Zinc supplementation for dysgeusia in patients with unresectable pancreatic cancer.

BACKGROUND: Although patients with advanced pancreatic cancer (PC) often experience dysgeusia with zinc deficiency during chemotherapy, data on zinc supplementation for dysgeusia and its effects on nutritional status are scarce. We aimed to examine the efficacy of zinc supplementation in patients with advanced PC. METHODS: Thirty-three patients with unresectable PC who presented with dysgeusia and zinc deficiency during chemotherapy and received zinc acetate hydrate between January 2018 and December 2022 were included. We evaluated the changes in serum zinc levels and the improvement in dysgeusia. Among the 26 patients who received zinc supplementation for 12 weeks, we also compared patient characteristics and changes in serum zinc and albumin levels between patients who showed improvement in dysgeusia (effective group) and those who did not (non-effective group). RESULTS: The serum zinc level increased significantly after zinc supplementation (median: 60 µg/dL at baseline, 99.5 µg/dL at 4 weeks, 101 µg/dL at 8 weeks and 101 µg/dL at 12 weeks). The rate of improvement in dysgeusia increased over time (18.2% at 4 weeks, 33.3% at 8 weeks, and 42.4% at 12 weeks). Comparing the effective group and non-effective group revealed that while the median serum albumin level of the effective group did not change, the non-effective group showed a significant decrease from baseline to 12 weeks (3.2 g/dL to 3.0 g/dL, p = 0.03). CONCLUSION: Zinc supplementation significantly increased serum zinc levels, improving dysgeusia. Zinc supplementation might also contribute to maintaining nutritional status in patients with unresectable PC.

Availability of individual proteins for quantitative analysis in postmortem brains preserved in two different brain banks.

AIM: Postmortem brain research is necessary for elucidating the pathology of schizophrenia; an increasing number of studies require a combination of suitable tissue samples preserved at multiple brain banks. In this study, we examined whether a comparative study of protein expression levels can be conducted using postmortem brain samples preserved in different facilities. METHODS: We compared the demographic factors of postmortem brain samples preserved in two institutions and measured and compared the expression levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glial fibrillary acidic protein (GFAP) in the prefrontal cortex and superior temporal gyrus. GAPDH is generally used as a loading control for western blotting, and GFAP is considered as an astrocyte marker in the brain. RESULTS: We found significant differences between the two institutions in postmortem interval, age at death, and preservation time. To reduce the effects of these differences on our measurements, the parameters were set as covariates in our analyses of covariance. Subsequently, no differences in GAPDH and GFAP expression were found between institutions. CONCLUSIONS: When studies are conducted using brain samples preserved in different brain banks, differences in demographic factors should be carefully considered and taken into account by statistical methods to minimize their impact as much as possible. Since there was no significant difference in the protein expression levels of GAPDH and GFAP in either region between the two institutions that preserved the postmortem brains, we concluded that it is possible to perform protein quantitative analysis assuming that there is no effect of difference between two institutions.

Faster surgery initiation in oral cancer patients during the COVID-19 pandemic in Osaka, Japan.

BACKGROUND: We investigated the impact of the COVID-19 pandemic on oral cancer (OC), comparing diagnosis and number of pre-operative days in the diagnosis of OC in 2019 (pre-COVID-19) and that in 2020 (during the COVID-19 pandemic). METHODS: Using data from a cancer registry-based study on the impact of COVID-19 on cancer care in Osaka (CanReCO), we collected details of sex, age, residential area, cancer site, date of diagnosis, clinical stage at first treatment and number of pre-operative days in OC patients. RESULTS: A total of 1470 OC cases were registered. Incidence of OC before and during COVID-19 was 814 and 656 cases, respectively. During the first wave of the pandemic (March to May 2020), incidence was about half that in the same period in 2019 (2019; n = 271, 2020; n = 145). Number of pre-operative days (median number of days between the first hospital visit and surgery date) was significantly shorter during the COVID-19 year (24.5 days) than in the pre-COVID-19 year (28 days, p = 0.0015). CONCLUSIONS: Incidence of OC during the COVID-19 pandemic was lower than in pre-COVID-19. Despite disruption in the healthcare system, the number of pre-operative days for OC cases was shorter during the pandemic.

Drug interactions of tacrolimus with letermovir and azole antifungals following hematopoietic stem cell transplantation: A retrospective observational analysis.

Tacrolimus interacts with letermovir and azole antifungals, whereas letermovir has nonuniform effects on the pharmacokinetics of azole antifungals. We retrospectively investigated the interaction of tacrolimus (continuous infusion) with letermovir considering co-administered azole antifungals in adult hematopoietic stem cell transplantation patients. The extent of intraindividual variation in the ratio of tacrolimus concentration to dose normalized by body weight (C/D ratio) was investigated. The correlation between the C/D ratio and estimated glomerular filtration rate (eGFR) was analyzed. In 35 patients (795 points), the C/D ratio was higher in the tacrolimus plus letermovir period than in the tacrolimus alone period (1234.7 [566.2-2721.0] ng/mL/mg/kg vs. 564.4 [245.3-1861.3] ng/mL/mg/kg, p < .001). This trend was observed when co-administered with azole antifungals (n = 30, 1285.5 [662.7-2506.7] ng/mL/mg/kg vs. 547.1 [245.3-1861.3] ng/mL/mg/kg, p < .001), but not without azole antifungals (n = 5, 809.9 [566.2-1573.3] ng/mL/mg/kg vs. 616.1 [350.6-979.8] ng/mL/mg/kg, p = .125). For patients co-administered fluconazole, the tacrolimus C/D ratio increased in patients with letermovir than those without letermovir (n = 28, 1215.0 [662.7-2506.7] ng/mL/mg/kg vs. 529.9 [245.3-1654.4] ng/mL/mg/kg, p < .001). Tacrolimus C/D ratio did not correlate with eGFR under letermovir and fluconazole administrations (y = 0.1x + 1307.1, r = .008, p = .968). Close blood concentration monitoring of intravenous tacrolimus is required when patients administered letermovir and azole antifungals.

[New Attempt of Radiation Oncology Section to Radiotherapy for Head and Neck Cancer].

Oral care is important for patients with head and neck cancer who undergo radiotherapy because these patients encounter various symptoms, which decrease their quality of life(QOL). Oral mucositis is considered the major side effect of radiation, and the dose-volume parameters can serve as predictors of the occurrence of severe oral mucositis. Therefore, understanding radiation treatment planning(e. g., prescription dose and irradiated volumes of the organs at risk)and providing oral healthcare before, during, and after radiotherapy are essential for maintaining patients' QOL. METHODS: An RT viewer (Climb Medical Systems) was installed into the inhouse hospital information system to provide education regarding radiation treatment planning to medical staff members (dentists and nurses) by medical physicists. RESULTS: Patients can undertake appropriate oral care before radiotherapy, and this intervention has potential for reducing the radiation-related side effect. CONCLUSION: Education regarding radiation treatment planning by medical physicists using the RT viewer could improve the knowledge of medical staffs regarding the predictors of radiation-induced side effects for. By introducing the appropriate intervention of oral care before radiotherapy, it may be feasible to maintain patients' QOL.

Effects of Prophylaxis with Oral Supportive Care for Peri-implantitis in Patients Undergoing Malignancy Chemotherapy.

PURPOSE: Dental implants without proper maintenance may lead to serious consequences, such as peri-implantitis. Peri-implantitis in patients undergoing antitumour chemotherapy can negatively affect the prognosis of treatment. The purpose of this study was to examine the association between the onset of peri-implantitis and the effects of oral hygiene management in patients with dental implants undergoing antitumour chemotherapy. MATERIALS AND METHODS: Twenty-three patients (n = 23) with dental implants who received oral supportive care during malignancy chemotherapy were included. They were categorised into two groups based on the presence of peri-implantitis and were analysed for oral hygiene conditions, maintenance after implant insertion, and adverse effects such as febrile neutropenia. Statistical analysis was performed using the Fisher's exact test and the Mann-Whitney U-test, with p < 0.05 considered statistically significant. RESULTS: The average number of implants was higher in patients with peri-implantitis; these implants generally did not receive appropriate maintenance. There were statistically significantly fewer peri-implantitis sites in patients receiving continuous implant maintenance therapy than those who did not (p < 0.05). The severity of febrile neutropenia was reduced by dental interventions. CONCLUSION: Dental intervention before malignancy chemotherapy effectively prevented peri-implantitis and contributed to alleviating febrile neutropenia, even when it was initiated amidst chemotherapy. Dental intervention before chemotherapy seems essential in malignancy patients with dental implants.

[A CASE OF PERSISTENT RETROPERITONEAL ABSCESS CAUSED BY RESIDUAL SILK SUTURE AFTER SURGERY].

A 61-years-old male with left renal cancer and ipsilateral adrenal tumor had carried out partial nephrectomy and adrenalectomy via open retroperitoneal approach. Fourteen days after surgery, febrile reaction occurred and CT revealed an abscess developed in the retroperitoneal space. Open drainage and lavage of retroperitoneal space had performed, and irrigation of drainage tract had been continued for persistent flow of purulent discharge from abscess touching upper pole of the kidney for about 4 months. After 127 days of second surgery, two clusters of silk suture were sucked out during irrigation. Soon after the episode, flood of purulent discharge from drainage tract was ceased and retroperitoneal abscess was diminished drastically. It should be in mind that the foreign boy like silk suture used during surgery would cause persistent retroperitoneal abscess.

Antiresorptive agent-related osteonecrosis of the jaw in prostate cancer patients with bone metastasis treated with bone-modifying agents.

INTRODUCTION: The incidence rate and risk factors of antiresorptive agent-related osteonecrosis of the jaw (ARONJ) in prostate cancer patients with bone metastasis are not clear. MATERIALS AND METHODS: We retrospectively reviewed patients' records of prostate cancer patients with bone metastasis who were treated with zoledronic acid or denosumab between 1/Dec/2008 and 31/Mar/2019. ARONJ-free survival rate was analyzed with Kaplan-Meier analysis, and risk factors for ARONJ were analyzed with Cox proportional hazard model. RESULTS: We identified 124 and 67 patients treated with zoledronic acid and denosumab, respectively. Seventy-six patients were hormone sensitive, and 115 patients were castration resistant when they started bone-modifying agents (BMA). Twenty-eight patients developed ARONJ during the observation period (median: 23 months, range 1-130 months). Their number of doses of BMA ranged 3-69 (median: 21.5). The 2-year ARONJ-free survival rate was 91.1%, and the 5-year ARONJ-free survival rate was 72.5%. There was no significant difference in the incidence rate of ARONJ between zoledronic acid and denosumab. However, multivariate analysis revealed that use of denosumab (hazard ratio [HR] 3.67, 95% confidence interval [CI] 1.01-13.31; p = 0.0484), serum calcium < 9.2 mg/dL (HR 3.16, 95% CI 1.10-9.13; p = 0.033)), and concomitant or prior use of chemotherapeutic agents (HR 4.71, 95% CI 1.51-14.71; p = 0.0076) were independent risk factors for the development of ARONJ. CONCLUSION: Almost one-quarter of patients had a risk of developing ARONJ within 5 years after starting BMA. Low serum calcium, use of chemotherapeutic agents, and use of denosumab might contribute to the development of ARONJ.

Impact of physician-pharmacist collaborative protocol-based pharmacotherapy management for HIV outpatients: a retrospective cohort study.

BACKGROUND: Effective treatment for human immunodeficiency virus (HIV) infection requires close cooperation among healthcare professionals. This is because maintaining continuity with treatment regimens is important in anti-HIV therapy. In addition, explaining medication use is more important than that for other diseases. Since 2010, pharmacists at the Mie University Hospital have been interviewing patients, selecting drugs, and formulating medication plans for HIV-positive patients. In August 2011, we established the physician and pharmacist-led collaborative Protocol-based Pharmacotherapy Management (PBPM) to increase the efficacy and safety of treatment, while reducing the burden on physicians. In the present study, we evaluated the outcomes associated with PBPM for HIV pharmacotherapy. METHODS: We prepared protocols for drug selection, timing of interventions, and methods of intervention according to various guidelines. This study included 40 HIV-positive patients receiving outpatient care between January 2009 and February 2017. Of these patients, 17 received treatment before implementing PBPM and 23 patients received treatment afterward. We compared the intervention parameters between before and after the implementation of PBPM. RESULTS: The proportion of patients receiving prescription proposals from pharmacists was markedly higher after introducing PBPM (6 out of 17 patients vs. 23 out of 23 patients). All prescription proposals were accepted by physicians before and after PBPM. The number of interviews before antiretroviral therapy (ART) initiation (median [range]) decreased from 2 [1-5] to 1 [1-3] after PBPM introduction, suggesting the time to introduction of treatment has been shortened. Before the introduction of PBPM, nine patients required a change in their ART prescriptions and four patients were hospitalized (one patient was hospitalized due to an error in the self-administration of anti-HIV medicines, two patients were hospitalized due to interruptions in medication, and one patient was hospitalized for the treatment of other diseases). Only one patient was hospitalized after PBPM, and was unrelated to drug adherence. The proportion of patients with a reduced HIV-RNA load increased from 71 to 100%. Furthermore, the proportion of patients who maintained levels below the limit of quantitation increased from 59 to 91% after implementing PBPM. CONCLUSION: The implementation of PBPM for HIV outpatients improves the efficacy and safety of HIV pharmacotherapy.

Oral cavity cancer incidence rates in Osaka, Japan between 2000 and 2014.

BACKGROUND: We investigated trends in oral cavity cancer incidence from 2000 to 2014 in Osaka, Japan. METHODS: Using Osaka Cancer Registry (OCR) data, oral cavity cancer incidence number and age-standardized incidence rates were calculated according to three 5-year-time-periods: 2000-2004, 2005-2009 and 2010-2014. We calculated the distribution of clinical stage for each 5-year period and the proportion of oral cavity cancer among all cancers. RESULTS: A total of 6,086 oral cavity cancers were registered in OCR in 2000-2014. Across the period, between 55.6% and 65.0% were 65 years+ and approximately 60% were men. Tongue cancer accounted for 30.4% to 43.8% of the registrations, while gum accounted for 30.7% to 34.7%. 36.3% to 37.3% were regional, while 1.8% to 2.8% were distant. The age-standardized incidence rate of oral cavity cancer increased from 2.1/100,000 in 2000 to 3.8/100,000 in 2014, although the proportion of oral cavity cancer among all cancers only increased slightly from 0.71% in 2000 to 0.92% in 2014. Proportion of localized stage cancer was 60.8%-67.5% for tongue and 31.0%-49.5% for gum or floor of mouth. Proportion of distant stage cancer was 0.3%-1.0% for tongue and 2.5%-4.2% for gum or floor of mouth. CONCLUSIONS: Age-standardized incidence rate of oral cavity cancer increased, but was not higher than other countries. The proportion of localized stage tongue cancer was higher, while that of distant stage cancer was lower than other sites. Tongue cancer might be easier to detect in its earlier stages than other sites.

The prevalence of human papillomavirus in oral premalignant lesions and squamous cell carcinoma in comparison to cervical lesions used as a positive control.

BACKGROUND: Previous reports concerning the prevalence of human papillomavirus (HPV) in oral squamous cell carcinoma (OSCC) have observed varied results. The aim of this study was to evaluate the prevalence of HPV in oral premalignant lesions (OPL) and OSCC. For accurate HPV detection in oral lesions, comparative analysis was performed on cervical lesions as positive controls. METHODS: Fifty-seven cases with OPL and 50 with OSCC were selected. Twenty-nine control cases were selected from cervical lesions. The HPV infection rate was analysed by consensus polymerase chain reaction (PCR) using the My09/My11 and Gp5+/Gp6+ primers, and genotyping detection was employed using a PCR-based micro-array. Immunohistochemical staining for p16(INK4a) was performed. RESULTS: Twenty-eight (96.6%) cases of cervical lesions were positive for HPV by consensus PCR and 24 cases (82.8%) were positive by genotyping. The total HPV-positive rate in cervical lesions was 96.6%. HPV-DNA was detected in nine cases (15.8%) of OPL and six cases (12.0%) of OSCC by consensus PCR. Six cases (10.5%) of OPL and three cases (6.0%) of OSCC were positive by genotyping. The total HPV-positive rate in oral lesions was 22.4% (26.3% of OPL and 18.0% of OSCC). In cervical lesions, immunohistochemistry of p16(INK4a) identified 27 cases (93.1%) as positive. Fifteen cases (26.3%) of OPL and eight cases (16.0%) of OSCC were positive for p16(INK4a). CONCLUSIONS: The HPV infection and p16(INK4a)-positive rates in oral lesions are lower than previously reported. This suggests that HPV may not play a major role in oral lesions although its involvement cannot completely be ruled out.

Drug interaction between itraconazole and bortezomib: exacerbation of peripheral neuropathy and thrombocytopenia induced by bortezomib.

STUDY OBJECTIVE: To investigate whether a drug interaction exists between bortezomib and the cytochrome P450 (CYP) 3A4 inhibitor itraconazole and/or the CYP2C19 inhibitor lansoprazole that results in increased severity of bortezomib-induced peripheral neuropathy and thrombocytopenia. DESIGN: Retrospective medical record review. SETTING: Hematology-oncology ward of a university-affiliated hospital in Japan. PATIENTS: Six adults with relapsed multiple myeloma who received intravenous bortezomib plus oral dexamethasone as the first course of a 21-day cycle between July 2007 and December 2008. Four of the six patients were treated concomitantly with itraconazole or lansoprazole: two with itraconazole, one with lansoprazole, and one with both itraconazole and lansoprazole. MEASUREMENTS AND MAIN RESULTS: Using the National Cancer Institute's Common Terminology Criteria for Adverse Events, we identified the presence and graded the severity of peripheral neuropathy and thrombocytopenia before and during each patient's first 21-day course of bortezomib plus dexamethasone therapy. All three patients who received itraconazole experienced new or worsening peripheral neuropathy; they also experienced grade 4 thrombocytopenia. The patient who received lansoprazole alone, as well as the two patients who did not receive itraconazole or lansoprazole, had no changes in either adverse effect. We also evaluated the relationship between peripheral neuropathy and bortezomib plus dexamethasone therapy by using the Naranjo adverse drug reaction probability scale, and a probable relationship was found. We further assessed whether a drug interaction between bortezomib and itraconazole and/or lansoprazole had occurred involving the CYP3A4 and/or the CYP2C19 pathways, respectively-resulting in increased severity of the bortezomib-induced peripheral neuropathy and thrombocytopenia-by using the Horn drug interaction probability scale. We found that the occurrence of this drug interaction was strongly supported. CONCLUSIONS: Itraconazole appears to exacerbate peripheral neuropathy and thrombocytopenia induced by bortezomib; however, the mechanism of this drug interaction is unknown. Clinicians should closely monitor for bortezomib-induced adverse effects when itraconazole, or any other potent CYP3A4 inhibitor, is administered concomitantly with bortezomib.

Rotational movement of the anterior maxillary segment by hybrid distractor in patients with cleft lip and palate.

OBJECTIVE: Maxillary anterior segmental distraction osteogenesis (MASDO) is an effective surgical orthodontic treatment for the retruded maxilla in cleft lip and palate because of its benefit of the conservation of velopharyngeal function. Some reports showed MASDO using various devices, but they do not allow the rotational movement of the distracted anterior segment. In this article, we showed MASDO using hybrid distracters (DynaForm System: Stryker Osteosymthesis, Leibinger Micro Implants, Kalamazoo, MI), which allow the advance of the distracted segment with rotational movement. METHOD: The hybrid distractor with 4 metal arms is secured beyond both alveolar osteotomy lines on each side. These 2 distractors permit rotational movement of the segment by controlling the amount of advancement on each side. RESULTS: For 6 patients with cleft lip and palate, MASDO using hybrid distractors was performed and the anterior segment moved at planned positions without any complications except lip discomfort, which disappeared after removal of the distractor. CONCLUSION: MASDO, using an institutionally diagnosed hybrid distractor can successfully achieve the necessary rotational movements of the anterior maxillary segment owing to its design, which incorporates some mechanical flexibility.

Postmortem computed tomography is an informative approach for prevention of sudden unexpected natural death in the elderly.

INTRODUCTION: Less than 10% of unnatural death cases have been examined by autopsy in Japan. In particular, the causes of death in the elderly have not yet been actively investigated. Here, we evaluated the possible use of postmortem computed tomography (PMCT) to investigate the causes of sudden unexpected natural death (SUND) in the elderly. METHODS AND SUBJECTS: Death cases confirmed within 24 hours since the onset of symptoms at the Emergency Department of Mie University Hospital were defined as sudden death cases. A total of 212 sudden death cases, including 175 SUND cases, that occurred in a 3-year period from September 2006 to August 2009 were investigated. RESULTS AND DISCUSSION: The number of sudden death cases was highest in patients in their seventies (56 cases, 26%), followed by patients in their eighties and sixties. Sudden death occurred more in men than in women in their fifties to seventies, while it occurred more in women than in men over the age of 90. PMCT was performed in more than 80% of SUND cases regardless of age of the deceased. The causes in 26 cases (27.1%) were established by PMCT, many of which were hemorrhagic diseases. Signs of aortic aneurysm rupture were detected by PMCT in the thoracic and abdominal areas of 8 patients in their seventies and over, whereas signs were absent in the younger group. Also, more than 18% of sudden death cases in patients in their seventies and over were bathing-related sudden death (BRSD). BRSD was rarely caused by hemorrhagic diseases, suggesting that a drop in blood pressure caused by bathing is an important factor in BRSD. CONCLUSION: PMCT is a method that is relatively acceptable by bereaved families. It is useful for establishing the causes of approximately 30% of the SUND cases examined. The PMCT findings suggested that early detection and treatment of thoracic and abdominal aortic aneurysms and preventive measurements of bathing-related drop in blood pressure are important for the prevention of SUND in the elderly.

[Severe advanced lower gingival carcinoma effectively reduced by chemoradiation with S-1--report of a case].

Severe advanced head and neck carcinoma which can not be removed via surgical procedure combined with a large lymph node metastasis has a poor prognosis. We administered concurrent chemoradiotherapy with S-1 for a lower gingival carcinoma. As a direct result, we discovered that the treatment greatly reduced the size of tumor, and we consider that this treatment prolonged the patient.s life. The treatment results suggest that the so-called dormancy state of the tumor was continued. In this case study, radiotherapy with S-1 showed a highly effective response from the viewpoint of QOL improvement.