The natural course of the paravertebral muscles after the onset of osteoporotic vertebral fracture.

This study revealed the change in the paravertebral muscles in patients with osteoporotic vertebral fracture. Increased pain is likely to be the driver for reduced activity, reduced activities of daily living, and consequent increase in fat infiltration of the paravertebral muscles, assumed to be secondary to reduced activity level or, conversely, partial immobilization. INTRODUCTION: To reveal the time courses and impact of the paravertebral muscles (PVMs) on the healing process of osteoporotic vertebral fractures and risk factors for PVM decrease. METHODS: Consecutive patients with symptomatic osteoporotic vertebral fractures were enrolled in 11 hospitals. At enrollment and 3- and 6-month follow-up, PVMs, including the multifidus and erector spinae, were examined using magnetic resonance imaging (MRI). The PVM cross-sectional area (CSA) and fat signal fraction (FSF) were measured at L3. Low back pain (LBP), activities of daily living (ADLs), and risk factors for PVM decrease at the 6-month follow-up were investigated. PVM decrease was defined as > 1 standard deviation decrease of the CSA or > 1 standard deviation increase of the FSF. RESULTS: Among 153 patients who completed the 6-month follow-up, 117 (92 women, 79%) had MRI of L3 at enrollment and 3- and 6-month follow-up (mean age at enrollment, 78.5 years). The CSA did not change 6 months from onset (p for trend = 0.634), whereas the FSF significantly increased (p for trend = 0.033). PVM decrease was observed in 30 patients (26%). LBP was more severe, and delayed union was more frequent in patients with PVM decrease (p = 0.021 mixed-effect model and p = 0.029 chi-square test, respectively). The risk factors for PVM decrease were ADL decline at the 3-month follow-up (adjusted odds ratio = 5.35, p = 0.026). CONCLUSION: PVM decrease was significantly related to LBP and delayed union after osteoporotic vertebral fracture onset. ADL decline at the 3-month follow-up was a risk factor for PVM decrease. Therefore, restoring ADLs within 3 months after onset is important.

The incidence of nerve root injury by high-speed drill can be reduced by chilled saline irrigation in a rabbit model.

AIMS: We aimed to evaluate the temperature around the nerve root during drilling of the lamina and to determine whether irrigation during drilling can reduce the chance of nerve root injury. MATERIALS AND METHODS: Lumbar nerve roots were exposed to frictional heat by high-speed drilling of the lamina in a live rabbit model, with saline (room temperature (RT) or chilled saline) or without saline (control) irrigation. We measured temperatures surrounding the nerve root and made histological evaluations. RESULTS: In the control group, the mean temperature around the nerve root was 52.0°C (38.0°C to 75.5°C) after 60 seconds of drilling, and nerve root injuries were found in one out of 13 (7.7%) immediately, three out of 14 (21.4%) at three days, and 11 out of 25 (44.0%) at seven days post-operatively. While the RT group showed a significantly lower temperature around the nerve root compared with the control group (mean 46.5°C; 34.5°C to 66.9°C, p < 0.001), RT saline failed to significantly reduce the incidence of nerve root injury (ten out of 26; 38.5%; odds ratio (OR) 0.96; 95% confidence interval (CI) 0.516 to 1.785; p = 0.563). However, chilled saline irrigation resulted in a significantly lower temperature than the control group (mean 39.0°C; 35.3°C to 52.3°C; p < 0.001) and a lower rate of nerve root injury (two out of 21; 9.5%, OR 0.13; 95% CI 0.02 to 0.703, p = 0.010). CONCLUSION: Frictional heat caused by a high-speed drill can cause histological nerve root injury. Chilled saline irrigation had a more prominent effect than RT in reducing the incidence of the thermal injury during extended drilling. Cite this article: Bone Joint J 2017;99-B:554-60.

Anti-IL-31 receptor antibody is shown to be a potential therapeutic option for treating itch and dermatitis in mice.

BACKGROUND AND PURPOSE: IL-31, which is described as a pruritogenic cytokine, is linked to the itching that is associated with allergic and non-allergic eczema, but the precise pruritogenic mechanism of IL-31 and its potential as a therapeutic target for atopic dermatitis (AD) have not been determined. EXPERIMENTAL APPROACH: We investigated the effects of existing drugs on the scratching behaviour induced by an i.v. injection of IL-31 to clarify whether IL-31 induced pruritus indirectly. In addition, we studied the effects of an anti-IL-31 receptor α subunit (anti-IL-31 receptor α) neutralizing antibody on chronic pruritus-inducing dermatitis in an AD-like model to determine whether IL-31 not only induces scratching behaviour, but is also the causative factor in an AD phenotype. KEY RESULTS: The scratching behaviour induced by an i.v. injection of IL-31 was inhibited by pretreatment with an anti-IL-31 receptor α-neutralizing antibody. In contrast, it was not inhibited significantly by a non-sedative antihistamine (terfenadine), immunosuppressants (dexamethasone and tacrolimus), or a µ-opioid receptor antagonist (naloxone). The anti-IL-31 receptor α-neutralizing antibody reduced the ear swelling and dermatitis score in a chronic pruritus-inducing AD-like model. Moreover, treatment with the anti-IL-31 receptor α-neutralizing antibody showed therapeutic effects on the dermatitis even if it was injected after the disease had developed. CONCLUSIONS AND IMPLICATIONS: Anti-IL-31 receptor α is a potential novel therapeutic approach for escaping from the itch-scratch cycle and also a treatment for dermatitis in AD.

Learning curve of laparoscopy-assisted gastrectomy using a standardized surgical technique and an established educational system.

BACKGROUND AND AIMS: The learning curve of a trainee for laparoscopy-assisted gastrectomy in a high volume center, in which an educational system and a standardized laparoscopic procedure are already established, remains unclear. MATERIAL AND METHODS: The early surgical outcomes of the patients of two trainees were investigated. Both trainees followed a training program where they performed at least 20 cases being the camera assistant, 20 cases being the first assistant, before performing the surgery as an operator. RESULTS: The average operation time, intraoperative bleeding, the number of retrieved lymph nodes, and morbidity rate were 240.2 min, 45.7 ml, 35.4, and 13.0%, respectively. There was no learning curve effect observed except with the operation time of one trainee. CONCLUSIONS: In a high volume center with an established educational system, trainees could perform laparoscopy-assisted gastrectomy safely, although there might be a -learning curve effect in operation time and the surgeries took longer operation time in trainee's initial cases.

Laparoscopic and endoscopic cooperative surgery for gastrointestinal stromal tumor dissection.

BACKGROUND: Laparoscopic wedge resections are increasingly applied for gastric submucosal tumors such as gastrointestinal stromal tumor (GIST). Despite this, no defined strategy exists to guide the surgeon in choosing the appropriate laparoscopic technique for an individual case on the basis of tumor characteristics such as location or size. This study aimed to introduce a laparoscopic and endoscopic cooperative surgery (LECS) for gastric wedge resection that is applicable for submucosal tumor resection independent of tumor location and size. METHODS: Seven patients underwent LECS for the resection of gastric submucosal tumors. Both mucosal and submucosal layers around the tumor were circumferentially dissected using endoscopic submucosal dissection via intraluminal endoscopy. Subsequently, the seromusclar layer was laparoscopically dissected on the exact three-fourths cut line around the tumor. The submucosal tumor then was exteriorized to the abdominal cavity and dissected with a standard endoscopic stapling device. RESULTS: In all cases, the LECS procedure was successful for dissecting out the gastric submucosal tumor. In four of seven cases, the tumor was located in the upper gastric portion near the esophagogastric junction. The remaining three tumors were in the posterior gastric wall. In two cases, the tumors were more than 5 cm in diameter, and one was a GIST of the remnant stomach. The mean operation time was 169 +/- 17 min, and the estimated blood loss was 7 +/- 2 ml. The postoperative course was uneventful in all cases. CONCLUSIONS: The LECS procedure for dissection of gastric submucosal tumors such as GIST may be performed safely with reasonable operation times, less bleeding, and adequate cut lines. In addition, the success of the procedure does not depend on the tumor location such as the vicinity of the esophagogastric junction or pyloric ring.

The significance of the aberrant left hepatic artery arising from the left gastric artery at curative gastrectomy for gastric cancer.

BACKGROUND: An aberrant left hepatic artery (ALHA) is occasionally encountered during esophagogastric surgery. However, at curative gastrectomy for gastric cancer, it is questionable as to whether the ALHA need to be divided in order to maximize lymph node clearance and the issue requires clarification. METHODS: We encountered 50 patients with an ALHA during curative gastrectomy for gastric cancer between 1997 and 2001. Data concerning operative feasibility, postoperative liver function and therapeutic value of nodal dissection were analyzed retrospectively. RESULTS: For 27 patients, we preserved the ALHA, and for the remaining 23 patients, we divided the ALHA at the origin of the left gastric artery (LGA). Serum levels of aspartate aminotransferase and alanine aminotransferase were statistically significant higher on postoperative day (POD) 1 (P=0.0008 and P=0.0007), and on POD 3 (P=0.001 and P=0.008), respectively, in the ALHA-divided group. Patients who underwent a total gastrectomy predominated in the ALHA-divided group, the total number of dissected lymph nodes being higher in the ALHA-divided group (P=0.018). However, the total numbers of dissected lymph nodes and metastatic lymph nodes around the LGA were similar in the 2 groups (P=0.447 and P=0.128), respectively. No significant differences were seen between the 2 groups in morbidity and mortality. The overall 5-year survival rates were also comparable. CONCLUSIONS: Although a prospective study is required, this study suggested that routine division of the ALHA may not always be required for curative gastrectomy.

Clinical outcome of high segmental gastrectomy for early gastric cancer in the upper third of the stomach.

BACKGROUND: Reflux oesophagitis is commonly encountered in the surgical treatment of cancer of the upper third of the stomach. The aim of this study was to describe a novel surgical technique and evaluate the clinical outcome of high segmental gastrectomy for early-stage proximal gastric cancer. METHODS: Thirty consecutive patients with early gastric cancer located in the upper third of the stomach were included, of whom 12 underwent high segmental gastrectomy and 18 underwent proximal gastrectomy with jejunal interposition. The incidence of reflux oesophagitis and nutritional parameters were compared between the two groups at 1 year after operation. RESULTS: One patient had mild reflux symptoms and two had endoscopic evidence of oesophagitis 1 year after high segmental gastrectomy. Half of the patients who had proximal gastrectomy had reflux symptoms of varying severity and 14 had endoscopic evidence of oesophageal changes at 1 year after surgery. There were significant differences between groups in the incidence of reflux symptoms (P = 0.016) and endoscopically detected gastro-oesophagitis (P < 0.001). There were no adverse events in either group, and the survival rate after high segmental gastrectomy appeared favourable. CONCLUSION: Selected patients with early-stage proximal gastric cancer benefit from high segmental gastrectomy in terms of reduced reflex oesophagitis, without jeopardizing curability.

Familial clustering in subgroups of gastric cancer stratified by histology, age group and location.

AIM: To assess the risk of gastric cancer in a Japanese patient population with the disease by stratification with histology, age, tumour location and the association with family history of gastric or non-gastric tumours. METHODS: A retrospective analysis of 1400 consecutive patients with gastric cancer and 13,467 age- and gender-matched controls from a pre-recorded database using conditional logistic regression models. RESULTS: Young patients (< or = 43 years of age) with gastric cancer of intestinal type had a strong association with family history of gastric cancer in first degree-relatives (OR=12.5). Moreover, when a history of gastric cancer was observed in both parents, there was an increased risk of gastric cancer intestinal type (OR=7.8), more commonly in the proximal and mid-stomach. In contrast, there was an increased risk of diffuse-type cancer when both parents suffered non-gastric cancers (OR=2.1). CONCLUSION: These data suggest that the degree of familial clustering differ in gastric cancer subgroups stratified by histology, age, and stomach location in this Japanese population.

Clinical value of multidetector row computed tomography in detecting lymph node metastasis of early gastric cancer.

AIMS: To evaluate the clinical value of multidetector row computed tomography (MDCT) as a pre-operative staging tool for lymph node metastasis in patients with early gastric cancer (EGC). METHODS: In 278 consecutive patients with EGC, lymph node metastasis was evaluated pre-operatively with MDCT at a slice thickness of 2.5mm (n=57), 5.0mm (n=188), or 7.5mm (n=33). RESULTS: Overall accuracy of nodal category from N0 to N3 was 86% for MDCT and 95% for operative assessment. Regarding accuracy in detecting at least one metastatic lymph node, area under curves (AUC) of receiver operating characteristics for 2.5, 5.0, and 7.5-mm slices and assessment during surgery were 0.87, 0.67 and 0.47, and 0.70, which were significantly different (P<0.0001). MDCT image with 2.5-mm could discriminate the presence of lymph node metastasis with diagnostic accuracy: sensitivity 80%; specificity 92%; positive predictive value (PPV) 50%; negative predictive value (NPV) 98%, whereas assessment during surgery was as follows: sensitivity 65%; specificity 98%; PPV 72%; and NPV 97%. CONCLUSIONS: These results suggest that pre-operative assessment with MDCT using thinner slices may detect at least one lymph node metastasis as accurately as assessment during surgery for patients with EGC.

L-homoarginine suppresses exocrine pancreas in rats.

Previously, we found that guanidinated casein, a L-homoarginine-containing protein, was a more potent stimulator of pancreatic enzyme secretion than intact casein in rats. In this study, we examined secretory response and adaptation of the exocrine pancreas to the administration of free L-homoarginine in normal and bile-pancreatic juice (BPJ)-diverted rats. An intraperitoneal injection of L-homoarginine (10 mg/rats) produced immediate and transient reduction in pancreatic secretion in BPJ-diverted rats, but not in normal rats. The BPJ-diverted rats were fed with either a 25% casein, 45% casein, or 45% casein diet supplemented with L-homoarginine (19 g/kg diet) for 4 days. Feeding of a diet containing L-homoarginine inhibited the pancreatic adaptation induced by the high-protein diet. These results indicate that L-homoarginine has an inhibitory effect on the secretion and production of exocrine pancreatic enzyme in BPJ-diverted rats, and L-homoarginine may have an antagonistic effect on CCK receptors.

[Three cases of small intrapulmonary lymph nodes coincidental with primary lung cancer].

We report three cases of intrapulmonary lymph nodes coincidental with primary lung cancers. In the first case, a 56-year-old man had a small subpleural nodule in the right lower lobe associated with adenocarcinoma of the right upper lobe. The small nodule was 10 mm in diameter and was difficult to differentiate radiologically from intrapulmonary metastasis. Wedge resection of this small nodule was performed. Histologic examination of the nodule revealed an intrapulmonary lymph node with anthracotic pigmentation. A right upper lobectomy for adenocarcinoma was performed, and was completely curative. The second patient, a 77-year-old woman, had adenocarcinoma in the right lower lobe diagnosed by transbronchial biopsy. Computed tomography (CT) revealed a small nodule 5 mm in diameter in the right upper lobe. Histologic examination of the small wedge-resected nodule revealed a lymph node. Lower lobectomy was performed with completely curative results. In the third case, a 63-year-old man was admitted for investigation of a mass shadow in the right upper lobe. CT showed a small nodular shadow in the right middle lobe, confirmed histologically to be lymphoid tissue, in addition to the original mass, which was diagnosed by transbronchial biopsy as squamous cell carcinoma. Upper lobectomy was performed and proved to be curative. Small intrapulmonary lymph nodes are very difficult to diagnose by methods other than surgical resection. When a small intrapulmonary nodule is detected in a patient with primary lung cancer, the presence of an intrapulmonary lymph node must be considered. If radiological characters compatible with an intrapulmonary lymph node are found and there is no other metastasis indicating poor prognosis, it should be considered as a possible indication for surgical resection.

Potential fascial dome made by the upper leaf of the phreno-esophageal membrane.

We describe the configuration and size of the artificial fascial dome created in 57 cadavers. This dome protrudes into the thoracic cavity from the esophageal hiatus. This dome was a potential space realized by finger dissection (i.e., a specific but common surgical procedure during surgery of the upper part of the stomach). The vagus nerves penetrated the top of the dome and ran down along the esophagus. The height of the ventral wall of the dome ranged from 10-60 mm, while the dorsal wall was 10-40 mm longer than the ventral one since the dorsal wall attached to the lower, dorsal limb of the esophageal hiatus. Accordingly, the dorsal wall separated the "thoracic" aorta from the "abdominal" esophagus. We considered that the upper leaf of the phreno-esophageal membrane forms the fascial dome, although the lower leaf of the membrane was not identified in this study. According to the results, we proposed a schematic representation of the phreno-esophageal membrane.

Endogenous cholecystokinin plays a role in down-regulation of pancreatic amylase independent of dietary carbohydrate in rats.

The role of cholecystokinin (CCK) in the regulation of pancreatic amylase has not been fully clarified. We examined the effects of hyperCCKemia with chronic pancreatico-biliary diversion (PBD) and blockade of CCK(A)-receptor on rat pancreatic amylase activity and mRNA abundance. Also, we examined the relationship between diet and CCK in terms of regulation of pancreatic amylase. PBD was produced by transposition of the duodenal segment containing the ampulla of Vater to the upper ileum. A potent CCK(A)-receptor antagonist, devazepide, was injected (6 mg/kg body weight per day for 5 days) in the PBD rats fed with diets containing normal or low level of carbohydrate (695 or 345 g sucrose/kg diet). The specific activity and mRNA abundance of the pancreatic amylase were constantly lower 4, 10 and 28 days after PBD than those after the sham operation. Devazepide treatment completely restored the amylase activity lowered by PBD without any increases in amylase mRNA. Feeding a high-protein low-carbohydrate diet suppressed the pancreatic amylase activity and mRNA abundance in PBD rats to a similar degree in those treated, and those untreated, with devazepide. We conclude that endogenous CCK suppresses pancreatic amylase production, and we speculate that CCK reduced translational efficiency of amylase mRNA. The effect of CCK on amylase production is independent of regulation by dietary carbohydrate.

Selective production of staplabin and SMTPs in cultures of Stachybotrys microspora fed with precursor amines.

Staplabin and SMTPs, a family of triprenyl phenol metabolites of Stachybotrys microspora, enhance fibrinolysis by modulating plasminogen conformation to increase its susceptibility to activation by plasminogen activators. We found that the production of these metabolites were markedly elevated by feeding the microbial culture with an amino acid or an amino alcohol that is a partial molecular constituent of the compound. Thus, the addition of 5-aminovaleric acid, 2-aminoethanol, Ser, Phe, Leu, Trp, Orn and Lys at 100 mg/ml resulted in 7- to 45-fold increases in the production of staplabin, SMTP-1, -3, -4, -5, -6, -7 and -8, respectively. Although the feeding at day 0 to 3 of culture supported the selective production, the supplementation after 5 days had little or no effect. When non-constituent amino acids were supplemented to cultures, production of hitherto uncharacterized congeners was observed.

Non-lupus nephropathy associated with antiphospholipid antibodies.

Renal biopsy was performed in a 12-year-old girl with hematuria and proteinuria which was first detected at the age of 7, and the findings were the mesangial proliferative glomerulonephritis with IgG and C3 deposits. The routine blood examination for the biopsy disclosed the presence of the prolonged activated partial thromboplastin time and the biological false positive reaction in the syphilis test. These results led us to the further investigation, which revealed the presence of high titers of anticardiolipin antibodies. Since this girl presented no extra-renal symptoms of systemic lupus erythematosus (SLE) and had negative serologic tests for SLE, we hypothesize that her nephritis is closely related to antiphospholipid antibodies.

Luminal dietary protein, not amino acids, induces pancreatic protease via CCK in pancreaticobiliary-diverted rats.

We determined whether pancreatic adaptation to a high-protein diet depends on ingested protein in the intestinal lumen and whether such adaptation depends on a CCK or capsaicin-sensitive vagal afferent pathway in pancreaticobiliary-diverted (PBD) rats. Feeding a high-casein (60%) diet but not a high-amino acid diet to PBD rats increased pancreatic trypsin and chymotrypsin activities compared with those after feeding a 25% casein diet. In contrast, feeding both the high-nitrogen diets induced pancreatic hypertrophy in PBD rats. These pancreatic changes by the diets were abolished by treatment with devazepide, a CCK-A receptor antagonist. Protease zymogen mRNA abundance in the PBD rat was not increased by feeding the high-casein diet and was decreased by devazepide. Perivagal capsaicin treatment did not influence the values of any pancreatic variables in PBD rats fed the normal or high-casein diet. We concluded that luminal protein or peptides were responsible for the bile pancreatic juice-independent induction of pancreatic proteases on feeding a high-protein diet. The induction was found to be dependent on the direct action of CCK on the pancreas. Pancreatic growth induced by high-protein feeding in PBD rats may depend at least partly on absorbed amino acids.

[Surrogate and true endpoints in cancer clinical trials].

To facilitate the proper and quick evaluation of cancer chemotherapy, the issues of surrogate and true endpoints in clinical trials were reviewed. Surrogate endpoints are defined as response variables that can substitute for a true endpoint due to their close correlation with the true endpoint, and their occurrence earlier than true endpoint. The response rate in cancer chemotherapy has been used as a surrogate or true endpoint for the evaluation of treatments. However, recent studies revealed that response rates do not always correlate with survival time (time to failure), and better surrogate endpoints such as time to progression, median survival time, or various surrogate biomarkers are now under investigation.

Activation of fibrinolysis by SMTP-7 and -8, novel staplabin analogs with a pseudosymmetric structure.

Two novel staplabin analogs, SMTP-7 and -8, have been isolated from cultures of Stachybotrys microspora IFO 30018. Spectroscopic analyses showed that the SMTP-7 molecule consisted of two identical staplabin core structures and ornithine which bridges the two partial structures. In the SMTP-8 molecule, the bridging unit was lysine. At concentrations of 80 approximately 150 microM, the two compounds caused 2- to 12-fold increase in urokinase-catalyzed plasminogen activation, fibrin binding of plasminogen, and urokinase- and plasminogen-mediated fibrinolysis. These activities of SMTP-7 and -8 were two to ten times higher than those of staplabin and previously isolated SMTPs, which exerted such effects at concentrations ranging from 150 to 800 microM.