Background: Febuxostat is recommended for lowering serum uric acid (sUA) concentration in chronic kidney disease (CKD) patients with hyperuricemia. However, it remains uncertain how febuxostat affects associations between several laboratory variables related to glomerular filtration and renal tubular reabsorption of uric acid. Methods: We retrospectively analyzed the records of 148 patients with CKD and hyperuricemia: 122 were treated with febuxostat, and 26 were not. Clinical and laboratory variables were used to calculate estimated glomerular filtration rate (eGFR), fractional excretion of uric acid (FEUA), and estimated 24-h urinary excretion of uric acid (eEUA). We examined correlations of those variables and compared patients who did and did not receive febuxostat. Results: eGFR and FEUA were significantly inversely regardless of febuxostat-treatment status. eGFR was significantly inversely correlated with sUA in patients who received febuxostat, but not in those who did not. Similarly, there was a significant positive correlation between FEUA and eEUA only in patients treated with febuxostat. Conclusions: FEUA increased as eGFR decreased in our patients. Febuxostat changed correlation patterns for clinical and laboratory variables. Additional administration of uricosuric agents might help further lower sUA by increasing FEUA and eEUA in patients treated with febuxostat.

Background: Anorectal melanoma is a rare disease with a poor prognosis. Symptoms are often nonspecific, which complicates preoperative diagnosis. Here, we describe the establishment of MELS, a new anorectal melanoma cell line derived from resection of a rectal tumor in a 40-year-old Japanese man. Methods: Histological, electron microscopic, and immunohistochemical features of S-100, HMB-45, Melan-A, and NSE positivity of the tumor were typical of surgically resected anorectal melanoma. Results: MELS cells are round or oval and have sharp thorn-like protrusions on some or all cell membranes. The cells form irregular attached colonies with numerous floating cells in two-dimensional culture. Transmission electron microscopy revealed that some MELS cells have cytoplasmic melanosomes. Immunocytochemically, MELS cells and surgical tissues had the same staining pattern. MELS cells had lower growth rates than Caco-2 (a colon adenocarcinoma cell line) and A375 (a cutaneous melanoma cell line) cells. Oxaliplatin and irinotecan were more effective in MELS cells than in Caco-2 and A375 cells. Conclusions: No previous report provided detailed clinical information on an anorectal melanoma cell line. Thus, MELS cells should improve our understanding of the biological characteristics of anorectal melanoma and provide a novel platform for examining the effects of therapies for anorectal melanoma.

Background: Altered metabolism in the blood of cancer patients is closely related to changes in amino acids. Amino acids play an important physiological role as essential metabolites and regulators of metabolism. AminoIndex Cancer Screening (AICS) uses multivariate analysis of plasma-free amino acid profiles to screen for seven cancer types, including breast cancer. Methods: To determine the clinical utility of AICS (breast), we retrospectively analyzed associations of AICS (breast) score with clinical and laboratory variables in 390 patients who underwent AICS (breast) testing. The mean age of participants was 50.7 years (range: 26-87 years) and all were female. Results: The AICS (breast) grade was A, B, and C for 250 (64.1%), 90 (23.1%), and 50 (12.8%) participants, respectively. AICS (breast) was significantly correlated with AICS (gastric) (r = 0.487, p < 0.0001) and AICS (lung) (r = 0.523, p < 0.0001). Multivariate linear regression analysis showed no significant difference of AICS (breast) grade with age, body mass index, estimated glomerular filtration rate, dyslipidemia, or blood pressure. However, neutrophil-to-lymphocyte ratio significantly differed in relation to AICS (breast) grade (cut-off value, 1.7; p = 0.030), although only data from 72 patients were analyzed. Conclusion: To our knowledge, this is the first study to report associations of AICS (breast) grade with clinical variables.

Background: The pedicle sign is a radiographic indicator of spinal metastases. However, it is not only the pedicle sign that is important in radiographic diagnosis of bone metastases. In the present study, the radiological features of symptomatic spinal metastases in patients without the pedicle sign were retrospectively examined. Materials and Methods: Among 186 patients with symptomatic spinal metastases who visited our department between January 1, 2011, and December 31, 2017, 64 without the pedicle sign and with available computed tomography (CT) and magnetic resonance imaging (MRI) data in the first visit were enrolled and their data were analyzed. One author evaluated radiographs for findings suggestive of spinal metastases, CT to assess bone destruction, and MRI to evaluate the extent of lesions. Clinical variables were also examined and compared between patients with and without bone changes on radiography. Results: Bone changes strongly suggesting bone metastasis, other than the pedicle sign, were observed in 31 out of 64 patients: bone cortical disappearance in 20, increased radiolucency of the central area in the vertebral body in 8, an irregular osteoblastic change in 5, and asymmetrical vertebral collapse in 10. An analysis of CT data revealed that intertrabecular, mildly osteolytic, and mildly osteoblastic types were more frequent in patients without any changes suggestive of bone metastases on radiographs. Conclusion: Radiographic findings other than the pedicle sign are useful for diagnosing bone metastases. The key to a radiographic diagnosis of spinal metastases is to pay attention to changes in the bone cortex of all vertebral components on radiographs in addition to the pedicle.

Background: The number of suicides in Japan decreased during the period from 2012 through 2019. Because data on factors associated with this decline are limited, we conducted a retrospective longitudinal study of psychiatric diagnoses of serious suicide attempters before 2012 and after 2019. Methods: Serious suicide attempters admitted to the critical care medicine (CCM) department of Nippon Medical School Hospital between 2006 and 2017 were included and classified as those before and after the suicide decline in 2012. Chi-square test and residual analysis were used to analyze changes in the proportion of suicide attempters among all patients admitted to CCM and to examine differences in the proportion of psychiatric diagnoses. Results: The proportion of suicide attempters among CCM hospitalized patients decreased overall (χ² (1) =18.29, p<.01). The proportion of psychiatric diagnoses changed significantly (χ² (8) =62.21, p<0.001); specifically, it decreased for schizophrenia (residual: −2.28), depressive disorders (residual: −5.39), persistent mood disorders (residual: −3.58), and reaction to stress disorders (residual: −2.73). Depressive disorders decreased and had a large contribution ratio in both sexes. Conclusions: The decrease in the proportion of attempted suicides among patients admitted to CCM was consistent with the decline in suicides in Japan. Analysis by psychiatric diagnosis confirmed a significant decrease in the proportion of suicide attempts associated with depressive disorders, schizophrenia, and reaction to stress disorders, which were the most common disorders associated with attempted suicide. Depressive disorders made the greatest contribution to the reduction in suicide attempts.

Background: Pain after colon cancer surgery can be effectively relieved by transversus abdominis plane (TAP) block. We aimed to determine the optimal dose of dexmedetomidine for preemptive analgesia when combined with TAP block after colon cancer surgery. Methods: A total of 120 patients undergoing laparoscopic resection for colon cancer from March 2018 to October 2019 were randomly assigned to control (group C), low-dose (group L, 0.5 μg/kg), moderate-dose (group M, 1 μg/kg), and high-dose groups (group H, 1.5 μg/kg) (n=30 each). After puncture under ultrasound guidance, the designated dexmedetomidine dose and 0.25% ropivacaine were injected on both sides (20 mL each side). Mean arterial pressure (MAP), heart rate (HR), numeric rating scale (NRS) score, and Ramsay score were compared at 2 h (T0), 4 h (T1), 8 h (T2), 12 h (T3), 24 h (T4), and 48 h (T5) after surgery. The area sensitive to mechanical stimulation-induced pain at the incision was measured at T4, T5, and 72 h after surgery (T6). Adverse reactions were compared. Results: MAP and HR were lower in the dexmedetomidine groups, especially groups M and H, than in group C (P<0.05). NRS scores at T0-T5 and pain-sensitive areas at T4-T6 were lower in the dexmedetomidine groups than in group C (P<0.05), but Ramsay scores were similar (P>0.05). Compared with group L, groups M and H had lower NRS scores and pain-sensitive areas (P<0.05). The incidence rates of adverse reactions were lower in the dexmedetomidine groups than in group C (P<0.05). Conclusions: Dexmedetomidine 1 or 1.5 μg/kg is effective and did not increase adverse reactions. A dose of 1 μg/kg is recommended as an adjuvant to ropivacaine for TAP block.

Background: Few studies have used simulation models to examine long-term improvement in microsurgical technique. We investigated whether improvement in surgical technique could be assessed by continuous, objective, contest-format evaluation of the same microsurgical task. Methods: Since 2014, neurosurgeons with 1-10 years of experience participated in a biannual competition-format test. The task involved creating as many sutures as possible during the 5-minute interval after arteriotomy of a 1-mm artificial vessel. A modified version of the Objective Structured Assessment of Technical Skills examination was created and used. Changes and differences in scores over time were examined for each evaluator. Results: Overall, 103 neurosurgeons participated in the study at least once, and those who participated more than once were divided into two groups: those who had the highest score in each contest and those who had the lowest score. The linear regression equations for the highest and lowest scorers were y=7.62x+81.56 (R²=0.628) and y=1.94x+67.93 (R²=0.0433), respectively. High scorers had high scores from the first time they participated, and their scores tended to increase further, while scores for low scorers tended not to increase with additional experience. Scores for the four evaluators did not significantly differ. Conclusions: Our results suggest that technical improvement in surgery can be assessed by long-term, continuous evaluation of microsurgical technique and that the present evaluation system might help increase surgical safety.

Background: Chemosensitivity tests have long been a widely discussed research topic. Our group performed collagen gel droplet-embedded culture-drug sensitivity testing (CD-DST) of patients with advanced gastric cancer during the period from December 2012 to December 2017. To verify how CD-DST should be used, we invested correlations of sensitivities to cisplatin (CDDP), docetaxel (DOC), paclitaxel (PTX), and CPT11 with clinical outcome. Methods: Patients with advanced gastric cancer underwent gastrectomy with lymph node dissection at Nippon Medical School Tama Nagayama Hospital, and surgical samples were retrospectively examined by CD-DST to assess chemosensitivity. The patients later received adjuvant chemotherapy as standard adjuvant therapy or chemotherapy. The CD-DST test was not performed for S-1 because it is commonly used in chemotherapy for gastric cancer. Although oxaliplatin has also recently become a key drug for advanced gastric cancer, it had not been adopted for gastric cancer in 2012, so CD-DST testing was not performed. The χ² test was used for all statistical analyses. A p-value of <0.05 was assumed to indicate statistical significance. Three-year survival rates were estimated using the Kaplan-Meier method, and the log-rank test was used to compare the obtained curves. Results: Of the tumors from gastric cancer patients, 67.0% (77/115) could be cultured. The rate of sensitivity was 41.1% (30/73) for CDDP, 82.6% (57/69) for DOC, 82.8% (58/70) for PTX, and 49.2% (33/67) for CPT11. CDDP sensitivity and outcome were not correlated in patients who received CDDP. Sensitivities to CDDP, DOC, PTX, and CPT11 were not correlated with any patient characteristic. Patients with poorly differentiated adenocarcinoma tended to be sensitive to CDDP (P=0.051). Conclusions: No difference between CDDP sensitivity or outcome was observed in patients receiving CDDP. The CD-DST showed a high sensitivity to DOC and PTX in the present patients.

Background: Because they suppress cytokine production, corticosteroids are a candidate therapy for coronavirus disease 2019 (COVID-19). However, the effectiveness of corticosteroids is unclear for non-severe COVID-19 that does not require supplemental oxygen. This study investigated the effectiveness of corticosteroid therapy for patients with non-severe COVID-19. Methods: This retrospective observational study analyzed data from 10 patients with non-severe COVID-19 who received corticosteroid therapy at our center between July 1, 2020 and January 31, 2021. Results: The median age of the 10 patients was 60 years, and nine were male. Nine of the 10 patients had multiple comorbid conditions (e.g., hypertension, diabetes, and obesity). Although blood oxygen saturation was maintained above 95%, all patients had persistent fever and deterioration in chest imaging findings, which led to initiation of corticosteroid treatment. The median duration symptom onset to initiation of corticosteroid therapy was 8 days. All patients received dexamethasone 6 mg/day as corticosteroid therapy, and the median period was 7.5 days. After the start of corticosteroid therapy, clinical improvement was rapid in all patients, and no patient developed severe disease. Conclusion: The latest World Health Organization guidance recommends against corticosteroid treatment for patients with non-severe COVID-19. In this report, early administration of corticosteroids during the non-critical phase, when oxygen supplementation was not required, was associated with early improvement and prevention of severe disease in patients with risk factors for severe COVID-19 and worsening clinical symptoms.

Background: In Japan, little is known of the severity of and factors associated with psychological distress among caregivers of patients with advanced or recurrent cancer who die. Methods: This prospective cohort study of cancer patients at the National Cancer Center Hospital East, Japan, and their caregivers followed the participants from the initial palliative care consultation (T1) to 6 months (T2) and 13 months (T3) after the patient's death. At T1, patients and caregivers were interviewed separately. After T1, telephone interviews were conducted periodically, and a mail survey was distributed at T2 and T3. The Patient Health Questionnaire-9 (PHQ-9) was used to assess depression, and the Distress and Impact Thermometer (DIT) was used to screen for psychological distress. Items on end-of-life attitudes, including awareness, discussion, and willingness of cancer care and death, were developed. Results: Thirty-one of 86 eligible pairs participated in this study. The participation rate was low (36%) and enrollment was thus halted. Data were collected up to T3 for 22 pairs (completion rate 71%). PHQ-9 scores at T2 and T3 were higher than at T1, but the difference was not significant (p = 0.07). PHQ-9 score at T3 was significantly associated with caregiver PHQ-9 and distress at T1, with patient distress and impact at T1, and with caregiver health problems at T2. Conclusions: Caregiver depression persisted up to 13 months after the patient's death, which suggests that pre-bereavement screening with the DIT might be useful. The present paired enrollment process requires improvement.

Background: We evaluated the association of prostate volume (PV) with the efficacy and safety of transurethral enucleation with bipolar energy (TUEB) for treatment of benign prostatic hyperplasia (BPH). Methods: We retrospectively evaluated data from 180 patients with symptomatic BPH who underwent TUEB between 2008 and 2015. Efficacy was assessed by perioperative changes in international prostate symptom score (IPSS), Quality of Life Score (QOLS), maximum flow rate on uroflowmetry (Qmax), and serum prostate-specific antigen level (PSA), which were recorded at 3 months postoperatively. Safety was assessed by perioperative incidence of adverse events (AEs). AEs were recorded up to 2 years after surgery. Patients were divided into two groups based on PV as the standard group (SG; PV < 80 mL) and large group (LG; PV ≥ 80 mL). Results: A total of 132 (73%) patients were grouped as the SG, and 48 (27%) were grouped as the LG. No significant differences between the groups were observed in the preoperative variables age, IPSS, and QOLS. However, the LG had a significantly larger PV and higher serum PSA levels. Analysis of surgical outcomes revealed that postoperative changes in IPSS, QOLS, Qmax, serum PSA, serum sodium, and hemoglobin levels did not differ significantly between groups. However, LG had a significantly longer operative time and heavier specimen weight. The rates of early complications, including hyponatremia and blood transfusion, and late complications after surgery did not differ between the groups. Conclusion: The present findings suggest that TUEB is safe and effective for treatment of BPH, regardless of PV.

Background: The concept of "see one, do one, teach one" raises concerns regarding patient safety in the intensive care unit (ICU) and highlights the need for prior preparation of residents/fellows for ICU rotation. This study assessed the need for an adult pre-ICU "boot camp" training course. Methods: An online questionnaire regarding the current ICU training and desirable course framework was distributed via e-mail to the ICU directors of 269 educational centers certified by the Japanese Society of Intensive Care Medicine. Results: The response rate was 39% (106/269). The number of residents/fellows undergoing ICU rotation was 5.5 (IQR 2-12) /ICU/year, and the majority (63%) were second to fourth year post-graduate residents and fellows. ICU directors opined that of the fundamental critical care skills, residents/fellows performed well or very well in only seven out of 29 skills (24%). Only 18% of the ICU directors had an established ICU training curriculum. Overall, 72% of the directors were interested in the boot camp. The desirable course framework was 3-5 hours per day with simulations and lectures. The core skills that directors considered as important to acquire during ICU rotation were central venous catheter insertion, tracheal intubation, defibrillation, initiation of mechanical ventilation, physical examination of critically ill patients, and shock assessment. Conclusions: Residents/fellows began ICU rotations with suboptimal skills as reported by ICU directors. In addition, most of the ICUs had not established a training curriculum. Therefore, having an ICU boot camp is necessary to enhance critical care skills and to decrease medical errors.

Carcinoma of unknown primary (CUP) is a malignant tumor with histological characteristics indicating metastasis in a patient with an unidentified primary lesion after whole-body evaluation at the time of examination. CUP incidence is similar in men and women, and average age at diagnosis is 60 years. Reports of overall incidence vary but CUP is believed to account for 1-5% of all cancers. We encountered a case of apparently metastatic squamous cell carcinoma of the inguinal region in a patient without a detectable primary lesion. We report this case and review the literature on CUP, to increase awareness of this rare lesion.

Background: Adenoid cystic carcinoma of the trachea (ACCT) is a rare cancer; ACCT with thyroid invasion is particularly rare. We first suspected anaplastic thyroid carcinoma (ATC) but diagnosed ACC after performing fine-needle aspiration cytology (FNAC). Tracheal origin was confirmed postoperatively. Case Description: A 77-year-old woman presented to our hospital with acute inspiratory dyspnea requiring emergency tracheotomy. Physical examination revealed swelling of the right anterior neck and a hard, immobile mass. Computed tomography (CT) and ultrasonography (US) showed tumor extension to the right thyroid lobe and between the first and third tracheal rings, which caused severe stenosis of the lumen. We performed FNAC. Clinical findings were highly suggestive of ACCT with thyroid invasion. She underwent total laryngectomy, cervical esophagectomy, and thyroidectomy with bilateral selective neck dissection at another hospital. The tumor was located in the right posterior wall of the trachea and extended into the right thyroid gland. Pathological examination showed infiltrative carcinomatous proliferation with tubular and cribriform patterns. The tumor was classified as pT4N1. A definite diagnosis was made after histopathological analysis of the surgical specimen confirmed ACCT. The tumor was positive for FABP7, a putative prognostic marker of ACC, and metastasized to the lungs 3 years after surgery. Conclusions: ACCT with thyroid invasion is an extremely rare malignant neoplasm. FNAC was useful for differentiating ACCT from other diagnoses and enabled appropriate surgical treatment.

Postoperative rhabdomyolysis is a rare but potentially fatal surgical complication. We experienced a case of rhabdomyolysis after laparoscopic radical nephrectomy (LRN). Right renal carcinoma was diagnosed in a 31-year-old woman with a body mass index of 28.5 kg/m². She underwent right retroperitoneal LRN in the lateral decubitus position. The operating time was approximately 5 hours. Immediately after surgery, she reported pain in the left buttock, and reddish discoloration of the urine was observed. On the basis of these symptoms, an elevated serum creatine kinase level, and computed tomography findings, we diagnosed rhabdomyolysis of the left gluteal muscle secondary to its intraoperative compression caused by prolonged placement in a fixed position. She was treated with hydration therapy and discharged 6 days postoperatively. Prolonged surgery, obesity, and placement in the lateral decubitus position are risk factors for postoperative rhabdomyolysis. Surgeons should attempt to reduce operating time for LRN when obese patients are placed in the lateral decubitus position.