[Timing of Administration of Pegfilgrastim and Prophylaxis for Febrile Neutropenia for Patients with Early Breast Cancer Receiving Chemotherapy].

Febrile neutropenia(FN)causes a prolonged treatment schedule and decreased relative dose intensity(RDI)during cancer chemotherapy, which adversely affects prognosis. In recent years, dose-dense(dd)chemotherapy has been used as adjuvant chemotherapy for patients with breast cancer based on the results of improved disease-free survival according to meta-analysis data. Regarding neoadjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer, taxanes and trastuzumab with the addition of pertuzumab have shown higher pathological complete response rates and elevated incidences of FN. One hundred seventy-six patients received pegfilgrastim(PEG)prophylaxis between January 2011 and January 2023. Until 2019, the median day of PEG prophylaxis was day 4 from chemotherapy completion(days 2- 3, 14 cases; day 4, 41 cases; and day 5, 8 cases)with antibiotic prophylaxis in 58 patients(92%). FN was observed in 19 cases(30%). The RDIs of TC and FEC were 96.8% and 96.0%, respectively. Meanwhile, the median day of PEG prophylaxis after 2020 was day 2 from chemotherapy completion(days 2-3, 108 cases; day 4, 4 cases; and day 5, 1 case)without antibiotic prophylaxis. FN was not observed in any of the cases. The RDI of all regimens was 99.7%. Although there were some differences in chemotherapy regimens, an earlier timing of PEG prophylaxis(especially 24-48 hours from chemotherapy completion)has been shown to reduce the incidence of FN and increase the RDI.

Denosumab effect on bone mineral density and urinary-NTX in breast cancer patients receiving aromatase inhibitors.

INTRODUCTION: Aromatase inhibitors are used post-surgical intervention in postmenopausal patients with breast cancer. However, these drugs accelerate decline in bone mineral density (BMD), which is countered by use of denosumab, and the efficacy of the drug can be assessed by bone turnover markers. We investigated the effects of denosumab administration for 2 years on BMD and urinary N-telopeptide of type I collagen (u-NTX) levels in breast cancer patients treated with aromatase inhibitors. MATERIALS AND METHODS: This was a single-center retrospective study. Postoperative hormone receptor-positive breast cancer patients with low T-scores biannually received denosumab from the time of initiation of aromatase inhibitor therapy for 2 years. BMD was measured every 6 months, and u-NTX levels were assessed after 1 month and thereby every 3 months. RESULTS: The median patient age of the 55 patients included in this study was 69 (range: 51-90) years. BMD gradually increased in the lumbar spine and femoral neck and u-NTX levels were lowest at 3 months post-initiation of therapy. Patients were divided into two groups based on the change ratio of u-NTX 3 months post-denosumab administration. Of these, the group with higher change ratio showed a higher degree of BMD restoration in the lumbar spine and femoral neck 6 months post-denosumab treatment. CONCLUSION: Denosumab increased BMD in patients treated with aromatase inhibitors. The u-NTX level decreased soon after start of denosumab treatment, and its change ratio is predictive of improvement in BMD.

[A Case of Pancreatic Cancer That Was Radically Resected after Chemotherapy and Radiation Therapy, but Recurred Early and Followed a Rapid Course].

A 71-year-old man presented to our hospital with abdominal pain. He was diagnosed with acute pancreatitis and pancreatic cancer. Peritoneal washing cytology(CY)was positive, and laparotomy findings revealed severe inflammatory changes of pancreatitis, suggesting a high likelihood of the need for combined resection of other organs. Therefore, following the exploratory laparotomy, mFOLFIRINOX was initiated as chemotherapy. After 24 courses of mFOLFIRINOX, he developed drug-induced pneumonia. Therefore, chemotherapy was interrupted, and a steroid was started. Radiotherapy was administered during steroid tapering. There was no evidence of local progression or distant metastasis. A radical resection that included pancreaticoduodenectomy and right hemicolectomy was performed 23 months after the exploratory laparotomy. CY was negative and R0 resection was achieved. However, 5 months after the operation, he developed liver abscesses and cholangitis and was suspected to have liver metastasis. He underwent PTAD and PTCD, but died due to liver failure 8 months postoperatively. The early recurrence of this case might have been caused by the lack of postoperative chemotherapy due to his frailty. Surgical indications should be carefully judged if there is a high risk of recurrence after NAC and a high possibility that ACT cannot be performed after radical surgery.

[Ischemic Colitis after Closure of Temporary Ileostomy for Low Anterior Resection of Rectal Cancer in a Dialysis Patient-A Case Report].

Dialysis patients are at increased risk of ischemic colitis and are likely to develop irreversible ischemic colitis. We report a rare case of ischemic colitis after the closure of a temporary ileostomy for low anterior resection(LAR)of rectal cancer in a dialysis patient. A 77-year-old man undergoing maintenance dialysis was diagnosed as having colorectal cancer with a type 2 tumor at the anastomosis site of high anterior resection performed for sigmoid colon cancer 14 years ago. After undergoing excision which included the anastomosis site of the previous operation, LAR with anastomosis in the transverse colon and rectum and temporary ileostomy were performed. Seven months later, closure of the temporary ileostomy was performed, which resulted in ileus and septic shock. Computed tomography(CT)revealed inflammation in the colon on the oral side of the anastomosis, which was diagnosed as ischemic colitis. Ischemic colitis did not improve with conservative treatment, and fever reoccurred at each maintenance dialysis session. Therefore, ileostomy was performed again, but multiple organ failure due to disseminated intravascular coagulopathy(DIC)progressed and he died. It is considered that Hartmann's operation should be selected for dialysis patients with serious underlying diseases, and if ischemic colitis is observed after closure of the stoma temporary colostomy in such patients, the lesion site of ischemic colitis should be excised promptly and colostomy should be performed again.

Multicentre, phase II study of eribulin in combination with S-1 in patients with advanced breast cancer.

BACKGROUND: We previously reported the synergistic effect of S-1 and eribulin in preclinical models. In addition, our phase I study revealed the recommended dose for the phase II study of the combination therapy in advanced breast cancer (ABC) patients pre-treated with anthracycline and taxane. Our current study reports on the efficacy and safety of the combined use of eribulin and S-1 in patients with ABC and poor prognosis. METHODS: Patients with breast cancer who received prior anthracycline- and/or taxane-based therapy were assigned to receive a combination therapy of eribulin (1.4 mg/m2 on days 1 and 8, every 21 days) and S-1 (65 mg/m2, on days 1 to 14, every 21 days) for advanced/metastatic disease. All patients had at least one clinicopathological factor such as being oestrogen receptor negative, Human Epidermal Growth Factor Receptor 2 (HER2) receptor negative, presence of visceral involvement, presence of three or more metastatic sites, or having a disease-free interval shorter than 2 years. The primary endpoint was the independent-reviewer assessed objective response rate (ORR). Secondary endpoints were clinical benefit rate, disease control rate, progression-free survival (PFS), and overall survival (OS). RESULTS: This study enrolled 33 patients. Confirmed ORR was 33.3% (95% CI: 17.3 to 52.8). Median PFS was 7.5 months (95% CI: 4.0 to 14.3). Median OS time was not reached during the current experimental periods. The most common grade 3/4 adverse event was neutropenia (68.8%). CONCLUSIONS: The combination of eribulin and S-1 is safe and effective for treatment in patients with ABC and poor prognosis. TRIAL REGISTRATION: Current Controlled Trials UMIN000015049 , date of registration: September 5th 2014.

[Eribulin Administration Methods to Extend the Survival Time of Patients with Advanced or Recurrent Breast Cancer, Consideringthe Relative Dose Intensity, Time to Treatment Failure, Pretreatment Regimen Number, and Tumor Subtype].

Eribulin is evaluated as the only agent that can extend the survival time of patients with advanced or recurrent breast cancer, when used as or after third-line chemotherapy. We retrospectively analyzed the efficacy of eribulin for the treatment of advanced or recurrent breast cancer in our hospital, considering the relative dose intensity(RDI), time to treatment failure (TTF), pretreatment regimen number, and tumor subtype. Of the 36 patients who were treated with eribulin between December 2011 and August 2016, we studied 31 patients who received eribulin as a single agent. The median RDI was 0.75 (range: 0.44-1). The response rate was 22.5%, the disease control rate was 80.6%, and the clinical benefit rate was 45.2%. Overall survival(OS)was not associated with the RDI, previous regimen number, or tumor subtype; however, OS was affected by the TTF. Eribulin is a novel drug that has a different mechanism of action compared with those of conventional anticancer drugs. Therefore, prolonging the duration of eribulin administration may be more important than maintaining the RDI.

Unmasked renal impairment and prolonged hyperkalemia after unilateral adrenalectomy for primary aldosteronism coexisting with primary hyperparathyroidism: report of a case.

We herein report the case of a patient with critical hyperkalemia after unilateral adrenalectomy (ADX) for aldosterone-producing adenomas, which were coexisting with primary hyperparathyroidism. A right adrenal tumor oversecreting mineral corticoid was identified in a 62-year-old female whose kidney function had been impaired due to primary hyperaldosteronism and hyperparathyroidism. The ADX improved her hypertension with normalization of the plasma aldosterone concentration, but without adequately increasing her plasma renin activity. Her eGFR further decreased postoperatively, hyperkalemia appeared and the serum potassium level rose to 6.3 mEq/L at 3 months after ADX. Then, treatment with calcium polystyrene sulfonate jelly was started. Eight months after ADX, a left lower parathyroidectomy was performed, and the serum calcium and intact parathyroid hormone levels decreased to the normal range. The hyperkalemia was difficult to control within 20 months postoperatively without treatment with calcium polystyrene sulfonate jelly or hydrocortisone. This suggests that unmasking the renal impairment and relative hypoaldosteronism after ADX might induce critical hyperkalemia.

A MEN2A family with two asymptomatic carriers affected by unilateral renal agenesis.

Accumulating evidences suggest RET gene's involvement in development of the kidney in mice and humans. Although it is well known that RET mutation causes multiple endocrine neoplasia type 2A (MEN2A), thus far only 3 individuals have been reported to have MEN2A and renal agenesis/dysgenesis. We report a MEN2A family with RET mutation in which two asymptomatic carriers presented with unilateral renal agenesis. A 48-year-old woman underwent total thyroidectomy with regional lymph node dissection in our department for medullary thyroid carcinoma. She had earlier surgical treatment for a left adrenal pheochromocytoma at the age of 45. In the screening for MEN type 2 for her three sons, a CT scan for adrenal pheochromocytoma incidentally found unilateral renal agenesis in two of the sons, one of whom had suffered from Hirschsprung's disease (HSCR). They had contralateral kidneys exhibiting compensatory hypertrophy and normal renal function. Genetic analysis detected C618R RET mutation in the proband and her 3 sons, and no other mutations were found in RET as well as glial cell line-derived neurotrophic factor (GDNF). Our data lend support to the hypothesis that constitutive active RET mutation in MEN type 2 might partially impair RET function and thereby cause loss of function phenotype such as renal agenesis or HSCR.

Pheochromocytoma as the first manifestation of MEN2A with RET mutation S891A: report of a case.

We report a rare case with pheochromocytoma as the first manifestation of multiple endocrine neoplasia type 2A with RET mutation S891A. Bilateral pheochromocytomas were identified in a 54-year-old woman. Screening for RET revealed a rare S891A mutation located in the intracellular tyrosine kinase domain. This mutation was previously recognized as one of the mutations only in cases manifesting solely medullary thyroid carcinomas (MTCs). Since calcitonin stimulation test indicated positive result, total thyroidectomy was performed 1 year after the bilateral adrenalectomy, and C-cell hyperplasia was diagnosed by histopathological examination. Our report suggests that cases with S891A mutation, akin to those with other RET mutations, require screening for pheochromocytoma. In addition, it is indicated that calcitonin stimulation test should be performed even in the unaffected elder cases with S891A mutation although the mutation is classified as lowest risk group on MTC in guidelines.

Increased protein kinase A type Iα regulatory subunit expression in parathyroid gland adenomas of patients with primary hyperparathyroidism.

Protein kinase A (PKA) regulatory subunit type Iα (RIα) is a major regulatory subunit that functions as an inhibitor of PKA kinase activity. We have previously demonstrated that elevated RIα expression is associated with diffuse-to-nodular transformation of hyperplasia in parathyroid glands of renal hyperparathyroidism. The aim of the current study was to determine whether or not RIα expression is increased in adenomas of primary hyperparathyroidism (PHPT), because monoclonal proliferation has been demonstrated in both adenomas and nodular hyperplasia. Surgical specimens comprising 22 adenomas and 11 normal glands, obtained from 22 patients with PHPT, were analyzed. Western blot and immunohistochemical analyses were employed to evaluate RIα expression. PKA activities were determined in several adenomas highly expressing RIα. RIα expression was also separately evaluated in chief and oxyphilic cells using the "Allred score" system. Expression of proliferating cell nuclear antigen (PCNA), a proliferation marker, was also immunohistochemically examined. Western blot analysis revealed that 5 out of 8 adenomas highly expressed RIα, compared with normal glands. PKA activity in adenomas was significantly less than in normal glands. Immunohistochemical analysis further demonstrated high expression of RIα in 20 out of 22 adenomas. In adenomas, the greater RIα expression and more PCNA positive cells were observed in both chief and oxyphilic cells. The present study suggested that high RIα expression could contribute to monoclonal proliferation of parathyroid cells by impairing the cAMP/PKA signaling pathway.

Doublet or Triplet Antiemetic Prophylaxis for Nausea and Vomiting Induced by Trastuzumab Deruxtecan: an Open-Label, Randomized, and Multicenter Exploratory Phase 2 Study.

Background: Trastuzumab deruxtecan is classified as an anticancer agent that poses a moderate emetic risk in the international guidelines for antiemetic therapy. The guidelines recommend emesis prophylaxis using a two-drug combination therapy comprising a 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) and dexamethasone (DEX). However, the high incidence of nausea and vomiting associated with trastuzumab deruxtecan is problematic. The National Comprehensive Cancer Network guideline version 1.2023 classified trastuzumab deruxtecan as having a high risk of emesis and changed its recommendation to a triplet regimen including a neurokinin-1 receptor antagonist (NK1RA). However, the emetogenic potential of trastuzumab-deruxtecan and the optimal antiemetic prophylaxis are controversial. Hence, this exploratory phase 2 study aimed to assess the efficacy and safety of treatment comprising 5-HT3RA and DEX with or without a NK1RA in preventing trastuzumab deruxtecan-induced nausea and vomiting. Methods: We conducted an open-label and randomized exploratory phase 2 study at 14 centers in Japan. Patients with breast cancer who were scheduled to receive trastuzumab deruxtecan were enrolled in this study. The patients were randomly assigned to receive granisetron and DEX (arm GD) or granisetron, DEX, and aprepitant (fosaprepitant; arm GDA). The primary endpoint was complete response (CR; no emesis or no rescue therapy) during the overall phase (120 h after the start of trastuzumab deruxtecan). Results: Between September 2020 and March 2023, 40 patients were randomly assigned to the GD (n = 19) or GDA (n = 21) arm. In the GDA arm, one patient who did not complete the use of the rescue medication listed in the diary was excluded from the efficacy analysis, which included the use of rescue medication. The CR rates during the overall phase were 36.8% and 70.0% in the GD and GDA arms, respectively (odds ratio 0.1334; 95% confidence interval [CI]: 0.0232-0.7672; P = 0.0190), with a difference of 33.2%. No grade 3 or 4 toxicity related to antiemetic therapy was observed. Conclusions: Patients receiving trastuzumab deruxtecan require triple therapy, including mandatory NK1RA administration.

[How quality of life indices reflect the behaviors of elderly people with dementia on dementia care mapping and the relationship among well-being, ill-being and the behavior category code].

PURPOSE: Dementia Care Mapping (DCM) is an observation and evaluation technique intended to improve the quality of care for elderly people with dementia, based on aims of person-centered care. The purpose of this study was to clarify that well-being and ill-being (WIB) levels affects the behavior category code (BCC) in long-term care insurance facilities. METHODS: In this study, we evaluated people with dementia who used care facilities between April 2005 and July 2007. The evaluation indices used were the 6-hour DCM, the Mini-Mental State Examination (MMSE), and the Gottfries-Brane-Steen Scale (GBS). RESULTS: The total number of subjects whose families submitted written informed consent to participate was 256 (50 men and 206 women). The mean MMSE score of the total subjects was 10.83 (±8.58), and that of individuals receiving home care was the highest 17.14 (±6.38). The next highest mean MMSE score was that of the group home residents: 16.56 (±6.83). The lowest mean MMSE score was of individuals in health services facilities for the elderly (serious dementia ward), at 2.16 (±3.88). Multiple regression analysis was performed after controlling for age, sex, type of dementia and GBS, and we used the WIB value as dependent variables. The BCC variables of L (Labor) in group homes, and E (Expression) and H (handicrafts) variables in welfare institutions and long-term care facilities for the elderly significantly promoted WIB value. CONCLUSIONS: Among BCC indices such as L in group homes, and E and H in welfare institutions and long-term care facilities for the elderly, which reflect WIB values (and therefore, quality of life), it was found that those activities associated with work reflected quality of care. However, the BCC indices of B (Borderline) C (Cool), and U (Unresponsiveness) significantly inhibited WIB level; these behaviors are categorized as passive behaviors in the DCM. It is probable that these behaviors in elderly people with dementia reflect problems in long-term care insurance facilities. It is necessary to further examine these passive behaviors, because they can accurately reflect the quality of care for elderly people with dementia.

Meta-analysis of nanoparticle albumin-bound paclitaxel used as neoadjuvant chemotherapy for operable breast cancer based on individual patient data (JBCRG-S01 study).

BACKGROUND: Nanoparticle albumin-bound paclitaxel (nab-PTX), a novel taxane formulation, was developed to avoid cremophor/ethanol-associated toxicities including peripheral neuropathy and hypersensitivity. At least 35 phase II studies using combined nab-PTX and anthracycline in neoadjuvant settings are registered in Japan. We analyzed the efficacy and safety of nab-PTX based on patient characteristics in these studies. METHODS: We conducted a meta-analysis using individual patient data (IPD) to investigate the average efficacy of nab-PTX-containing regimens as neoadjuvant chemotherapy for operable breast cancer. IPD were provided by principal investigators who agreed to participate. The primary endpoint was pathological complete response (pCR) rate of each breast cancer subtype. RESULTS: We analyzed the data of 16 studies involving 753 patients. The overall crude frequencies of pCR (ypT0 ypN0, ypT0/is ypN0, and ypT0/is ypNX) were 18.1, 26.0, and 28.6%, respectively. Specifically, the frequencies were 6.7, 10.2, and 13.4% for luminal (n = 343); 40.5, 63.5, and 68.9% for human epidermal growth factor receptor 2 (HER2)-rich, (n = 74); 21.9, 40.6, and 42.7% for luminal/HER2 (n = 96); and 26.3, 31.5, and 32.3% for triple-negative breast cancers (TNBC) (n = 232). The multivariate analyses indicated that HER2 positivity, TNBC, high Ki-67, high nuclear grade, and weekly nab-PTX administration were significantly associated with the pCR. The proportion of hematological toxicities (neutropenia (39.7%) and leukopenia (22.5%)), peripheral sensory neuropathy (9.7%), myalgia (5.7%), and arthralgia (4.7%) was higher than grade 3 adverse events, but most patients recovered. CONCLUSIONS: Nab-PTX is a safe and acceptable chemotherapeutic agent in neoadjuvant settings, particularly for aggressive cancers. UMIN-CTR#: UMIN000028774.

Clinical outcomes of neoadjuvant chemotherapy for patients with breast cancer: Tri-weekly nanoparticle albumin-bound paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide: a retrospective observational study.

Neoadjuvant chemotherapy (NAC) using the combination of anthracycline and taxanes is the standard regimen for patients with primary breast cancer. Among the taxanes, conventional paclitaxel (PTX) and docetaxel have usually been adopted in the neoadjuvant or adjuvant setting. Nanoparticle albumin-bound paclitaxel (nab-PTX) is a solvent-free formulation that can be delivered to cancer cells at higher doses than conventional PTX. This study is a retrospective observational study in a single institution. We evaluated the efficacy and safety of nab-PTX followed by 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) in the neoadjuvant setting. In this study, 50 patients with primary breast cancer received nab-PTX (q3w, 260 mg/m2 ± trastuzumab 6 mg/kg) followed by FEC (q3w, 5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2) prior to surgery. The efficacy was evaluated using the clinical response rate (CRR), pathological complete response (pCR) rate, and Ki67 labeling index. Safety was evaluated using the frequency of treatment-related adverse events and relative dose intensity (RDI). All patients received at least one course of chemotherapy. The CRR and pCR rate were 88.0% and 40.0%, respectively. The mean Ki67 labeling index was significantly decreased from 47.7% to 24.6% after NAC. The safety profiles were comparable with previously reported regimens, and high RDIs were obtained (97.2% for nab-PTX and 95.5% for FEC). This study illustrated the efficacy and tolerability of a neoadjuvant regimen of nab-PTX followed by FEC.

Utility of urinary type I collagen cross-linked N-telopeptide as a prognostic indicator in breast cancer patients with bone metastases.

BACKGROUND: Breast cancer patients with bone metastases are usually managed with bone modifying agents, such as zoledronic acid and denosumab, and some bone turnover markers (BTMs) have been recognized as prognostic indicators in such patients. Although several studies have demonstrated the validity of BTMs as prognostic markers in patients treated with zoledronic acid, few studies have reported the utility of BTMs with denosumab treatment. In this study, we evaluated whether urinary N-telopeptide of type I collagen (u-NTX) can be a prognostic indicator in patients treated with denosumab. METHODS: Thirty-six breast cancer patients newly diagnosed with bone metastases were evaluated retrospectively. Patients were treated with denosumab and anti-cancer drugs. u-NTX levels were measured 1 month before and after administration of denosumab, and the ratio of u-NTX levels before and after denosumab (change ratio) was assessed for its association with prognosis. RESULTS: Levels of u-NTX decreased after denosumab administration in all patients except for one. The median value of the u-NTX change ratio was 0.766. Based on the change ratio, patients were divided into either a "high group" (n = 18) or a "low group" (n = 18). The low group showed significantly shorter overall survival (OS) compared with the high group (low group 15.0 months; high group 54.0 months; P = 0.012). Multivariate analysis indicated that the "low group" was an independent prognostic factor for OS (P = 0.028). CONCLUSION: We demonstrated that the u-NTX change ratio in denosumab-treated breast cancer patients with bone metastases can be a prognostic marker.

Physical complications for elderly inpatients with senile dementia in the Imaise Branch of Ichinomiya City Hospital.

BACKGROUND: In the present study, we investigated the physical complications of elderly patients with senile dementia in the Department of Psychogeriatrics, Imaise Branch, Ichinomiya City Hospital. METHODS: Physical complications that occurred in our ward in the 12 months from April 2007 to March 2008 were recorded. Our ward has 50 beds and, over the 12 months, the average occupation rate was approximately 90%. We subdivided physical complications into two categories: (i) serious emergencies occurring in the ward with a possible high risk of mortality within a few days (e.g. pneumonia and upper airway obstruction); and (ii) life-threatening complications arising in the ward that required diagnosis and treatment by specialists from other medical departments (e.g. bone fracture and cancer). RESULTS: Serious emergencies with a high risk of mortality occurred 56 times. Six patients died. Life-threatening complications requiring diagnosis and treatment by specialists from other departments occurred 44 times. Both categories of physical complications in occurred at a high rate, with various types of diseases recorded. CONCLUSIONS: The present study confirms the high frequency of physical complications that require treatment in facilities for patients with senile dementia. It is necessary to diagnose and treat these various physical complications and to cooperate with specialists from other medical departments.

Effectiveness and safety of surgical glove compression therapy as a prophylactic method against nanoparticle albumin-bound-paclitaxel-induced peripheral neuropathy.

BACKGROUND: We have developed a surgical glove (SG)-compression therapy and reported that this method significantly reduced the overall occurrence of grade 2 or higher nanoparticle albumin-bound-paclitaxel (nab-PTX)-induced peripheral neuropathy (PN) from 76.1% to 21.4%. In this multicenter single-arm confirmatory study, we investigated the efficacy and safety of SG-compression therapy for the prevention of nab-PTX-induced PN, compared with the incidence of grade 2 or higher PN in published literature as controls. PATIENTS AND METHODS: Primary breast cancer patients who received 260 mg/m2 of nab-PTX were eligible for this study. Patients wore two SGs (one size smaller than the tight-fitting size) in each hand for 90 min. PN was evaluated at each treatment cycle using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and the Patient Neurotoxicity Questionnaire (PNQ). The temperature of each fingertip was measured using thermography. RESULTS: Between October 2016 and June 2017, 58 patients were evaluated. The incidence of CTCAE grade 2 or higher PN was as low as 13.8% following SG-compression therapy. A goodness-of-fit test proved that the overall incidence of 13.8% grade 2 or higher PN in this study was comparable to the hypothesis-predicted value (13%). No adverse events, including compression intolerance or skin disorders caused by use of SG, were observed. SG-compression therapy significantly reduced the temperature of each fingertip by 1.3°C-2.3 °C compared to pre-chemotherapy level. CONCLUSIONS: This study suggested the safety and efficacy of SG-compression therapy for the amelioration of CIPN. CLINICAL TRIAL NUMBER: UMIN 000024836.

[Dementia Care Mapping-Japanese version(DCM-J) as a research evaluation method for measuring quality of life among elderly patients with dementia: reliability and validity of Well-being and Ill-being value].

AIM: Dementia Care Mapping is a behavior evaluation tool that can be used to measure and improve the quality of life of elderly patients with dementia. However, the reliability and validity of the Dementia Care Mapping-Japanese version (DCM-J) has not yet been established. Therefore, the purpose of this research was to clarify the reliability and validity of the Well-being and Ill-being (WIB) value of the DCM-J as a method for evaluating quality of life. METHODS: The study was conducted from April 1, 2005 to June 30, 2006. The participants included 130 elderly patients (men 31, women 99, average age 82.65+/-7.69 years) who were given a diagnosis of dementia. We established inter-rater reliability during a parallel observation method and also used test-retest for reliability. The correlation between the WIB value of the DCM-J and the Japanese Quality of Life Inventory for Elderly with Dementia (QOL-D) was used to establish criterion-related validity. RESULTS: Forty-nine (37.7%) subjects were given a diagnosis of dementia of Alzheimer's type, 80 (61.5%) had vascular dementia and 1 (0.8%) had dementia with Lewy bodies. The results showed correlation between the WIB value and social withdrawal measured by the behavioral category code (BCC) on the DCM-J and the three subscales of QOL-D: "interacting with surroundings", "expressing self", and "experiencing minimum negative behaviors". There was good internal consistency among these items. The interclass correlation coefficient was 82.32 (+/-5.85) for the WIB value of the DCM-J. The correlation coefficient of the retest, administered one week later, was 0.836 (p=0.001). The WIB value was significantly correlated with three sub-scales of QOL-D, and the correlation coefficient was greater than 0.53. CONCLUSION: We demonstrated that the WIB value of the DCM-J has good inter-rater reliability and test re-test reliability and criterion-related validity. In this study, the WIB value was shown to have similar reliability to the WIB value of the original DCM. Furthermore, our results suggest that the DCM-J could be useful for evaluating quality of life among elderly Japanese patients with dementia.

[Case of Alzheimer's disease with gastric antral vascular ectasia presenting severe anemia].

The difficulties regarding the diagnosis and treatment of physical complications of senile dementia were considered through focusing on a case of Alzheimer's disease with severe anemia. The first problem encountered is related to medical policies. Recently, there is growing concern about the lack of facilities dealing with physical complications of senile dementia. Few psychiatric hospitals can provide a complete diagnosis and treatment of such complications. In addition, it is economically very difficult to diagnose and treat them in wards for the elderly with senile dementia within the existing medical fee system. It is also very difficult in general hospitals, because most do not have the beds to deal with the behavioral and psychological symptoms of dementia. The second issue regards problems with patients. Many patients with senile dementia do not realize that they are ill. It is difficult to obtain their informed consent, and they often have a sudden change of mind. The third issue concerns problems with the patient's family. It is also difficult to obtain the family's consent because of the death of a spouse and/or children of patients with senile dementia, and/or their weak family ties. The fourth problem involves the recognition of physicians in medical departments who must diagnose and treat physical complications. Their prejudices regarding mental disorders must be brought into the open, and they may well have a similar prejudice regarding dementia. It is a considerable physical and mental load, even for medical doctors without bias in relation to dementia, to frequently obtain informed consent from elderly persons with senile dementia and their non-cooperative families. Despite the various problems mentioned above, if appropriate diagnoses and treatments of physical complications are carried out, it is natural even for the elderly with senile dementia to obtain good prognoses and QOL. Doctors must diagnose and treat physical complications of the elderly with senile dementia, considering their physical and mental conditions, giving due consideration to the treatments possibilities for various diseases, and having careful discussions with patients and their families, while making use of every available method of diagnosis and treatment. Close cooperation with other unbiased medical doctors is extremely important.

Expression of delta-like 3 is downregulated by aberrant DNA methylation and histone modification in hepatocellular carcinoma.

Delta-like 3 (DLL3) is a member of the Delta/Serrate/Lag-2 family of ligands for the Notch receptor and plays a role in Notch signaling. We have previously revealed that the expression of DLL3 is silenced by aberrant DNA methylation and that overexpression of DLL3 in the HuH2 hepatocellular carcinoma (HCC) cell line induced apoptosis. In the present study, we first confirmed the methylation of DLL3 in HuH2 cells and analyzed the methylation status of the DLL3 promoter region by bisulfite sequencing. Furthermore, we investigated whether other epigenetic modifications, such as histone acetylation and histone methylation, affected the expression of DLL3. Treatment with the DNA methylation inhibitor, 5-azadeoxycytidine (5-Aza-dC) slightly reactivated DLL3 mRNA expression and bisulfite sequencing revealed that CpG sites in the DLL3 promoter region of the HuH2 cells were densely-methylated. In addition, a significant increase in the expression of DLL3 was observed when the cells were treated with 5-Aza-dC in combination with the histone deacetylase inhibitor trichostatin A. However, an inhibitor of the dimethylation of histone H3 lysine 9 (H3K9me2) or the trimethylation of histone H3 lysine 27 (H3K27me3), modifications that are associated with gene silencing, had no effect on DLL3 reactivation. In combination with the findings from our previous study, these results indicated that DLL3 expression was silenced in HCC cells by DNA methylation and was more readily affected by histone acetylation than histone methylation (H3K9me2 or H3K27me3).