The safety and effectiveness of naldemedine for opioid-induced constipation in patients with advanced cancer in real-world palliative care settings: a multicenter prospective observational study.

PURPOSE: In this study, we aimed to evaluate the safety and effectiveness of naldemedine for treating opioid-induced constipation (OIC) in patients with advanced cancer, who are receiving palliative care, and particularly explored its early effects. METHODS: Palliative care teams and inpatient palliative care units across 14 institutions in Japan were included in this multicenter, prospective, observational study. Patients who were newly prescribed a daily oral dose of 0.2 mg naldemedine were enrolled. The spontaneous bowel movement (SBM) within 24 h after the first dose of naldemedine was considered the primary outcome, whereas, the secondary outcomes included weekly changes in SBM frequency and adverse events. RESULTS: A total of 204 patients were enrolled and 184 completed the 7-day study. The average age of the participants (103 males, 101 females) was 63 ± 14 years. The primary cancer was detected in the lungs (23.5%), gastrointestinal tract (13.7%), and urological organs (9.3%). A considerable proportion of patients (34.8%) had ECOG performance status of 3-4. Most patients were undergoing active cancer treatment, however, 40.7% of the patients were receiving the best supportive care. Within 24 h of the first naldemedine dose, 146 patients (71.6%, 95% CI: 65.4-77.8%) experienced SBMs. The weekly SBM counts increased in 62.7% of the participants. The major adverse events included diarrhea and abdominal pain, detected in 17.6% and 5.4% of the patients, respectively. However, no serious adverse events were observed. CONCLUSION: Conclusively, naldemedine is effective and safe for OIC treatments in real-world palliative care settings. TRIAL REGISTRATION NUMBER: UMIN000031381, registered 20/02/2018.

Preoperative Weight Loss Program for Hepatocellular Carcinoma Patients with High Body Mass Index in Hepatectomy.

BACKGROUND: This study aimed to investigate the usefulness of a weight-loss program (WLP) in patients with a high body mass index (BMI) prior to liver resection (Hx) for hepatocellular carcinoma (HCC). METHODS: Among 445 patients with HCC who underwent initial Hx between 2000 and 2020, 19 with a high BMI (≥25.0) were enrolled in our WLP since 2014. For calorie restriction, the amount of energy consumed was calculated as the standard body weight (SBW) kg × 20-25 kcal/day. Protein mass was calculated as SBW kg × 1.0-1.2 g/day to maintain skeletal muscle mass. Patients also performed both aerobic and resistance exercises. The before-and-after changes were compared, and the effect of WLP on the short- and long-term results was investigated. RESULTS: The average length of WLP was 21 days, and weight loss was successfully achieved in all patients. Body fat mass was reduced during the program, while skeletal muscle mass was maintained. WLP led to improvements in liver function and fibrotic markers, without tumor progression. There were no postoperative complications (≥Clavien-Dindo [CD] III). A retrospective comparison between with and without WLP using propensity score-matching analysis revealed that WLP group showed better NLR value, however, there were no significant differences in both short and long-term outcomes after Hx based on participation in the WLP. CONCLUSIONS: WLP with multidisciplinary intervention improved immune-nutrition status and liver function of obese patients. WLP had not affected both short and long-term outcomes after Hx.

Palliative care unit treatment and care for a terminal breast cancer patient with untreated obsessive-compulsive disorder.

OBJECTIVES: Although palliative care units treat patients with various comorbidities, there are no reports of patients with obsessive-compulsive disorder (OCD). METHODS: The treatment and care of a breast cancer patient with OCD are presented. RESULTS: A woman in her 40s was admitted to the palliative care unit for terminal breast cancer. She spent most of the day cleaning the bath and bed areas, ignoring efforts to restrain her actions by the staff. After being diagnosed with OCD, the above symptoms improved through the coordinated action of the staff and medication. SIGNIFICANCE OF RESULTS: This is the first report of the diagnosis and treatment of a patient with OCD in a palliative care unit. Early psychiatric diagnosis and subsequent staff response contributed to improvement in the patient's quality of life.

Single-cell DNA and RNA sequencing reveals the dynamics of intra-tumor heterogeneity in a colorectal cancer model.

BACKGROUND: Intra-tumor heterogeneity (ITH) encompasses cellular differences in tumors and is related to clinical outcomes such as drug resistance. However, little is known about the dynamics of ITH, owing to the lack of time-series analysis at the single-cell level. Mouse models that recapitulate cancer development are useful for controlled serial time sampling. RESULTS: We performed single-cell exome and transcriptome sequencing of 200 cells to investigate how ITH is generated in a mouse colorectal cancer model. In the model, a single normal intestinal cell is grown into organoids that mimic the intestinal crypt structure. Upon RNAi-mediated downregulation of a tumor suppressor gene APC, the transduced organoids were serially transplanted into mice to allow exposure to in vivo microenvironments, which play relevant roles in cancer development. The ITH of the transcriptome increased after the transplantation, while that of the exome decreased. Mutations generated during organoid culture did not greatly change at the bulk-cell level upon the transplantation. The RNA ITH increase was due to the emergence of new transcriptional subpopulations. In contrast to the initial cells expressing mesenchymal-marker genes, new subpopulations repressed these genes after the transplantation. Analyses of colorectal cancer data from The Cancer Genome Atlas revealed a high proportion of metastatic cases in human subjects with expression patterns similar to the new cell subpopulations in mouse. These results suggest that the birth of transcriptional subpopulations may be a key for adaptation to drastic micro-environmental changes when cancer cells have sufficient genetic alterations at later tumor stages. CONCLUSIONS: This study revealed an evolutionary dynamics of single-cell RNA and DNA heterogeneity in tumor progression, giving insights into the mesenchymal-epithelial transformation of tumor cells at metastasis in colorectal cancer.

Efficacy of sedation with dexmedetomidine plus propofol during esophageal endoscopic submucosal dissection.

BACKGROUND AND AIM: During endoscopic submucosal dissection for superficial esophageal cancer, patient body movement can sometimes occur, which may cause discontinuation of the procedure. Propofol and dexmedetomidine have recently been found to be useful sedatives for endoscopic submucosal dissection. This study investigated whether sedation using propofol plus dexmedetomidine can suppress the patient's body movements during esophageal endoscopic submucosal dissection and compared this combination with sedation using propofol alone. METHODS: This was a prospective double-blind randomized controlled trial. Patients with superficial esophageal cancers who underwent esophageal endoscopic submucosal dissection at Yokohama City University Hospital were prospectively enrolled and were randomly assigned to the propofol and the propofol plus dexmedetomidine groups. The primary endpoint was the incidence of restlessness. The secondary endpoints were the satisfaction score, maintenance dose of propofol, and number of rescue propofol injections. RESULTS: Sixty-six patients (propofol group: n = 33; combination group: n = 33) were included. The combination group had a significantly lower incidence of restlessness than the propofol group (3.0% vs 27.3%, P = 0.02). In the combination group, the satisfaction scores of the endoscopists were significantly higher, the maintenance dose of propofol was significantly lower, and the number of rescue propofol injections was lower than those in the propofol group (3.0% vs 18.2%, P < 0.001). Although the incidence of bradycardia was significantly higher in the combination group (30.3% vs 3.0%, P < 0.01), no serious adverse effects occurred. CONCLUSION: The propofol plus dexmedetomidine combination provided excellent sedation that effectively suppressed the patient's body movements during esophageal endoscopic submucosal dissection.

Relationship between Stool Form and Quality of Life in Patients with Chronic Constipation: An Internet Questionnaire Survey.

INTRODUCTION: Chronic constipation (CC) is a highly prevalent functional bowel disorder with low treatment satisfaction and impaired quality of life (QOL). However, physicians tend to emphasize only "stool frequency," and relationship between "stool form" and QOL remains unclear. In this study, we aimed to investigate the actual situation of CC treatment in Japan and elucidate the relationship between stool form and QOL in patients with CC. METHODS: We conducted an online questionnaire survey in September 2018 targeting Japanese adult patients already diagnosed with CC and taking prescribed drugs. Assessments included the type of drug treatment, treatment duration, frequency of drug use, frequency of bowel movements (BMs), Bristol Stool Form Scale (BSFS), and Japanese version of the Patient Assessment of Constipation QOL (PAC-QOL) scores. Relationship between BSFS and Japanese PAC-QOL scores was analyzed, and most important factor that influences QOL was investigated. RESULTS: A total of 614 subjects were enrolled. Of these, 398 (64.8%) regularly used magnesium oxide and 162 (26.4%) used stimulant laxative, especially 81 (50.0%) used stimulant laxative "everyday." Mean score of the PAC-QOL was 1.29 ± 0.74, and the lowest score (highest QOL) of 0.94 ± 0.61 was observed in BSFS type 4. Significant difference was seen between BSFS type 4 and all the other types except type 7. Multivariate analysis revealed that normal stool form (BSFS type 4) and BMs ≥3/week are strongly related to decreases of PAC-COL score. In BSFS types 6 and 7, 36% of individuals experienced self-discontinuation of prescribed drugs and 53% self-reduced drug intake because of excessive effects. CONCLUSIONS: Stool form and frequency of BMs are relevant to QOL, especially normal stool form (BSFS type 4) is important for improving the QOL in patients with constipation. Physicians should focus on "stool form" and reconsider the prescription especially in BSFS types 6-7 patients.

Organoid-based ex vivo reconstitution of Kras-driven pancreatic ductal carcinogenesis.

The organoid culture technique has been recently applied to modeling carcinogenesis in several organs. To further explore its potential and gain novel insights into tumorigenesis, we here investigated whether pancreatic ductal adenocarcinoma (PDA) could be generated as subcutaneous tumors in immunocompromised nude mice, by genetic engineering of normal organoids. As expected, acute induction of KrasG12Din vitro occasionally led to development of tiny nodules compatible with early lesions known as pancreatic intraepithelial neoplasia (PanIN). KrasG12D-expressing cells were enriched after inoculation in the subcutis, yet proved rather declined during culture, suggesting that its advantage might depend on surrounding environments. Depletion of growth factors or concurrent Trp53 deletion resulted in its robust enrichment, invariably leading to development of PanIN or large high-grade adenocarcinoma, respectively, consistent with in vivo mouse studies for the same genotype. Progression from PanIN was also recapitulated by subsequent knockdown of common tumor suppressors, whereas the impact of Tgfbr2 deletion was only partially recapitulated, illustrating genotype-dependent requirement of the pancreatic niche for tumorigenesis. Intriguingly, analysis of tumor-derived organoids revealed that KrasG12D-expressing cells with spontaneous deletion of wild-type Kras were positively selected and exhibited an aging-related mutation signature in nude mice, mirroring the pathogenesis of human PDA, and that the sphere-forming potential and orthotopic tumorigenicity in syngenic mice were significantly augmented. These observations highlighted the relevance of the subcutis of nude mice in promoting PDA development despite its ectopic nature. Taken together, pancreatic carcinogenesis could be considerably recapitulated with organoids, which would probably serve as a novel disease model.

The efficacy of a leukotriene receptor antagonist in the treatment of human rectal aberrant crypt foci: a nonrandomized, open-label, controlled trial.

BACKGROUND: Leukotriene receptor antagonists (LTRAs) are broadly used for the management of allergic asthma and have recently been indicated to inhibit carcinogenesis and cancer cell growth. In colorectal cancer (CRC) chemoprevention studies, the occurrence of adenoma or CRC itself is generally set as the trial endpoint. Although the occurrence rate of CRC is the most confident endpoint, it is inappropriate for chemoprevention studies because CRC incidence rate is low in the general population and needed for long-term monitoring. Aberrant crypt foci (ACF), defined as lesions containing crypts that are larger in diameter and darker in methylene blue staining than normal crypts, are regarded to be a fine surrogate biomarker of CRC. Therefore, this prospective study was designed to explore the chemopreventive effect of LTRA on colonic ACF formation and the safety of the medicine in patients scheduled for a poly resection as a pilot trial leading the CRC chemoprevention trial. METHODS: This study is a nonrandomized, open-label, controlled trial in patients with colorectal ACF and polyps scheduled for a polypectomy. Participants meet the inclusion criteria will be recruited, and the number of ACF in the rectum will be counted at the baseline colonoscopic examination. Next, the participants will be assigned to the LTRA or no treatment group. Participants in the LTRA group will continue 10 mg of oral montelukast for 8 weeks, and those in the no treatment group will be observed without the administration of any additional drugs. At the end of the 8-week LTRA intervention period, a polypectomy will be conducted to evaluate the changes in the number of ACF, and cell proliferation in the normal colorectal epithelium will be analyzed. DISCUSSION: This will be the first study to investigate the effect of LTRAs on colorectal ACF formation in humans. TRIAL REGISTRATION: This trial has been registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000029926 . Registered 10 November 2017.

The efficacy of aspirin and metformin combination therapy in patients with rectal aberrant crypt foci: a double-blinded randomized controlled trial.

BACKGROUND: The incidence and mortality rates of colorectal cancer (CRC) continue to increase worldwide. Therefore, new preventive strategies are needed to lower the burden of this disease. Previous studies reported that aspirin could suppress the development of sporadic colorectal adenoma. In addition, metformin is a biguanide derivative that is long widely used for the treatment of diabetes mellitus and has recently been suggested to have a suppressive effect on carcinogenesis and cancer cell growth. Both drugs exhibit a chemopreventive effect, but their efficacy is limited. Aberrant crypt foci (ACF), defined as lesions containing crypts that are larger in diameter and stain more darkly with methylene blue than normal crypts, are more prevalent in patients with cancer and adenomas, and considered a reliable surrogate biomarker of CRC. Thus, we designed a prospective trial as a preliminary study prior to a CRC chemoprevention trial to evaluate the chemopreventive effect of aspirin combined with metformin on colorectal ACF formation in patients scheduled for polypectomy. METHODS: This study is a double-blind randomized controlled trial that will be conducted in patients with both colorectal ACF and colorectal polyps scheduled for polypectomy. Eligible patients will be recruited for the study and the number of ACF in the rectum will be counted at the baseline colonoscopy. Then, the participants will be allocated to one of the following two groups; the aspirin plus placebo group or the aspirin plus metformin group. Patients in the aspirin plus placebo group will receive oral aspirin (100 mg) and placebo for 8 weeks, and those in the aspirin plus metformin group will receive oral aspirin (100 mg) and metformin (250 mg) for 8 weeks. After 8 weeks of administration, polypectomy will be performed to evaluate changes in the number of ACF, and the cell-proliferative activity in the normal colorectal mucosa and colorectal polyps. DISCUSSION: This is the first study proposed that will explore the effect of aspirin combined with metformin on the formation of colorectal ACF in humans. TRIAL REGISTRATION: This trial has been registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000028259 . Registered 17 July 2017.

Long-Term Outcomes of Arthroscopic Debridement With or Without Drilling for Osteochondritis Dissecans of the Capitellum in Adolescent Baseball Players: A ≥10-Year Follow-Up Study.

PURPOSE: To evaluate the long-term clinical outcomes of arthroscopic debridement for capitellar osteochondritis dissecans (OCD) in adolescent baseball players. METHODS: This retrospective study evaluated clinical outcomes of arthroscopic debridement for capitellar OCD in adolescent baseball players seen between 2003 and 2006. Inclusion criteria were at least 10 years of follow-up after surgery. Exclusion criteria were previous elbow surgery and age <12 years or >19 years. Patients were examined for presence of pain, inflammation (effusion), and range of motion. Outcome measures were determined using Timmerman/Andrews scores. Defect severity on preoperative radiographs was classified into 3 grades: small, moderate, and large. Return to baseball, pre- and postoperative range of motion and Timmerman/Andrews elbow score were evaluated according to defect severity. RESULTS: Twenty-three elbows of 23 baseball players (mean age, 14.7 [range, 13-17] years) underwent arthroscopic debridement for capitellar OCD. Mean follow-up duration was 11.5 (range, 10-13) years. Twenty patients (87%) returned to competitive baseball at their preoperative level; of these, 15 were non-pitchers and returned to the same position but only 1 of 5 pitchers returned to playing pitcher. One patient with a large defect and drilling underwent reoperation 11 years after the initial operation. Mean change in extension was 4.3° and that in flexion was 3.7°. Timmerman/Andrews score improved significantly from 160 (95% confidence interval 146.7-173.3) to 195 (95% confidence interval 185.2-204.8) at the most recent follow-up (P ˂ .0001). Osteochondral defects detected on preoperative radiographs were small in 10 patients, moderate in 7, and large in 6. There was no significant between-group difference in extension, flexion, or Timmerman/Andrews score preoperatively or at the most recent follow-up. CONCLUSIONS: Arthroscopic debridement with or without drilling allowed return to play in adolescent baseball players for positions other than pitchers. Long-term outcomes are likely durable regardless of lesion size. LEVEL OF EVIDENCE: Level IV, Case series.

Correlation between playing position, elbow physical findings and elbow pain in elementary school baseball players: Results of a multi-regional study in Japan.

BACKGROUND: Elbow injuries are common in young baseball players and evaluating the characteristics of young baseball players in a large-scale population is necessary. However, few studies have compared playing position, length of baseball experience, physical findings, and elbow pain in young baseball players. This retrospective multi-regional cohort study sought to document the physical findings at the elbow in Japanese elementary school baseball players and to examine the relationship between playing position, length of baseball experience, physical findings at the elbow, and elbow pain. METHODS: In 2014, 720 fifth-grade baseball players from four regions in Japan were invited to participate in a questionnaire survey and undergo physical examination to obtain data on position played, length of baseball experience, presence of elbow pain, and physical findings at the elbow, including range of motion, tenderness, and valgus stress test results. Potential risk factors associated with elbow pain and correlations between physical findings and playing position, length of baseball experience, and elbow pain were investigated. RESULTS: The 720 subjects had a mean age of 10.4 years and 29.4% reported having experienced elbow pain for ≥1 week. Risk factors for elbow pain included playing pitcher and catcher, playing pitcher and fielder, and length of baseball experience. The most frequent finding was limitation of flexion (21.1%) followed by tenderness of the medial epicondyle (18.3%) and a positive valgus stress test (14.3%). These three findings were also significantly associated with elbow pain. Elbow extension was limited in 14.9% of subjects but there was no correlation with length of baseball experience or elbow pain. CONCLUSIONS: Our data show that elementary school baseball players who experienced elbow pain are likely to have valgus stress overload. Elbow pain might be prevented by not playing pitcher and catcher.

Factors correlating with recovery of quadriceps strength after double-bundle anterior cruciate ligament reconstruction with hamstring tendon autografts.

PURPOSE: Recovery of quadriceps strength after anterior cruciate ligament (ACL) reconstruction is one of the criteria used to promote rehabilitation and return to play. The purpose of this study was to investigate the factors associated with recovery of quadriceps strength after ACL reconstruction with hamstring tendon autografts. METHODS: Isokinetic quadriceps strength at 60°/s was measured preoperatively and 6 months after surgery in 101 patients (54 males and 47 females) who underwent double-bundle ACL reconstruction with hamstring tendon autografts. The quadriceps strength index (%) was calculated by normalizing the peak torque of the operated leg with that of the contralateral leg. Details on age, sex, body mass index, time from injury to surgery, pre-injury Tegner activity scale score, previous meniscus repair, and preoperative quadriceps strength index were recorded. The factors associated with the postoperative quadriceps strength index were investigated in univariate and multivariate regression analyses. RESULTS: Multivariate regression analysis showed that preoperative quadriceps strength index (p = 0.001) was independently associated with the quadriceps strength index at 6 months after surgery. There was a marginally significant inverse association between age and postoperative quadriceps strength, but no statistically significant association was found for any of the other factors investigated. CONCLUSIONS: Postoperative quadriceps strength index at 6 months after double-bundle ACL reconstruction with hamstring tendon autografts was affected by preoperative quadriceps strength index. Adequate preoperative quadriceps strength may need to be considered in order to facilitate better recovery of quadriceps strength after ACL reconstruction and to support an earlier return to sports activities.

Kras-driven heterotopic tumor development from hepatobiliary organoids.

Cancers arising from the biliary tract are refractory to conventional therapies, requiring the development of novel therapeutics. However, only a limited number of genetically engineered mouse models have been created, partly because of time-consuming work required. Besides, liver-specific gene manipulation mostly resulted in concurrent development of hepatocellular carcinoma, another type of liver cancer, and gallbladder-restricted gene targeting is still not feasible. Consequently, establishment of cancer type-specific disease modeling remains a technical challenge. To address this issue, we took an alternative cell-based approach to quickly induce tumorigenesis ex vivo. Specifically, murine primary organoids from liver and gallbladder were transduced with lentiviral vectors to reconstitute genetic alterations common in biliary tract cancers, followed by inoculation in immunodeficient mice. Although any single genetic alteration did not induce tumors, mutant Kras and repression of major tumor suppressors cooperated for tumor development within 2 months. Induced lesions varied among normal, dysplastic and papillary lesions to adenocarcinoma, recapitulating multistep tumorigenesis even in a heterotopic situation. We further demonstrated that two putative oncogenes in intrahepatic cholangiocellular carcinoma, mutant Pik3ca and FGFR2-AHCYL1 fusion, were rather modest drivers for liver-derived organoids, probably requiring additional mutations or hepatic niche to robustly induce full-blown tumors. Thus, we showed that cancer cells could be readily generated from primary cells in the biliary tract, at least in cases where genetic factors play dominant roles. Collectively, this study will likely contribute to gaining mechanistic insights into biliary carcinogenesis and providing valuable resources for drug discovery.

Cumulative Incidence of Osteochondritis Dissecans of the Capitellum in Preadolescent Baseball Players.

PURPOSE: To quantify the 1-year cumulative incidence of capitellar osteochondritis dissecans (OCD) in preadolescent baseball players and identify the risk factors associated with this condition. METHODS: In total, 1,275 school-aged baseball players (aged 6-11 years) without an established diagnosis of capitellar OCD were enrolled in this longitudinal, observational study. One year later, all players underwent ultrasonographic examination of the throwing elbow on the playing field. Elbows with abnormal ultrasonographic findings at this time then underwent radiographic examination. Data for the groups with and without capitellar OCD were analyzed using multivariate logistic regression models. RESULTS: The 1-year cumulative incidence of capitellar OCD was 1.8% (95% confidence interval, 1.1%-2.7%). On multivariate analysis, players aged 10 to 11 years were 3.96 times more likely to have capitellar OCD (95% confidence interval, 1.10-18.97) than those aged 6 to 9 years; however, starting baseball at an earlier age, number of years played, training hours per week, player position, and history of elbow pain were not significantly associated with capitellar OCD. Only 34.8% of players with capitellar OCD reported elbow pain. CONCLUSIONS: The risk of OCD of the capitellum developing within a 1-year period in preadolescent baseball players was 1.8%. Players aged 10 to 11 years had a significantly greater risk of capitellar OCD development than those aged 6 to 9 years. LEVEL OF EVIDENCE: Level III, local nonrandom sample cohort.

Shoulder and elbow pain in junior high school baseball players: Results of a nationwide survey.

BACKGROUND: Despite proposals and guidelines to prevent baseball injuries in young players by societies and organizations, many shoulder and elbow injuries continue to occur among junior high school baseball players. In order to investigate the training conditions of junior high school baseball players and the risk factors for shoulder and elbow pain in the players, we conducted a questionnaire survey among junior high school baseball players throughout the country. METHODS: The questionnaire survey was conducted among junior high school baseball players in September 2016. RESULTS: A total of 11,134 junior high school baseball players belonging to 495 teams responded to the survey. Among these, 4004 players trained every day of the week and 1151 players played baseball games every month with no off-season. Among 9752 players who did not have shoulder and/or elbow pain in the spring and summer of 2015, 19.2% of players experienced elbow pain over the course of one year, 13.6% of players experienced shoulder pain, and 28.0% complained of shoulder and/or elbow pain. The frequency of elbow pain was more than that of shoulder pain. At risk for shoulder pain were pitchers and catchers and second-year students, while risk factors for elbow pain were playing pitcher and catcher positions, pitching or throwing ≥300 balls per week, playing ≥10 games on average per month and being left-handed. CONCLUSION: Risk factors for shoulder pain were different from those for elbow pain. To prevent elbow pain, coaches should pay attention to pitchers and catchers and left-handed players and not allow players to pitch or throw ≥300 full-power balls per week or participate in ≥10 games per month. They should also pay attention to pitchers and catchers and second-year students to prevent shoulder pain. It is important for coaches to train multiple pitchers and catchers.

[A Case of Malignant Ameloblastoma Associated with Uncontrollable Hypercalcemia].

Approximately 20-30% of cancers are associated with hypercalcemia, and this is a complication often encountered in cancer care. Hypercalcemia causes disorders such as disturbance of consciousness and, in severe cases, kidney failure and even death. In this report, we present a case of malignant ameloblastoma associated with uncontrollable hypercalcemia followed by a life-threatening disease course. In this case, hypercalcemia shortened the period of home care, and the medical staff could have extended this period by acquiring knowledge that leads to early detection and better control of hypercalcemia. In addition, the choice of the place for end-of-life care may have been expanded by considering the treatment of not only the malignant tumor but also hypercalcemia as its complication.

[Are the Medical Staff Ready to Respond to the Suffering from Sexuality of Terminal Cancer Patients ?]

The goal of palliative care is to support the ideal life of cancer patients and their partners, but the medical staff does not listen to all the needs of cancer patients and their partners. Cancer patients choose opponents and situations and express their suffering. Additionally, the typical problem of hidden suffering is not the issues of sexuality ? The suffering from sexuality of cancer patients is not expected to be expressed unless there is a suitable opponent. Are we the medical staff ready to respond to the suffering from sexuality of terminal cancer patients ? In this study, we thought that it was necessary to investigate the preparation of medical staff for the suffering from sexuality of terminal cancer patients, through a relationship with the hospitalized inpatient who reported suffering from sexuality.

[Retrospective Observational Study on Chemical Coping].

Chemical coping also has an idea that it is an early stage of abuse and dependence of opioids, it is important to grasp the frequency, complaints, and risk factors of chemical coping. In this study, observational research was performed backwardly with 549 people using opioids who were newly requested to the palliative care team. Results revealed that 13 of 549 patients (2.4%)were diagnosed with chemical coping. In terms of a breakdown of the complaint, and it was following rate and reasons, 6 people(46%)felt easy, 2 people(15%)were anxious, 2 people(15%)could sleep, 2 people(15%)had unknown reasons, and 1(8%)was calm. Characteristics of each patient diagnosed with chemical coping included frequent psychiatric symptoms such as life expectancy of 3 months, opioid oral administration period of 1 year or more, disease incidence period of 1 year or more, anxiety, delirium, and depression. One benign disease also confirmed the transition to opioid dependence.

Clinical Outcome of Arthroscopic Treatment for Posteromedial Elbow Impingement in Adolescent Baseball Players.

PURPOSE: To evaluate the clinical outcomes of arthroscopic treatment in adolescent baseball players with posteromedial elbow impingement. METHODS: This retrospective study evaluated the clinical outcome of arthroscopic treatment for posteromedial elbow impingement in adolescent baseball players. Patients were eligible for participation if they had undergone surgery at least 2 years earlier and excluded if they had arthritis, loose bodies, osteochondritis dissecans, ulnar collateral ligament tear, flexor/pronator injuries or medial epicondylitis, or nerve problems. Patients were also excluded if they had undergone prior elbow surgery, were younger than 13 years, or were older than 19 years. Arthroscopic treatment included debridement of posteromedial synovitis, fragment removal, and olecranon spur excision. At a mean follow-up of 26.7 (range 24-42) months, patients were evaluated based on a questionnaire, examination, and the previously reported elbow outcome score. RESULTS: This retrospective study involved 15 male patients, comprising 6 pitchers, 3 catchers, and 6 fielders, of mean age 15.7 (range 14-17) years. Mean time from onset of symptoms to surgery was 4.9 (range 3-18) months. Intraoperative findings included posteromedial synovitis and olecranon spurs in all patients and fragments in 10. The elbow outcome score was considered excellent in 11 patients and good in 2, with a mean score of 92 points (maximum 100 points). The mean postoperative range of motion at the elbow was 5° to 139.7° of flexion. All patients were able to return to their previous level of play after an average of 3.4 (range 2.5-4.5) months. No patient developed medial instability that later required reconstructive surgery. CONCLUSIONS: Arthroscopic debridement, excision of the olecranon spur, and removal of fragments yield reliable subjective and objective results and allow a return to baseball in adolescent patients. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

[Combination Therapy of Oxycodone and Tapentadol Was Effective for Intractable Pain Caused by Breast Cancer Bone Metastasis - A Case Report].

A 52-year-old woman had been prescribed oral medication of acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), and oxycodone for intractable pain associated with thoracic metastasis of breast cancer. However, the pain control was poor. Although pregabalin and gabapentin were used as supplementary analgesics, they could not be continued because of their side effects. Based on the noradrenalin reincorporation-inhibiting action of tapentadol, a combination therapy of tapentadol and oxycodone was introduced and satisfactory pain control was achieved. No side effects from the combined opioids were observed. This finding indicates the potential of administrating a combination therapy of m-opioid receptor agonists(such as morphine, oxycodone, and fentanyl)with tapentadol, which has a noradrenaline reincorporation-inhibiting action, as an effective remedy for alleviating intractable pain complicated with neuropathic pain.