Kensuke Kumamoto

Comparison of integrated whole-body PET/MR and PET/CT: Is PET/MR alternative to PET/CT in routine clinical oncology?

AbstractPurposenTo compare the diagnostic accuracy of whole-body PET/CT and integrated PET/MR in relation to the total scan time durations.MethodsnOne hundred and twenty-three (123) patients (40 males and 83 females; mean age 59.6xa0years; range 20–83xa0years) with confirmed primary cancer and clinical suspicion of metastatic disease underwent whole-body 18F-FDG-PET/CT and 18F-FDG-PET/MR. Data acquisition was done after intravenous administration of 110–301xa0MBq radioactivity of 18F-FDG, and PET/MR data were acquired after the PET/CT data acquisition. The mean uptake times for PET/CT and PET/MR acquisition were 68.0xa0±xa08.0 and 98.0xa0±xa014xa0min, respectively. Total scan time was 20.0 and 25.0xa0min for whole-body PET/CT and PET/MR imaging.ResultsThe reconstructed PET/CT and PET/MR data detected 333/355 (93.8xa0%) common lesions in 111/123 (90.2xa0%) patients. PET/CT and PET/MR alone detected 348/355 and 340/355 lesions, respectively. No significant (pxa0=xa00.08) difference was observed for the overall detection efficiency between the two techniques. On the other hand, a significant difference was observed between the two techniques for the detection of lung (pxa0=xa00.003) and cerebrospinal (pxa0=xa00.007) lesions. The 15 lesions identified by PET/CT only included 8 lung, 3 lymph nodes, 2 bone, and 1 each of peritoneal and adrenal gland lesions. On the other hand, 7 (6 brain metastatic lesions and 1 bone lesion) were identified by PET/MR only.ConclusionIntegrated PET/MR is a feasible whole-body imaging modality and may score better than PET/CT for the detection of brain metastases. To further prove diagnostic utility, this technique requires further clinical validation.

Lower prevalence of Lynch syndrome in colorectal cancer patients in a Japanese hospital-based population

PurposeThe aim of this study was to investigate the prevalence of Lynch syndrome among Japanese patients with surgically resected colorectal cancer at a single institution.MethodsOf 616 colorectal cancer patients who underwent surgical operation in our institution from January 2005 to August 2010, immunohistochemistry analyses for mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) and microsatellite instability (MSI) testing for surgically resected, formalin-fixed paraffin-embedded colorectal cancer specimens from 138 colorectal cancer patients under 60xa0years of age were undertaken. Hypermethylation of the MLH1 promoter and BRAF mutation were analyzed where necessary.ResultsSeven patients were identified as candidates for genetic testing by mismatch repair protein loss (nxa0=xa07) or MSI-H (nxa0=xa06). Methylation of MLH1 was detected in one case. Three patients were diagnosed with Lynch syndrome, comprising 2.2xa0% of the total colorectal cancer patients younger than 60xa0years of age.ConclusionThe prevalence of Lynch syndrome among hospital-based diagnosed cancer patients may therefore be lower than expected in Japan compared with Western populations.

Prevalence of laparoscopic surgical treatment and its clinical outcomes in patients with familial adenomatous polyposis in Japan

BackgroundLaparoscopic surgery is becoming the preferred technique for most colorectal interventions. This study aimed to clarify the time trend of surgical treatment for familial adenomatous polyposis (FAP) and its relevance to clinical outcomes in Japan over a 13-year period.MethodsThis was a multicenter retrospective cohort study comprising 23 specialist institutions for colorectal disease and a cohort of 282 FAP patients who underwent total colectomy or proctocolectomy during 2000–2012. Patient clinical backgrounds and surgical outcomes were compared between the first and second halves of the study period.ResultsThe proportion of surgical types adopted over the entire study period was 46, 21, 30, and 3xa0% for ileoanal anastomosis (IAA), ileoanal canal anastomosis, ileorectal anastomosis, and permanent ileostomy, respectively. FAP patients undergoing laparoscopic surgery have increased since 2008 and reached 74xa0% in the past 3xa0years. In particular, the number of patients undergoing laparoscopic proctocolectomy with IAA increased approximately four-fold from the first to the second half of the study period. A laparoscopic approach was increasingly used in patients with coexisting colorectal malignancies. Despite this trend, surgical results of the laparoscopic approach between the two study periods showed similar morbidity, pouch operation and stoma closure completion rates. No postoperative mortality was observed in this series, and laparoscopic surgery was comparable to open surgery in terms of stoma closure rate, incidence of intra-abdominal/abdominal desmoid tumors, and postoperative survival rate in both study periods.ConclusionLaparoscopic approach is increasingly being adopted for prophylactic FAP surgery in Japan and may provide clinically acceptable practical outcomes.

Blue laser imaging endoscopy system for the early detection and characterization of colorectal lesions: a guide for the endoscopist

Blue laser imaging is a new system for image-enhanced endoscopy using laser light. Blue laser imaging utilizes two monochromatic lasers (410 and 450 nm) instead of xenon light. A 410 nm laser visualizes vascular microarchitecture, similar to narrow band imaging, and a 450 nm laser provides white light by excitation. According to three recently published reports, the diagnostic ability of polyp characterization using blue laser imaging compares favorably with narrow band imaging. No published data are available to date regarding polyp detection with blue laser imaging. However, blue laser imaging has the possibility to increase the detection of colorectal polyps by depicting brighter and clearer endoscopic images, even at a distant view, compared with first-generation image-enhanced endoscopy. A clinical trial to compare the detection between blue laser imaging and xenon light is warranted.

Comparison of the risk of surgical site infection and feasibility of surgery between sennoside versus polyethylene glycol as a mechanical bowel preparation of elective colon cancer surgery: a randomized controlled trial

PurposeTo validate the usefulness of sennoside as a substitute for polyethylene glycol (PEG) as a mechanical bowel preparation (MBP) for elective colon cancer surgery.MethodsWe performed a prospective randomized non-inferiority trial comparing the use of sennoside and PEG in MBP for elective colon cancer surgery, in terms of the risk of surgical site infection (SSI) and the feasibility of surgery.ResultsThe overall incidence of SSIs was 2.9xa0% in the sennoside group (nxa0=xa068) and 6.3xa0% in the PEG group (nxa0=xa063) with a difference of 3.4xa0% (95xa0% confidence interval 6.9–10.6xa0%). The intraoperative spillage of the stool materials in the sennoside and PEG groups was 4.4 and 3.1xa0%, respectively, and was not significantly different (pxa0=xa00.71), even the upstream stool consistency, was more frequently observed to be non-stool in the PEG group (65.1 vs. 30.9xa0%, pxa0<xa00.01).ConclusionMBP with sennoside could be a substitution for PEG in elective colon cancer surgery.

Impact of the Visceral Fat Area Measured by Dual Impedance Method on the Diagnostic Components of Metabolic Diseases in a Middle-aged Japanese Population.

Objective The aim of this study was to examine the associations between the visceral fat area (VFA) and the subcutaneous fat area (SFA) as estimated by the dual impedance method with a body composition monitor (BCM) and the diagnostic components of metabolic syndrome in a middle-aged Japanese population. Methods The subjects included 303 men (average age 51.3±9.0 years old) and 345 women (average age 40.0±9.4 years old). The VFA and SFA were estimated by BCM, and the associations among the components of metabolic syndrome (waist circumference, blood pressure and related blood sample tests) were evaluated. Results VFA showed positive correlations with waist circumference, HbA1c, high-density lipoprotein (HDL)/low-density lipoprotein (LDL) cholesterol, triglyceride and uric acid level in men, while showing positive correlations with waist circumference, HDL cholesterol, triglyceride and HbA1c in women. The estimated SFA showed positive correlations with systolic blood pressure, HDL/LDL cholesterol and triglyceride in men, and HDL cholesterol and triglyceride in women. A receiver operating characteristic (ROC) analysis showed the estimated VFA to be as effective as WC to identify subject with metabolic syndrome. Conclusion By estimating the VFA using BCM, it may be possible to identify patients at risk of developing metabolic syndrome and hyperuricemia.

Identification of a Japanese Lynch syndrome patient with large deletion in the 3′ region of the EPCAM gene

Germline deletion of the 3 portion of the Epithelial Cell Adhesion Molecule (EPCAM) gene located 5 upstream of MutS Homolog 2 (MSH2) is a novel mechanism for its inactivation in Lynch syndrome. However, its contribution in Japanese Lynch syndrome patients is poorly understood. Moreover, somatic events inactivating the remaining allele of MSH2 in cancer tissue have not been elucidated in Lynch syndrome patients with such EPCAM deletions. We identified a Japanese Lynch syndrome patient with colon cancer who evidenced germline deletion of a 4130 bp fragment of EPCAM encompassing exons 8 and 9 (c.859-672_*2170del). In normal colonic mucosa, two known fusion-transcripts of EPCAM/MSH2 generated from the rearranged gene were observed and heterozygous methylation of the MSH2 gene promoter was detected. In cancer tissue, dense methylation of MSH2 was observed and MLPA analysis demonstrated somatic deletion of the remaining EPCAM allele including exon 9, indicating that somatic deletion of EPCAM is responsible for complete inactivation of MSH2.

Update on our investigation of malignant tumors associated with Peutz–Jeghers syndrome in Japan

PurposeTo investigate the recent incidence of malignant tumors associated with Peutz–Jeghers syndrome (PJS) in Japan to clarify if there are any differences in malignant tumor risk and the spectrum of malignancies by reviewing the literature on this subject.MethodsWe reviewed PJS cases reported in 1115 papers in Japan between January, 1989 and December, 2014.ResultsMalignant tumors were identified in 186 of the total 583 PJS cases from 523 evaluable studies. The estimated cumulative risk of a malignant tumor was 83.0xa0% at 70xa0years of age. Compared with a previous study, on a collective 91 cases reported up until 1988 in Japan, the reported proportion of gastrointestinal malignancies decreased, from 82.4 to 48.3xa0%, whereas that of gynecological malignancies increased, from 8.8 to 34.3xa0% (Pxa0<xa00.01). Moreover, breast cancers were occasionally reported (4.8xa0%), even though none were reported in the previous study. Adenocarcinoma of the uterine cervix was the most common malignant tumor (46.8xa0%) among women with PJS.ConclusionsThe increased number of reports of cervical adenocarcinoma in women with PJS is the prominent trend in Japan, and a subject of concern among gynecologists. The risk of breast cancer seems to be increasing, but confirmation of this trend will require further investigation.

Projections from a single NUCB2/nesfatin-1 neuron in the paraventricular nucleus to different brain regions involved in feeding.

The anorexigenic neuropeptide NEFA/nucleobindin 2 (NUCB2)/nesfatin-1-containing neurons are distributed in the brain regions involved in feeding regulation, including the hypothalamic paraventricular nucleus (PVN). Functionally, NUCB2/nesfatin-1 neurons in the PVN regulate feeding through the hypothalamus and brain stem. However, the neural network of PVN NUCB2/nesfatin-1 neurons has yet to be elucidated. Axon collateral branches allow individual neurons to target multiple neurons. In some cases, each target neuron can be located in different nuclei. Here we show that a single neuron in the PVN projects axonal collaterals to both the dorsal vagal complex (DVC) and the arcuate nucleus (ARC), which are important brain regions for feeding regulation. In this study, after injection of different retrograde tracers into the DVC and ARC, both tracer-labeled neurons were detected in the identical PVN neuron, indicating the axon collateral projections from the single PVN neuron to the DVC and ARC. Furthermore, immunohistochemical analysis revealed that approximately 50xa0% of the neurons with axon collateral projections from the PVN to the DVC and ARC were found to be NUCB2/nesfatin-1 neurons. Our data suggest that a single NUCB2/nesfatin-1 neuron in the PVN projects to both the ARC and the DVC with axon collateral projection. Although the physiological significance remains to be elucidated, our data offer new perspectives on NUCB2/nesfatin-1 function at the neural network level and food intake regulation.

Clinicopathological significance of lymphangiogenesis detected by immunohistochemistry using D2-40 monoclonal antibody in breast cancer.

To elucidate the association between the lymphangiogenesis and clinicopathological factors including the survival in breast cancer, 91 Japanese patients with breast cancer were investigated.u3000The lymphangiogenesis was evaluated by the count of lymph vessel density (LVD) with immunohistochemical method using D2-40 monoclonal antibody, a specific marker for lymphatic endothelial cells.D2-40-positive lymph vessels were detected in 87 of 91 cases, and were mainly distributed in the peritumoral lesions or around the tumor edge.u3000There was a significant difference in disease-free survival (DFS) and overall survival (OS) between patients with high LVD and with low LVD (p=0.02, 0.01, respectively, log-rank test).u3000In addition, LVD significantly correlated with the following clinicopathological factors: menopausal status (p<0.01), tumor size (p<0.01), lymph-node status (p=0.01) lymphatic vessel invasion (LVI) (p<0.01), blood vessel invasion (BVI) (p=0.03) and estrogen receptor status (ER) (p=0.02).Those data suggest that D2-40 monoclonal antibody is a useful marker for evaluating the LVD and its evaluation is helpful to predict the survival in breast cancer.