Recurrent Stroke with Rapid Development of Intracranial Artery Stenosis and Subsequent Successful Mechanical Thrombectomy in Essential Thrombocythemia.

Essential thrombocythemia is a myeloproliferative neoplasm. Ischemic stroke is frequently the first manifestation of essential thrombocythemia. We herein report a patient with JAK2V617 mutation-positive essential thrombocythemia who developed recurrent ischemic stroke with rapid development of intracranial artery stenosis and subsequently underwent successful mechanical thrombectomy. The high JAK2V617F allele burden in our patient (58.4%) may have affected the patient's condition. We discuss similar reports in the literature and the possible pathophysiologic mechanism of large artery involvement in these patients.

Simplified Transradial Access for Aneurysms Treatment: A Guiding System Using Solo Distal Access Catheter and Anatomical Considerations.

OBJECTIVE: The recent shift from transfemoral access to transradial access in neurointervention has led to gaps in guiding systems. We propose a useful guiding system, the solo distal access catheter system without a conventional guiding catheter or a sheath in transradial access for aneurysms treatment. We also assessed the anatomical features required for suitable patient selection. METHODS: We retrospectively collected data from consecutive patients with aneurysms treated with the solo distal access catheter system at our institution between April 2022 and April 2023, and evaluated the anatomical factors that appeared to affect the procedure. RESULTS: Of the 20 patients who underwent transradial access, 11 were treated using the solo distal access catheter system, and 10 (90.9%) completed the procedure. No radial artery occlusion was detected. The entry angle of the target vessel ranged from 37° to 139°, and the mean proximal parent artery diameter was 9.34 ± 1.48 mm. A double subclavian innominate curve was observed in 3 of 5 patients whose target vessels were the right common carotid artery. CONCLUSIONS: Using a solo distal access catheter as a guiding system for treating aneurysm proved effective and feasible with appropriate patient selection. Anatomical assessment of the entry angle of the target vessel, proximal parent artery diameter, and tortuosity may be important factors for the success of this method.

Effect of the number of cycles of docetaxel + S-1 therapy on long-term survival in adjuvant chemotherapy for stage III gastric cancer. A pooled analysis of the OGSG0604 and OGSG1002 trials.

BACKGROUND: S-1 plus docetaxel (DS) therapy followed by S-1 is the standard of care in Japan in postoperative adjuvant chemotherapy for stage III gastric cancer, but long-term survival and the number of DS cycles required are unclear. The purpose of this study was to investigate the impact of the number of cycles of DS therapy on the 5-year survival in stage III gastric cancer in a pooled analysis of two phase II trials (OGSG0604 and OGSG1002). PATIENTS AND METHODS: Patients with histologically confirmed stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were enrolled in this pooled analysis. They received DS therapy for four or eight cycles, followed by S-1 until 1 year postgastrectomy. The 5-year overall survival (OS) and the 5-year disease free survival (DFS) by the landmark analysis was evaluated. RESULTS: In total, 113 patients from the OGSG0604 and OGSG1002 trials were enrolled in this study. The landmark analysis showed a 5-year OS that was better with four to eight cycles of DS therapy than with one to three cycles of DS therapy, with the best 5-year OS of 77.4% (95% confidence interval, 66.5-90.1%) for eight cycles. The 5-year DFS was approximately 66% when four or eight cycles of DS therapy were given. CONCLUSION: Although eight cycles of DS therapy may prolong prognosis, the present study did not provide a clear conclusion as to how many DS therapy cycles are needed to improve prognosis after D2 gastrectomy for stage III gastric cancer. TRIAL REGISTRATION: Registration number: UMIN00000714 and UMIN000004440.

Association between Genetic Variation in the TAS2R38 Bitter Taste Receptor and Propylthiouracil Bitter Taste Thresholds among Adults Living in Japan Using the Modified 2AFC Procedure with the Quest Method.

Individual taste sensitivity influences food preferences, nutritional control, and health, and differs greatly between individuals. The purpose of this study was to establish a method of measuring and quantifying an individual's taste sensitivity and to evaluate the relationship between taste variation and genetic polymorphisms in humans using agonist specificities of the bitter taste receptor gene, TAS2R38, with the bitter compound 6-n-propylthiouracil (PROP). We precisely detected the threshold of PROP bitter perception by conducting the modified two-alternative forced-choice (2AFC) procedure with the Bayesian staircase procedure of the QUEST method and examined genetic variation in TAS2R38 in a Japanese population. There were significant differences in PROP threshold between the three TAS2R38 genotype pairs for 79 subjects: PAV/PAV vs AVI/AVI, p < 0.001; PAV/AVI vs AVI/AVI, p < 0.001; and PAV/PAV vs PAV/AVI, p < 0.01. Our results quantified individual bitter perception as QUEST threshold values: the PROP bitter perception of individuals with the PAV/PAV or PAV/AVI genotypes was tens to fifty times more sensitive than that of an individual with the AVI/AVI genotype. Our analyses provide a basic model for the accurate estimation of taste thresholds using the modified 2AFC with the QUEST approach.

Reduced H3K27me3 levels in diffuse gliomas: association with 1p/19q codeletion and difference from H3K27me3 loss in malignant peripheral nerve sheath tumors.

Trimethylation of histone H3 at lysine 27 (H3K27me3) acts as a transcriptional repressor of target genes. Recent immunohistochemical studies have reported a loss of H3K27me3 modification in diffuse (especially 1p/19q-codeleted) gliomas. However, we did not observe H3K27me3 loss in diffuse gliomas using routine immunostaining conditions for the detection of H3K27me3 loss in malignant peripheral nerve sheath tumors (MPNSTs). Therefore, we conducted immunohistochemical analysis of surgically resected specimens to understand the differences in the H3K27me3 status in MPNSTs and diffuse gliomas and evaluate the diagnostic utility of H3K27me3 immunohistochemistry. Staining with a standard 1:200 dilution of the C36B11 antibody showed a complete loss of H3K27me3 in 5 out of 11 MPNSTs, whereas most diffuse gliomas (149/151, 98.7%) showed diffuse immunoreactivity. At a 1:2000 antibody dilution, 12.6% (19/151) of the diffuse gliomas showed H3K27me3 loss, which was significantly associated with 1p/19q codeletion (P < 0.001). H3K27me3 loss predicted 1p/19q codeletion in IDH-mutant gliomas with lower sensitivity (56.2%) and higher specificity (100%) than ATRX retention or p53 negative result. In conclusion, reduction in H3K27me3 levels was associated with 1p/19q codeletion in diffuse gliomas; however, the extent of reduction differed from that in MPNSTs, and the results depended on the immunostaining conditions.

Five-year outcomes of a phase II study of adjuvant chemotherapy with S-1 plus docetaxel for stage III gastric cancer after curative D2 gastrectomy (OGSG1002).

BACKGROUND: Adjuvant S-1 monotherapy is standard of care for stage II and III gastric cancer (GC), but there is still a need to improve the efficacy of treatment for stage III disease. We conducted phase II study of eight cycles of S-1 plus docetaxel (DS) followed by S-1 monotherapy for up to 1 year after D2 gastrectomy for stage III GC. PATIENTS AND METHODS: Sixty-two patients with stage III GC were enrolled. They received oral S-1 (80 mg/m2/day) for 2 consecutive weeks and intravenous docetaxel (40 mg/m2) on day 1, repeated every 3 weeks for 8 cycles, followed by S-1 until 1 year postgastrectomy. Treatment safety, tolerability, and survival were evaluated. RESULTS: The completion rate for eight cycles of DS therapy was 77.4% [95% confidence interval (CI) 65.0-87.1%]. Subsequent S-1 monotherapy for 1 year was feasible in 71.0% (95% CI 58.1-81.8%) of patients. The incidence of neutropenia, leukopenia, anorexia, and fatigue of grade 3 or higher was 10% or higher. There were no treatment-related deaths. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 72.4% (95% CI 62.1-84.5%) and 60.0% (95% CI 48.8-73.9%), respectively. Subgroup analyses by disease stage showed 5-year OS and DFS rates of 74.5% (95% CI 60.7-91.5%) and 59.3% (95% CI 43.8-80.2%) for stage IIIA and 70.0% (95% CI 55.4-88.5%) and 60.0% (95% CI 44.8-80.4%) for stage IIIB, respectively. CONCLUSIONS: Adjuvant eight cycles of DS therapy might be safe and manageable and has promising OS and DFS for stage III GC.

[Consideration of Nutritional Support for Decreased Caloric Intake in Patients with Severe Weight Loss after Esophageal Cancer Surgery].

OBJECTIVE AND METHODS: We evaluated factors that caused the decrease in caloric intake early after surgery, which led to weight loss after esophageal cancer surgery. We selected 35 patients whose weights at 1 year after surgery were ≥10% lower than their preoperative weights. In these patients, the caloric intake and nutritional support received at discharge and 1 month after operation were investigated. At discharge, the caloric intake of 25 patients was lower than the required caloric intake, which was <85% in 17 patients. However, among the 17 patients, only 2 received nutritional support with increased enteral nutrition. One month later, the number of patients with caloric intake less than and <85% of the required caloric intake increased to 29 and 23, respectively. In addition, none of the patients received increased enteral nutrition at home. Many complained of gastrointestinal symptoms after surgery and while receiving enteral nutrition, even under weight loss status. In these patients, oral intake at discharge was inadequate and the caloric intake via enteral nutrition was also not adjusted enough to meet the nutritional requirement. On the basis of this study, flexible nutritional management for oral intake and enteral nutrition is deemed necessary for severe weight loss early after esophageal cancer surgery.

Feasibility of International Proposed Standardized Enteral Connector for Semi-Solid Formula Feeding.

BACKGROUND/AIMS: The current study was undertaken to assess if the semi-solid formulas could be used with a new ENFit connector with similar force to current percutaneous endoscopic gastrostomy (PEG) tubes. METHODS: Experiment 1: We measured the applied pressure (force) needed to compress the syringe containing 7 viscous semi-solid formulas with a 20 Fr PEG tube and low-profile tube through the ENFit connector or the current connector. Experiment 2: This experiment was conducted to evaluate the compression force through 2 connectors in 3 infusion velocity, 7 PEG tube types with 2 semi-solid formulas. RESULTS: Experiment 1: The force needed to compress the syringe through the ENFit connector was higher in 3 semi-solid formulas with a 20 Fr low-profile tube; otherwise, there were no significant differences. Experiment 2: Each formula required a higher force in the ENFit connector in 6 settings out of 21. CONCLUSIONS: The ENFit connector will likely not show any remarkable change in the force to administer the semi-solid formula. However, a higher force was required under some conditions in the prototype ENFit connector. Further investigation of sensory test is needed to confirm the feasibility of the ENFit connector for using the semi-solid formulas.

Hepatosplenic γδ T Cell Lymphoma Involving the Brain.

BACKGROUND: Brain involvement of hepatosplenic T cell lymphoma (HSTL) has not been reported so far. CASE DESCRIPTION: We observed an extremely rare case of HSTL, which is a rare and aggressive variant of peripheral T cell lymphoma, generally showing predominant infiltration to the liver, spleen, and bone marrow and involving the brain. A 41-year-old Japanese woman presented with dysarthria and numbness of the right hand. Radiologic examination revealed a single 3-cm mass in the left frontal cortex, which was totally removed. Pathologic examination of the specimen demonstrated T cell lymphoma with a γδ cytotoxic T cell phenotype. Multiplex polymerase chain reaction analyses confirmed monoclonality of T cell receptor γ. Systemic examination revealed infiltration of atypical T lymphoid cells of the same phenotype in bone marrow and the presence of hepatosplenomegaly. We diagnosed HSTL involving the brain. The patient was treated with several courses of intensive chemotherapy, but it failed to achieve remission. She died of sepsis 4 months after the surgery. CONCLUSIONS: HSTL can involve the brain. A diagnosis of HSTL involving the brain needs careful systemic evaluation. Timely and precise diagnosis that considers the systemic condition is important for appropriate treatment and better outcome.

[Relationship between Nutritional Biochemical Parameters and Body Weight Loss in Patients with Esophageal Cancer Up to One Year after Surgery].

SUBJECTS AND METHODS: The subjects comprised 21 patients with esophageal cancer who underwent surgery, without adjuvant chemotherapy. Caloric intake, body weight loss, and biochemical parameters(serum albumin[Alb], hemoglobin[Hb], transthyretin[TTR], and total cholesterol[T-Cho])were measured up to 1 year after surgery, and relationships between all parameters were investigated. RESULTS: The caloric intake dropped to about 87% of base-line intake at 1 month after surgery and recovered to 100% at 1 year after the operation. Body weight also dropped to about 89% of baseline at 6 months after surgery and then was relatively stable. Caloric intake was significantly positively correlated with TTR(r=0.82, p=0.02), and it also tended to be positively correlated with T-Cho(r=0.70, p=0.14). Body weight loss was significantly negatively correlated with Alb(r=-0.82, p=0.01)and Hb(r=-0.87, p=0.01). CONCLUSION: Alb and Hb were recovered in the early postoperative period when body weight was still decreased. However, TTR appeared to be a good parameter of caloric intake in the short-term, postoperatively.

Appropriate nutritional management in patients with impaired mastication and those with mild dysphagia: a multicenter study of the usefulness of novel foods processed and softened by enzymes.

BACKGROUND AND OBJECTIVES: Our aim was to investigate the safety of iEAT (a food that is softened by heat and enzyme homogeneous permeation) and iEAT-affected nutrition parameters, e.g., nutrition intake (calculated from the consumption rate in patients with impaired mastication and those with mild dysphagia). METHODS AND STUDY DESIGN: A multicenter, randomized, cross-over study of iEAT was conducted in 50 patients (mean age 77.0±11.0 years) with dysphagia due to Occasional aspiration (4 points on the Dysphagia Severity Scale [DSS]) or Oral problems (5 points) randomly assigned to the study diet (iEAT) or its opposite (the modified traditional [control] diet) for 1 week and then switched for 1 week to the opposing diet. Intake of energy, protein, lipid, carbohydrate, and sodium were evaluated along with questionnaire-assessed levels of satisfaction. RESULTS: The mean intake was significantly lower for the study diet, whereas the intakes of energy, protein, carbohydrate on day 1, intake of protein on day 7, and body weight on day 7 were significantly higher for the study diet. We found no between-group differences in hematologic and blood biochemistry parameters, no diet-related adverse events, greater satisfaction with the appearance of the study diet (p<0.001), and comparable levels of satisfaction with ease of eating, ease of swallowing, and taste for both diets. CONCLUSIONS: iEAT was provided to patients with mild dysphagia as safely as a blender diet or other diets usually provided at each study site, and can serve as an efficient nutrition source.

CUBIC pathology: three-dimensional imaging for pathological diagnosis.

The examination of hematoxylin and eosin (H&E)-stained tissues on glass slides by conventional light microscopy is the foundation for histopathological diagnosis. However, this conventional method has some limitations in x-y axes due to its relatively narrow range of observation area and in z-axis due to its two-dimensionality. In this study, we applied a CUBIC pipeline, which is the most powerful tissue-clearing and three-dimensional (3D)-imaging technique, to clinical pathology. CUBIC was applicable to 3D imaging of both normal and abnormal patient-derived, human lung and lymph node tissues. Notably, the combination of deparaffinization and CUBIC enabled 3D imaging of specimens derived from paraffin-embedded tissue blocks, allowing quantitative evaluation of nuclear and structural atypia of an archival malignant lymphoma tissue. Furthermore, to examine whether CUBIC can be applied to practical use in pathological diagnosis, we performed a histopathological screening of a lymph node metastasis based on CUBIC, which successfully improved the sensitivity in detecting minor metastatic carcinoma nodules in lymph nodes. Collectively, our results indicate that CUBIC significantly contributes to retrospective and prospective clinicopathological diagnosis, which might lead to the establishment of a novel field of medical science based on 3D histopathology.

[Sequential Post-Operative Nutrition Care at Home for Patients Receiving Surgical Treatment for Esophageal Cancer].

OBJECTIVE AND METHODS: We evaluated the outcomes of sequential nutrition care provided at home to patients who had undergone surgery for esophageal cancer. For 44 such patients, we investigated caloric intake(kcal), percentage of preoperative body weight(%), and requests and complains related to home nutrition care every 3 months for 1 year after surgery. RESULTS: Duringthe observation period, the mean postoperative caloric intake decreased to a minimum level at 1 month, but nearly recovered to the baseline at 12 months. The percentage of preoperative body weight decreased postoperatively, and this decrease was maintained. The average weight percentage reached 87%at 6 months after surgery, and recovered to only 89% at 12 months. Regarding requests and complaints, many reports of digestive symptoms related to gastrointestinal surgery were reported up to 3 months postoperatively. Additionally, the large number of requests for cancellation of enteral support indicates the difficulty in managing home enteral nutrition. On the other hand, guidance about dietary quality with oral intake enhancement increased at 6 months postoperatively. CONCLUSION: The aims of postoperative nutrition care should change over time with the patient's postoperative progress. In the early stage, weight loss management is important. In addition to dietary guidance with regard to digestive reconstruction, nutrition support with acceptable enteral nutrition is recommended. Guidance regarding problems with dietary behavior is needed for every patient when the digestive adaptation has advanced.

[A Case of Recurrent Gastric Cancer with Recurrent Celiac Lymph Node Metastasis Successfully Treated with Chemoradiotherapy and CPT-11 plus CDDP Therapy].

Chemotherapy is performed for the recurrence of gastric cancer in many cases. We report a case of recurrent lymph node metastasis successfully treated with chemoradiotherapy and chemotherapy. A man in his 60s underwent total gastrectomy and D2 dissection in 2009. The pathological diagnosis was poorly differentiated adenocarcinoma, T4a, int, INF b, ly2, v2, LN#2: 2/3, #3: 1/4, #7, 8, and 9: 3/4, stage III B. Although we administered S-1/UFT as postoperative adjuvant chemotherapy, a strong rash appeared and the patient ceased chemotherapy. Eight months later, the rash had disappeared. We started chemotherapy with paclitaxel(PAC). CT performed 1 year postoperatively showed celiac lymph node(#9)metastasis. Chemoradiotherapy( RT+PAC)and additional CPT-11(98mg)and CDDP(49mg)treatment were administered. The lymph node (#9)was cicatrized after 8 cycles. Forty-two months after the end of treatment, the patient has had no recurrence. It is thought that chemoradiotherapy is an effective cure for local recurrence of gastric cancer.

[A Case of Small Intestinal Cancer Repeating an Ileus Symptom Complicated with Refractory Arrhythmia].

A 56-year-old man had been treated for hypertrophic cardiomyopathy since childhood. He had been treated for refractory ventricular tachycardia (VT) with interventricular septum cauterization, catheter ablation, and implantation of a defibrillator. He had been treated at home for several years. The ileus that developed in July 2014 was relieved by conservative medical treatment once, but it recurred after oral intake of food a short time later. The obstruction was due to a small intestine cancer that was diagnosed by enteroscopy. After considering the risks of surgery due to the cardiac problem and the quality of life due to ileus caused by the mass, we resected it. This surgery was not a radical resection because of peritoneal dissemination. He started oral food intake postoperatively, and returned to home care. Three months after surgery, oral chemotherapy was administered after considering his stable cardiac function in addition to his coherent mental status. An adverse event of severe watery diarrhea developed, and VT caused by dehydration occurred. After the chemotherapy was discontinued, he recovered in intensive care. He returned to home care at his prior status for 9 months postoperatively.

[A Case of Carcinosarcoma of the Esophagus Treated with Chemoradiotherapy].

Carcinosarcoma of the esophagus is a rare malignant neoplasm. We report a case of an 87-year-old man treated with chemoradiotherapy. The main presenting complaint was hiccups. Histological analysis of a biopsy from the tumor demonstrated a carcinosarcoma. The clinical diagnosis was T2N0M0, cStageⅡ. In consideration of his advanced age, a past history of cerebral infarction, high blood pressure, aortic valve sclerosis, and chronic renal failure (Cr 1.5-1.8 mg/dL), chemoradiotherapy consisting of TS-1 40 mg/day with radiotherapy of 66 Gy was administered to the patient. The carcinosarcoma decreased in size on endoscopic examination in response to the chemoradiotherapy. Surgery with extended lymphadenectomy for esophageal carcinosarcoma is the standard treatment, but chemotherapy may be a good choice for local control for patients who cannot undergo surgical resection.

[Investigation of the Safety of and Patient Satisfaction with iEat®, the Support Food for the Recovery of Eating Function in Patients with Carcinomatosis - Related Gastrointestinal Passage Disorder].

OBJECTIVE: iEat®, a support food for the recovery of eating function, is food that can be easily masticated with little power and has suitable fluidity for enzyme processing, regardless of its normal appearance. We provided iEat® to 5 patients with carcinomatosis-related gastrointestinal passage disorder who could take fluid foods and investigated the stability of iEat® and patient satisfaction with the food. METHODS: We provided regular diets for lunch on the first and 7th day, and provided iEat® from the 2nd to the 6th day. The stability of iEat(R) was evaluated based on the presence and grade of abdominal pain, diarrhea, sense of abdominal distension, nausea, and vomiting, according to the Common Terminology Criteria for Adverse Events (CTCAE v4.0, JCOG). The patients assessed their satisfaction by using 6 grades of taste, appearance, amount, difficulty of intake, and overall valuation. RESULTS: One patient could not continue the study because of vomiting from overeating of iEat(R). In the other patients, iEat(R) induced approximately the same adverse events as did the regular diets. All of the patients expressed better satisfaction with iEat® than with the regular diets. CONCLUSION: Although patient management for overeating is necessary, iEat® might provide good quality of life in terms of eating satisfaction to the patients with carcinomatosis-related gastrointestinal passage disorder.

Randomized phase II trial of S-1 plus irinotecan versus S-1 plus paclitaxel as first-line treatment for advanced gastric cancer (OGSG0402).

BACKGROUND: S-1-based regimens are commonly used for advanced gastric cancer (AGC) in Japan. We performed this trial to evaluate the efficacy and safety of S-1 plus irinotecan (SIri) and S-1 plus paclitaxel (SPac) as first-line treatments for AGC in order to select the optimal regimen for a subsequent phase III trial. PATIENTS AND METHODS: Patients with previously untreated, locally advanced or metastatic measurable gastric adenocarcinoma were randomly assigned to receive SIri (irinotecan 80 mg/m(2) was administered intravenously (i.v.) on day 1 and 15, while 40 mg/m(2) S-1 was orally administered twice daily for three weeks from days 1-21 followed by a two-week pause) or SPac (paclitaxel 50 mg/m(2) was administered i.v. on day 1 and 8, while 40 mg/m(2) S-1 was orally administered twice daily for two weeks from day 1-14 followed by a one-week pause) regimen. The primary end-point was the overall response rate (ORR), and the secondary end-points were progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: A total of 102 patients were enrolled. The ORR was 33.3% for SIri and 31.4% for SPac, which did not achieved the predicted ORR in either group. PFS and OS were 5.7 and 12.4 months for SIri, 4.6 and 11.9 months for SPac respectively. No treatment-related deaths occurred during the study. Although grade 3/4 neutropenia and anemia were more frequent in the Siri group, both regimens were well-tolerated. CONCLUSION: Both regimens were well-tolerated in patients with AGC, but we conclude that neither regimen was optimal for a phase III trial.

Phase II study of S-1 monotherapy in patients over 75 years of age with advanced gastric cancer (OGSG0404).

BACKGROUND: S-1+cisplatin (CDDP) is the standard treatment for advanced gastric cancer (AGC) in Japan and Korea. However, the usefulness of S-1 based chemotherapy for elderly patients is unclear. Therefore, we conducted a multicenter phase II study of S-1 monotherapy for AGC in elderly patients. MATERIALS AND METHODS: Chemotherapy-naïve patients aged over 75 years with AGC were enrolled. The starting dose of S-1 was determined on the basis of body surface area and modified according to the creatinine clearance value. S-1 was administered twice a day during a 4-week period followed by a 2-week rest period. RESULTS: Thirty-five patients were enrolled. The response rate (RR) was 14.3% and the median overall survival was 14.6 months. Grade 3 or more severe adverse events consisted of anaemia (3%), neutropaenia (3%), anorexia (3%), and fatigue (6%). There were no treatment-related deaths. CONCLUSION: Our study indicates that S-1 monotherapy is safe and well tolerated in chemotherapy-naïve elderly patients with AGC, but exerts limited activity when given using a tailor-made dosing strategy based on renal function.