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Background: It is not well known whether diabetic peripheral neuropathy diagnosed using a non-invasive point-of-care nerve conduction device called DPN-Check® is associated with diabetic nephropathy. Thus, we aimed to evaluate the association of diabetic peripheral neuropathy with urinary albumin excretion in patients with type 2 diabetes using DPN-Check®. Methods: This retrospective observational study included 323 Japanese patients with type 2 diabetes. The urinary albumin-to-creatinine ratio in a spot urine sample was defined as urinary albumin excretion. Multiple linear regression analysis was used to determine the association of DPN-Check®-determined diabetic peripheral neuropathy with urinary albumin excretion. Results: Patients with DPN-Check®-determined diabetic peripheral neuropathy had significantly higher urinary albumin excretion than those without, while there was no difference in urinary albumin excretion between patients with and without diabetic peripheral neuropathy determined by simplified diagnostic criteria. In the multivariate model, the DPN-Check® determined that diabetic peripheral neuropathy was significantly associated with urinary albumin excretion even after adjustment for covariates (standardized β, 0.123; p = 0.012). Conclusions: Our study found a significant association between diabetic peripheral neuropathy diagnosed using DPN-Check® and urinary albumin excretion in patients with type 2 diabetes.

This study aimed to analyze the incidence of subclinical rejection (SCR) in kidney transplantation patients and risk factors associated with SCR.We assessed 80 protocol biopsies taken within 2 years postoperatively in 41 adult patients who underwent living donor kidney transplantation between 2017 and 2020. All patients were on immunosuppressant therapy that included tacrolimus, mycophenolate mofetil, and steroids.The prevalence of Banff Borderline classification at 3, 6, and 12 months after transplantation was 4%, 5%, and 8 %, respectively, whereas none of the biopsies met the Banff criteria for acute T cell-mediated rejection throughout the study period. Active antibody-mediated rejection (ABMR) was only present in 8% of patients at 3 months after transplantation and chronic active ABMR at 6, 12, and 24 months after transplantation was detected in 10%, 13%, and 11% of the patients, respectively. Subgroup analysis revealed that 50% of the 6 patients with preformed anti-donor specific antibodies (DSAs) developed clinical or subclinical active ABMR within 3 months after transplantation, followed by chronic active ABMR according to serial histologic assessment. Conversely, only a small proportion of patients (3%) without preformed DSAs exhibited clinically active ABMR.SCR occurs too infrequently in patients with low immunologic risk and strong contemporary immunosuppression therapy to justify the diagnostic effort of serial protocol biopsies. However, protocol biopsies remain an indispensable tool in renal transplant monitoring and may be especially important in immunologically high-risk patients with pre-existing DSAs.

Background This study aimed to investigate the relationship between tooth loss and cognitive function in community-dwelling elderly. Methods A total of 438 men and 715 women aged 60–84 years who participated in the Toon Study—an epidemiological study conducted among local residents of Toon City, Ehime Prefecture, Japan from 2014 to 2018—were included. A self-administered questionnaire was used to assess oral health status (number and bite of teeth). Mild cognitive impairment (MCI) was assessed using the Japanese version of the Montreal Cognitive Assessment, with scores

Fat repositioning is a common surgical technique for treating tear trough deformity. As this technique is mainly performed for cosmetic purposes, its functional outcomes have rarely been evaluated. The purpose of this study was to evaluate the changes in eye movements that occur after fat repositioning for tear trough deformity. The authors performed fat repositioning on 18 eyelids of 9 patients and evaluated their eye movements and binocular vision before surgery and at 1, 3, and 6 months after surgery. Hess screen and Binocular single vision tests were performed during each follow-up examination and the scores were recorded. The authors observed that fat repositioning did not affect binocular vision; however, vertical and horizontal eye movements worsened at 3 months after surgery. Nevertheless, there was no significant difference between the eye movements recorded before surgery and those recorded 6 months after surgery. Regardless of this finding, it should be noted that vertical or horizontal strabismus might occur after fat repositioning for tear trough deformity.

Involutional ectropion is a disease in which the eyelids are everted outwards, and because the eyelids move away from the eyeballs, the ocular surface and conjunctiva are exposed causing inflammation, pain, photophobia, foreign body sensation, epiphora, and blurred vision. It is thought to be caused by horizontal and vertical laxity. Various surgical methods have reportedly been used to correct involutional ectropion. Shortening the lower eyelid retractor (LER) is an indispensable surgical operation for medial ectropion. When the LER is shortened, it is usually fixed to the lower edge of the tarsal plate. Herein we describe a new type of surgery that has now been performed on 6 eyes in 4 patients. The procedure involves separating the conjunctiva from the tarsal plate, inserting the LER between the conjunctiva and the tarsal plate, and then fixing it to the back of the tarsal plate. In all 6 eyes, the lower eyelid now contacts the eyeball, and morphological improvements were achieved. This new surgical method is a useful way to raise the tarsal plate.

The usual surgical approaches for zygomaticomaxillary complex fracture are subciliary incision, transconjunctival incision, eyebrow incision, lateral canthal incision, coronal incision, preauricular incision, and superior gingivobuccal incision. In the intraoral approach, a horizontal mucoperiosteal incision is performed at the superior gingivobuccal region, and sometimes, includes the upper labial frenum. This may cause discomfort in the oral cavity because of postoperative scarring and shortening of the upper labial frenum. To avoid these complications, the authors performed a novel approach using gingival sulcus incision instead of oral mucosal incision to treat 5 zygomatic fractures. The authors evaluated the regression of the gingival interdental papillae, gingival swelling, and gingival perception at 2 weeks, 1 month, 3 months, and 6 months after the operation. The regression of the gingival papillae and gingival swelling disappeared 3 months and 1 month after the operation, respectively. No paresthesia was observed in any of the cases. The gingival sulcus approach can lead to scarless results and contribute considerably to the aesthetic appearance of the oral cavity.

Muscle biopsy can be used to confirm the diagnosis of neuromuscular diseases. However, it is unclear whether antibiotic prophylaxis prior to muscle biopsy is needed to prevent surgical site infection (SSI). We are conducting a phase 2, single-center, open-labeled, prospective randomized trial to clarify the need for antibiotic prophylaxis in patients at low risk for SSI undergoing muscle biopsy. Patients will be randomized to an antibiotic prophylaxis group or a control group, and the incidence of SSI will be compared between the groups. Our findings will clarify the need for antibiotic prophylaxis in this patient population.

An efficient gold-catalyzed cyclization of 2-alkynylaldehyde cyclic acetals has been developed for the synthesis of indenone derivatives. A wide variety of functionalized indenone derivatives can be obtained in good-to-excellent yields. HMBC and NOESY NMR analyses and mechanistic elucidation experiments revealed that the cyclization occurs via a 1,5-H shift. The cyclic acetal group promoted the 1,5-H shift by activating the benzylic C-H bond and preventing the migration of the alkoxy group by tethering both alkoxy groups.

Two different types of palladium catalysts supported on dual-pore monolithic silica beads [5% Pd/SM and 0.25% Pd/SM(sc)] for chemoselective hydrogenation were developed. Alkyne, alkene, azide, and nitro functionalities and the aromatic N-Cbz protecting group were chemoselectively hydrogenated using 5% Pd/SM. On the other hand, 0.25% Pd/SM(sc) showed unique and higher hydrogenation catalyst activity toward a wide variety of reducible functionalities. Furthermore, the catalyst activities of both 5% Pd/SM and 0.25% Pd/SM(sc) under flow hydrogenation conditions were also evaluated. A pre-packed 5% Pd/SM cartridge could be used continuously for at least 72 h without any loss of catalyst activity. The 0.2% Pd/SM(sc) catalyst prepacked in a cartridge showed high catalyst activity for the flow hydrogenation of trisubstituted alkenes under mild reaction conditions.

Anorexia nervosa not only results in severe malnutrition but also carries a high risk of sudden death. Although fatal arrhythmias are the most common cause of sudden death, it is often unclear what exactly causes them. To the best of our knowledge, there have been no reports of cerebellar tonsillar herniations in patients with anorexia nervosa.A 17-year-old girl with anorexia nervosa and autism spectrum disorder was admitted to the pediatric ward for extreme weight loss. Since she refused to take oral nutrition or tube feeding, we started continuous intravenous fluids. Eight hours after admission, she suddenly went into cardiopulmonary arrest and died despite resuscitation. A postmortem autopsy revealed the unexpected findings of generalized severe cerebral edema and cerebellar tonsillar herniation.Intracranial hypertension may need to be considered when the condition of patients with anorexia nervosa suddenly worsens during refeeding periods. Postmortem autopsy and autopsy imaging are recommended to determine the exact cause of sudden death.Level IV: Evidence obtained from multiple time series analysis such as case studies. (NB: Dramatic results in uncontrolled trials might also be regarded as this type of evidence).

BACKGROUND The aim of this study was to evaluate the potential of liquid biopsy for prediction of the efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment and for assessment of the changes in genetic alterations during such treatment. METHODS Plasma samples were prospectively collected from non-small cell lung cancer patients with EGFR-activating mutations during EGFR-TKI treatment until disease progression and were analyzed for such mutations with droplet digital polymerase chain reaction and for other somatic alterations with next-generation sequencing. RESULTS One hundred patients, including 87 who were EGFR-TKI naive, were enrolled. Median progression-free survival was significantly shorter for EGFR-TKI-naive patients with EGFR-activating mutations detected in plasma at baseline than for those without them (7.9 vs 19.0 months; P

Background: Gastric cancer cases with tumor thrombus in the portal vein system (PVTT) are rare, frequently develop liver metastasis, and have a very poor prognosis. Case presentation: A 65-year-old man presented to a physician with a complaint of upper abdominal pain persisting for 2 months. Esophagogastroduodenoscopy revealed a Borrmann type 2 tumor, and he was referred to our hospital. Computed tomography (CT) showed wall thickening of the stomach, bulky swelling of lymph nodes in the lesser curvature and along the pancreas body, and tumor thrombus in the splenic to the portal vein. CT showed no liver or lung metastases, ascites, or peritoneal nodules. Staging laparoscopy revealed P0CY0. We planned to administer neoadjuvant chemotherapy (NAC), consisting of 2 courses of TS-1 and cisplatin combined chemotherapy. However, the second course of the chemotherapy was canceled on day 8 because of influenza. CT after chemotherapy showed no remarkable change, but we decided to undertake the planned operation. Total gastrectomy and pancreaticosplenectomy, along with lymphadenectomy, thrombectomy, and cholecystectomy, was performed. The patient was discharged on postoperative day 12 without complications. Histopathologic examination showed a well to moderately differentiated adenocarcinoma with 45 lymph node metastases. The specimen of the tumor thrombus also showed a moderately differentiated adenocarcinoma. Because he did not want additional chemotherapy, we selected follow-up observation. The patient has remained disease-free for 60 months after the operation. Conclusion: We described a patient with advanced gastric cancer with PVTT, who could undergo R0 resection with a good clinical course.

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) generally has a poor prognosis and the consensus is that it needs to be treated with clone-directed therapy. However, the prognosis of PGNMID is heterogenous and some cases have been successfully treated using other therapeutic strategies. We herein report a case of PGNMID that responded favorably to steroids without clone-directed therapy. An 18-year-old woman was referred to a nephrologist with proteinuria detected in an annual health check-up. Over a 3-year period, the concentration of creatinine (Cr) increased from 0.76 to 1.00 mg/dL and proteinuria from 0.35 to 1.9 g/g Cr. Monoclonal gammopathies were not detected in her serum or urine. Based on the findings of kidney biopsy at the age of 21 years, the patient was diagnosed with proliferative glomerulonephritis with monoclonal IgG1-kappa deposits. The histological feature was mesangial proliferative glomerulonephritis with advanced glomerulosclerosis, which is a rare presentation of PGNMID. Intravenous methylprednisolone pulse therapy was initiated, followed by oral prednisolone at a dose of 30 mg daily. One year later, a second kidney biopsy revealed a significant decrease in mesangial deposits of IgG1-kappa. Prednisolone was gradually tapered and discontinued 2 years after the first kidney biopsy. At the time of prednisolone withdrawal, urinalysis showed proteinuria of 0.2 g/g Cr without hematuria. Kidney function remained stable throughout the treatment period.

The frontalis suspension procedure is a common surgical method for patients with severe blepharoptosis. While frontalis suspension is a very effective method, the transplant material may be visualized after surgery in patients with a deep sulcus and severe blepharoptosis. To prevent this complication, we performed a combination of dermal fat grafting and frontalis suspension using a polytetrafluoroethylene sheet in 5 patients (6 eyelids). We followed-up the patients for at least 6 months postoperatively (mean: 6.8 months) and observed no transplant material visualization or occurrence of infection. The mean pre- and postoperative margin reflex distance-1 was -3.75 (-5 to -2) and 2.10 (1-3), respectively. Bulky upper eyelids were observed 6 months postoperatively in 1 patient (2 eyelids). None of the patients underwent reoperation. In conclusion, the combination of frontalis suspension using a polytetrafluoroethylene sheet and dermal fat grafting for severe blepharoptosis and a deep upper eyelid sulcus was effective in preventing visualization of the transplant material.

We aimed to compare the effects of saline with and without heparin on the catheter-occlusion rate and coagulation-related blood test results for the management of arterial catheters among patients admitted to a short-term intensive care unit postoperatively. This prospective, triple-blinded, randomized controlled study recruited patients aged 20–90 years scheduled to undergo radial arterial catheter insertion and postoperative intensive care unit admission between February and August 2019. Patients were randomly allocated to two groups (1:1 ratio) depending on the use of heparin: study (normal saline with heparin, 3000 units to 500 ml of normal saline) and control (normal saline without heparin) groups with arterial catheters. The allocated management method was employed immediately after intensive care unit admission. Occlusion assessment (every 12 h), arterial blood gas tests (every 6 h), and blood sample collection (every 24 h) were performed. The occlusion of arterial catheter was assessed using occlusion rate, and blood test results were assessed using a linear mixed model. There were 147 patients in the arterial catheter groups. There were no significant differences in occlusion rates and changes in platelet counts and activated partial thromboplastin time between the groups with arterial (p = 0.98, 0.16, and 0.32, respectively) catheters during the first 6 days after intensive care unit admission. Normal saline with and without heparin showed similar efficiency for both the prevention of occlusion and the results of coagulation.

Pulse granuloma is a rare pathologic condition considered to be a benign inflammatory reaction to foreign materials originated from ingested legume matter. As for pulse granulomas of the gastrointestinal tract, association with diverticular diseases is relatively common, but only a few pulse granuloma cases associated with appendicitis have been reported. This report presents histopathologic findings of pulse granuloma lesions observed in two appendectomy cases, with some histochemical examinations of cellulose matter which is reportedly a major component to provoke pulse granuloma reaction. Our patients in both cases were girls in their teens, and they underwent interval appendectomy for acute appendicitis. Both appendectomy specimens revealed ruptured walls with inflammatory granulation tissue with marked foreign body reaction including characteristic collections of ring-like, curled ribbon-like, and/or lobulated nephrosclerosis-like hyaline structures and various foreign bodies, in which microorganisms or amyloid deposition were not identified. The presence of cellulose matter was suggested by Sirius red stain, the IKI (iodine potassium iodide)-H2SO4 method, and birefringence by polarized light. Appendectomy materials due to acute appendicitis would include pulse granuloma reaction provoked by ingested materials with cellulose. Pathologists should be familiar with the concept and histopathologic features of pulse granulomas to avoid misinterpreting them as vascular lesions and/or amyloid deposition, or any infectious organisms.

// Keiichi Ota 1 , Taishi Harada 1, 2 , Kohei Otsubo 1 , Akiko Fujii 1 , Yuko Tsuchiya 1 , Kentaro Tanaka 1 , Isamu Okamoto 1 and Yoichi Nakanishi 1, 3 1 Research Institute for Diseases of The Chest, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan 2 Department of Respiratory Medicine, Japan Community Health Care Organization (JCHO) Kyushu Hospital, Kitakyushu City, Fukuoka, 806-8501, Japan 3 Center for Clinical and Translational Research, Kyushu University Hospital, Higashi-ku, Fukuoka 812-8582, Japan Correspondence to: Taishi Harada, email: harada-t@kokyu.med.kyushu-u.ac.jp Keywords: epidermal growth factor receptor (EGFR), lung cancer, proximity ligation assay, receptor dimerization, tyrosine kinase inhibitor (TKI) Received: February 06, 2017 Accepted: June 27, 2017 Published: July 25, 2017 ABSTRACT Objectives: Activation of the epidermal growth factor receptor (EGFR) results from receptor homodimerization and autophosphorylation and confers sensitivity to tyrosine kinase inhibitors in some tumors. However, the visual detection and quantitation of activated EGFR in the clinical setting has not been established. Materials and Methods: A proximity ligation assay (PLA) was applied to detect EGFR homodimers in non–small cell lung cancer (NSCLC) cell lines and tissue specimens. Results: PLA signals corresponding to EGFR homodimers were higher in NSCLC cell lines and tissue specimens positive for activating EGFR mutations than in those wild type (WT) for EGFR . Stimulation with EGF in NSCLC cells WT for EGFR or forced overexpression of EGFR in Ba/F3 cells resulted in marked EGFR homodimerization. The extent of EGFR homodimerization appeared related to that of EGFR autophosphorylation in NSCLC cells WT for EGFR . Conclusion: PLA may provide a new tool for detection and quantitation of EGFR homodimers in NSCLC and other tumors.

Duodenal cancers are rare. Histopathologically, most duodenal cancers are adenocarcinoma. Signet ring cell carcinoma (SRCC) is a rare tumor more commonly found in the stomach than at other sites in the digestive tract. SRCC is extremely uncommon in the duodenum, with most of these tumors occurring in the ampulla. Until now, there are few case reports of duodenal cancers with SRCC. To accumulate case reports, we report a rare case of nonampullary duodenal bulb SRCC. A 74-year-old man was admitted to our hospital with melena. Esophagogastroduodenoscopy (EGD) showed a duodenal bulb ulcer. He was treated with a proton pump inhibitor. However, 1 month later, he was readmitted to our hospital with epigastric pain and nausea. A second EGD examination showed an ulcer at the duodenal bulb. Biopsies taken from the ulcer showed SRCC. Distal gastrectomy and duodenal bulb resection were performed. Histologic examination of the specimen showed a type 4 lesion located from the duodenal bulb to the pyloric antrum. The tumor was composed of poorly differentiated adenocarcinoma (por) with SRCC. The distal margin of the duodenal bulb was invaded with tumor. Therefore, pancreatoduodenectomy was performed. One year after the initial operation, he is alive and had no relapse. We described a rare case of por with SRCC of the duodenal bulb. It is important to bear in mind that an ulcer following an abnormal clinical course should be biopsied, and we have to select a suitable operation in cases of duodenal bulb cancer.

An 83-year-old Japanese man had a history of chronic heart failure due to bradycardia-tachycardia syndrome. He was admitted to our hospital because of macrohematuria and acute kidney injury (AKI), which were detected by an urologist at an outpatient visit. He had a history of recurrent macrohematuria and transurethral resection of bladder tumors twice in the preceding 2 years. He had been on warfarin for 12 years, with a stable international normalized ratio (INR) that was usually less than 2.1. Urinalysis revealed numerous red blood cells (RBCs) and mild proteinuria without RBC casts. His serum creatinine level was elevated to 2.41 mg/dL from 0.96 mg/dL at 3 weeks before admission. INR was 1.44. Hydronephrosis was not observed. Ureteroscopy detected invasive urothelial carcinoma of the renal pelvis, and right laparoscopic nephroureterectomy was performed at 41 days after diagnosis of AKI. The background renal parenchyma displayed tubular obstruction by red blood cell casts and acute tubular injury, which were changes compatible with warfarin-related nephropathy (WRN). Warfarin was discontinued, and the serum creatinine level recovered to 1.66 mg/dL after 3 months. In the present patient with nephrosclerosis, WRN occurred at a therapeutic INR level after 12 years of uneventful warfarin therapy, and the coexisting urothelial malignancy was a unique feature.

Although we commonly observe eyebrow drooping during and after blepharoptosis surgery, it may not occur in some cases. After levator resection was performed in 47 patients (84 eyelids) with blepharoptosis, the eyebrow heights at the medial canthus, the center of the pupil, and the lateral canthus were measured using scanned photographs obtained preoperatively and 3 months postoperatively. In the 84 eyelids, after levator resection, the eyebrow position was lowered at the medial canthus in 76 patients (90%), at the center of the pupil in 75 (89%), and at the lateral canthus in 76 (90%). The mean distance of eyebrow drooping in the 84 pupils was 2.74 mm at the medial canthus, 2.91 mm at the center of the pupil, and 2.58 mm at the lateral canthus. In addition, there was a significant difference between the extra skin excision group and the no skin excision group at the medial canthus (p = 0.027), the center of the pupil (p = 0.001), and the lateral canthus (p 0.001) (Mann-Whitney test). Unfortunately, there was a significant difference in ages between the extra skin excision group and the no skin excision group. In conclusion, eyebrow drooping was caused after levator resection in most cases. However, it is difficult to anticipate eyebrow drooping distance before surgery.

Background Primary gastric squamous cell carcinoma (SCC) is a very rare disease. The origin of this tumor remains unclear, although there are some hypotheses. Case summary A 60-year-old man consulted a previous physician complaining of upper abdominal pain. Esophagogastroduodenoscopy revealed type 2 gastric cancer, and the patient was referred to our hospital. After close examination, the patient was diagnosed as cStage IIA gastric adenocarcinoma, and distal gastrectomy was performed. Histochemical studies showed typical findings of SCC, and the tumor was surrounded by intestinal metaplasia. Immunohistochemical examination was positive for cytokeratin (CK) 5/6 and caudal-type homeobox protein 2 (CDX2) and negative for p63/p40. Conclusion The results of immunostaining for CK5/6 supported that this tumor was SCC, but the question why p63/p40 were negative and CDX2 was positive still remained. Concerning about the origin of p63/p40 and CDX2, it was suggested that the tumor cells were not derived from ectopic squamous epithelium but from intestinal metaplasia. And tumor cells looked like homogeneous and squamous metaplasia was not observed. These findings supported the idea that these tumor cells arose from stem cells in the intestinal metaplasia of the stomach.

Patients often develop eyebrow drooping after blepharoplasty or ptosis repair. After aponeurosis advancement was performed in 53 patients (100 eyelids) with blepharoptosis, the eyebrow heights at the medial canthus, center of the pupil, and lateral canthus were measured using scanned photographs obtained preoperatively and 3 months postoperatively. In the 100 eyelids subjected to aponeurosis advancement, the eyebrow position was lowered at the medial canthus in 81 eyelids (81%), at the center of the pupil in 84 eyelids (84%), and at the lateral canthus in 80 eyelids (80%). The mean distance of eyebrow drooping in the 100 eyelids was 2.80 mm at the medial canthus, 2.87 mm at the center of the pupil, and 2.50 mm at the lateral canthus. The preoperative margin reflex distance (MRD) was significantly associated with the distance of eyebrow drooping at the medial canthus, the center of the pupil, and the lateral canthus in the 100 eyelids, but the postoperative MRD was not significantly associated with these parameters in the 100 eyelids. In conclusion, eyebrow drooping developed after aponeurosis advancement in most cases, and the distance of eyebrow drooping was associated with the severity of blepharoptosis.

TAFRO (Thrombocytopenia, Anasarca, Fever and/or elevated C-reactive protein, Renal dysfunction or Reticulin fibrosis, and Organomegaly) syndrome is a unique systemic inflammatory disease, which has recently been proposed from Japan. We report a case showing TAFRO symptoms, the patient’s condition of which allowed histopathological examinations of several biopsy tissues including the kidney. A 37-year-old man was admitted to our hospital for evaluation of fever of unknown origin, pleural effusion and ascites, renal dysfunction, and lymphadenopathy. Serum IL-6 and VEGF were elevated. Histopathologic findings of the lymph node resembled those of mixed type Castleman disease. The bone marrow biopsy specimen revealed normocellular marrow with a mildly increased number of megakaryocytes, but without obvious fibrosis. The renal biopsy material showed glomerular microangiopathy with double contour of the capillary loops and mesangiolysis. In immunohistochemistry, VEGF was retained in podocytes, whereas IL-6 expression was not limited to the specific sites. Glomerular microangiopathy is regarded as a crucial change in TAFRO syndrome, which should be studied further with regard to VEGF and IL-6.

Purpose The adequacy of pain management for individuals with cancer who receive outpatient chemotherapy is unclear. The primary objective of this study was to assess pain prevalence and intensity in such patients. The secondary objectives included assessment of pain management with the pain management index (PMI) and exploration of predictors of inadequate pain management. Methods Cancer patients who received outpatient chemotherapy were enrolled. Patients were required to complete questionnaires covering demographic data and including the Brief Pain Inventory and the Distress Thermometer and Impact Thermometer. The PMI score was determined twice with an interval of at least 3 weeks. Results Of the 740 patients enrolled in the study, 524 individuals (70.8%) completed all questionnaires. Totals of 282 patients (53.8%) and 264 patients (50.4%) reported pain at baseline and follow-up, respectively, with ∼14% of patients having moderate or severe pain at each assessment. Totals of 365 patients (69.7%) at baseline and 320 patients (61.1%) at follow-up reported pain or were prescribed analgesics, with the rate of inadequate pain management for these patients being 39.7 and 51.6%, respectively. Multivariable analysis for 418 patients (79.8%) who had pain or required analgesics at baseline or follow-up (or both) revealed that the most significant predictor of inadequate pain management was depressive state. Conclusions Pain in cancer patients receiving outpatient chemotherapy is prevalent and at risk for undertreatment. Pain management should be assessed on a regular basis and is likely to be improved by screening for depression.

A 65-year-old man with non-ischemic cardiomyopathy, underwent an autopsy 2 months after the successful ablation of a sustained left ventricular (LV) summit ventricular tachycardia (VT). The patient died due to interstitial pneumonia from amiodarone use. The earliest activation sites of the VT were documented from both inside the anterior interventricular vein (AIV) and epicardial surface. The diameter of the AIV was 3-4 mm, and the radiofrequency (RF) lesion inside the AIV was a slight lesion due to high impedance with a high temperature. The lesion from the epicardial surface was also superficial and insufficient due to neighboring coronary arteries and the existence of epicardial fat. A successful application was performed from the LV endocardium, and diffuse myocardial fibrosis was observed in the mid-myocardium including inside the RF lesions. The actual relationship between the myocardial fibrosis and LV summit VT remains unclear, but this case showed the difficulty of achieving a successful ablation from the epicardial side, when the focus exists in the mid-myocardium around the LV summit.

Some gastric epithelial neoplasms show predominant chief cell differentiation (oxyntic gland neoplasms), in which the entity of “gastric adenocarcinoma of fundic gland type” was firstly designated, whereas a possible more aggressive subgroup “gastric adenocarcinoma of fundic gland mucosa type” (GA-FGM) was subsequently proposed. However, the histopathologic progression mode of these neoplasms has not been sufficiently reported. In this article, we describe a case of GA-FGM in which we could observe its progression during 5 years. The tumor was removed by endoscopic submucosal dissection 5 years after the first biopsy, which had already shown a feature of oxyntic gland neoplasm. During the follow-up period, the endoscopy revealed little change in the tumor appearance. However, the histology of endoscopic submucosal dissection showed submucosal extension with its histological progression. Besides, other oxyntic gland neoplasms of the stomach were observed metachronously or synchronously, giving an implication about a common pathogenetic basis of these lesions.

Summary Eyebrow descent commonly occurs after ptosis repair or blepharoplasty surgery. The procedures used to correct acquired blepharoptosis are primarily classified into four groups. These procedures target the levator aponeurosis, Muller's muscle, both the aponeurosis and Muller's muscle, or the frontalis muscle. In this study, we used a new technique called external Muller's muscle tucking (EMMT) on 51 patients (94 eyelids), which targets the Muller's muscle for involutional blepharoptosis. The patients were assessed by comparative analysis using pre- and post-operative digital photographs. The distances between the medial canthi, in addition to the eyebrow heights at the medial canthus, pupil and lateral canthus, were measured on a computer screen. Eyebrows descended after surgery at the medial canthus in 53 eyelids (56.4%), at the center of the pupil in 55 eyelids (58.5%) and at the lateral canthus in 48 eyelids (51.1%). The mean distances of eyebrow descent in the 94 eyelids were 0.24, 0.51 and 0.32 mm at the medial, center and lateral positions, respectively. The mean preoperative margin reflex distance (MRD) was −0.05 mm, the mean postoperative MRD was 3.79 mm and the mean change in MRD was 3.83 mm. Preoperative MRD and change in MRD were weakly associated with changes in eyebrow position in 94 eyelids. In conclusion, these findings suggest that eyebrow drooping distance is related to the preoperative severity of ptosis.

Objectives To conduct histopathological studies on various organs in three different groups of female rats for adverse effects of pulsed magnetic stimulation (MS). Blood tests and body and organ weights were also studied. Methods A high-frequency continuous magnetic stimulator was used (SMN-X, Nihon Kohden, Tokyo). Thirty-four female Sprague-Dawley rats (SPF) were randomly divided into three groups: treatment (MS) groups with 12 and 36 stimulations (seven rats in each); sham groups exposed only to sounds of stimulation for 12 and 36 times; (seven rats in each); and control groups with no stimulation or sound during the same periods of 12 and 36 stimulations (five rats in each). The MS group received magnetic stimulation at the maximum output level (560 mT peak) at 10 Hz for 25 min once daily for 5 days a week. After treatment various organs including genital organs were removed for histological and endocrinological examinations. Results No changes were seen in body and organ weights and daily behaviors among the three groups. No adverse influence of magnetic stimulation was noted on histopathological examinations of liver, spleen, kidney, lung, heart, thymus, urinary bladder, skeletal muscle and bone marrow. No intragroup changes were seen among the three groups with regard to endocrinological findings including blood cell counts, adrenocorticotropic hormone (ACTH), estrogen and progesterone levels. Conclusions Pulsed magnetic stimulation exerted no apparent adverse effect on the various organs, hormone levels, body weight, and daily behaviors in female rats.

Atypical hemolytic uremic syndrome (aHUS) in allograft kidney transplantation is caused by various factors including rejection, infection, and immunosuppressive drugs. We present a case of a 32 year old woman with aHUS four years after an ABO-incompatible kidney transplantation from a living relative. The primary cause of end-stage renal disease was unknown; however, IgA nephropathy (IgAN) was suspected from her clinical course. She underwent pre-emptive kidney transplantation from her 60 year old mother. The allograft preserved good renal function [serum creatinine (sCr) level 110-130 μmol/L] until a sudden attack of abdominal pain four years after transplant, with acute renal failure (sCr level, 385.3 μmol/L), decreasing platelet count, and hemolytic anemia with schizocytes. On allograft biopsy, there was thrombotic microangiopathy in the glomeruli, with a cellular crescent formation and mesangial IgA and C3 deposition. Microvascular inflammation, such as glomerulitis, peritubular capillaritis, and arteriole endarteritis were also detected. A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) did not decrease and Shiga toxin was not detected. Donor-specific antibodies or autoantibodies, including anti-neutrophil cytoplasmic antibody and anti-glomerular basement membrane (anti-GBM) antibody, were negative. The patient was diagnosed with aHUS and received three sessions of plasmapheresis and methylprednisolone pulse therapy, followed by oral methylprednisolone (0.25-0.5 mg/kg) instead of tacrolimus. She temporarily required hemodialysis (sCr level, 658.3 μmol/L). Thereafter, her sCr level improved to 284.5 μmol/L without dialysis therapy. This case is clinically considered as aHUS after kidney transplantation, associated with various factors, including rejection, glomerulonephritis, and toxicity from drugs such as tacrolimus.

Nearly one half of all cases of acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for non–small-cell lung cancer (NSCLC) are due to the T790M mutation in EGFR exon 20. The T790M mutation is a C→T transition mutation at a CpG dinucleotide. DNA methylation of cytosine (5-methylcytosine (5-mC)) in CpG dinucleotides is a common DNA modification; CpG dinucleotides are considered to be mutational hotspots that cause genetic diseases and cancers through spontaneous deamination of 5-mC, resulting in C→T transition mutations. This study aimed to examine the methylation level of cytosine of EGFR codon 790 and investigate whether DNA methylation was involved in acquiring the T790M mutation. We examined 18 NSCLC tumor tissues, 7 normal lymph node tissues, and 4 NSCLC cell lines (PC9, HCC827, 11-18, and A549). 5-mC was checked by bisulfite sequencing and quantified by pyrosequencing. We found that all tissue samples and cell lines had 5-mC in EGFR codon 790. The 5-mC range was 58.4–90.8%. Our results imply that hypermethylation of the CpG dinucleotide in EGFR codon 790 leads to the C→T transition mutation, causing resistance to EGFR-TKI treatment.

Objectives Given our previously published study, α 1 nicotinic acetylcholine receptor (nAChR) plays an essential role in nicotine-induced cell signaling and nicotine-induced resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in non-small cell lung cancer (NSCLC) PC9 cells. The aim of this study was to investigate the potential mechanism between nAChR and EGFR for nicotine-induced resistance to EGFR-TKI erlotinib in the NSCLC xenograft model. Materials and methods We identified the role of nicotine to EGFR/AKT/ERK pathways and to erlotinib-resistance in NSCLC PC9 and HCC827 cells by MTS assay and western blot. Then, we established the PC9 xenograft model with nicotine exposure and treated mice with erlotinib combined with vehicle or nicotine. Results We confirmed the effects of nicotine on EGFR/AKT/ERK pathways and determined nicotine's potential in preventing from the effect of erlotinib on NSCLC cells. Then, we showed that nicotine exposures can promote tumor growth and induce resistance to erlotinib in the PC9 xenograft model. Our results also indicated that chronic oral administration of nicotine can cause more significant erlotinib-resistance compared with acute i.v. injection of nicotine through activating α 1 nAChR and EGFR pathways. Conclusions These results suggest that nicotine contributes to the progression and erlotinib-resistance of the NSCLC xenograft model via the cooperation between nAChR and EGFR.

Background: The relationship between dialysis amyloid (DA) deposition in the aortic valve (AV) and aortic stenosis (AS) is unknown. Methods: This was a cross-sectional study. AV specimens of dialysis patients (median vintage: 8.8 years) consecutively collected from cardiac surgeries (n = 56) or autopsies (n = 13) were examined by a board-certified pathologist blinded to clinical data. DAs were considered to be present if deposits were stained both by Congo red with apple-green birefringence under polarized light and by anti-β2-microblobulin antibody. Degree of deposition was graded as follows: Amyloid (-), no deposit; Amyloid (1+), occasional small deposits; Amyloid (2+), multiple small to large deposits or a single large deposit. Calcification was defined as a calcified deposit with a diameter >1 mm in the specimen. Severe AS (sAS) was defined as a mean gradient >50 mm Hg by echocardiogram. We examined the proportion of DAs and the association between DAs and the sAS. Results: DAs were present in 71% (n = 49) of specimens and primarily co-localized with calcification. Non-dialysis related amyloid was found in one specimen. After excluding this specimen, sAS was associated with ‘Amyloid (1+) and Calcification >1 mm' and ‘Amyloid (2+) and Calcification >1 mm' (vs. ‘Amyloid (-) and Calcification ≤1 mm', odds ratios (ORs): 13.5 and 34.2, respectively). Furthermore, after adjustment for covariates, sAS was found to be associated with ‘Amyloid (2+) and Calcification >1 mm' (OR: 24.3). Conclusions: DA deposition in the AV was prevalent among dialysis patients. DA deposition with accompanying calcification might contribute to the severity of AS.

Background Neurofibromatosis type 1 (NF1) is an autosomally dominant inherited disorder characterized by multiple pigmented skin spots (café-au-lait spots) and neurofibroma. NF1 is associated with a wide variety of benign or malignant tumors. We report a NF1 patient who received surgical treatment for rectal carcinoma and multifocal small intestinal gastrointestinal stromal tumors (GISTs). Case presentation A 70-year-old female patient with NF1 was referred to our hospital after a positive fecal occult blood test. Locally advanced rectal carcinoma was detected in the upper rectum using colonoscopy. A submucosal tumor 20 mm in diameter was detected in the duodenal bulb during the upper gastrointestinal endoscopy. The biopsy specimen from the duodenum was GIST with positive immunostaining of KIT and CD34 microscopically. Laparoscopic low anterior resection for rectal carcinoma and local excision of the duodenal GIST were performed successfully. During the operation, five white small nodules were found on the serosa of the jejunum. One nodule was excised for histological examination. The resected rectal tumor was a well-differentiated adenocarcinoma with multiple lymph nodes metastases according to the histology. The duodenal tumor was found to be low-risk GIST. Moreover, the nodule from the jejunum was very low risk GIST. An excised skin wart was neurofibroma according to the histology. Conclusions GIST or carcinomas have been reported to occasionally occur in the digestive tract of the patients with NF1. We present a rare case of a NF1 patient with GISTs and colorectal carcinoma.