In most cases of sporadic colorectal cancers, tumorigenesis is a multistep process, involving genomic alterations in parallel with morphologic changes. In addition, accumulating evidence suggests ...that the human gut microbiome is linked to the development of colorectal cancer. Here we performed fecal metagenomic and metabolomic studies on samples from a large cohort of 616 participants who underwent colonoscopy to assess taxonomic and functional characteristics of gut microbiota and metabolites. Microbiome and metabolome shifts were apparent in cases of multiple polypoid adenomas and intramucosal carcinomas, in addition to more advanced lesions. We found two distinct patterns of microbiome elevations. First, the relative abundance of Fusobacterium nucleatum spp. was significantly (P < 0.005) elevated continuously from intramucosal carcinoma to more advanced stages. Second, Atopobium parvulum and Actinomyces odontolyticus, which co-occurred in intramucosal carcinomas, were significantly (P < 0.005) increased only in multiple polypoid adenomas and/or intramucosal carcinomas. Metabolome analyses showed that branched-chain amino acids and phenylalanine were significantly (P < 0.005) increased in intramucosal carcinomas and bile acids, including deoxycholate, were significantly (P < 0.005) elevated in multiple polypoid adenomas and/or intramucosal carcinomas. We identified metagenomic and metabolomic markers to discriminate cases of intramucosal carcinoma from the healthy controls. Our large-cohort multi-omics data indicate that shifts in the microbiome and metabolome occur from the very early stages of the development of colorectal cancer, which is of possible etiological and diagnostic importance.
Stereotactic neurosurgery is an established technique, but it has several limitations. In frame-based stereotaxy using a stereotactic frame, frame setting errors may decrease the accuracy of the ...procedure. Frameless stereotaxy using neuronavigation requires surgeons to shift their view from the surgical field to the navigation display and to advance the needle while assuming a physically uncomfortable position. To overcome these limitations, several researchers have applied augmented reality in stereotactic neurosurgery. Augmented reality enables surgeons to visualize the information regarding the target and preplanned trajectory superimposed over the actual surgical field. In frame-based stereotaxy, a researcher applies tablet computer-based augmented reality to check for the setting errors of the stereotactic frame, thereby improving the safety of the procedure. Several researchers have reported performing frameless stereotaxy guided by head-mounted-display-based augmented reality that enables surgeons to advance the needle at a more natural posture. These studies have shown that augmented reality can address the limitations of stereotactic neurosurgery. Conversely, they have also revealed the limited accuracy of current augmented reality systems for small targets, which indicates that further development of augmented reality systems is needed.
Background Endoscopic submucosal dissection (ESD) is accepted as a minimally invasive treatment for early gastric cancer, although it is not widely used in the colorectum because of technical ...difficulty. Objective To examine the current status of colorectal ESDs at specialized endoscopic treatment centers. Design and Setting Multicenter cohort study using a prospectively completed database at 10 specialized institutions. Patients and Interventions From June 1998 to February 2008, 1111 colorectal tumors in 1090 patients were treated by ESD. Main Outcome Measurements Tumor size, macroscopic type, histology, procedure time, en bloc and curative resection rates and complications. Results Included in the 1111 tumors were 356 tubular adenomas, 519 intramucosal cancers, 112 superficial submucosal (SM) cancers, 101 SM deep cancers, 18 carcinoid tumors, 1 mucosa-associated lymphoid tissue lymphoma, and 4 serrated lesions. Macroscopic types included 956 laterally spreading tumors, 30 depressed, 62 protruded, 44 recurrent, and 19 SM tumors. The en bloc and curative resection rates were 88% and 89%, respectively. The mean procedure time ± standard deviation was 116 ± 88 minutes with a mean tumor size of 35 ± 18 mm. Perforations occurred in 54 cases (4.9%) with 4 cases of delayed perforation (0.4%) and 17 cases of postoperative bleeding (1.5%). Two immediate perforations with ineffective endoscopic clipping and 3 delayed perforations required emergency surgery. Tumor size of 50 mm or larger was an independent risk factor for complications, whereas a large number of ESDs performed at an institution decreased the risk of complications. Limitations No long-term outcome data. Conclusions ESD performed by experienced endoscopists is an effective alternative treatment to surgery, providing high en bloc and curative resection rates for large superficial colorectal tumors.
Hereditary colorectal cancer (HCRC) accounts for < 5% of all colorectal cancer cases. Some of the unique characteristics commonly encountered in HCRC cases include early age of onset, ...synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics necessitate different management approaches, including diagnosis, treatment or surveillance, from sporadic colorectal cancer management. There are two representative HCRC, named familial adenomatous polyposis and Lynch syndrome. Other than these two HCRC syndromes, related disorders have also been reported. Several guidelines for hereditary disorders have already been published worldwide. In Japan, the first guideline for HCRC was prepared by the Japanese Society for Cancer of the Colon and Rectum (JSCCR), published in 2012 and revised in 2016. This revised version of the guideline was immediately translated into English and published in 2017. Since then, several new findings and novel disease concepts related to HCRC have been discovered. The currently diagnosed HCRC rate in daily clinical practice is relatively low; however, this is predicted to increase in the era of cancer genomic medicine, with the advancement of cancer multi-gene panel testing or whole genome testing, among others. Under these circumstances, the JSCCR guidelines 2020 for HCRC were prepared by consensus among members of the JSCCR HCRC Guideline Committee, based on a careful review of the evidence retrieved from literature searches, and considering the medical health insurance system and actual clinical practice settings in Japan. Herein, we present the English version of the JSCCR guidelines 2020 for HCRC.
Background
Endoscopic piecemeal mucosal resection (EPMR) is a widely accepted treatment for colorectal tumefaction. However, as it is associated with a significant recurrence rate, the technique ...remains controversial. The purpose of our study was to evaluate the risk factors for the local recurrence of colorectal neoplasms after EPMR.
Methods
The study population of our retrospective evaluation comprised 222 patients who had undergone EPMR from January 2002 to July 2007 and who had had at least 1 surveillance colonoscopy 3–6 months after the initial treatment.
Results
Local recurrence was detected in 42 patients (19%) between 6 and 15 months after EPMR. Our multivariate analysis revealed that the resection of 5 or more neoplasm specimens, compared with fewer than 5, was 3 times more likely to result in local recurrence (
P
= 0.005). No statistically significant correlation of local recurrence with lesion size, location, macroscopic type, or histology was detected.
Conclusion
The removal of 5 or more neoplasm specimens is an independent risk factor for local recurrence after EPMR. Careful colonoscopic surveillance should be performed after multiple piecemeal resection.
Background Sessile serrated adenomas/polyps (SSAs/Ps) are premalignant lesions susceptible to being easily overlooked by endoscopists. A detailed description of the endoscopic appearance of SSAs/Ps ...might help endoscopists to recognize these lesions to improve the effectiveness of colonoscopy. Objective To identify various endoscopic features of SSAs/Ps using high-resolution white-light endoscopy (HR-WLE) and narrow-band imaging (NBI). Design Retrospective image evaluation study. Setting Single tertiary referral center. Patients Forty-5 patients with serrated polyposis syndrome undergoing surveillance colonoscopies. Intervention HR-WLE and NBI images of 150 polyps (50 SSAs/Ps, 50 hyperplastic polyps HPs, and 50 adenomas) were systematically assessed by 5 experts using various endoscopic descriptors. Main Outcome Measurements The prevalence of specific endoscopic features observed in SSAs/Ps versus HPs. Results Multivariate analysis demonstrated that indistinct borders (OR, 3.11; 95% CI, 1.57-6.15) and a cloud-like surface (OR, 2.65; 95% CI, 1.21-5.78) were associated with SSA/P histology on HR-WLE. On NBI, a cloud-like surface (OR, 4.91; 95% CI, 2.42-9.97), indistinct borders (OR, 2.38; 95% CI, 1.14-4.96), irregular shape (OR, 3.17; 95% CI, 1.59-6.29), and dark spots inside the crypts (OR, 2.05; 95% CI, 1.02-4.11) were found to be endoscopic predictors of SSA/P histology. The sensitivity, specificity, and accuracy of NBI for differentiating serrated polyps containing either none or all 4 endoscopic SSA/P features were, respectively, 89%, 96%, and 93%. Limitations Retrospective, image evaluation analysis. Conclusions The current study demonstrates that SSAs/Ps possess several specific endoscopic features compared with HPs. Recognition of these characteristics might assist endoscopists in the differentiation of these lesions and could possibly facilitate endoscopic detection of these rather subtle lesions.
•Augmented reality is useful for tumor resection.•Tablet type augmented reality is suitable for macroscopic procedures.•Presurgical discussions is essential for augmented reality.
To date, several ...researchers have introduced augmented reality navigation (ARN) into neurological surgery. While its application in brain tumor surgery seems promising, reports on its utility have been limited, thus warranting further evaluation. To clarify the stages and approaches in which ARN is useful and assess the effect of presurgical discussion with surgeons, we assessed usefulness using a hand-held ARN system we had developed, which displays three-dimensional (3D) virtual structures overlaid on a real-time image of the surgical field via a tablet PC monitor. The system was tested in 20 patients undergoing various procedures, with the first 10 consecutive cases being unselected and the following 10 cases being selected, for whom 3D models were prepared per the surgeons’ request. Thereafter, the surgeons ranked its usefulness during each stage of surgery. Consequently, case selection and presurgical discussions with surgeons considerably improved the usefulness, with the “useful” gradings improving from 50% to 88% across all surgical stages. Accordingly, usefulness improved from 50% to 90%, 67% to 100%, and 40% to 80% during the skin incision and craniotomy, dura incision, and intradural procedure stages, respectively. ARN was useful for superficial tumor resection, but less so for deep-seated tumor resection, except when using the transcortical and interhemispheric approaches. In conclusion, a tablet-type ARN can be useful during skin incisions, craniotomy and dura incisions, superficial tumor resections, and transcortical and interhemispheric approaches for deep-seated tumors. Case selection and presurgical discussions with surgeons were essential for the efficacy of ARN.
AADC deficiency causes severe motor and intellectual disability as a result of reduced catecholamine levels. Kojima et al. report beneficial effects of gene therapy in six patients with heterogeneous ...genetic backgrounds. Gene delivery into putamen improved motor function in all patients, plus verbal and cognitive skills in one moderate-phenotype patient.
Abstract
In patients with aromatic l-amino acid decarboxylase (AADC) deficiency, a decrease in catecholamines and serotonin levels in the brain leads to developmental delay and movement disorders. The beneficial effects of gene therapy in patients from 1 to 8 years of age with homogeneous severity of disease have been reported from Taiwan. We conducted an open-label phase 1/2 study of population including adolescent patients with different degrees of severity. Six patients were enrolled: four males (ages 4, 10, 15 and 19 years) and one female (age 12 years) with a severe phenotype who were not capable of voluntary movement or speech, and one female (age 5 years) with a moderate phenotype who could walk with support. The patients received a total of 2 × 1011 vector genomes of adeno-associated virus vector harbouring DDC via bilateral intraputaminal infusions. At up to 2 years after gene therapy, the motor function was remarkably improved in all patients. Three patients with the severe phenotype were able to stand with support, and one patient could walk with a walker, while the patient with the moderate phenotype could run and ride a bicycle. This moderate-phenotype patient also showed improvement in her mental function, being able to converse fluently and perform simple arithmetic. Dystonia disappeared and oculogyric crisis was markedly decreased in all patients. The patients exhibited transient choreic dyskinesia for a couple of months, but no adverse events caused by vector were observed. PET with 6-18Ffluoro-l-m-tyrosine, a specific tracer for AADC, showed a persistently increased uptake in the broad areas of the putamen. In our study, older patients (>8 years of age) also showed improvement, although treatment was more effective in younger patients. The genetic background of our patients was heterogeneous, and some patients suspected of having remnant enzyme activity showed better improvement than the Taiwanese patients. In addition to the alleviation of motor symptoms, the cognitive and verbal functions were improved in a patient with the moderate phenotype. The restoration of dopamine synthesis in the putamen via gene transfer provides transformative medical benefit across all patient ages, genotypes, and disease severities included in this study, with the most pronounced improvements noted in moderate patients.
10.1093/brain/awy331_video1
awy331media1
5991361892001
Many clinical studies on narrow‐band imaging (NBI) magnifying endoscopy classifications advocated so far in Japan (Sano, Hiroshima, Showa, and Jikei classifications) have reported the usefulness of ...NBI magnifying endoscopy for qualitative and quantitative diagnosis of colorectal lesions. However, discussions at professional meetings have raised issues such as: (i) the presence of multiple terms for the same or similar findings; (ii) the necessity of including surface patterns in magnifying endoscopic classifications; and (iii) differences in the NBI findings in elevated and superficial lesions. To resolve these problems, the Japan NBI Expert Team (JNET) was constituted with the aim of establishing a universal NBI magnifying endoscopic classification for colorectal tumors (JNET classification) in 2011. Consensus was reached on this classification using the modified Delphi method, and this classification was proposed in June 2014. The JNET classification consists of four categories of vessel and surface pattern (i.e. Types 1, 2A, 2B, and 3). Types 1, 2A, 2B, and 3 are correlated with the histopathological findings of hyperplastic polyp/sessile serrated polyp (SSP), low‐grade intramucosal neoplasia, high‐grade intramucosal neoplasia/shallow submucosal invasive cancer, and deep submucosal invasive cancer, respectively.
Both frame-based stereotaxy and frameless stereotaxy are established surgical procedures. However, they each have their respective disadvantages when used in the biopsy of a deep-seated lesion. To ...overcome the drawbacks associated with these procedures, we evaluated the feasibility of applying augmented reality (AR) to stereotactic biopsy. We applied our trans-visible navigator (TVN) to frame-based stereotactic biopsy in five cases of deep-seated lesions. This navigation system uses the AR concept, allowing surgeons to view three-dimensional virtual models of anatomical structures superimposed over the surgical field on a tablet personal computer. Using TVN, we could easily confirm a clear trajectory avoiding the important structures as well as the target point’s location in the lesion. Use of the stereotactic apparatus allowed the surgeon to easily advance the biopsy probe to the target point. Consequently, a satisfactory histopathological diagnosis without complication was achieved in all cases. In conclusion, applying AR to stereotactic biopsy is feasible and may improve the safety of the procedure.