Multicenter epidemiological survey of pneumatosis intestinalis in Japan.

BACKGROUND: Pneumatosis intestinalis (PI) is a rare condition characterized by gas collection in the intestinal wall. We aimed to determine the etiology and affected segments associated with complications, treatment, and outcome. METHODS: We conducted a multicenter epidemiological survey using a standardized data collection sheet in Japan. Complicating PI was defined as strangulation or bowel necrosis, bowel obstruction, adynamic ileus, sepsis, shock, and massive gastrointestinal bleeding requiring blood transfusion. RESULTS: We enrolled 167 patients from 48 facilities. Multivariate analysis revealed that older age (adjusted OR, 1.05 and 95% confidence intervals [CI], 1.02-1.09, P = 0.0053) and chronic kidney disease (adjusted OR, 13.19 and 95% CI 1.04-167.62, P = 0.0468) were independent predictors of the small-bowel-involved type. Complicating PI was associated with the small-bowel-involved combined type (adjusted OR, 27.02 and 95% CI 4.80-152.01, P = 0.0002), the small-bowel-only type (adjusted OR, 3.94 and 95% CI 1.02-15.27, P = 0.0472), and symptomatic PI (adjusted OR, 16.24 and 95% CI 1.82-145.24, P = 0.0126). Oxygen therapy was performed in patients with a past history of bowel obstruction (adjusted OR, 13.77 and 95% CI 1.31-144.56, P = 0.0288) and surgery was performed in patients with complicating PI (adjusted OR, 8.93 and 95% CI 1.10-72.78, P = 0.0408). Antihypertensives (adjusted OR, 12.28 and 95% CI 1.07-140.79, P = 0.0439) and complicating PI (adjusted OR, 11.77 and 95% CI 1.053-131.526; P = 0.0453) were associated with exacerbation of PI. The complicating PI was the only indicator of death (adjusted OR, 14.40 and 95% CI 1.09-189.48, P = 0.0425). DISCUSSION: Small-bowel-involved type and symptomatic PI were associated with complications which were indicators of poor prognosis.

Cancer risk and genotype-phenotype correlation in Japanese patients with Cowden syndrome.

BACKGROUND: Cowden syndrome (CS) is an autosomal-dominant hereditary disorder caused by a germline PTEN variant and characterized by multiple hamartomas and a high risk of cancers. However, no detailed data on CS in Asian patients nor genotype-phenotype correlation have been reported. METHODS: We performed the first Japanese nationwide questionnaire survey on CS and obtained questionnaire response data on 49 CS patients. RESULTS: Patients included 26 females (median age 48 years). The incidence of breast, thyroid, endometrium, and colorectal cancer was 32.7%, 12.2%, 19.2% (among females), and 6.1%, respectively. The incidence of any cancers was relatively high among all patients (46.9%, 23/49), and particularly female patients (73.1%, 19/26), compared with previous reports from Western countries. Gastrointestinal (GI) polyps were more frequently found throughout the GI tract compared with previous studies. PTEN variants were detected in 95.6% (22/23) of patients; 12 in the N-terminal region (11 in phosphatase domain) and 10 in the C-terminal (C2 domain) region. The incidence of cancer in the C2 domain group was significantly higher than in the N-terminal region (phosphatase) group. All female patients with C2 domain variant had breast cancer. CONCLUSION: Our data suggest that Japanese patients with CS, particularly female patients and patients with C2 domain variant may have a high risk of cancers.

Efficacy and safety of oral sulfate solution for bowel preparation in Japanese patients undergoing colonoscopy: Noninferiority-based, randomized, controlled study.

OBJECTIVES: To compare the efficacy and safety of oral sulfate solution administered using the same-day dose and the split-dose regimens with those of polyethylene glycol plus ascorbate solution, used for bowel preparation in Japanese patients undergoing colonoscopy. METHODS: This multicenter (n = 13), randomized, active-controlled, colonoscopist- and image evaluator-blinded, noninferiority study with parallel-group comparison recruited 632 patients from December 2018 to June 2019. Of these, 602 patients were divided into the oral sulfate solution same-day dose group (n = 200); oral sulfate solution split-dose group (n = 202); and polyethylene glycol plus ascorbate same-day dose group (n = 200). Differences in the efficacy rates between the polyethylene glycol plus ascorbate group and each oral sulfate solution group were calculated using the asymptotic method. The safety of the oral sulfate solution was evaluated, based on the occurrence of adverse events and reactions. RESULTS: Both oral sulfate solution protocols were confirmed as noninferior to the polyethylene glycol plus ascorbate protocol for bowel-cleansing. The occurrence of adverse reactions was significantly lower in the oral sulfate solution same-day dose group than in the polyethylene glycol plus ascorbate group (P = 0.010). The occurrence of adverse reactions was not significantly different between the oral sulfate solution split-dose and the polyethylene glycol plus ascorbate group. CONCLUSIONS: Oral sulfate solution is not only safe and efficacious but also not inferior to polyethylene glycol plus ascorbate solution (active control). It could be used for bowel preparation in Japanese patients scheduled for colonoscopy (Clinical trial registration number: NCT03794310).

A Simple Method to Avoid Bile Duct Injury during Percutaneous Radiofrequency Ablation Therapy for Hepatocellular Carcinoma.

Hepatocellular carcinoma represents a major global health burden. Its treatment is often complicated by the anatomical location of tumors, which can lead to adverse outcomes. Radiofrequency ablation has recently gained attention as a safe method for treating hepatocellular carcinoma, but only in tumors that are not adjacent to bile ducts. Here, we report a new method for cooling the bile duct during radiofrequency ablation therapy, in which the outer jacket of an elastor needle was fixed and flash-cooled with chilled saline. This method was applied in a patient with hepatocellular carcinoma tumors near the main bile duct. The patient underwent successful radiofrequency ablation with bile duct cooling. The advantages of this method include low medical cost, simpler securing of nonexpanded bile ducts, and simultaneous removal upon termination of the radiofrequency ablation therapy. Bile duct complications associated with radiofrequency ablation typically have delayed onset. Computed tomography examination 2 months after treatment showed no bile duct injury in this case.

Procedure of Direct Hepatic Artery Puncture for the Treatment of Hepatocellular Carcinoma: Two Case Reports.

Recently, treatment options for hepatocellular carcinoma (HCC) have expanded due to the development of the tyrosine kinase inhibitor ramucirumab and immune checkpoint inhibitors. Transcatheter arterial chemoembolization is the standard therapy for intermediate-stage HCC; however, in cases with anatomical problems, normal approaches are not possible. In such rare cases, direct hepatic puncture may be considered as an effective therapy and an indispensable treatment. We report our novel method of direct hepatic artery puncture in this case report. In 2011 and 2017, we reported 2 cases in the journal of the Japan Society of Hepatology in Japanese. This therapy is difficult and is associated with a high risk of complications; however, we succeeded in both cases in a similar way. We believe this method may provide an alternative treatment when standard treatment is not possible or when urgent therapy is required. In case 1, direct hepatic artery puncture was performed under ultrasonographic guidance, and we were able to control the disease with percutaneous lipiodol chemotherapy. Case 2 was an emergency case of ruptured HCC. Direct hepatic puncture successfully stopped tumor bleeding; furthermore, tumor necrosis also occurred, as seen on the enhanced computed tomography image. Our new method requires advanced puncture techniques and is not the treatment of choice if there are other safe alternatives available. However, it can be considered as an option if there are no other viable, effective treatments.

High-power DUV picosecond pulse laser with a gain-switched-LD-seeded MOPA and large CLBO crystal.

We report the generation of a 266 nm deep ultraviolet (DUV) picosecond pulse with an average output power of 14 W by the fourth-harmonic generation (FHG) from two consecutive frequency-doubling stages of a 1064 nm pulse based on a gain-switched-laser-diode (LD)-seeded hybrid fiber/solid-state master oscillator and power amplifier (MOPA) system. Through the gain-switched operation of a narrow-spectral-linewidth distributed-feedback laser diode and by using a Yb-doped fiber and a two-stage ${\rm Nd}:{{\rm YVO}_4}$Nd:YVO4 solid-state amplifier, we achieved an average power of 46.5 W near the Fourier transform limit for a 13 ps pulse with a repetition rate of 200 kHz. The narrow linewidth pulse characteristics enabled highly efficient frequency conversion, and the efficiency of conversion from 532 to 266 nm was 54%, and from 1064 to 266 nm was 31%. The beam quality factor ${M^2}$M2 of the generated DUV pulse was below 1.2. The highly efficient FHG process resulted in appeasing thermal stress caused by nonlinear absorption in the crystal, and more than 5000 h of continuous operation were achieved without any power down or beam profile degradation.

Predictors of invasive cancer of large laterally spreading colorectal tumors: A multicenter study in Japan.

BACKGROUND AND AIM: Although colorectal laterally spreading tumors (LSTs) can be classified into four subtypes, the histopathological characteristics are known to differ among these subtypes. We therefore performed a logistic regression analysis to determine whether the risk of pathological T1 cancer of large colorectal LSTs can be predicted based on factors such as endoscopic findings in a large group of patients enrolled in a multicenter study in Japan. METHODS: In the main study, we assessed 1236 colorectal adenomas or early cancers that were classified as LSTs measuring 20 mm or more in diameter and treated endoscopically. Logistic regression analysis was performed to determine whether factors such as the subtype of LST could be used to predict the risk of pathological T1 cancer. A validation study of 356 large colorectal LSTs was conducted to confirm the validity of the results obtained in the main study. RESULTS: The locations and tumor diameter of the LSTs in the main study were found to differ significantly according to the LST subclassification (P < 0.001). The frequency of pathological T1 cancers was the highest at 36% of LST nongranular pseudodepressed type, followed by 14% of LST nongranular flat-elevated type, 11% of LST granular nodular mixed type, and 3% of LST granular homogenous type lesions. The risk of pathological T1 cancer was significantly associated with LST subclassification and tumor diameter. The area under the curve (AUC) was high (0.743). In the validation study, the AUC was 0.573. CONCLUSIONS: In patients with large colorectal LSTs resected endoscopically, the risk of pathological T1 cancer can be predicted on the basis of the LST subclassification and tumor diameter.

Optimization of laser emission at 2.8 µm by Er:Lu2O3 ceramics.

We have demonstrated the continuous-wave operation of a highly efficient 2.8 µm Er-doped Lu2O3 ceramic laser at room temperature. An Er:Lu2O3 ceramic with a doping concentration of 11 at.% afforded a slope efficiency of 29% and an output power of 2.3 W with pumping at 10 W. To our knowledge, these are the highest slope efficiency and output power obtained to date for an Er:Lu2O3 ceramic laser at 2.8 µm. In addition, we prepared ceramics with various doping concentrations and determined their emission cross sections by fluorescence lifetime measurements and emission spectroscopy.

Efficient continuous wave and quasi-continuous wave operation of a 2.8 µm Er:Lu2O3 ceramic laser.

We have demonstrated a highly efficient 2.8 µm Er-doped Lu2O3 ceramic laser and investigated the lasing dynamics by time-resolved spectroscopy. During room-temperature continuous wave operation, a slope efficiency of 22% was achieved with a high-quality transparent ceramic. To our knowledge, this is the highest slope efficiency obtained by an Er:Lu2O3 ceramic laser. In addition, an output peak power of 1.2 W was obtained during quasi-continuous wave operation. Time-resolved spectroscopy showed that the emission wavelengths exhibited a red shift from 2715 to 2845 nm, which indicated that continuous wave operation may be possible at 2740 and 2845 nm.

Involvement of herbal medicine as a cause of mesenteric phlebosclerosis: results from a large-scale nationwide survey.

BACKGROUND: Mesenteric phlebosclerosis (MP) is a rare disease characterized by venous calcification extending from the colonic wall to the mesentery, with chronic ischemic changes from venous return impairment in the intestine. It is an idiopathic disease, but increasing attention has been paid to the potential involvement of herbal medicine, or Kampo, in its etiology. Until now, there were scattered case reports, but no large-scale studies have been conducted to unravel the clinical characteristics and etiology of the disease. METHODS: A nationwide survey was conducted using questionnaires to assess possible etiology (particularly the involvement of herbal medicine), clinical manifestations, disease course, and treatment of MP. RESULTS: Data from 222 patients were collected. Among the 169 patients (76.1 %), whose history of herbal medicine was obtained, 147 (87.0 %) used herbal medicines. The use of herbal medicines containing sanshishi (gardenia fruit, Gardenia jasminoides Ellis) was reported in 119 out of 147 patients (81.0 %). Therefore, the use of herbal medicine containing sanshishi was confirmed in 70.4 % of 169 patients whose history of herbal medicine was obtained. The duration of sanshishi use ranged from 3 to 51 years (mean 13.6 years). Patients who discontinued sanshishi showed a better outcome compared with those who continued it. CONCLUSIONS: The use of herbal medicine containing sanshishi is associated with the etiology of MP. Although it may not be the causative factor, it is necessary for gastroenterologists to be aware of the potential risk of herbal medicine containing sanshishi for the development of MP.

Local recurrence after endoscopic resection for large colorectal neoplasia: a multicenter prospective study in Japan.

OBJECTIVES: Conventional endoscopic resection (CER) is a widely accepted treatment for early colorectal neoplasia; however, large colorectal neoplasias remain problematic, as they necessitate piecemeal resection, increasing the risk of local recurrence. Endoscopic submucosal dissection (ESD) can improve the en bloc resection rate. This study aimed to evaluate local recurrence and its associated risk factors after endoscopic resection (ER) for colorectal neoplasias ≥20 mm. METHODS: A multicenter prospective study at 18 medium- and high-volume specialized institutions was conducted in Japan. Follow-up colonoscopy was performed after 12 months in cases of complete resection and after 3-6 months in cases of incomplete resection. Local recurrence was confirmed by endoscopic findings and/or pathological analysis. RESULTS: Follow-up colonoscopy was performed in 1,524 of 1,845 enrolled colorectal neoplasias (mean age, 65 years; 885 men; median tumor size, 32.8 mm). The local recurrence rates were 4.3% (65/1,524), 6.8% (55/808), and 1.4% (10/716) for the entire cohort, for CER, and for ESD, respectively. The relative risks of local recurrence were 0.21 (95% confidence interval, 0.11-0.39) with ESD compared with CER, 0.32 (95% confidence interval, 0.11-0.92) with en bloc ESD compared with en bloc CER, and 0.90 (95% confidence interval, 0.39-2.12) with piecemeal ESD compared with piecemeal CER. Significant factors associated with local recurrence were piecemeal resection, laterally spreading tumors of granular type, tumor size ≥40 mm, no pre-treatment magnification, and ≤10 years of experience in CER, and piecemeal resection only in ESD. CONCLUSIONS: En bloc ESD reduces the local recurrence rate for large colorectal neoplasias. Piecemeal resection is the most important risk factor for local recurrence regardless of the ER method used.

Factors associated with technical difficulties and adverse events of colorectal endoscopic submucosal dissection: retrospective exploratory factor analysis of a multicenter prospective cohort.

BACKGROUND: Colorectal endoscopic submucosal dissection (C-ESD) is a promising but challenging procedure. We aimed to evaluate the factors associated with technical difficulties (failure of en bloc resection and procedure time, ≥2 h) and adverse events (perforation and bleeding) of C-ESD. METHODS: We conducted a retrospective exploratory factor analysis of a prospectively collected cohort in 15 institutions. Eight-hundred sixteen colorectal neoplasms larger than 20 mm from patients who underwent C-ESD were included. We assessed the outcomes of C-ESD and risk factors for technical difficulties and adverse events. RESULTS: Of the 816 lesions, 767 (94 %) were resected en bloc, with a median procedure time of 78 min. Perforation occurred in 2.1 % and bleeding in 2.2 %. Independent factors associated with failure of en bloc resection were low-volume center (<30 neoplasms), snare use, and poor lifting after submucosal injection. Factors significantly associated with long procedure time (≥2 h) were large tumor size (≥4 cm), low-volume center, less-experienced endoscopist, CO2 insufflation, and use of two or more endoknives. Poor lifting was the only factor significantly associated with perforation, whereas rectal lesion and lack of a thin-type endoscope were factors significantly associated with bleeding. Poor lifting after submucosal injection occurred more frequently for nongranular-type laterally spreading tumors (LST) and for protruding and recurrent lesions than for granular-type LST (LST-G). CONCLUSIONS: Poor lifting after submucosal injection was the risk factor most frequently associated with technical difficulties and adverse events on C-ESD. Less experienced endoscopists should start by performing C-ESDs on LST-G lesions.

Multicenter study of endoscopic mucosal resection using 0.13% hyaluronic acid solution of colorectal polyps less than 20 mm in size.

PURPOSE: Endoscopic mucosal resection (EMR) of colorectal polyps should be curative and safe. This study aimed to determine the efficacy and safety of colorectal EMR using 0.13% hyaluronic acid (HA) solution. METHODS: This was a single-armed multicenter prospective open trial conducted at 11 Japanese institutions. Lesion characteristics and various measures of clinical outcome, including en bloc resection, histopathologically complete resection, and postoperative bleeding were analyzed for 624 consecutive patients who underwent EMR of colorectal polyps at ≤20 mm in size from August 2010 to September 2011. RESULTS: En bloc and complete resection were achieved in 93.3 and 78.3% of 624 lesions. The median EMR procedure time was 2.1 ± 1.5 min. The rates of postoperative bleeding and perforation were 1.1 and 0%. The rate of en bloc resection was higher for polyps at 5-10 mm than for polyps at 11-20 mm (95.1 vs. 85.1%; P < 0.001) and was higher for protruding polyps than for superficial polyps (94.5 vs. 87.1%; P < 0.05). The rate of en bloc resection was also higher for polyps in the left-side colon than for those in the right-side colon or rectum (96.7 vs. 91.6 vs. 90.8%; P < 0.05). Multivariate analysis showed that polyp at 11-20 mm in size and location not on the left-side colon was significantly independent risk factors for failure of en bloc resection. CONCLUSION: EMR using 0.13% HA of colorectal polyps less than 20 mm in size had high rates of en bloc and complete resection and few complications.

12 W Q-switched Er:ZBLAN fiber laser at 2.8 µm.

A diode-pumped, actively Q-switched 2.8 µm fiber laser oscillator with an average output power of more than 12 W has been realized through the use of a 35 µm core erbium-doped ZBLAN fiber and an acousto-optic modulator; to our knowledge, this is the first 3 µm pulsed fiber laser in the 10 W class. Pulse energy up to 100 µJ and pulse duration down to 90 ns, corresponding to a peak power of 0.9 kW, were achieved at a repetition rate of 120 kHz.

Stable 10 W Er:ZBLAN fiber laser operating at 2.71-2.88 µm.

We have developed a diode-pumped tunable 3 µm fiber laser with a cw output power of the order of 10 W with the use of an erbium-doped ZBLAN fiber. A tunability range of 110 nm (2770 to 2880 nm) with an output power between 8 and 11 W was demonstrated. As the pump power was increased, the center of the wavelength range was shifted toward longer wavelengths, but the width of the wavelength range was largely unaffected. The total tunability range for various pump power levels was 170 nm (2710 to 2880 nm). To our knowledge, this is the highest performance (output power and tunability) obtained from a tunable 3 µm fiber laser.

Liquid-cooled 24 W mid-infrared Er:ZBLAN fiber laser.

A 24 W liquid-cooled CW 3 microm fiber laser with a multimode-core Er-doped ZBLAN fiber has been developed. The output power of 24 W and an optical-to-optical efficiency of 14.5% (with respect to incident pump power) were obtained with 975 nm diode pumping. Efficient cooling was implemented by a combination of fluid cooling over the entire length of the fiber and conductive cooling at both end faces of the fiber. Consequently, stable high-power operation was demonstrated. To our knowledge, this is the highest output power obtained by a 3 microm fiber laser. Furthermore, the high power can be further scaled up, since the output power in the present work is limited only by the available pump power.

Volumetric intensity dependence on the formation of molecular and atomic ions within a high intensity laser focus.

The mechanism of atomic and molecular ionization in intense, ultra-short laser fields is a subject which continues to receive considerable attention. An inherent difficulty with techniques involving the tight focus of a laser beam is the continuous distribution of intensities contained within the focus, which can vary over several orders of magnitude. The present study adopts time of flight mass spectrometry coupled with a high intensity (8 x 10(15) Wcm(-2)), ultra-short (20 fs) pulse laser in order to investigate the ionization and dissociation of the aromatic molecule benzene-d1 (C(6)H(5)D) as a function of intensity within a focused laser beam, by scanning the laser focus in the direction of propagation, while detecting ions produced only in a "thin" slice (400 and 800 microm) of the focus. The resultant TOF mass spectra varies significantly, highlighting the dependence on the range of specific intensities accessed and their volumetric weightings on the ionization/dissociation pathways accessed.

Genetic risk for restenosis after coronary balloon angioplasty.

Plain old balloon angioplasty (POBA) is a useful therapeutic strategy especially for angioplasty of small coronary arteries. An association study was performed to identify genes that confer susceptibility to restenosis after POBA. The study population comprised 730 individuals (424 men, 306 women) who underwent successful POBA in at least one major coronary artery and were examined angiographically 6 months after the procedure. A total of 469 subjects (273 men, 196 women) exhibited no restenosis after POBA for any of the coronary lesions, whereas 261 subjects (151 men, 110 women) manifested restenosis for all lesions. The genotypes for 40 polymorphisms of 34 genes were determined with a fluorescence- or colorimetry-based allele-specific DNA primer-probe assay. Multivariate logistic regression analysis with adjustment for age, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, hypercholesterolemia, and hyperuricemia revealed that two polymorphisms (242C --> T in the NADH/NADPH oxidase p22 phox (p22-PHOX) gene and 2136C --> T in the thrombomodulin (THBD) gene) in men and two polymorphisms (584G --> A in the paraoxonase 1 (PON1) gene and 2445G --> A in the fatty acid-binding protein 2 (FABP2) gene) in women were significantly associated with restenosis after POBA. A stepwise forward selection procedure revealed that the effects of these polymorphisms on restenosis were statistically independent of conventional risk factors for coronary artery disease. Genotyping of these polymorphisms may prove informative for assessment of genetic risk for restenosis after POBA.