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Pemetrexed is a folate analog inhibitor for the treatment of non-small-cell lung cancer (NSCLC). Prophylactic supplementation with vitamin B 12 and folic acid reduces hematotoxicity associated with pemetrexed. Metformin, the antidiabetic agent, has been associated with the potential side effect of vitamin B 12 deficiency. This retrospective observational study aimed to evaluate the effect of concomitant metformin use on hematologic adverse events in patients with NSCLC undergoing pemetrexed-based chemotherapy using the Medical Data Vision Database. Patients with stage III or higher NSCLC who received pemetrexed from April 2008 to May 2021 were categorized into metformin-treated (MTF) and non-metformin-treated (non-MTF) groups. The primary outcome was the proportion of granulocyte colony-stimulating factor (G-CSF) administration during cycle (C) 1 to C2 or C2 to C3 of pemetrexed therapy. Propensity score matching (PSM) was used to balance the baseline characteristics between the groups. A total of 1174 patients met the inclusion criteria (54 in MTF and 1120 in non-MTF). After PSM, 52 patients were included in each group. The median metformin dosage in the MTF group was 500 mg/d before and 625 mg/d after PSM. There were no significant differences between the MTF and non-MTF groups in G-CSF administration (15.4 vs. 21.2%, p=0.446). Multivariate logistic regression analysis also showed that metformin use did not significantly affect hematologic toxicity (odds ratio: 1.208, 95% CI: 0.554-2.634). This suggests that the concomitant use of a relatively low dose of metformin is unlikely to significantly increase the risk of hematotoxicity in Japanese patients with NSCLC receiving pemetrexed-based chemotherapy.

In cancer patients, pain control is reportedly affected by the quality of their nutritional status as the disease progresses. We conducted a study of patients who were continuously using oral opioid analgesics for the treatment of cancer pain at Chibaken Saiseikai Narashino Hospital from September 2020 to August 2022. Patient characteristics and pain treatments were compared between the well-nourished group(mGPS 0 or 1, n=20)and poorly nourished group(mGPS 2, n=47). Univariate analysis revealed significant differences between the 2 groups in terms of sex and the presence or absence of concomitant analgesic adjuvant(p<0.05). According to the multivariate analysis, the presence or absence of concomitant analgesic adjuvant was a significant related factor, with an odds ratio of 11.409(95% confidence interval: 2.645-49.217, p=0.001). For patients in the poorly nourished group who were able to maintain a general condition that allowed for oral administration, treatment was continued without affecting pain control. In the well-nourished group, most patients used gabapentinoids as an analgesic adjuvant, whereas in the poorly nourished group, avoidable side effects, such as dizziness and lightheadedness, might affect the patient's quality of life.

Adenomyoepithelioma(AME)of the breast is a rare condition, and comorbidity with carcinoma is even more unusual. Herein, we report a case of both AME and apocrine carcinoma in different breasts of a single patient. A 48-year-old woman presented to our clinic with a right breast tumor. Fine needle aspiration cytology(FNAC)was indeterminate and suspicious for both papilloma and non-invasive ductal carcinoma, but excisional biopsy indicated an AME. Immuno-histochemical staining showed EMA(+), AE1/3(+), and CK7(+)mammary duct cells and αSMA(+), CK5/6(+), and p63(+) myoepithelial cells. Six months later, the patient noticed a left breast tumor, and although FNAC indicated no malignancy, after 6 additional months, the tumor size had increased and a mammography revealed tumor microcalcification, suggesting malignancy. Vacuum-assisted biopsy revealed an apocrine carcinoma. The patient underwent partial mastectomy and sentinel node biopsy, followed by radiotherapy and chemotherapy. The post-surgical pathology was pT1pN0M0, Stage Ⅰ, triple- negative, and the patient was disease-free for 12 years postoperatively. To our knowledge, this is only the second case of AME and breast cancer in different breasts reported in Japan.

Purpose: Radiography training for students in colleges of radiology should be based on real clinical situations. The purpose of this study was to verify the clinical validity of our originally developed scenarios for chest X-ray training and the instructional contents using gaze information of experienced radiology technologists (RTs)., Methods: We divided 8 RTs with different experiences into an evaluator group (3 RTs) and a subject group (5 RTs). The evaluator group created a validation model consisting of 31 items, a chest X-ray scenario, instructional contents, and gaze attention objects during the scenario. The subject group simulated chest X-ray wearing an eye tracker. The evaluator group evaluated fit rates of the validation model to subjects' procedures based on gaze information to verify the clinical validity of the validation model., Results: The subject group procedures did not deviate from the scenario. We obtained a fit rate of 91.6±6.70%., Conclusion: Our validation model showed more than 90% fitting with the chest X-ray techniques of five RTs with different backgrounds. This result suggested that the scenario and instructional contents in this study had clinical validity.

The purpose of this study was to identify patient outcomes after pharmacist interventions in the home health care context using pharmaceutical care records accumulated during daily operations. We focused on 591 cases at Nakajima Pharmacy from April 2020 to December 2021, where dispensing fees were charged to prevent duplication of medication and unnecessary interactions of home patients (excluding those related to adjustment of ongoing medications). The study investigated the content and background of prescription changes, the follow-up rate, and patient outcomes. The most common circumstances that led to pharmacist intervention for homebound patients were symptom occurrence (uncontrolled symptom, new symptom, drug adverse event). Of the patients for whom pharmacist intervention was provided for symptoms, 72.8% received follow-up according to the pharmaceutical care records. Furthermore, 59.2% of patients with follow-up showed an improvement of their symptoms. In addition, many patients had their medications discontinued or the dosage reduced by the pharmacist despite stable symptoms. More than 90% of these patients showed no change in symptoms. Besides interventions associated with the occurrence of symptoms, many interventions related to medication adherence were found to result from the patient's physical condition, such as poor swallowing function. The results suggest that tracking pharmacy drug histories may help pharmacists to better understand the need for follow-up implementation and the changes in patient outcomes after interventions.

Intentional overdose (OD) of over-the-counter (OTC) and prescription drugs is becoming a significant social issue all over the world. While previous research has focused on drug misuse, there has been limited analysis using social networking service data. This study aims to analyze posts related to a drug overdose on Twitter ® (X ® ) to understand the characteristics and trends of drug misuse, and to examine the applicability of social media in understanding the current situation of OD through natural language processing techniques. We collected posts in Japanese containing the term "OD" from January 10 to February 8, 2023, and analyzed 30203 posts. Using a pre-trained, fine-tuned bidirectional encoder representations from transformers (BERT) model, we classified the posts into categories, including direct mentions of OD. We examined the content for drug types and emotional context. Among the 5283 posts categorized as "Posts describing ODing," about one-third included specific drug names or related terms. The most frequently mentioned OTC drugs included active ingredients such as codeine, dextromethorphan, ephedrine, and diphenhydramine. Prescription drugs, particularly benzodiazepines and pregabalin, were also common. Tweets peaked at midnight, suggesting a link between negative emotions and potential OD incidents. Our classifier showed high accuracy in distinguishing OD-related posts. Analyzing Twitter ® posts provides valuable insights into the patterns and emotional contexts of drug misuse. Monitoring social networking services for OD-related content could help identify high-risk individuals and inform prevention strategies. Enhanced monitoring and public awareness are crucial to reducing the risks associated with both OTC and prescription drug misuse.

We report 5 cases of breast cancer that developed after cosmetic augmentation using silicone breast implants. The chief complaints were breast tumor in 3 cases, skin change in 1 case, and nipple bleeding in 1 case. Intervals between silicone breast implants and breast cancer surgeries ranged from 10 to 31 years. The pTNM stages included were Stage 0, Ⅰ, ⅡA, ⅢB, and Ⅳ, respectively, and the subtypes included were 3 Luminal types and 2 Luminal-HER2 types. Silicone bag rupture was noted in 1 case, and all bags were removed during surgery. The breast cancer surgeries performed were four breast- conserving surgeries and one mastectomy. The follow-up period ranged between 1.8 and 14 years(mean 5.1 years). All cases survived, but 2 cases had recurrences; the Stage ⅢB case experienced lung metastasis 2 years postoperatively and Stage Ⅳ case had induced pCR by chemotherapy postoperatively, but therapeutic self-interruption led to recurrences at the contralateral axillary nodes and contralateral breast and lung metastases 3 years postoperatively. Judging from limited reports of breast cancer after silicone breast implant in Japan, their incidence seems to be extremely low, and the incidence in our clinic during these 15 years(5 out of 1,851 primary breast cancers)is 0.27%.

Decision tree analysis, a flowchart-like tree framework, is a typical machine learning method that is widely used in various fields. The most significant feature of this method is that independent variables (e.g., with or without concomitant use of vasopressor drugs) are extracted in order of the strength of their relationship with the dependent variable to be predicted (e.g., with or without adverse drug reactions), forming a tree-like model. Specifically, users can easily and quantitatively estimate the proportion of event occurrences considering "interrelationships among multiple combinations of factors" by answering the questions in the constructed flowchart. Previously, we applied the decision tree model to vancomycin-associated nephrotoxicity and demonstrated that this method can be used to analyze the factors affecting adverse drug reactions. However, the number of cases that can be analyzed decreases significantly as the number of branches increases. Thus, many cases are necessary to generate highly accurate findings. In attempt to solve this problem, we combined big data and decision tree analyses. In this review, we present the results of our research combining big data (electronic medical record database) and a machine learning method. Furthermore, we discuss the limitations of these methods and factors to consider when applying the results of big data and machine learning analyses to clinical practice.

In 2018, the World Health Organization revised its cancer pain therapy, abolishing the three-step pain relief ladder and recommending the use of opioid analgesics(OA)according to the pain intensity. Of opioid naive patients who were admitted to Chibaken Saiseikai Narashino Hospital from July 2015 to June 2017, treatment with weak OA was initiated in 13 patients(WOA group)and low-dose strong OA in 12 patients(SOA group). The numerical rating scale values immediately before the start of OA and 3, 7 and 14 days later were not significantly different between the 2 groups. As for adverse events, the frequency of occurrence(p=0.01)and the prolongation of the last onset date(p=0.02)were significant in the WOA group for constipation. When the factors related to OA selection were analyzed using logistic regression analysis, there was no significance. We reported the analysis results regarding OA selection in OA naive patients.

The present study reviewed 9 cases of pregnancy and delivery after breast cancer in our clinic, between 2007 and 2019, to evaluate treatment options for their safe and successful management. The mean age at primary surgery was 31.7 years(27- 37); the study included 1, 5, 2, and 1 cases of pTNM Stage 0, Ⅰ, ⅡA, and ⅡB, respectively. The pregnancies were allowed after at least 1 year since completion of treatment to wash out chemotherapy or endocrine therapy agents. There were a total of 17 natural pregnancies, including 15 natural deliveries and 2 spontaneous abortions. Four patients achieved 1 birth, 4 achieved 2 births, and 1 achieved 3 births. The mean age at the first delivery after surgery was 36 years(30-40), and the highest age at the last delivery was 45 years. The molecular subtypes of breast cancer involved included 5 Luminal types, 1 Luminal-HER2 type, 1 HER2-enrich type, and 2 triple-negative types. The mean interval between the primary surgery and the first delivery was 4.3 years(3-6). Six patients were disease-free, and 3 patients experienced recurrences. Among the 3 patients with recurrence, 1 patient suffered from a local recurrence 43 months after the surgery; it was successfully resected, and she delivered 2 children after the second surgery and is now disease-free. One patient delivered 2 children after surgery; 12 years after surgery, she suffered from bone metastasis, but fortunately, endocrine therapy plus zoledronic acid treatment induced complete remission. One patient achieved pregnancy 4 years after the surgery and routine examination demonstrated the liver and bone metastases. The patient safely delivered at 9th-month pregnancy; the metastases and recurrences were treated chemo-endocrine therapy, and the patient is currently doing well. In conclusion, although the present study includes only 9 patients with 15 births, it suggests that a safe and successful pregnancy and delivery can be achieved through a variety of patient-orientated post-surgical treatment options that consider fertility preservation.

Objective: We examined the applicability and safety of staging laparoscopy(SL)in the treatment of advanced gastric cancer., Methods: We retrospectively reviewed the gastric cancer cases that were examined using SL between January 2015 and December 2019 at our hospital., Results: Within this period, 59 gastric cancer patients underwent SL, of whom 53 were diagnosed with SL at first examination. The rare complications of SL were postoperative nausea and vomiting(1 case). In 47.5%(28/59)of patients, we observed peritoneal dissemination including positive lavage cytology. In 2 cases, peritoneal dissemination was found during curative resection despite not being detected by SL. Thus, the false negative rate of peritoneal dissemination discovery was 6.7%(2/30). Among the individuals who were diagnosed as P1 or CY1 at first, subsequent SLs were performed in 6 cases, and 5 patients were re-assigned as P0CY0, of whom 4 underwent conversion surgery., Conclusions: SL is an essential and safe examination method for defining the treatment strategy in advanced gastric cancer. However, further improvements are needed to reduce the false negative discovery rate and to advance gastric cancer treatment by increasing reliability of diagnosis.

With the coronavirus disease 2019 pandemic, businesses are rapidly expanding their online practices, and the online medical care system has been established and is growing. The field of pharmacy education is also looking for ways to conduct practical online training. Hence, we developed an online role-play-based medical interview training method for fourth-year pharmacy students. The purpose of this study was to describe in detail this method and to clarify the effect of online on medical interviewing practice. The training sessions were conducted using video teleconferencing software. Two settings were used for the role-play scenarios: the pharmacy and hospital. To evaluate the effectiveness of the sessions, a questionnaire was sent to the students, and the results were analyzed using text mining. The most important requirement for successfully conducting the interviews was a stable voice connection, and we reduced audio interruptions and delays by connecting the host personal computer to a wired local area network. We also solved the problem of howling when multiple terminals were installed in the same room by muting all devices in the room. Results of the analysis of the questionnaires suggested that students were more tense online. We also found that students perceived a difference between online and face-to-face interviews in terms of eye contact and the presentation of documents. In this way, we succeeded in conducting smooth online role-playing sessions while taking countermeasures against infection. In the future, it will be necessary to devise nonverbal communication methods and digital methods of presenting the training material.

Naldemedine (Nal) is widely used as a therapeutic drug against opioid-induced constipation. However, patients in phase III trials are limited to those with good performance status (PS). Cancer patients may have inferior PS owing to progression of symptoms and adverse events from chemotherapy. Therefore, it is important to survey the efficacy of Nal in patients with poor PS. This study aimed to evaluate Nal efficacy in patients with poor PS. We retrospectively investigated patients from July 2017 to June 2019 and compared Nal efficacy between patients with good and poor PS. The efficacy of Nal was evaluated using changes in the number of spontaneous bowel movements 7 days before and after the introduction of Nal with reference to previous reports. Multivariate analysis was performed to reveal whether poor PS affects Nal efficacy. In total, 141 patients at the Hokkaido University Hospital were analyzed. The effective rate of Nal from day 1 to day 7 of administration was 71.7% and 71.4% in the patients with good and poor PS, respectively, that from day 1 to day 2 of administration was 61.1% and 57.1%, respectively, and that from day 3 to day 7 of administration was 60.2% and 71.4%, respectively, suggesting an absence of significant differences. Furthermore, results of multivariate analysis showed that "best supportive care" and "body weight (55 kg and above)" reduced Nal efficacy. In conclusion, Nal showed similar effectiveness in patients with poor PS as that in those with good PS.

This case is a 62-year-old man diagnosed with metastatic renal cell carcinoma. He was referred to our department due to the left renal mass pointed with ultra sound examination. Radiographical examination showed left-side 42 mm renal tumor with multiple lung tumors, suggesting renal cell carcinoma, cT1bN0M1 (pul). As an induction therapy, we selected Pembrolizumab plus Axitinib combination therapy. After 4 course of the therapy, the left kidney tumor shrank to 27 mm, and the lung metastasis disappeared with computed tomography imaging. For the next step, we performed laparoscopic partial nephrectomy. The pathological diagnosis was clear cell carcinoma, grade 2 with central necrosis. Since then, complete remission has been maintained without any treatment for 21 months.

The JMDC Claims Database ® contains completely anonymized receipt information on the insured members of health insurance associations. The number of registered users is approximately 9.6 million (6% of the population) as of May 2020. In this database, it is possible to track even outpatient treatment, even if the patient changes the medical facility, as long as the insurer of the subscriber's health insurance does not change, so that long-term medical treatment could be targeted as a research theme. However, as the data do not contain medical record information, it is not possible to obtain laboratory values, although it is possible to know whether clinical tests have been performed. For pharmaceutics-related research, the most suitable use of the receipt database like JMDC Claims Database ® seems to be the investigation of actual prescriptions. However, the research topics that pharmacists are interested in are probably comparisons of drug effects, drug-drug interactions, or causal analysis of drugs and side effects. However, laboratory data for evaluating drug efficacy is not available in the receipt database, and the accuracy of the disease name in the database becomes problematic when using the disease name as information indicating the occurrence of side effects. In this review, we introduce our studies performed by using JMDC Claims Database ® and how to manage the above-described problems. We hope that this study will be helpful to those who are going to engage in research using medical big data.

We report the case of a 74-year-old man with metastatic castration-resistant prostatic cancer (CRPC), who underwent treatment with cabazitaxel. Initially, he underwent docetaxel treatment for 2 years and exhibited severe neuropathy in his hands caused by its toxicity. As a result, we replaced docetaxel with cabazitaxel. On receiving 100% of the dose of cabazitaxel in the first course, febrile neutropenia (FN) was observed on the seventh day. However, he soon recovered from the FN and we began relative dose intensity (RDI) treatment with an adequate dose-volume and interval of treatments. He was successfully administered 51 cabazitaxel treatment courses without severe adverse effects. Cabazitaxel is a highly effective drug used as second-line chemotherapy following docetaxel, and it causes fewer adverse effects compared with docetaxel. Cabazitaxel may be a suitable alternative for outpatient treatment. Given that the patient in this case had a long overall survival of more than 3.5 years and received over 50 courses of cabazitaxel, it is crucial for RDI to be taken very seriously.

Medical big data, also referred to as 'real-world data' (RWD) is defined as "data related to patient health status and/or health care delivery collected routinely from a variety of sources". This includes data from disease and drug registries, electronic health records, claims and billing data and census data collected from clinicians, hospitals, and payers. Observational studies using RWD collected during general clinical practice are considered complementary to randomized control trials. However, since this design does not allow the random assignment of patients, causal inference analyses are required. Researchers should study the protocol properly before considering the combination of study design, the characteristics of data source, calculation of the appropriate sample size and the validity of outcomes. Data definition using data code should also be considered. Furthermore, the reliability of the source studies must be considered and discussed when the article is written. This review aims to outline the methods for performing reliable observational studies using RWD.

A 26-year-old man visited our hospital with a complaint of macrohematuria. Cystoscopy revealed a nodular tumor around the right ureteral orifice. Transurethral resection of bladder tumor was performed, and the tumor was pathologically diagnosed as the nested variant of urothelial carcinoma (NVUC). Radical cystectomy and modified Studer orthotopic neobladder reconstruction were performed. The pathological stage was pT2a, pN2. The patient received 2 courses of adjuvant chemotherapy consisting of gemcitabine and cisplatin. The patient is currently free from disease at 31 months after the treatment. To our knowledge, this case report represents the youngest case of NVUC.

Brain metastasis(BM)is the final stage of metastatic breast cancer(MBC), but its course and outcomes after the first metastasis(FM)to various sites are not fully clarified. Furthermore, the survival of patients with BM appears to be improving with the recent development in MBC control according to the subtype analysis. The present study included 35 patients with BM between 2008 and 2018, and was designed to clarify the effects of the FM sites and subtypes on the outcome of these patients. Subtypes included 8 Luminal(L), 8 L-HER2+(LH), 8 HER2(H), and 11 triple-negative(TN)types, and FM sites included 14 lungs or pleurae, 4 livers, 4 brains, 4 bones, and 9 local or lymph node(LN)metastases. The median interval between FM and BM(IFB)was 33 months(M)for overall patients; 50M for LH, 37M for L, 22M for H, and 19M for TN (p=0.0463); and 24M for the high risk(HR)FM(lung, pleura, liver)and 47M for the low risk(LR)FM group(bone, local, LN)(p=0.0385). The median overall survival(OS)after BM diagnosis was 13M for overall patients; 27M for LH, 13M for H, 10M for L, and 5M for TN(p=0.0112). There were no significant differences in the OS after BM diagnosis between HR FM and LR FM patients. Multivariate analyses for OS after BM revealed that patients with HER2(+)and estrogen receptor(+) tumors had a significantly better survival(risk ratio[RR]=0.644, p=0.0413; RR=0.290, p=0.0251, respectively). Three patients are surviving longer than 10 years after BM, including 2 with L-type and 1 with LH-type tumors, and their FM sites were 1 local, 1 brain, and 1 liver. The present study indicated that subtypes and FM site(HR or LR)had significant impact on the clinical course and prognosis of patients with BM. Focusing on the subtypes and FM site can improve the early detection and treatment results of BM.

A 55-year-old man with esophageal cancer underwent esophagectomy along with lymph node dissection and reconstruction with gastric conduit through the sternal route. He developed a continuous cough with sputum production, 3 years postoperatively. Chest radiography revealed a right middle lung field infiltrate. Chest computed tomography revealed communication between the reconstructed esophagus and the gastric conduit( pull-up) and right middle lobe airways. Upper gastrointestinal examination revealed ulcerative lesions involving the gastric mucosa;however, biopsy of the ulcer showed no malignancy. Conservative therapy including fasting and proton-pump inhibitor administration did not improve symptoms caused by gastropleural fistula. Thoracotomy was performed through the anterolateral intercostal space under the right-up supine position, and the partial lung resection and direct closure of the stomach with muscle flap wrapping was performed.

We report a radiation-associated angiosarcoma(RAAS)of the breast, which is a rare but important complication after breast-conserving surgery(BCS)and radiotherapy(RT)for breast cancer. A7 2-year-old woman had undergone BCS for invasive ductal carcinoma of the right breast(pT2pN1M0, StageⅡB), followed by RT of 50 Gy; she was treated with doxifluridine and anastrozole for 5 year. She noticed a bloody cutaneous bulla in the right breast 64 months later, and the skin lesions gradually expanded. She was brought to our clinic for the treatment of massive bleeding from the skin lesions. Ulcer biopsy revealed cutaneous AS(cells were CD31[+], CD34[+], VEGF[-], and VEGF-R[+]). She underwent mastectomy and latissimus dorsal flap surgery. She died of local recurrence and liver metastasis 13 months later. RAAS is rare, but it should be considered in patients with skin lesions, such as erosion and bloody bulla, after BCS and RT for breast cancer. To our knowledge, only 12 cases of RAAS, including the present case, have been reported in Japan, and we reviewed the Japanese RAAS cases in comparison with those reported in the Western literature.

Linezolid (LZD), an antimicrobial agent against methicillin-resistant Staphylococcus aureus, demonstrates good bone and joint penetration, and is used for prosthetic bone and joint infections. Recently, we observed vomiting in several patients administered LZD. However, there are few reports on the incidence rate of, and risk factors for, LZD-induced nausea and vomiting. In this study, we aimed to verify the relationship between LZD administration and vomiting. Patients administered LZD at the Department of Orthopedic Surgery of Hokkaido University Hospital between November 2008 and December 2017 were enrolled in the study. The primary endpoint was the comparison of the vomiting rate between patients administered LZD (LZD group) and those administered other antibiotics (non-LZD group). For the secondary endpoint, to verify the risk factors of vomiting, a univariate logistic regression analysis was performed. In total, 130 patients were included in this study; 77 patients in the LZD group, and 53 in the non-LZD group. Vomiting occurred in 18 patients in the LZD group and 4 patients in the non-LZD group (23.4% and 7.5%, respectively); this was significantly higher in the LZD group. In the univariate logistic regression analysis, LZD administration, gender (female), age ≥65 years, renal impairment (creatinine clearance <60 mL/min) and concomitant use of rifampicin were extracted as potential risk factors of vomiting. The results of this study reveal a possible relationship between LZD administration and vomiting.

Purpose: Ichihara et al. (Fujita Med J 2015; 1(1): 9-14) developed a method to simultaneously obtain both coronary computed tomography (CT) angiography and CT myocardial perfusion (CTP) using 64-multi detector CT (MDCT). An input-function (time enhancement curve, TEC) of the ascending aorta (Ao) and myocardial CT density are necessary to calculate absolute myocardial blood flow (ml/g/min) using a two-compartment model. Helical scan starting timing is important to capture the peak (P) of Ao time enhancement curve (TEC). The purpose is to search the optimal timing of starting helical scan to capture the P., Methods: We performed 14 CTPs using Definition AS+ (SIEMENS). A dynamic scan at the Ao level was started at 7 s after contrast injection and helical scan was started at various trigger on bolus tracking. Definition AS+ needs 2 s (other scanner may need 4 s) for changing from a dynamic to helical scan mode. We created TECs of pulmonary artery (PA) and Ao using the fifth function fitting. We measured the time from trigger point to the P (t200, t250, t300 and tCP)., Results: Mean t200, t250, t300 and tCP were 9.1±1.9, 7.9±2.0, 6.6±1.9 and 3.9±1.2 s, respectively. In additional other 16 CTP studies using the cross point method, we can capture the P in all (100%) examinations., Conclusion: Scan starting at the cross point is best for Definition AS+, and the Ao=300 HU may be best for other scanner that needs 4 s for changing scan mode to obtain a fine input function for calculating absolute myocardial blood flow.

Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect frequently caused by taxanes. Because the mechanisms underlying CIPN pathogenesis remain to be fully elucidated, there is no indicator for objective diagnosis like a biomarker. In addition, treatment options for CIPN is still unsatisfactory. We have previously demonstrated that paclitaxel preferentially impair myelin-forming Schwann cells, and consequently induce dedifferentiation and demyelination of Schwann cells. Recently, in a paclitaxel CIPN model mouse, we found that an inflammatory factor is released from dedifferentiated Schwann cells in the mouse sciatic nerve into the blood, highly correlated with the on-set of mechanical hypersensitivity. On the other hand, considering our previous findings, it seems that some drugs, which supply newly formed mature Schwann cells at the sites of demyelinated lesions, may be a new beneficial therapy for taxane-induced peripheral neuropathy. In this review, we will introduce our findings about new therapeutic drug candidate for taxane-related CIPN based on this concept, and plasma biomarker to detect CIPN on-set and progression.

This study compared the treatment results of over 80-year-old(O-80) 54 and 157 septuagenarian(70s)women with breast cancer(BC)from 1996 to 2015, to clarify the best treatment option for O-80BC patients. No differences were observed in the stages and subtypes. More than 70% of women in both groups underwent breast-conserving surgery(BCS), and 48.1% and 12.1% of O-80BC and 70sBC patients did not undergo axillary dissection, respectively. About 3.2% and 18.5% of 70sBC and O-80BC patients did not receive adjuvant therapies, respectively. Most ER-positive patients in both groups received endocrine therapy. Most patients in both groups received no intravenous chemotherapy; however, oral chemotherapy was administered in 80.3% of 70sBC and 64.8% of O-80BC patients. Approximately 75.2% of 70sBC and 11.1% of O-80BC patients received post-surgical radiotherapy(RT). No differences in both relapse-free survival and overall survival (OS)rates were observed between the 2 groups. Breast cancer-related death(57.1%)and natural death from old age (57.1%)were the most commonly observed cause of death in the 70sBC and O-80BC groups, respectively. Multivariate analyses on OS demonstrated that BCS and intravenous chemotherapy were significantly associated with poor prognosis and RT was significantly associated with better prognosis in 70sBC group, whereas BCS was significantly associated with better prognosis in O-80BC group. In conclusion, surgery, especially BCS, plays an important role in the primary treatment of O- 80BC patients; however, axillary dissection, RT, endocrine therapy, and chemotherapy cannot be performed.

A 48-year-old woman with severe interstitial pneumonitis was diagnosed with right breast cancer(invasive ductal carcinoma, T1aN1M0, ER+, PgR-, HER2 3+)and underwent modified radical mastectomy.The patient was administered tamoxifen as adjuvant therapy.However, 1 year after the mastectomy, multiple liver metastases were found and the patient received 2 anti-HER2 agents, trastuzumab and pertuzumab.A complete response(CR)was observed with the disappearance of the liver metastases in 7 months.CR was maintained for 2 years after the initiation of treatment, and then, we started trastuzumab monotherapy, which has resulted in long-term disease control.

Only minimal information exists regarding the treatment outcomes of patients suffering from methicillin-resistant Staphylococcus aureus (MRSA) bacteremia treated with teicoplanin (TEIC) when the TEIC minimum inhibitory concentration (MIC) is close to the upper limit of the "susceptibility range" according to the Clinical Laboratory Standards Institute (CLSI). We investigated the outcome of TEIC-treated patients in MRSA bacteremia, focusing on TEIC MIC against MRSA. A retrospective cohort study was conducted on patients with MRSA bacteremia. TEIC treatment failure was defined as any of the following: (1) all-cause 60-day mortality, (2) persistent bacteremia until the end of TEIC treatment, or (3) 30-day recurrence of MRSA bacteremia. Nineteen patients were enrolled, of whom 15 exhibited TEIC MICs ≤2 μg/mL and the remaining 4 exhibited >2 μg/mL. The rate of treatment failure and all-cause 60-day mortality in patients with MIC >2 μg/mL were significantly higher than those in patients with MIC ≤2 μg/mL [4 patients (100%) versus 4 patients (26.7%) (p=0.018) and 4 patients (100%) versus 2 patients (13.3%) (p=0.004), respectively]. Three of four patients (75%) with MIC >2 μg/mL had persistent bacteremia, which was quantitatively higher than in patients with MIC ≤2 μg/mL (1 of 7 patients, 14.3%). Our finding suggests that TEIC MIC >2 μg/mL may be related to poor treatment outcome in MRSA bacteremia, and that TEIC should not be used in this case.

The present study was designed to estimate the clinical efficacy of bevacizumab(BV)combined with paclitaxel(PTX)(BVPTX) as third- and fourth-line therapies in 31 patients with metastatic breast cancer(MBC). Most patients were previously treated with docetaxel and/or epirubicin. Patients were intravenously treated with BV at 5-10mg/kg and PTX at 3-5mg/kg at 2-3week intervals, and when the effect of BV-PTX was low, other chemotherapeutic agents(CTAs)and/or trastuzumab (Tr)were additionally administered. Twelve MBC patients were treated with BV-PTX alone and 19 MBC patients were treat- ed with other CTAs and/or Tr in addition to BV-PTX. No serious adverse events were observed in any regimen. Three complete responses(9.7%), 4 partial responses(12.9%), 8 stable diseases(25.8%), and 16 progressive diseases(51.6%)were observed; the response rate was 22.6%, and the clinical benefit rate was 48.4%. The median progression-free survival(PFS) and median overall survival(OS)after the initiation of BV-PTX were 7.0 and 16.0 months, respectively. All 13 HER2-positive MBC patients were treated with Tr in addition to BV-PTX, and the OS and PFS were significantly higher in the BV-PTX+Tr+ CTAs group than in the BV-PTX+Tr group. In 18 HER2-negative MBC patients, PFS and OS were better in the BV-PTX+CTAs group than in the BV-PTX alone group, though this difference was not significant. Multivariate analyses demonstrated that an additional CTAs was a variable for significantly better PFS, and additional CTAs, Tr, and endocrine therapy were significant variables for better OS. These results indicated that additional CTAs and Tr should be combined with BV-PTX for third- and fourth-line chemotherapies.

Bacteremia is one of the most serious infectious illness resulting from nosocomial infection. Therefore, appropriate antimicrobial chemotherapy should be provided as soon as possible to patients exhibiting symptoms of infectious disease and having positive blood culture results. Antimicrobial stewardship (AS) guidelines were recently released by the Infectious Diseases Society of America. The guidelines recommend "proactive intervention and feedback" as one of the core strategies for implementing optimal antimicrobial drug use to improve patient outcomes in clinical settings. We began using the AS program for optimizing antimicrobial chemotherapy in patients with positive blood culture results. The results of blood cultures and antimicrobial prescriptions for the corresponding patients were daily reviewed by a pharmacist and a physician, members of the infection control team (ICT). If the antimicrobial agents selected were inappropriate, ICT made a recommendation to the attending physicians who prescribed the antibiotics. To evaluate the outcomes of this program, we conducted a single-center, retrospective investigation for near a hundred of patients who underwent intervention by infection-control physician and pharmacist. Resolution of bacteremia (determined by blood culture results) was 96.3% in the group that accepted intervention, whereas only 16.7% of the cases resolved in the group that did not accept intervention. These results strongly suggest the importance of the infection disease-specialist team intervention. This program could become an important method for improving clinical outcomes in patients with bacteremia.

Based on the predictive performance in our previous study, we switched the therapeutic drug monitoring (TDM) analysis software for dose setting of vancomycin (VCM) from "Vancomycin MEEK TDM analysis software Ver2.0" (MEEK) to "SHIONOGI-VCM-TDM ver.2009" (VCM-TDM) in January 2015. In the present study, our aim was to validate the effectiveness of the changing VCM TDM analysis software in initial dose setting of VCM. The enrolled patients were divided into two groups, each having 162 patients in total, who received VCM with the initial dose set using MEEK (MEEK group) or VCM-TDM (VCM-TDM group). We compared the rates of attaining the therapeutic range (trough value; 10-20 μg/mL) of serum VCM concentration between the groups. Multivariate logistic regression analysis was performed to confirm that changing the VCM TDM analysis software was an independent factor related to attaining the therapeutic range. Switching the VCM TDM analysis software from MEEK to VCM-TDM improved the rate of attaining the therapeutic range by 21.6% (MEEK group: 42.6% vs. VCM-TDM group: 64.2%, p<0.01). Patient age ≥65 years, concomitant medication (furosemide) and the TDM analysis software used VCM-TDM were considered to be independent factors for attaining the therapeutic range. These results demonstrated the effectiveness of switching the VCM TDM analysis software from MEEK to VCM-TDM for initial dose setting of VCM.

Triple-negative breast cancers(TNBCs)are associated with early recurrence after surgery and unfavorable prognoses. To date, no effective therapies for TNBCs have been established. The present study was designed to evaluate the efficacy of adjuvant chemotherapy(ACT)for 111 TNBCs using a retrospective multivariate analysis(MVA). The intravenous(iv)ACTs included docetaxel, epirubicin, gemcitabine, and vinorelbine. The oral ACTs included UFT, doxifluridine, and cyclophosphamide. The 10-year disease-free survival(DFS)and overall survival(OS)rates were 77.5% and 86.0%, respectively. Recurrences were observed in 17 patients, and the first recurrence was most frequently located in the lung. MVA revealed that pT was a significant independent variable for poor DFS and OS. UFT was the only significant independent variable for improved DFS. The survival analysis also demonstrated that UFT alone may be an effective option for Stage I TNBCs. Furthermore, it suggested that the addition of further iv ACTs to UFT could improve the outcome in patients with Stage II-III TNBCs.

We report a case of pancreatic metastasis from prostate cancer. A 65 year-old man developed gross hematuria, and was found to have a markedly elevated PSA and abnormal CT findings indicating mass lesions in bilateral lungs, and pancreatic head, and osteoblastic lesions in pelvic bone. He was referred to the department of Urology and Gastroenterology at Seirei Hamamatsu General Hospital. Digital rectal examination revealed a hen's egg-sized, stony-hard prostate. A systematic needle biopsy of the prostate demonstrated adenocarcinoma (Gleason score 4+4=8). We diagnosed multiple lung and bone metastases from prostate cancer, and suspected that a primary pancreatic ductal carcinoma. The patient was started on an androgen deprivation therapy (ADT) with bicalutamide and degarelix. After 4 months from the initiation of ADT, an MRI of the pancreas showed decreased size of the pancreatic head mass from 18 mm to 7 mm in diameter. We concluded that the pancreatic head mass was metastasis from prostate cancer, and currently continue ADT. Pancreatic metastasis from prostate cancer is very rare, and further accumulation of cases will be required.

Purpose: Several technological advances have been made in laparoscopic surgery, and the use of reduced port surgery (RPS)has gradually become widespread. To assess the safety and usefulness of RPS, we compared the short -term outcomes of conventional laparoscopy-assisted total gastrectomy(LATG)and LATG with the RPS approach., Patients and Methods: From April 2009 to February 2012, 16 cases with gastric cancer underwent conventional LATG with 5 ports as well as minilaparotomy for anastomosis(Conventional group). From February 2012 to November 2012, 12 cases underwent RPS LATG(RPS group). In the RPS group, a multi-instrument port at the umbilicus was used during surgery. This port held 3 trocars and 2 5-mm trocars that were inserted under the right lumbocostal arch., Results: The mean operation time was 333 minutes in the Conventional group, and 370 minutes in the RPS group. The mean postoperative hospital stay was 23 days in the Conventional group, and 17 days in the RPS group. Postoperative mortality was 0% in both groups. Anastomotic leakage occurred in 2 cases in the Conventional group, whereas pancreatic fistula occurred in 2 cases in the RPS group. Due to postoperative bleeding, 1 case in the RPS group underwent redo laparoscopic operation. Anastomotic stenosis was noted in 4 cases in each group. The patients with stenosis required endoscopic balloon dilation several times and the symptom eventually resolved in all cases., Conclusion: By comparing the short-term outcomes for conventional LATG and RPS LATG, we noted that reduced port laparoscopy-assisted total gastrectomy is a feasible procedure.

Recently, studies on the mechanisms of aging and longevity have been making significant progresses. Through those studies, the SIR2 (silent information regulator 2) family proteins, now called "sirtuins" , have drawn much attention as important regulators that connect metabolism, aging, and longevity. The general feature of sirtuin function is to maintain the robustness of the physiological system in response to or prevent its destruction from various internal and external perturbations. This particular function of sirtuins allows them to play critical roles in the regulation of many biological processes, including the regulation of aging and longevity. In this review article, recent findings in this quickly evolving field of sirtuin biology will be summarized, and the importance of sirtuins on the regulation of aging and longevity will be discussed.

Since the February 2004 FDA advisory's warning of activation syndrome involving antidepressants, growing concerns have emerged over aggression and violence reported in subjects prescribed these drugs. However, activation syndrome remains poorly defined, and controversy regarding the nature of this syndrome continues in the field of psychiatry. Here, we present four medico-legal cases involving activation syndrome, in which one of us served as an expert witness. Analysis of the court's decisions indicated that the court appeared to focus on whether the acts were associated with the subjects' personality or not, leaving the controversy over activation syndrome as an open question. These cases highlighted the need for joint examination by jurists and psychiatrists, since society is likely to continue to be faced with cases of behavioral problems associated with the use of antidepressants.

We analyzed the clinical efficacy of pre-operative combination chemotherapy using docetaxel, cisplatin and S-1 for advanced gastric cancer. Four patients were enrolled and staging laparoscopy was performed. Patients received intravenous docetaxel and cisplatin (35 mg/m2) on day 1 and 15, and oral S-1 80 mg/m2 on day 1-14 every 4 weeks. Two patients received two courses of chemotherapy and two patients received three courses of chemotherapy. Neutropenia of more than grade 3 was found in 3 cases. All cases were PR on preoperative imaging. Curative operation was performed on three cases. Histological anti-tumor effect was judged to be grade 2 in 1 case and grade 1a in 3 cases. In the postoperative period, all patients received S-1-based adjuvant chemotherapy. The combination chemotherapy using docetaxel, cisplatin and S-1 plus operation was a candidate for the standard treatment strategy for advanced gastric cancer.

Molecular biomarkers are keys to the development of new diagnostic protocols and therapies. Recently, significant research effort has been devoted to the development of these biomarkers using various approaches. Perhaps the most promising approach is disease proteomics. This method involves analyzing and identifying changes in the expression pattern at the protein level in the diseased condition (disease-related proteins) by using two-dimensional differential gel electrophoresis analysis (2D-DIGE). In the case of disease proteomics, hundreds of candidate disease-related proteins can be identified at a time. Therefore, how to pick the really valuable proteins up from a number of candidate drug targets is the most important issue to be solved worldwide. Here, we introduce a novel approach, termed "antibody proteomics", which addresses this issue. Using antibody proteomics it is possible to identify a variety of disease-related proteins by 2D-DIGE and simultaneously prepare monoclonal antibodies to these proteins by using a phage antibody library. The advantage of this technology is that the target proteins are identified in a high-throughput manner. Our approach relies on the fact that tissue microarray analysis can evaluate the relationship between disease-related proteins and disease progression, based on clinical and pathological information. In this review, we discussed the development and application of antibody proteomics and gave an overview of future work.

We report a 37-year-old woman who complained of chest discomfort as of August 2004, and was found to have advanced esophageal cancer in the upper thoracic area in December 2004.S he was diagnosed as Stage IVa (T4N1M0) because chest computed tomography (CT) indicated trachea invasion and lymph node metastasis. We diagnosed it to be a case of unresectable esophageal cancer, and she underwent chemoradiation therapy. CT showed regression of the main tumor and metastatic lymph nodes when the CRT course was completed. The main tumor disappeared macroscopically. We again considered an operation, but the CRT was so effective that the patient wished to continue CRT and underwent three courses. Endoscopy showed disappearance of the main tumor and Lugol's solution. Following this, 10 courses of the treatment with CDDP alone (CDDP 10 mg/weekly) were continued until the appearance of renal dysfunction. S-1 (100 mg/body/day)was started in September 2005. The treatment is currently ongoing, and no recurrence or metastases had occurred as of March 2009.

The patient was a 54-year-old male. In July 2004, he underwent resection of the pancreatic body tail region to treat pancreatic body tail cancer. On histopathological examination, the stump of the extirpated specimen was positive for tumor cells. After surgery, 10 courses of therapy with gemcitabine hydrochloride(GEM, 1, 000 mg/m(2), 3-week administration followed by 1-week discontinuation)were performed, and follow-up was continued. In February 2006, local relapse was detected. Chemotherapy with GEM was administered for 1 year and 9 months. However, in November 2007, an increase in the recurrent lesion size and right lung metastasis were noted. The regimen was switched to combination therapy with S-1 and GEM(S-1 60 mg/m(2) day, continuous administration on days 1 to 14 and 2-week discontinuation; and GEM 1, 000 mg/ m(2), administered on days 8 and 15). After the end of the 11th course, PET-CT revealed the disappearance of FDG accumulation in the recurrent and metastatic lesion sites. During the treatment period, there were no grade 3 or higher adverse reactions. The patient is being treated at the outpatient clinic (as of January 2009).

We report a case of a 52-year-old female with multiple skin metastases from breast cancer who responded to S-1. She underwent surgery of her right breast in March 2000 and the left in June 2006. Multiple skin metastases were later detected. As there was no hormone sensitivity, chemotherapy was selected. We started treatment with administration of S-1 at 120mg/day(4 weeks)and trastuzumab. Thoracic CT at the end of the three courses revealed the disappearance of the multiple skin metastases. No major side effects were seen. It was concluded from these findings that S-1 could be safely and effectively administered to advanced breast cancer patients.

We report an 83-year-old female with axillary node metastasis from breast cancer who responded to trastuzumab/ capecitabine combination therapy. In April 2007, she underwent surgery and at the same time axillary node metastasis was detected. As there was no hormone sensitivity, chemotherapy was selected, and administration of capecitabine at 1,800 mg/day(2 divided doses)and trastuzumab was initiated. Thoracic CT at the end of the six courses revealed the disappearance of the axillary node metastasis. No major side effects were produced. It was concluded from these findings that trastuzumab/capecitabine combination therapy could be safely and effectively administered to elderly advanced breast cancer patients.

Purpose: Hepaticarterial infusional(HAI)5-FU chemotherapy, which involves the use of interventional radiology technique, has matured technically in Japan in the 1990's. The antitumor effect of 5-FU is enhanced by combination with leucovorin. This study was performed to evaluate the efficacy and toxicity of HAI 5-FU and leucovorin chemotherapy for patients with unresectable liver metastases from colorectal cancer., Methods: Treatment was given to 20 patients with unresectable liver metastases from colorectal cancer. The chemotherapy regimen consisted of weekly HAI of 5-FU(1,000 mg/body)and leucovorin(250 mg/body)over five hours. The survival and response rates to the therapy were assessed according to RECIST. Hematologic and non-hematologic toxicity was assessed according to CTCAE v3.0., Results: Combined HAI 5-FU and leucovorin therapy was carried out an average of 27 times. The response rate for liver tumors was 75%, and the median survival time was 22 months. The applied regimen caused only mild adverse events. There was no evidence of myelosuppression except for platelet decrease(grade 3)in a patient with chronic renal failure., Conclusion: This HAI approach using 5-FU and leucovorin was effective and the therapy for unresectable liver metastases from colorectal cancer was tolerated well. Therefore the HAI approach should be reconsidered as an effective therapy against this disease in Japan.

A 73-year-old woman underwent chemotherapy, radiotherapy, and hormonal therapies for right advanced breast cancer (T4, N3, M1, Stage IV) in 1993. She obtained a complete response in pathological evaluation (pCR) in 1998. For adjuvant therapies, she had been treated with hormonal therapies for five years until 2003. After the interruption of hormonal therapies, the serum levels of tumor markers had been elevated, and she had a right axillary local recurrence and a right ovarian metastasis detected by a FDG-PET/CT in February 2006. The right axillary local recurrence lesion was then resected, and she has since been treated with hormonal therapy of aromatase inhibitor (AI). The serum levels of tumor markers have been remarkably reduced, and FDG-PET/CT has showed the disappearance of the right axillary local recurrence, and the decrease of FDG accumulation of the right ovarian metastases in February 2007. We present a case of non-operated advanced breast cancer with local recurrence surviving successfully long term when treated with AI.

In February, 19 9 8, a 48-year-old female patient underwent an operation for breast cancer. In November 2003, abdominal MRI revealed metastatic lesions in S 3 and S 5 of the liver, and chemotherapy (trastuzumab+weekly paclitaxel) was started, after which the metastatic lesions quickly reduced in size. No lesions could be detected by April 2004, and she was diagnosed as a complete response (CR). She now visits our hospital as an outpatient without any evidence of recurrence or any side effects of chemotherapy for 8 years and 8 months after surgery. For advanced breast cancer, there is no standard criteria regarding the time when to stop chemotherapy after obtaining a CR. This time, we experienced a case of liver metastasis of breast cancer responding to a regimen of trastuzumab plus weekly paclitaxel chemotherapy maintaining CR for a long period. We discuss the timing of the termination of chemotherapy in such a case in light of our experience and the literature.

The present study investigated the efficacy and safety of weekly administration of paclitaxel (PTX) for 37 patients with advanced or recurrent breast cancer. PTX was administered at a dose of 60 mg/m(2), 6 times every 8 weeks. The mean number of treatment cycles was 2.1, and the mean number of administrations was 12.7. Response rate was 35.1%. Two patients achieved CR, 11 PR, 13 NC (3 patients of long NC), 9 PD, and 2 NE. The clinical benefit rate (CR+PR+NC) was 70.3%. Median survival time was 733 days, and median time to treatment failure was 151 days. Grade 3 or more leucopenia and neutropenia occurred in 3 of patients (8.1%), and no patients showed hypersensitivity reaction after administration of PTX. Weekly PTX (60 mg/m(2)) is one of the treatment options in advanced or recurrent breast cancer from the standpoint of palliation.