival between patients treated with and without antiangiogenic agents in any treatment period based on vascular endothelial growth factor receptor 2 expression. Immune checkpoint inhibitor efficacy was limited in patients expressing vascular endothelial growth factor receptor 2 in immune cells.

Conveying Intention by Motions With Awareness of Information Asymmetry.

Humans sometimes attempt to infer an artificial agent's mental state based on mere observations of its behavior. From the agent's perspective, it is important to choose actions with awareness of how its behavior will be considered by humans. Previous studies have proposed computational methods to generate such publicly self-aware motion to allow an agent to convey a certain intention by motions that can lead a human observer to infer what the agent is aiming to do. However, little consideration has been given to the effect of information asymmetry between the agent and a human, or to the gaps in their beliefs due to different observations from their respective perspectives. This paper claims that information asymmetry is a key factor for conveying intentions with motions. To validate the claim, we developed a novel method to generate intention-conveying motions while considering information asymmetry. Our method utilizes a Bayesian public self-awareness model that effectively simulates the inference of an agent's mental states as attributed to the agent by an observer in a partially observable domain. We conducted two experiments to investigate the effects of information asymmetry when conveying intentions with motions by comparing the motions from our method with those generated without considering information asymmetry in a manner similar to previous work. The results demonstrate that by taking information asymmetry into account, an agent can effectively convey its intention to human observers.

SP142 evaluation contributes to the prediction of immune checkpoint inhibitor efficacy in non-small cell lung cancer with high PD-L1 expression assessed by 22C3.

Background: It remains unclear whether assessing programmed death-ligand 1 (PD-L1) expression by SP142 plus 22C3 adds value for predicting the response to immunotherapy in non-small cell lung cancer (NSCLC). Methods: This retrospective multicenter study included patients with advanced NSCLC treated with immune-checkpoint inhibitors. We constructed tissue microarrays (TMAs) and performed immunohistochemical staining with 22C3 and SP142 assays. We denoted the PD-L1 tumor proportion score (TPS) obtained from clinical medical records based on 22C3 staining as "22C3 (C)" and that obtained with 22C3 staining using our TMA as "22C3 (TMA)". SP142 staining was evaluated in both tumor cells and immune cells. We assessed the concordance between each PD-L1 assessment method and analyzed the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) based on the PD-L1 expression level determined using the 22C3 and SP142 assays. Results: In total, 288 patients were included. Among those with 22C3 (TMA) ≥50%, 60% of patients showed SP142 TC3 or IC3; among patients with 22C3 (C) <1%, 9% and 18% exhibited 22C3 (TMA) ≥1% and SP142 TC1/2/3 or IC1/2/3, respectively. Among patients with 22C3 (C) ≥50% treated with immune-checkpoint inhibitor monotherapy, the SP142 TC1/2/3 or IC1/2/3 group showed significantly better ORR, PFS and OS than the SP142 TC0 and IC0 group (54% vs. 29%, P=0.040, median =11.0 vs. 3.2 months, P=0.002, median =27.9 vs. 12.6 months, P=0.030, respectively). Multivariate analysis revealed that SP142 TC0 and IC0 was an independent unfavorable prognostic factor for PFS and OS in patients with 22C3 (C) ≥50% treated with immune-checkpoint inhibitor monotherapy. For those with 22C3 (C) ≥50% and SP142 TC0 and IC0, immune-checkpoint inhibitor concurrent with chemotherapy tended to result in a longer PFS and OS than immune-checkpoint inhibitor monotherapy (median =13.7 vs. 2.3 months, P=0.054, median = not estimable vs. 12.0 months, P=0.064, respectively). Conclusions: SP142 evaluation contributes to the prediction of immune-checkpoint inhibitor efficacy in NSCLC with high PD-L1 expression assessed by 22C3.

Lymphoproliferative disorder with pathological fracture of the femur in a patient with rheumatoid arthritis treated with methotrexate: A case report.

Methotrexate (MTX) is the key drug for the treatment of rheumatoid arthritis (RA). MTX-treated RA has been associated with the development of lymphoproliferative disorders (LPDs). Notably, the hyperimmune state of RA itself or the immunosuppressive state induced by MTX administration may contribute to development of LPD. Furthermore, Epstein-Barr virus (EBV) has been indicated to contribute to the development of MTX-LPD. MTX-associated LPD (MTX-LPD) may affect nodal or extranodal sites, including the gastrointestinal tract, skin, lungs, kidneys, and soft tissues, at an almost equal frequency. However, it is rare for MTX-LPD to manifest as multiple bone tumors with a pathological fracture. The present study reported the case of a 46-year-old Japanese woman with RA who had complications of EBV-positive MTX-LPD during an approximate 5-year course of MTX therapy. The present study indicated a rare case in which the LPD had spread to multiple bones in a patient with a pathologic fracture. Notably, the LPD was subclassified as diffuse large B-cell lymphoma (DLBCL).

[A case of neurosarcoidosis with recurrent brainstem infarction, obstructive hydrocephalus and brainstem atrophy].

We report the case of a 42-year-old female with neurosarcoidosis who was hospitalized in year 2017 for gait disturbance. In 2011, she suddenly had vertigo that lasted for a few days. In 2013, she noticed left hemiplegia. A brain MRI revealed an acute infarction on the right side of the upper pons extending longitudinally from the ventral surface. In 2017, she again had left lower limb paralysis. A Brain MRI showed another infarction on the right side of the mid-pons. Hydrocephalus and brainstem atrophy were also noted. The patient was referred to our hospital. Upon neurological examination, she presented with down beat nystagmus, muscle weakness on the left side, and a broad-based spastic gait. CSF findings included an increased number of cells and protein levels with decreased glucose levels. A contrast-enhanced MRI revealed basilar meningitis causing hydrocephalus. A contrast CT scan revealed inguinal lymph node swelling, and scintigram found gallium accumulation. We diagnosed sarcoidosis via a lymph node biopsy. We speculate that chronic basilar meningitis obstructed the patient's branching penetrating arteries inducing infarction together with obstruction of the spinal fluid flow causing hydrocephalus and cerebral atrophy.

Examination of cancer cells exposed to gastric serosa by serosal stamp cytology plus RT-PCR is useful for the identification of gastric cancer patients at high risk of peritoneal recurrence.

BACKGROUND: We sought to clarify the clinical value of the examination of cancer cells exposed to gastric serosa by our novel method of serosal stamp cytology and a real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. METHOD: A total of 70 patients who underwent gastrectomy were enrolled. Stamp cytology specimens were obtained by stamping the gastric serosa at the primary gastric tumor lesion, followed by Papanicolaou's staining. Samples obtained by brushing the serosa at the primary gastric tumor were analyzed by our RT-PCR of carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20). RESULTS: Among the 70 patients, 11 patients were diagnosed as stamp cytology-positive. Eight and five patients were found to be CEA-positive and CK20-positive, respectively. Since 21 of the 70 patients were either stamp cytology-positive or RT-PCR analysis-positive, these 21 patients were considered to be positive for cancer cells exposed to serosa of primary gastric tumor. The 3-year recurrence-free survival rate of the patients with a single positive result by our method (41.7%) was significantly (log rank p = 0.0002) worse than that of the patients with both negative results (81.0%). Our method showed 58.8% sensitivity and 79.2% specificity. A multivariate analysis revealed that a stamp cytology and/or RT-PCR result was an independent prognostic factor for recurrence. CONCLUSION: The examination of cancer cells exposed to gastric serosa by our serosal stamp cytology and RT-PCR system will be useful for the identification of patients at high risk for peritoneal recurrence after curative surgery for gastric cancer.

Chondroblastoma of extra-craniofacial bones: Clinicopathological analyses of 103 cases.

We elucidated clinicopathological characteristics of chondroblastoma (CB) in Japan, and reliable clinicopathologic parameters predicting local recurrence and/or metastasis. Clinicopathological profiles of 103 CB (80 male, 23 female) in extra-craniofacial bones were retrieved. Numerical scoring of nine pathological and five radiological features was statistically analyzed to determine prognostic significance. Age ranged 8-61 years (average 19.6 years). Frequently involved sites were femur, tibia, calcaneus, patella and humerus. Radiologically, tumors were 2-80 mm (average 31.1 mm) in size. Marginal sclerosis and calcification were common. Histologically, pink cartilage, mitoses, and chicken-wire calcification were often seen. Within a follow-up period [2-260 months (average 53.5 months)], the local recurrence rate was 15.5%. No patient had metastasis. Recurrence was most frequently observed at the femur. By log-rank analysis, only cyst formation in images was significant for predicting recurrence free survival (RFS). By Cox hazard analysis with representative clinico-radiological and pathological features, only age (≥16 years) and cyst formation were significant predictors for RFS. Pathological features were not significant in both uni- and multivariate analyses.

Results of surgery plus postoperative radiotherapy for patients with malignant parotid tumor.

PURPOSE: The latest version of the World Health Organization (WHO) histologic classification of salivary gland malignancies was published in 2005. To contribute to data accumulation on the basis of this latest version, a retrospective study was performed. MATERIALS AND METHODS: Participants comprised 27 patients who underwent postoperative radiotherapy between 2000 and 2013. Two, eight, and 17 patients were allocated to low, intermediate, and high-grade groups, respectively, in accordance with the latest WHO classification. The radiation field included the tumor bed and ipsilateral regional lymph nodes for 25 patients. The radiation dose was 46-60 Gy (median 56 Gy). RESULTS: Median duration of follow-up was 41 months. Five-year locoregional control was 89 %. Two patients experienced local recurrence and 7 patients developed distant metastases. No patients in the low or intermediate-grade groups developed distant metastases. Overall 3 and 5-year survival for all patients were 81 and 75 %, respectively. Five-year overall survival for patients in the low and intermediate-grade groups was 100 %, compared with 59 % for patients in the high-grade group (p = 0.03). CONCLUSION: Favorable locoregional control was achieved for patients with malignant parotid tumors who underwent surgery plus postoperative radiotherapy. Patients with high-grade tumors frequently experienced distant metastases and prognosis was poor.

Cytomegalovirus-associated ulceration of gastric conduit after chemoradiotherapy following esophagectomy for cancer.

A 64-year-old man underwent radical esophagectomy for cancer and simultaneous reconstruction using the gastric conduit through the posterior mediastinum. Two courses of adjuvant chemotherapy were performed. Twenty-eight months postoperatively, recurrence of the cancer was detected in the mediastinal lymph nodes, and he underwent concurrent chemoradiotherapy and boost chemotherapy. Endoscopy was then performed to investigate the cause of epigastralgia, and multiple ulcerations were found in the lesser curvature of the gastric conduit. Although a proton-pump inhibitor was orally administered, the ulceration was intractable. Re-examination of the original biopsy specimens and serological testing revealed positivity for cytomegalovirus. The ulcers began to heal after administration of foscarnet sodium. After the treatment, no signs of exacerbation associated with reinstitution of chemotherapy were observed.

Strategy of operative treatment of hyperparathyroidism using US scan and (99m)Tc-MIBI SPECT/CT.

We evaluated the efficacy of technetium-sestamibi ((99m) Tc-MIBI) SPECT/CT for planning parathyroidectomy in cases with primary hyperparathyroidism (pHPT), comparing with planar scintigraphy and ultrasound (US), in an aim to establish the proper surgical strategy according to the preoperative imaging studies. A retrospective review of consecutive 75 pHPT patients who had been operated on was conducted. The results of preoperative imaging modalities and the operative finding were analyzed. Seven cases were found to have multiple hyperplastic glands, and no responsible gland was found in three cases. Four cases underwent only US scan for preoperative imaging. Remaining 61 cases were found to have single adenoma, and were included in the evaluation of localization imaging. US scan, (99m) Tc-MIBI planar scan and (99m) Tc-MIBI SPECT/CT showed accurate localization in 77.0% (47/61), 75.4% (46/61) and 88.5% (46/52) of the evaluable cases, respectively. US and (99m) Tc-MIBI planar scan demonstrated consistent result in 42 cases (68.9%), and those cases showed accurate localization in 90.5% (38/42). When both US and (99m) Tc-MIBI SPECT/CT was consistent, all 37 lesions had been correctly indicated. No clinico-pathological features were suggested to influence in demonstrating the localization, other than only (99m) Tc-MIBI SPECT/CT exhibited 100% sensitivity in ectopic glands. Combination of US and (99m) Tc-MIBI SPECT/CT certainly contributes to the planning of minimally invasive operation in cases with pHPT by indicating correct localization of single adenoma.

[Ultrasound guided vacuum-assisted biopsy for diagnosis of malignant lymphoma].

Tailor-made treatment for lymphoma has been proposed, based on the information on prognostic on predictors or on molecular targets. This recent evolutions necessitated the collection of sufficient tissue samples for their preoperative evaluation. Since needle biopsy or needle aspiration cytology may not provide enough tissue for histo-pathologic diagnosis, incisional and excisional biopsies are commonly performed. In this study, we applied a handheld vacuum-assisted biopsy (VAB) system, as an alternative to the conventional incisional and excisional biopsies, to evaluate its feasibility in the biopsy -based diagnosis of malignant lymphoma. The subjects were nine patients with clinically suspected malignant lymphoma. All of them were correctly diagnosed with a diagnostic accuracy of 100%, and lymphoma sub-types could be defined according to the New WHO classification. There was no complication associated with the procedure. Lymph node biopsy for diagnosis of malignant lymphoma using this minimally invasive VAB technique allows a simple and safe collection of sufficient samples with good-quality, and promises to contribute to a precise molecular-based diagnosis.

Primary NK/T-cell lymphoma of the cauda equina: a case report and literature review.

STUDY DESIGN: A case report with a review of the literature. OBJECTIVE: To describe an unusual case of primary lymphoma of the cauda equina and provide a review of the literature of this condition. SUMMARY OF BACKGROUND DATA: Primary lymphoma of the cauda equina is extremely rare, and has been reported in 8 cases previously. This report is the first to describe a case of primary nasal type NK/T-cell lymphoma of the cauda equina. METHODS: We report the case of a 67-year-old man presenting the symptoms of cauda equina syndrome caused by primary lymphoma of the cauda equina. RESULTS: After laminectomy and removal of the tumor, the patient recovered from the symptoms of cauda equina syndrome except for bladder and bowel dysfunction. Further investigations including immunohistochemical stains made a diagnosis of primary nasal type NK/T-cell lymphoma of the cauda equina, and the patient received radiotherapy to the lumbosacral area. Brain metastasis was detected 8 months after surgery, and the patient died 14 months after his initial clinical presentation despite additional treatments including whole-brain radiotherapy and oral chemotherapy. CONCLUSION: Although primary lymphoma of the cauda equina is extremely rare, the prognosis of this condition is thought to be poor. Early definitive diagnosis with examination of the cerebrospinal fluid followed by combined treatment with radiotherapy and high-dose methotrexate should be considered.