Current Status and Issues Associated with Bariatric and Metabolic Surgeries in Japan.

Among Asian countries, laparotomic and laparoscopic bariatric surgeries were introduced in Japan after its establishment in Taiwan. However, despite high prevalence of potential patients with obesity and diabetes, the wider incorporation of surgery into treatment regimen has been stalling for decades in Japan. While the unique Japanese national health insurance system has guaranteed fair healthcare delivery, it might have worked as a barrier to the development of bariatric and metabolic surgeries (BMS). The present article reviews the status of BMS in Japan and discusses recent issues related to its use. To focus on and identify the major obstacles inhibiting the widespread use of BMS, we have comprehensively covered some major areas including the insurance system, surgical indication, accreditation and training system, original research, and national registry.

The long-term outcomes in adolescent and young adult patients with colorectal cancer -A multicenter large-scale cohort study.

Introduction: The prognosis of adolescent and young adult (AYA) patients with colorectal cancer (CRC) is still unclear. The aim of this study was to investigate the clinical features and prognosis in AYA patients compared with middle- aged patients. Methods: Participants were identified from a clinical database of the multicenter cohort in Japan. The AYA group was defined as those <40 years of age, whereas the middle-aged group was defined in 10-year ranges around the median age of all patients. The primary outcome was the overall survival (OS), and the secondary outcome was the recurrence-free survival (RFS). Results: A total of 502 patients were enrolled as the AYA group, and 7222 patients between 65 and 74 years of age were identified as the middle-aged group. The OS of colon cancer in stages II and III was significantly better in the AYA group (p = 0.033, 0.006, respectively) than in the middle-aged groups. There were no significant differences in the OS of rectal cancer in stages II and III between the two groups. Conclusion: The prognosis of AYA patients with CRC was the same or better than that in middle-aged patients.

Risk factors for postoperative stoma outlet obstruction in ulcerative colitis.

BACKGROUND: Current medical treatments can achieve remission of ulcerative colitis (UC). Surgery is required when potent drug treatment is ineffective or when colon cancer or high-grade dysplasia develops. The standard procedure is restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis, commonly performed as two- or three-stage RPC with diverting ileostomy. Postoperative stoma outlet obstruction (SOO) is frequent, but the causes are not well known. AIM: To identify the risk factors for SOO after stoma surgery in patients with UC. METHODS: We retrospectively reviewed the files of 148 consecutive UC patients who underwent surgery with stoma construction. SOO was defined as small bowel obstruction symptoms and intestinal dilatation just below the penetrating part of the stoma on computed tomography. Patients were divided into two groups: Those who developed SOO within 30 d after surgery and those who did not. Patient characteristics, intraoperative parameters, the stoma site, and rectus abdominis muscle thickness were collected. Moreover, we identified the patients who repeatedly developed SOO. Univariate and multivariate analyses were performed to identify risk factors for SOO and recurring SOO. RESULTS: Eighty-nine patients who underwent two-stage RPC were included between January 2008 and March 2020. Postoperatively, SOO occurred in 25 (16.9%) patients after a median time of 9 d (range 2-26). Compared to patients without SOO, patients with SOO had a significantly higher rate of malignant tumors or dysplasia (36.0% vs 17.1%, P = 0.032), lower total glucocorticoid dose one month before surgery (0 mg vs 0 mg, P = 0.026), higher preoperative total protein level (6.8 g/dL vs 6.3 g/dL, P = 0.048), higher rate of loop ileostomy (88.0% vs 55.3%, P = 0.002), and higher maximum stoma drainage volume (2300 mL vs 1690 mL, P = 0.004). Loop ileostomy (OR = 6.361; 95%CI 1.322-30.611; P = 0.021) and maximum stoma drainage volume (OR = 1.000; 95%CI 1.000-1.001; P = 0.015) were confirmed as independent risk factors for SOO. Eighteen patients with SOO were treated conservatively without recurrence (sSOO group). Seven (28.0%) patients repeatedly developed SOO (rSOO group) during the observation period. A significant difference was observed in the rectus abdominis muscle thickness between the two groups (sSOO 9.3 mm, rSOO 12.7 mm, P = 0.006). Muscle thickness was confirmed as an independent risk factor for recurring SOO (OR = 2.676; 95%CI 1.176-4.300; P = 0.008). CONCLUSION: In this study, high maximum stoma drainage volume and loop ileostomy are independent risk factors for SOO. Additionally, among patients with a thick rectus abdominis muscle, the risk of SOO recurrence is high.

The utility of longitudinal slicing method for rectal specimen: pathological analysis of circumferential resection margin of intersphincteric resection for low-lying rectal cancer.

The pathological assessment of the resection margin of rectal cancer is important to predict clinical outcome. The transverse slicing method of rectal specimens is recommended in Western countries. However, in Japan the longitudinal slicing method is traditionally advocated. The aim of this study was to assess the advantages of the longitudinal slicing method. The subjects were 197 consecutive patients with primary rectal cancer who underwent curative intersphincteric resection from 2000 to 2013. The resected rectal specimens were cut into 12 slices in the direction of the long axis. Resection margin was considered positive when it was less than or equal to 1 mm. Resection margin was positive in 23 patients (12%). They were classified into two groups, namely the DEEP group (n = 16, 70%), when the resection margin corresponded to the deepest tumor invasion area, and the ENTRY group (n = 7, 30%), when resection margin was around the initial cutting point of the anal canal. It was shown that resection margin tends to be positive not only in the deepest tumor invasion area but also in the entry area of the anal canal. The longitudinal slicing method may have some advantages for accurate assessment of resection margin especially in low-lying rectal cancer.

[Four Patients Who Underwent Proton Beam Therapy after Debulking Surgery and Omental Wrapping of the Residual Tumor as a Spacer for Unresectable Local Recurrence of Rectal Cancer].

We report 4 patients who underwent proton beam therapy after debulking surgery for unresectable local recurrence of rectal cancer. Case 1: A 55-year-old man underwent radiotherapy and systemic chemotherapy for local recurrence; however, the lesion exhibited evident regrowth. Combination therapy of debulking surgery, omental wrapping of the residual tumor as a spacer, and postoperative proton beam therapy was performed. He died of lung metastasis after 24 months. Case 2: A 79- year-old woman who underwent surgical resections and radiotherapy twice in a previous hospital was referred to our hospital. Similar to that in case 1, proton beam therapy after debulking surgery and omental wrapping was performed. She died of lymph node metastasis after 31 months. Case 3: A 75-year-old man was diagnosed with unresectable local recurrence of rectal cancer. He underwent combination therapy and is doing well without any recurrence for 43 months. Case 4: A 57-yearold woman was also diagnosed with unresectable local recurrence. She underwent the same combination therapy after systemic chemotherapy. She died of lymph node metastasis after 11 months.

Anal Function after Surgery for Low-Lying Rectal Cancer: Comparison of Mechanical and Hand-Sewn Coloanal Anastomosis.

BACKGROUND/AIMS: Mechanical coloanal anastomosis (MCAA) or hand-sewn coloanal anastomosis (HCAA) are used in anus-preserving surgery for low-lying rectal cancer. Either method can be used if the lower edge of the tumor is 4-6 cm from the anal verge. The goal of this study was to evaluate differences in the anal function after MCAA or HCAA. METHODS: The subjects were 305 consecutive patients with primary rectal cancer tumors situated 4-6 cm from the anal verge who underwent curative anus-preserving surgery between 2004 and 2013. Functional assessment was performed using a questionnaire at 3, 6, 12, and 24 months after stoma closure. RESULTS: Of the 305 patients, 145 underwent MCAA and 160 underwent HCAA. The median distance of the tumor from the anal verge was 6.0 cm (range 4.0-6.0) in the MCAA group and 4.5 cm (range 4.0-6.0) in the HCAA group (p < 0.001). A total of 192 patients (73%) responded to the 1-year questionnaire. The median Wexner score was 6 (range 0-17) in the MCAA group and 11 (range 0-20) in the HCAA group (p < 0.001). CONCLUSIONS: Retention of anal function is feasible after both MCAA and HCAA. MCAA may contribute to better postoperative anal function compared to HCAA.

Quantitative evaluation of 3D imaging in laparoscopic surgery.

PURPOSE: 3D images offer true depth perception, which overcomes one of the disadvantages of laparoscopic surgery. We evaluated differences in the use of 3D and 2D images in laparoscopic surgery based on the recording of traces of forceps. METHODS: Twelve surgeons at our hospital participated in the study. The task consisted of one suture and three ligations, using a training box. The completion time and number of hold errors were noted, and forceps traces were recorded using the Behavior Checker system (Miura Medical). Participants were divided into two groups based on faster and slower completion times with 2D images. RESULTS: The median completion time in seconds (s) was significantly shorter when using 3D images than when using 2D images (51 s, range 34-146 vs. 63 s, range 38-265 s; p = 0.013). The 3D/2D completion time ratio was significantly higher in the faster 2D group (0.93 vs. 0.69, p = 0.030) indicating a greater effect of the 3D images on less experienced participants. CONCLUSIONS: A quantitative evaluation showed that using 3D images enables more efficient use of laparoscopic forceps than 2D images. A system with 3D images is of particular benefit for inexperienced surgeons.

The acquisition process of musical tonal schema: implications from connectionist modeling.

Using connectionist modeling, we address fundamental questions concerning the acquisition process of musical tonal schema of listeners. Compared to models of previous studies, our connectionist model (Learning Network for Tonal Schema, LeNTS) was better equipped to fulfill three basic requirements. Specifically, LeNTS was equipped with a learning mechanism, bound by culture-general properties, and trained by sufficient melody materials. When exposed to Western music, LeNTS acquired musical 'scale' sensitivity early and 'harmony' sensitivity later. The order of acquisition of scale and harmony sensitivities shown by LeNTS was consistent with the culture-specific acquisition order shown by musically westernized children. The implications of these results for the acquisition process of a tonal schema of listeners are as follows: (a) the acquisition process may entail small and incremental changes, rather than large and stage-like changes, in corresponding neural circuits; (b) the speed of schema acquisition may mainly depend on musical experiences rather than maturation; and

Signature-tagged mutagenesis of Vibrio vulnificus.

Vibrio vulnificus is the causative agent of primary septicemia, wound infection and gastroenteritis in immunocompromised people. In this study, signature-tagged mutagenesis (STM) was applied to identify the virulence genes of V. vulnificus. Using STM, 6,480 mutants in total were constructed and divided into 81 sets (INPUT pools); each mutant in a set was assigned a different tag. Each INPUT pool was intraperitoneally injected into iron-overloaded mice, and in vivo surviving mutants were collected from blood samples from the heart (OUTPUT pools). From the genomic DNA of mixed INPUT or OUTPUT pools, digoxigenin-labeled DNA probes against the tagged region were prepared and used for dot hybridization. Thirty tentatively attenuated mutants, which were hybridized clearly with INPUT probes but barely with OUTPUT probes, were negatively selected. Lethal doses of 11 of the 30 mutants were reduced to more than 1/100; of these, the lethal doses of 2 were reduced to as low as 1/100,000. Transposon-inserted genes in the 11 attenuated mutants were those for IMP dehydrogenase, UDP-N-acetylglucosamine-2-epimerase, aspartokinase, phosphoribosylformylglycinamidine cyclo-ligase, malate Na (+) symporter and hypothetical protein. When mice were immunized with an attenuated mutant strain into which IMP dehydrogenase had been inserted with a transposon, they were protected against V. vulnificus infection. In this study, we demonstrated that the STM method can be used to search for the virulence genes of V. vulnificus.

Functional modulations in brain activity for the first and second music: a comparison of high- and low-proficiency bimusicals.

Bilingual studies have shown that brain activities for first (L1) and second (L2) languages are influenced by L2 proficiency. Does proficiency with a second musical system (M2) influence bimusical brains in a manner similar to that of bilingual brains? Our magnetoencephalography study assessed the influence of M2 proficiency on the spatial, strength, and temporal properties of brain activity in a musical syntactic-processing task (i.e., tonal processing) involving first (M1) and second (M2) music systems. Two bimusical groups, differing in M2 proficiency (high, low), listened to melodies from both their M1 and M2 musical cultures. All melodies ended with a tonally consistent or inconsistent tone. In both groups, tonal deviations in both M1 and M2 elicited magnetic early right anterior negativities (mERANs) that were generated from brain areas around the inferior frontal gyrus (IFG). We also analyzed the dipole locations, dipole strengths, and peak latencies of mERAN. Results revealed: (a) the distances between dipole locations for M1 and M2 were shorter in the M2 high-proficiency group than in the M2 low-proficiency group; (b) the dipole strengths were greater in the high than the low group; (c) the peak latencies of M2 were shorter in the high than low group. The dipole location results were consistent with those from bilingual studies in that the distances between the (left) IFG peak activations for L1 and L2 syntactic processing shortened as L2 proficiency increased. The parallel results for bimusicals and bilinguals suggest that the functional changes induced by proficiency in a second (linguistic or musical) system are defined by domain-general neural constraints.

Magnetoencephalography evidence for different brain subregions serving two musical cultures.

Individuals who have been exposed to two different musical cultures (bimusicals) can be differentiated from those exposed to only one musical culture (monomusicals). Just as bilingual speakers handle the distinct language-syntactic rules of each of two languages, bimusical listeners handle two distinct musical-syntactic rules (e.g., tonal schemas) in each musical culture. This study sought to determine specific brain activities that contribute to differentiating two culture-specific tonal structures. We recorded magnetoencephalogram (MEG) responses of bimusical Japanese nonmusicians and amateur musicians as they monitored unfamiliar Western melodies and unfamiliar, but traditional, Japanese melodies, both of which contained tonal deviants (out-of-key tones). Previous studies with Western monomusicals have shown that tonal deviants elicit an early right anterior negativity (mERAN) originating in the inferior frontal cortex. In the present study, tonal deviants in both Western and Japanese melodies elicited mERANs with characteristics fitted by dipoles around the inferior frontal gyrus in the right hemisphere and the premotor cortex in the left hemisphere. Comparisons of the nature of mERAN activity to Western and Japanese melodies showed differences in the dipoles' locations but not in their peak latency or dipole strength. These results suggest that the differentiation between a tonal structure of one culture and that of another culture correlates with localization differences in brain subregions around the inferior frontal cortex and the premotor cortex.

Two cis-acting regulatory elements are involved in the sucrose-inducible expression of the sporamin gene promoter from sweet potato in transgenic tobacco.

In this study, we generated transgenic tobacco plants that express the beta-glucuronidase (GUS) gene under the control of the 305-bp 5'-upstream region of a gene coding for sporamin A of sweet potato. Expression of GUS in excised tobacco leaves was induced by sucrose, mimicking the sugar-inducible expression of the endogenous sporamin genes in sweet potato. Deletion of the sequences extending from position -305 (relative to the transcription start site) to -283 and from -146 to -87 resulted in an approximately 40-fold enhancement in GUS reporter expression. Furthermore, the sequence from -282 to -165 conferred sucrose-inducibility on the -89 core promoter of the Cauliflower Mosaic Virus 35S RNA gene. Analysis of internal deletions, linker scanning and the introduction of base substitutions in the sequence between positions -282 and -165 indicated that sucrose-responsiveness conferred by this region was dependent on the presence of two cis-acting elements, termed CMSREs (carbohydrate metabolite signal responsive elements) 1 and 2, which are separated by a spacer. A sequence similar or identical to the core of CMSRE-1 (TGGACGG) is also present in the promoters of several other sugar-inducible genes, and sequences encopassing the TGGACGG-related motifs from two of these could functionally replace the CMSRE-1 in the truncated sporamin A promoter. These results suggest that the TGGACGG element plays an important role in the sucrose-inducible expression of a group of plant genes.