Toshio Shimokawa

Daily Repetitive Transcranial Magnetic Stimulation for Poststroke Upper Limb Paresis in the Subacute Period

BACKGROUND We conducted a randomized, double-blind, sham-controlled study to assess the efficacy in motor recovery and safety of daily repetitive transcranial magnetic stimulation (rTMS) in subacute stroke patients. METHODS Forty-one patients were randomly assigned to a real or sham stimulation group. Each patient underwent regular rehabilitation accompanied by a series of 10 daily 5-Hz rTMS of the ipsilesional primary motor cortex (M1) or sham stimulation. The primary outcome was motor recovery evaluated by the Brunnstrom stages (BS). The secondary outcomes were improvement in the Fugl-Meyer Assessment (FMA), grip power, National Institutes of Health Stroke Scale (NIHSS), Functional Independence Measure (FIM), a quantitative measurement of finger tapping movement, and the incidence of adverse events. RESULTS Thirty-nine patients completed the study and were included in the analyses. The real rTMS group demonstrated additional improvement in the BS hand score at the last follow-up compared to the sham. The grip power, the NIHSS motor score, and the number of finger taps in the affected hand improved in the real stimulation group but not in the sham group. The BS upper limb scores, the FMA distal upper limb score, the NIHSS total score, and the FIM motor score showed improvement from baseline at the earlier time points after the real rTMS. There were no additional improvements in the other scores after the real rTMS compared to the sham. No serious adverse events were observed. CONCLUSIONS Our results suggest that dailyhigh-frequency rTMS of the ipsilesional M1 is tolerable and modestly facilitates motor recovery in the paralytic hand of subacute stroke patients.

Lipid is absorbed in the stomach by epithelial neoplasms (adenomas and early cancers): a novel functional endoscopy technique

Background and study aims: The authors have successfully demonstrated that the white opaque substance (WOS) identified in gastric epithelial neoplasms is an accumulation of minute lipid droplets on the epithelial neoplasm. It is not known whether the lipid droplets originate from externally ingested lipids (typically foods). The purpose of this study was to investigate whether the oral ingestion of foods containing emulsified fats increases the density of the WOS in epithelial neoplasms. Patients and methods: We examined 92 gastric epithelial neoplastic lesions in 89 patients. The patients were given emulsified fatty foods before the procedure, and magnifying endoscopy with narrow-band imaging (M-NBI) was used to image the lesions. An increase in WOS density after the ingestion of emulsified fatty foods was defined as a positive fat-loading test result. The patients were divided into the following groups: control group, no emulsified fat administered; group 1, fatty food administered 16 hours prior; group 3, fatty food administered both 16 and 4 hours prior. The proportion of positive fat-loading test results was determined in all groups. Results: The rates of positive fat-loading test results were as follows: control group, 9 %; group 1, 26 %; group 2, 52 %; group 3, 78 %. The increase in the rates of positive fat-loading test results in groups 2 and 3 relative to the rate in the control group was statistically significant (chi-squared test). Conclusions: This study demonstrated for the first time that the ingestion of external lipids causes lipid droplets to aggregate in situ on the gastric epithelial neoplasm. These results can be used to develop a novel functional endoscopy technique that harnesses the lipid absorption capacity of neoplasms.

Severity of Premenstrual Symptoms Predicted by Second to Fourth Digit Ratio

Women of reproductive age often experience a variety of unpleasant symptoms prior to the onset of menstruation. While genetics may influence the variability of these symptoms and their severity among women, the exact causes remain unknown. We hypothesized that symptom variability originates from differences in the embryonic environment and thus development caused by variation in exposure to sex hormones. We measured the second to fourth digit ratios (2D:4D) in 402 young women and investigated the potential relationships of this ratio premenstrual symptoms using a generalized linear model. We found that two models (one with two predictors such as both hands’ digit ratios and the other with the difference between the two digit ratios, Dr-l) were significantly different from the constant model as assessed by chi-square test. The right digit ratio and Dr-l were negatively related to the symptom scores, and the left digit ratio was related to the scores. When premenstrual symptoms were classified into eight categories, five categories, including pain, concentration, autonomic reaction, negative affect, and control were associated with the digit ratios and Dr-l. Behavioral changes and water retention were not predicted by them. Arousal was predicted by Dr-l. The right 2D:4D is thought to be determined by the balance of testosterone and estrogen levels during early embryogenesis and is not affected by postpartum levels of sex hormones, while the left 2D:4D might be affected by the other prenatal environmental factors. We conclude that the embryonic environment, including the relative concentration of sex hormones an embryo is exposed to, is associated with the severity of premenstrual symptoms once menarche is reached.

Extending magnifying NBI diagnosis of intestinal metaplasia in the stomach: the white opaque substance marker

Background and aims Intestinal metaplasia (IM) of the stomach is associated with an increased risk of differentiated gastric cancer. While it is important to diagnose IM endoscopically, it can be difficult to observe by white-light endoscopy. In magnifying endoscopy with narrow-band imaging (M-NBI) of the stomach, a light-blue crest (LBC) is widely known to be a useful marker in the endoscopic diagnosis of IM. However, IM that exhibits only white opaque substance (WOS) without an LBC can also occur. The aim of this study was to elucidate whether the presence of WOS on M-NBI of the stomach could serve as a marker of IM in the same way that an LBC does. Methods The subjects were 40 consecutive patients who underwent M-NBI between July and December 2014. The primary endpoint in this study was to evaluate the diagnostic performance of M-NBI for histologically observed IM in WOS- and LBC-positive mucosa. Results The sensitivity and specificity of WOS for histologically diagnosed IM were 50.0 % (95 % confidence interval [CI] 40.0 % - 50.0 %) and 100.0 % (95 %CI 85.0 % - 100.0 %), respectively. Meanwhile, the sensitivity and specificity of LBC were 62.5 % (95 %CI 51.1 % - 65.9 %) and 93.8 % (95 %CI 76.7 % - 98.9 %), respectively. The sensitivity and specificity of WOS and/or LBC (WOS positive and LBC positive, WOS positive and LBC negative, or WOS negative and LBC positive) for histologically diagnosed IM were 87.5 % (95 %CI 76.9 % - 90.9 %) and 93.8 % (95 %CI 77.9 % - 98.9 %), respectively. Conclusions LBC and WOS are both useful markers for endoscopic diagnosis of IM. Combining both markers improves the sensitivity.Clinical trial number: UMINCTR000014453.

Mesenteric approach during pancreaticoduodenectomy for pancreatic ductal adenocarcinoma

Mesenteric approach is an artery‐first approach during pancreaticoduodenectomy (PD). In the present study, we evaluated clinical and oncological benefits of this procedure for pancreatic ductal adenocarcinoma (PDAC) of the pancreas head. Between 2000 and 2015, 237 consecutive PDAC patients underwent PD. Among them, 72 experienced the mesenteric approach (mesenteric group) and 165 the conventional approach (conventional group). A matched‐pairs group consisted of 116 patients (58 patients in each group) matched for age, gender, resectability status, and neoadjuvant therapy. Surgical and oncological outcomes were compared between the two groups in unmatched‐ and matched‐pair analyses. Intraoperative blood loss was lower in the mesenteric group than in the conventional group in both resectable PDAC (R‐PDAC) and borderline resectable PDAC (BR‐PDAC) on unmatched‐ and matched‐pairs analyses (R‐PDAC, unmatched: 312.5 vs 510 mL, P=.008; matched: 312.5 vs 501.5 mL, P=.023; BR‐PDAC, unmatched: 507.5 vs 935 mL, P<.001; matched: 507.5 vs 920 mL, P=.003). Negative surgical margins (R0) and overall survival (OS) rates in the mesenteric group were better in R‐PDAC patients (R0 rates, unmatched: 100% vs 87.7%, P=.044; matched: 100% vs 86.7%, P=.045; OS, unmatched: P=.008, matched: P=.021), although there were no significant differences in BR‐PDAC patients. Mesenteric approach might reduce blood loss by early ligation of the vessels to the pancreatic head. Furthermore, it might increase R0 rate, leading to improvement of survival for R‐PDAC patients. However, R0 and survival rates could not be improved only by the mesenteric approach for BR‐PDAC patients. Therefore, effective multidisciplinary treatment is essential to improve survival in BR‐PDAC patients.

The optimal stimulation site for high-frequency repetitive transcranial magnetic stimulation in Parkinson’s disease: A double-blind crossover pilot study

Many reports have shown improvements in motor symptoms after repetitive transcranial magnetic stimulation (rTMS). However, the best stimulation area in the brain has not currently been determined. We assessed the effects of high-frequency rTMS (HF-rTMS) on the motor and mood disturbances in Parkinsons disease (PD) patients and attempted to determine whether the primary motor area (M1), the supplementary motor area (SMA), and the dorsolateral prefrontal cortex (DLPFC) were the best treatment targets. In this randomized, double-blind crossover design study, we investigated the efficacy of 3 consecutive days of HF-rTMS over the M1, SMA, and DLPFC and compared these HF-rTMS to sham stimulations. We used motor and non-motor scales to evaluate the parkinsonian symptoms. The changes in the Unified Parkinsons Disease Rating Scale part III (UPDRS-III) scores after the application of HF-rTMS over the M1 and SMA were significantly greater than those after the sham stimulation. However, after the application of HF-rTMS over the DLPFC, the UPDRS-III scores were similar to those after the sham stimulation. No significant improvements were demonstrated in the mood disturbances after the stimulations over any of the targets. In conclusion, the application of HF-rTMS over the M1 and SMA significantly improved the motor symptoms in the PD patients but did not alter the mood disturbances.

Delineation of the extent of early gastric cancer by magnifying narrow-band imaging and chromoendoscopy: a multicenter randomized controlled trial

BACKGROUND Accurate delineation of tumor margins is necessary for curative resection of early gastric cancer (EGC). The objective of this multicenter, randomized, controlled study was to compare the accuracy with which magnifying narrow-band imaging (M-NBI) and indigo carmine chromoendoscopy delineate EGC margins. METHODS Patients with EGC ≥ 10 mm undergoing endoscopic or surgical resection were enrolled. The oral-side margins of the lesions were first evaluated with conventional white-light endoscopy in both groups and then delineated by either chromoendoscopy or M-NBI. Biopsies were taken from noncancerous and cancerous mucosa, each at 5 mm from the margin. Accurate delineation was judged to have been achieved when the histological findings in all biopsy samples were consistent with endoscopic diagnoses. The primary end point was the difference in rate of accurate delineation between the two techniques. RESULTS Data on 343 patients were analyzed. The accurate delineation rate (95 % confidence interval) was 85.7 % (80.4 - 91.0) in the chromoendoscopy group (n = 168), and 88.0 % (83.2 - 92.8) in the M-NBI group (n = 175; P = 0.63). Lower third tumor location (odds ratio [OR] 2.9; P = 0.01), nonflat macroscopic type (OR 4.4; P < 0.01), and high diagnostic confidence (OR 3.6; P < 0.001) were associated with accurate delineation, whereas use of M-NBI was not (OR 1.2; P = 0.39). Even after adjustment for identified confounders, the difference in accurate delineation between the groups was not significant (OR 1.0; P = 0.82). CONCLUSIONS M-NBI does not offer superior delineation of EGC margins compared with chromoendoscopy; the two methods appear to be clinically equivalent.

Molecular diagnosis of lymph node metastasis in patients with upper urinary tract cancer who underwent lymphadenectomy

To determine the significance of molecular diagnosis of lymph node metastasis using quantitative reverse transcription polymerase chain reaction in patients with upper urinary tract urothelial cancer.

Robotic versus laparoscopic gastrectomy with lymph node dissection for gastric cancer: study protocol for a randomized controlled trial

BackgroundLaparoscopic gastrectomy (LG) has several benefits as a treatment of gastric cancer (GC), including reduced pain, early recovery of intestinal function, and shorter hospital stay. LG still has several drawbacks, however, including limited range of movement, amplification of hand tremors, and inconvenient surgical positioning. Around the peripancreatic area, laparoscopic lymph node dissection, therefore, remains challenging; postoperative pancreatic fistula occurs in around 4–7% of patients undergoing LG. Robotic surgery, on the other hand, plays a role in ergonomics and offers several advantages, including 7° of wrist-like motion, less fatigue, tremor filtering, motion scaling, and three-dimensional vision. In our previous retrospective study, we compared the safety and feasibility of surgical outcomes of LG and robotic gastrectomy (RG) for patients with GC. In our previous results, in the LG group, intra-abdominal infectious complications were found in 11%. In the RG group, however, none were found. Our RG procedure may be associated with decreased incidence of intra-abdominal infectious complications. Prospective randomized controlled trials (RCTs) comparing LG and RG are required, however. We begin an RCT to compare short-term surgical and long-term oncological outcomes of LG and RG for GC patients.MethodsThis is a randomized, single-center clinical trial. All included patients are adults with primary carcinoma of the stomach, in whom the tumor is considered surgically resectable (stages I–III). Included in this trial are 240 patients with GC. The primary endpoint is to assess the incidence of postoperative intra-abdominal infectious complications including pancreatic fistula, intra-abdominal abscess, and anastomotic leakage. Secondary endpoints include the incidence of any complications (both related and unrelated to surgery), surgical results, postoperative course, and oncological outcomes.DiscussionAlthough its short-term outcomes have been proven comparable to LG in comparative studies, use of RG remains restricted, partly due to the lack of informative RCTs pertaining to it. To evaluate the surgical and oncological outcomes of RG, we therefore undertake a prospective RCT. The obtained results will be useful for reducing the restrictions and for adaptive expansion of RG for patients with GC.Trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry, ID: UMIN000031536. Registered on 1 March 2017.

Splenic vein resection together with the pancreatic parenchyma versus separated resection after isolation of the parenchyma during distal pancreatectomy (COSMOS-DP trial): Study protocol for a randomised controlled trial

BackgroundIn distal pancreatectomy (DP), it is customary to ligate and divide the splenic vein after isolating it from the pancreatic parenchyma. This is considered essential to prevent disruption of the stump of the splenic vein and consequent intra-abdominal haemorrhage in the event of pancreatic fistula (PF). However, this procedure can be technically demanding, especially when the vein is firmly embedded in the pancreatic parenchyma. The objective of the COSMOS-DP trial is to confirm the non-inferiority of resection of the splenic vein embedded in the pancreatic parenchyma compared with the conventional technique of isolating the splenic vein before resection during DP using a mechanical stapler.MethodsPatients with diseases of the pancreatic body and tail whose pancreatic parenchyma and splenic vein can be divided concurrently during open or laparoscopic DP are considered eligible for inclusion. This study is designed as a multicentre prospective randomised phase III trial. Eligible patients will be centrally randomised to either Arm A (resection of the splenic vein after isolation from the pancreatic parenchyma) or Arm B (co-resection of the vein together with the pancreas). This study aims to establish the non-inferiority of the safety of Arm B compared with that of Arm A; the primary endpoint is the incidence of PF (ISGPF grade B/C).DiscussionThe COSMOS-DP trial will establish the safety of this procedure, such that it can be recommended with more confidence. The use of this procedure will likely result in significant reductions in operative time and blood loss during DP.Trial registrationClinicalTrials.gov, NCT02871804. Registered on 27 July 2016.