Introduction: We report a case of intractable nausea due to zoledronic acid-refractory hypercalcemia for which the nausea was alleviated with denosumab, thereby improving quality of life. Case: A 54-year-old woman presented with metastatic renal pelvis cancer. Elevation of serum calcium level and nausea were noted. After multiple antiemetics were administered with no appreciable symptomatic improvement, treatment with zoledronic acid resulted in a decrease in the calcium level and an improvement of nausea from Japanese version Support Team Assessment Schedule （STAS-J） 3 to 1. After the third dose of zoledronic acid, the corrected calcium level was 11.8 mg/dl, indicating refractory. Because no improvement in nausea was noted, treatment with denosumab was initiated. After the treatment, the calcium level decreased to 9.4 mg/dl, and nausea improved from STAS-J 4 to 0. The patient could spend good time with her family, albeit for a short time, and no progression of the symptoms or adverse events due to denosumab occurred until her death. Discussion: Denosumab appears to be useful for improvement of intractable nausea in zoledronic acid-refractory hypercalcemia.

Dermal ulcers related to infiltration of advanced cancer often release destruction-associated effluvia (cancerous malodor). We encountered a patient in whom metronidazole (MTZ) was effective for cancerous malodor at the dermal ulcer site related to pleural metastasis, involving the thoracic wall, from gastric cancer. The patient was a male in his 60's. As left subphrenic abscess associated with suture failure at the anastomotic site after surgery for gastric cancer led to pyothorax via the transdiaphragmatic route, a thoracic drain was inserted. Furthermore, bilateral pulmonary metastases and pleural dissemination were detected. Subsequently, the metastatic pleural focus infiltrated the thoracic wall via the space between the thoracic drain and chest wall. Its destruction resulted in fetid ulcer formation. The application of MTZ ointment relieved cancerous malodor. In addition to assessment using an odorimeter, the patient's subjective evaluation-based score confirmed the efficacy of this agent. Palliat Care Res 2009; 4(2): 339-345

Introduction: The use of methadone in Japan is limited to cases being switched from the preceding use of strong opioids; the stop-and-go strategy is recommended in which the previously used opioid analgesic is discontinued and methadone is initiated at its full estimated dosage. Case: Refractory cancer pain due to an iliolumbar syndrome was temporarily exacerbated by the stop-and-go switching to methadone from morphine along with ketamine. Pain relief was achieved upon readministration and concomitant use of morphine with methadone after approximately two weeks. Discussion: Through examining this case, we believe that a stepwise switching strategy, rather than the stop-and-go strategy, could be more useful. Considering that overdosage may cause side effects, it is safer to initiate methadone with a small dose. However, more studies need to be conducted to decide whether the establishment of the initial dosage and dosage adjustment should be made more flexible to avoid pain intensification. Further investigation is required on whether the concomitant use of adjuvant analgesics such as ketamine, which similar to methadone is an NMDA receptor antagonist, should be continued when switching to methadone.

Continuous subcutaneous injections of medication are effective in controlling symptoms of the terminal stage of cancer. Chlorpromazine and levomepromazine occasionally cause skin irritation. We examined all patients who underwent continuous subcutaneous administration of psychotropic drugs (chlorpromazine, levomepromazine, midazolam) at the palliative care unit of our hospital from April 2010 to March 2013, the frequency of adverse skin reactions of Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade 3 or above. Of the 603 hospitalized patients, 389 (64.5%) underwent continuous subcutaneous administration of one of the three drugs. The frequency of grade 3 or above (ulceration or necrosis) adverse skin reactions was 4 out of 345 chlorpromazine cases (1.2%; 95% CI: 0.0-2.3%), 2 out of 90 levomepromazine cases (2.2%; 95% CI: −0.8-5.2%), and 0 out of 210 midazolam cases (0.0%; 95% CI: 0.0-0.0%). The frequency of serious adverse skin reactions caused by continuous subcutaneous administration of psychotropic drugs was low, suggesting that this treatment is relatively safe for the skin.

Vitamin D (VD) exerts a wide variety of biological actions in addition to its well-known roles in calcium homeostasis. Nutritional VD deficiency induces rachitic abnormalities in growing children and osteomalacia in adults, and it has been proposed to underlie the onset and development of multiple non-communicable chronic diseases. Therefore, the administration of VD or synthetic VD analogues represents a promising therapeutic strategy; indeed, VD and a VD agonist have shown clinical promise in mitigating osteoporosis and symptoms of insufficient calcium intake. However, even though high doses of VD analogues have shown pre-clinical efficacy against several diseases, including cancers, they have not yet had wide-spread clinical success. This difference may be due to limitation of clinical doses in light of the inherent calcemic action of VD. An approach to overcome this problem involves the development of VD analogues with lower calcemic activity, which could be administered in high doses to attenuate the onset and progress of disease. In a similar strategy, selective estrogen receptor modulators have had success as anti-osteoporosis drugs, and they have shown benefit for other estrogen target organs by serving as partial antagonists or agonists of estrogen receptor α. It is thus conceivable to generate synthetic partial antagonists or agonists for the VD receptor (VDR) that would exert beneficial effects on bone and other VD target organs. In this review, we discuss the molecular basis of the development of such synthetic VDR ligands from the viewpoint of roles of VDR in gene regulation.

Four-channel aortic dissection is quite rare, and is a highly life-threatening situation predisposing to aortic rupture. We report the case of a 70-year-old woman with non-Marfan syndrome. She was evaluated at our hospital for the diagnosis of another disease. She had no symptoms. Enhanced CT revealed an ascending aortic aneurysm, 68 mm in diameter with four-channel dissection. Because of the high risk of rupture, we performed ascending aortic replacement under deep hypothermia. The cardio-pulmonary bypass (CPB) was not discontinued due to right ventricle failure. Coronary arterial bypass grafting (CABG) to the right coronary artery using the great saphenous vein was added. Even after additional CABG, CPB was not discontinued. The surgery finished under percutaneous cardiopulmonary support (PCPS). PCPS was removed on the third postoperative day. Her postoperative course was uneventful, and she was discharged without any abnormal condition. Four-channel aortic dissection has a high risk of rupture, suggesting the need for early surgical treatment.

Tracheo-Innominate artery fistula is a rare but devastating complication after tracheostomy. We report a 17-year old man who underwent the transection of the innominate artery and tracheal patch closure (under partial sternotomy) after the endovascular covered stent placement for the recurrent tracheo-innominate artery fistula. Fortunately, his postoperative course was uneventful without any new neurological, bleeding, or infective complication 34 months after the surgery.

Objective: The purposes of this trial were to demonstrate the feasibility and effectiveness of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients in the phase I/II prospective clinical trial. Methods: Patients with FIGO stage IB2-IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by magnetic resonance imaging were eligible for this clinical trial. The protocol therapy included 30–30.6 Gy in 15–17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of HBT and pelvic radiotherapy with a central shield up to 50–50.4 Gy in 25–28 fractions. The primary endpoint of phase II part was 2-year pelvic progression-free survival (PPFS) rate higher than historical control of 64%. Results: Between October 2015 and October 2019, 73 patients were enrolled in the initial registration and 52 patients proceeded to the secondary registration. With the median follow-up period of 37.3 months (range, 13.9–52.9 months), the 2- PPFS was 80.7% (90% confidence interval [CI]=69.7%–88%). Because the lower range of 90% CI of 2-year PPFS was 69.7%, which was higher than the historical control ICBT data of 64%, therefore, the primary endpoint of this study was met. Conclusion The effectiveness of HBT were demonstrated by a prospective clinical study. Because the dose goal determined in the protocol was lower than 85 Gy, there is room in improvement for local control. A higher dose might have been needed for tumors with poor responses.

BACKGROUND: Age-related low-grade inflammation causing endothelial disruption influences sarcopenia, hypertension, and atherosclerosis. We reported previously that maintenance of muscle strength in elderly hypertensive men with high platelet levels is positively associated with subclinical atherosclerosis but not in those with low platelet levels. Since reduced tongue pressure is related to sarcopenia, tongue pressure may be associated with subclinical carotid atherosclerosis in hypertensive elderly subjects, and platelet levels may function as an indicator of the association between tongue pressure and subclinical carotid atherosclerosis. METHODS: We conducted a cross-sectional study of 342 hypertensive elderly Japanese men aged 60-89 who participated in an annual health check-up in 2015 and 2016. Subclinical carotid atherosclerosis was defined as a common carotid intima-media thickness (CIMT) of 1.1 mm or more. RESULTS: In the overall study population, 171 subjects demonstrated low platelets (< 21.4 × 10/μL). Tongue pressure was significantly inversely associated with subclinical carotid atherosclerosis in these subjects, but not in subjects with high platelets. The known cardiovascular risk factor adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of subclinical carotid atherosclerosis for a 1 standard deviation (SD) increment in tongue pressure (10.4 kPa) were 0.54 (0.35, 0.85) and 1.31 (0.87, 1.96), respectively. CONCLUSION Tongue pressure is inversely associated with subclinical carotid atherosclerosis in hypertensive elderly men with low platelet levels, but not in those with high levels. This finding may thus constitute an efficient tool for clarifying the background mechanism of age-related diseases such as sarcopenia, hypertension, and atherosclerosis.
Aged ; Aged, 80 and over ; Aging ; blood ; physiology ; Carotid Artery Diseases ; blood ; physiopathology ; Carotid Intima-Media Thickness ; Confidence Intervals ; Cross-Sectional Studies ; Humans ; Hypertension ; blood ; physiopathology ; Japan ; Male ; Middle Aged ; Odds Ratio ; Platelet Count ; Pressure ; Risk Factors ; Tongue ; physiology