Innovative design of bone quality-targeted intervertebral spacer: accelerated functional fusion guiding oriented collagen and apatite microstructure without autologous bone graft.

BACKGROUND CONTEXT: Although autologous bone grafting is widely considered as an ideal source for interbody fusion, it still carries a risk of nonunion. The influence of the intervertebral device should not be overlooked. Requirements for artificial spinal devices are to join the vertebrae together and recover the original function of the spine rapidly. Ordered mineralization of apatite crystals on collagen accelerates bone functionalization during the healing process. Particularly, the stable spinal function requires the ingrowth of an ordered collagen and apatite matrix which mimics the intact intervertebral microstructure. This collagen and apatite ordering is imperative for functional bone regeneration, which has not been achieved using classical autologous grafting. PURPOSE: We developed an intervertebral body device to achieve high stability between the host bone and synthesized bone by controlling the ordered collagen and apatite microstructure. STUDY DESIGN: This was an in vivo animal study. METHODS: Intervertebral spacers with a through-pore grooved surface structure, referred to as a honeycomb tree structure, were produced using metal 3D printing. These spacers were implanted into normal sheep at the L2-L3 or L4-L5 disc levels. As a control group, grafting autologous bone was embedded. The mechanical integrity of the spacer/bone interface was evaluated through push-out tests. RESULTS: The spacer with honeycomb tree structure induced anisotropic trabecular bone growth with textured collagen and apatite orientation in the through-pore and groove directions. The push-out load of the spacer was significantly higher than that of the conventional autologous graft spacer. Moreover, the load was significantly correlated with the anisotropic texture of the newly formed bone matrix. CONCLUSIONS: The developed intervertebral spacer guided the regenerated bone matrix orientation of collagen and apatite, resulting in greater strength at the spacer/host bone interface than that obtained using a conventional gold-standard autologous bone graft. CLINICAL SIGNIFICANCE: Our results provide a foundation for designing future spacers for interbody fusion in human.

Outstanding in vivo mechanical integrity of additively manufactured spinal cages with a novel "honeycomb tree structure" design via guiding bone matrix orientation.

BACKGROUND CONTEXT: Therapeutic devices for spinal disorders, such as spinal fusion cages, must be able to facilitate the maintenance and rapid recovery of spinal function. Therefore, it would be advantageous that future spinal fusion cages facilitate rapid recovery of spinal function without secondary surgery to harvest autologous bone. PURPOSE: This study investigated a novel spinal cage configuration that achieves in vivo mechanical integrity as a devise/bone complex by inducing bone that mimicked the sound trabecular bone, hierarchically and anisotropically structured trabeculae strengthened with a preferentially oriented extracellular matrix. STUDY DESIGN/SETTINGS: In vivo animal study. METHODS: A cage possessing an anisotropic through-pore with a grooved substrate, that we termed "honeycomb tree structure," was designed for guiding bone matrix orientation; it was manufactured using a laser beam powder bed fusion method through an additive manufacturing processes. The newly designed cages were implanted into sheep vertebral bodies for 8 and 16 weeks. An autologous bone was not installed in the newly designed cage. A pull-out test was performed to evaluate the mechanical integrity of the cage/bone interface. Additionally, the preferential orientation of bone matrix consisting of collagen and apatite was determined. RESULTS: The cage/host bone interface strength assessed by the maximum pull-out load for the novel cage without an autologous bone graft (3360±411 N) was significantly higher than that for the conventional cage using autologous bone (903±188 N) after only 8 weeks post-implantation. CONCLUSIONS: These results highlight the potential of this novel cage to achieve functional fusion between the cage and host bone. Our study provides insight into the design of highly functional spinal devices based on the anisotropic nature of bone. CLINICAL SIGNIFICANCE: The sheep spine is similar to the human spine in its stress condition and trabecular bone architecture and is widely recognized as a useful model for the human spine. The present design may be useful as a new spinal device for humans.

Effectiveness of Solution with 5% Detergent for Cleaning Transnasal Esophagogastroduodenoscopy Lens.

BACKGROUND/AIMS: Unsedated transnasal esophagogastroduodenoscopy (EGD) is affected by a poor scope lens-cleaning function. We have previously reported good, albeit limited, effects of an oolong tea washing solution; here, we evaluated the effectiveness of a 5% lens cleaning solution for cleaning an EGD lens. METHODS: Five percent lens cleaning solution (C), 5% dimethicone solution (D), and distilled water (W) were prepared. Study I: Lenses were soiled with pork grease, washed with each washing solution, and their image quality was judged. Study II: Patients (n=996) scheduled for transnasal EGD were randomly assigned to the C- or W-group. Lens cleanliness level, washing solution volume used, and endoscopist stress due to lens contamination were determined. RESULTS: Study I: The image quality of the lenses washed with (C) was significantly superior. (D) was clinically unsuitable because of spray nozzle clogging. Study II: Lens cleaning in the C-group was significantly superior (p<0.0001) and the solution volume required was significantly reduced (p<0.0001), while endoscopist stress was also lower (p<0.0001). CONCLUSION: For transnasal small-caliber EGD, the present 5% lens cleaning solution provided good visibility. It features a high detergency level and is simple to formulate for therapeutic endoscopy applications, such as endoscopic submucosal dissection.

Effect of Age on Effectiveness of Vonoprazan in Triple Therapy for Helicobacter pylori Eradication.

Objective We evaluated the efficacy of vonoprazan-based eradication therapy for Helicobacter pylori (H. pylori), including the effects of age, gender, and grade of atrophy in comparison to proton pump inhibitor-based therapy. Method We retrospectively reviewed the records of 1,172 patients who received first-line triple therapy with amoxicillin, clarithromycin, and vonoprazan or a proton pump inhibitor (PPI) for H. pylori eradication, as well as 157 patients treated with second-line therapy consisting of amoxicillin, metronidazole, and vonoprazan or a PPI. Results The eradication rate of all cases treated with first-line triple therapy was 86.9% (1,019/1,172), while that in those treated with vonoprazan-based therapy was 92.5% (384/415). Our analysis showed that the use of vonoprazan resulted in a significantly improved success rate of first-line eradication therapy in comparison to proton pump inhibitor-based therapy [odds ratio (OR), 2.36; 95% confidence interval (CI) 1.55 to 3.56]. The superiority of vonoprazan was remarkable in non-elderly patients, while its effect was unclear in elderly patients. When used as second-line eradication therapy, the advantage of vonoprazan over PPI administration was not clear. Conclusion The inclusion of vonoprazan increased the success rate of first-line eradication therapy; however, the advantage was reduced with aging and remained unclear in elderly patients.

Use of anticoagulant or antiplatelet agents is not related to epistaxis in patients undergoing transnasal endoscopy.

BACKGROUND AND STUDY AIMS: Unsedated transnasal endoscopy (uTNE) has become accepted as a safe and tolerable method for upper gastrointestinal tact examinations. Epistaxis is 1 of the major complications of TNE, though its risk factors have not been elucidated. Generally, patients administered an anticoagulant or antiplatelet drug are considered to have an increased risk of epistaxis during TNE. Here, we investigated risk factors of epistaxis in patients undergoing uTNE, with focus on those who received antithrombotic agents. PATIENTS AND METHODS: We enrolled 6860 patients (average age 55.6 ±â€Š12.97 years; 3405 males, 3455 females) who underwent uTNE and received the same preparations for the procedure. Epistaxis was evaluated using endoscopic images obtained while withdrawing the scope through the nostril. We also noted current use of medications including anticoagulant or antiplatelet agents prior to the endoscopic examination. RESULTS: Epistaxis occurred in 3.6 % of the enrolled patients (245/6860), and that rate was significantly higher in younger patients (average age 49.31 ±â€Š11.8 years for epistaxis group vs. 55.83 ±â€Š13.0 years for no epistaxis group, P  < 0.01) as well as females (4.78 % vs. 2.35 %, P  < 0.01). The odds ratio for occurrence of epistaxis was 2.31 (95 %CI: 1.746 - 3.167) in the younger patients and 2.02 (95 % CI: 1.542 - 2.659) in females. In contrast, there was no significant difference for rate of epistaxis between patients with and without treatment with an antithrombotic agent (3.0 % vs. 3.6 %). CONCLUSIONS: The rate of epistaxis was higher in younger and female patients. Importantly, that rate was not significantly increased in patients who were administered an antithrombotic agent.

Intrahepatic Cholangiolocellular and Cholangiocellular Carcinoma - Differences in the 18F-FDG PET/CT Findings.

Cholangiolocellular carcinoma is a minor primary cancerous tumor of the liver and its coexistence with intrahepatic cholangiocarcinoma in the liver is rare. We herein report a case of concurrent cholangiolocellular carcinoma and intrahepatic cholangiocarcinoma in the liver, in addition to a rectal G1 neuroendocrine tumor, a so-called carcinoid. The intrahepatic tumors showed a different uptake in the 18F-fluoro-2-deoxyglucose (FDG) positron-emission tomography (PET)/computed tomography (CT) findings. In addition to conventional dynamic contrast-enhanced CT, we concluded that FDG PET/CT could therefore be a helpful modality to identify the properties of both cholangiolocellular carcinoma and intrahepatic cholangiocarcinoma.

Helicobacter pylori-negative intestinal-type gastric adenoma successfully treated by endoscopic submucosal dissection: a case report.

BACKGROUND AND STUDY AIMS: A 49-year-old woman underwent an esophagogastroduodenoscopy as part of a health check at our hospital. Endoscopic observation revealed a flat elevated lesion 6 mm in diameter in the gastric antrum (Paris Classification type IIa). Magnifying endoscopy using narrow-band imaging showed a slightly irregular micro-surface pattern with round and oval pits, as well as a regular micro-vascular pattern without a demarcation line. Atrophy and intestinal metaplasia were not recognized in the background gastric mucosa. Furthermore, Helicobacter pylori infection was not detected by histologic, serologic, and urea breath test results. Endoscopic resection was performed for histologic evaluation, and a pathologic diagnosis of intestinal-type gastric adenoma occurring in pyloric mucosa without atrophy or metaplasia was established. Immunohistochemistry findings of the lesion showed the intestinal epithelium phenotype with positive staining for MUC2, CD10, and CDX2. Furthermore, irregular distribution with a higher positive proportion of Ki-67 was found in the lesion, indicating its malignant potential. We report here a rare case of gastric adenoma without surrounding intestinal metaplasia occurring in a Helicobacter pylori-negative patient.

Novel stenting method for malignant right colonic stenosis using ultra-thin endoscopy: Report of four cases.

Placement of a self-expandable metallic stent (SEMS) is recognized as a safe and effective procedure for patients with malignant severe colonic stenosis. However, reports of this stent for right-sided colonic stenosis are limited, possibly as a result of technical difficulties. We report a new method for delivering SEMS to the site of right-sided colonic stenosis in four patients with malignant right-sided colonic stenosis. Technical success was obtained with sequential use of a double-balloon endoscope and ultrathin endoscope, while we also injected non-ionic contrast agent into the submucosal layer as a marker for stenting under fluoroscopy. There were no adverse events noted during the procedure and clinical improvement was seen in all four cases. In conclusion, SEMS placement for right-sided malignant colonic stenosis with our newly developed method appears to be safe and effective, and can be used for decompression of the right colon.

Effects of Daikenchuto on Abdominal Bloating Accompanied by Chronic Constipation: A Prospective, Single-Center Randomized Open Trial.

BACKGROUND: Daikenchuto (DKT), a traditional Japanese herbal medicine, is widely used for treatment of gastrointestinal disorders. We evaluated the efficacy and safety of DKT for abdominal bloating in patients with chronic constipation. OBJECTIVE: To evaluate the efficacy and safety of DKT for the treatment of abdominal bloating. METHODS: After discontinuing as-needed use of laxatives, 10 patients received oral DKT for 14 days (15 g/d). To evaluate small intestinal bacteria overgrowth (SIBO), a glucose breath test was performed before and after treatment with DKT. Before beginning the treatment, 4 patients (40%) had a diagnosis of SIBO based on a positive glucose breath test result. In both the SIBO and non-SIBO groups, bowel movement frequency and stool form remained unchanged after DKT treatment. RESULTS: For all patients, median total Gastrointestinal Symptoms Rating Scale score and the median Gastrointestinal Symptoms Rating Scale indigestion and constipation subscales were significantly decreased, whereas the median visual analog score for decreased abdominal bloating was significantly increased. Improvements of those symptoms were the same in both the SIBO and non-SIBO groups, indicating that DKT does not have effects on small intestine bacteria. No serious side effects were reported. CONCLUSIONS: DKT treatment improved quality of life for patients with chronic constipation regardless of the presence of SIBO and showed no effects on small intestine bacteria. UMIN Clinical Trial Registry identifier: UMIN000008070.

Distinct molecular features of different macroscopic subtypes of colorectal neoplasms.

BACKGROUND: Colorectal adenoma develops into cancer with the accumulation of genetic and epigenetic changes. We studied the underlying molecular and clinicopathological features to better understand the heterogeneity of colorectal neoplasms (CRNs). METHODS: We evaluated both genetic (mutations of KRAS, BRAF, TP53, and PIK3CA, and microsatellite instability [MSI]) and epigenetic (methylation status of nine genes or sequences, including the CpG island methylator phenotype [CIMP] markers) alterations in 158 CRNs including 56 polypoid neoplasms (PNs), 25 granular type laterally spreading tumors (LST-Gs), 48 non-granular type LSTs (LST-NGs), 19 depressed neoplasms (DNs) and 10 small flat-elevated neoplasms (S-FNs) on the basis of macroscopic appearance. RESULTS: S-FNs showed few molecular changes except SFRP1 methylation. Significant differences in the frequency of KRAS mutations were observed among subtypes (68% for LST-Gs, 36% for PNs, 16% for DNs and 6% for LST-NGs) (P<0.001). By contrast, the frequency of TP53 mutation was higher in DNs than PNs or LST-Gs (32% vs. 5% or 0%, respectively) (P<0.007). We also observed significant differences in the frequency of CIMP between LST-Gs and LST-NGs or PNs (32% vs. 6% or 5%, respectively) (P<0.005). Moreover, the methylation level of LINE-1 was significantly lower in DNs or LST-Gs than in PNs (58.3% or 60.5% vs. 63.2%, P<0.05). PIK3CA mutations were detected only in LSTs. Finally, multivariate analyses showed that macroscopic morphologies were significantly associated with an increased risk of molecular changes (PN or LST-G for KRAS mutation, odds ratio [OR] 9.11; LST-NG or DN for TP53 mutation, OR 5.30; LST-G for PIK3CA mutation, OR 26.53; LST-G or DN for LINE-1 hypomethylation, OR 3.41). CONCLUSION: We demonstrated that CRNs could be classified into five macroscopic subtypes according to clinicopathological and molecular differences, suggesting that different mechanisms are involved in the pathogenesis of colorectal tumorigenesis.

Right colon cancer presenting as hemorrhagic shock.

A 67-year-old man visited our hospital with a history of continuous hematochezia leading to hemorrhagic shock. An abdominal computed tomography scan revealed a large mass in the ascending colon invading the duodenum and pancreatic head as well as extravasation of blood from the gastroduodenal artery (GDA) into the colon. Colonoscopy revealed an irregular ulcerative lesion and stenosis in the ascending colon. Therefore, right hemicolectomy combined with pylorus-preserving pancreaticoduodenectomy was performed. Histologically, the tumor was classified as a moderately differentiated adenocarcinoma. Moreover, cancer cells were mainly located in the colon but had also invaded the duodenum and pancreas and involved the GDA. Immunohistochemically, the tumor cells were positive for cytokeratin (CK)20 and carcinoembryonic antigen (CEA) but not for CK7 and carbohydrate antigen (CA)19-9. The patient died 23 d after the surgery because he had another episode of arterial bleeding from the anastomosis site. Although En bloc resection of the tumor with pancreaticoduodenectomy and colectomy performed for locally advanced colon cancer can ensure long-term survival, patients undergoing these procedures should be carefully monitored, particularly when the tumor involves the main artery.

Clinicopathological and molecular features of colorectal serrated neoplasias with different mucosal crypt patterns.

OBJECTIVES: Endoscopic examination shows that serrated neoplasias (SNs), such as serrated adenomas and sessile serrated adenomas, exhibit different mucosal crypt patterns. However, it remains unclear whether advanced serrated polyps with different mucosal crypt patterns have different clinicopathological or molecular features. METHODS: We classified the mucosal crypt patterns of 86 SNs into three types (hyperplastic, adenomatous, and mixed pattern) and evaluated their clinicopathological and molecular features. RESULTS: We found significant differences in the proliferative activity status between SNs with mixed/adenomatous patterns and those with the hyperplastic patterns. SNs with the hyperplastic pattern were frequently located in the proximal colon and had a macroscopically superficial appearance, whereas SNs with the adenomatous pattern were often located in the distal colon and had a protruding appearance. Furthermore, a significant difference was observed in the frequency of the CpG island methylator phenotype (CIMP), involving the methylation of two or more CIMP-related genes (MINT1, MINT2, MINT31, p16, and MLH1), between SNs with the hyperplastic pattern and those with the mixed/adenomatous patterns (18/32 (56%) vs. 8/28 (29%) or 7/26 (27%); P=0.0309 or P=0.0249, respectively). Moreover, the prevalence of KRAS mutations was significantly higher in SNs with the adenomatous pattern than in those with the hyperplastic pattern (7/26 (27%) vs. 1/32 (3%); P=0.0173). In comparison with other patterns, the mixed pattern was detected more frequently in mixed serrated polyps (MSPs), which contain separate histological components. Some MSPs exhibited concordant molecular alterations among the different histological components. CONCLUSIONS: The clinicopathological and molecular features of SNs correlated strongly with their mucosal crypt patterns, which were observed using chromoendoscopy.

Primary micropapillary carcinoma of the colon: a case report and literature review.

We report a case of micropapillary carcinoma (MPC) of the transverse colon. A 56-year-old woman was admitted to our hospital with hematochezia. A lower gastrointestinal examination revealed an irregular ulcerative tumor of approximately 60 mm diameter with marginal elevation in the transverse colon. Abdominal computed tomography showed multiple swollen lymph nodes. A histological examination of the resected specimen revealed that cancer cells had invaded the subserosa. Microscopically, small papillary cells proliferated with lacuna spaces and the cribriform glandular configuration was observed. Immunohistochemically, the basal surface of the neoplastic cell clusters was diffusely positive for MUC1. No primary tumor was observed except for the colon. Therefore, this tumor was diagnosed as a primary MPC of the colon. Since a colorectal MPC was first reported in 2005, seven case reports and three pathological reviews have been presented in the English literature. MPC has an aggressive behavior with a high incidence of lymphovascular invasion and nodal metastases. We should take intensive chemotherapy for colorectal MPC into account, even if surgical resection is curative.

The onset of angiogenesis in a multistep process of esophageal squamous cell carcinoma.

Microvessel density (MVD) is an excellent predictive biomarker regarding tumor stage and survival in esophageal squamous cell carcinomas (ESCCs). However, it is obscure when tissues initiate angiogenesis in the malignant transformation of human esophageal squamous epithelium. To investigate the onset of angiogenesis in the multistep progressive process of ESCCs, immunohistochemical staining for CD31, CD105, and vascular endothelial growth factor receptor 2 (VEGFR-2) was performed in normal epithelium, Lugol-unstained lesions with non-dysplastic epithelium (LULs-NDE), low-grade dysplasia (LGD), and high-grade dysplasia (HGD) samples. There were significant differences in the mean MVD for CD31 and CD105 between LULs-NDE and LGD (p less than 0.001, p less than 0.001), and between LGD and HGD (p less than 0.001, p=0.006), respectively. Furthermore, a significant difference in MVD for CD105 was seen in normal controls and LULs-NDE (p=0.002), while thick vessels (less than 10m m) stained with anti-CD105 were not present in normal controls and LULs-NDE despite the presence of these thickened vessels in dysplasia. Our results suggest that CD105 is an efficient marker protein to determine MVD, suggesting that the angiogenic switch occurs at the earliest stage of dysplastic transformation in ESCC.