Short-Term Evaluation of a Novel No-Touch Technique for Harvesting Saphenous Veins With Long-Shafted Ultrasonic Scalpel.

OBJECTIVE: Saphenous vein grafts (SVGs) are widely used as bypass conduits in coronary artery bypass grafting. Compared with the conventional technique, the "no-touch" technique, wherein the saphenous veins are harvested with the surrounding tissue, may improve SVG patency; however, there are concerns regarding wound complications. To address this issue, we describe our novel no-touch technique with separate skin incisions using a long-shafted ultrasonic scalpel and report the clinical outcomes. METHODS: We enrolled 66 male patients who underwent isolated coronary artery bypass grafting between April 2016 and April 2021. There were 30 and 36 patients treated using our no-touch technique and the conventional technique, respectively. The participants underwent coronary angiography before discharge and were followed clinically. SVG samples were taken for pathological examination. RESULTS: SVGs harvested using our no-touch technique displayed preservation of the vessel wall structure and surrounding tissues. Our no-touch technique demonstrated no inferiority in patency compared with the conventional technique, and there was no SVG occlusion in the no-touch group. The frequency of leg wound complications was higher in the no-touch group than the conventional group, but no surgical site infections and severe complications occurred in the no-touch group. CONCLUSIONS: SVGs harvested using our novel no-touch technique had similar pathological characteristics to those harvested using the original no-touch technique reported previously. Our no-touch technique maintained SVG patency and caused no severe wound complications. However, a large-scale, longitudinal study is required to accurately assess the clinical outcomes of our no-touch technique.

[Multiple Primary Pulmonary Meningiomas].

We report a rare case of multiple primary pulmonary meningiomas in a 52-year-old woman who presented with lung nodules identified on abdominal computed tomography(CT). She had a history of surgery and chemotherapy for an immature ovarian teratoma 33 years prior to presentation. She underwent resection of a mature retroperitoneal teratoma 16 years prior and a peritoneal teratoma 6 months prior to presentation. Chest CT revealed 3 solid nodules in the right S3, right S8, and left S6 lung segments, and we performed thoracoscopic resection. Histopathologically, the 3 tumors were diagnosed as meningiomas. Since these tumors did not have other histological component and magnetic resonance imaging of the central nervous system revealed no meningeal lesion, these tumors were diagnosed as primary pulmonary meningiomas.

Oncological and peri-surgical outcomes of radical prostatectomy for non-metastatic prostate cancer with prostate-specific antigen level of 50 ng/ml or greater.

BACKGROUND: The role of radical prostatectomy in treating non-metastatic prostate cancer patients with high prostate-specific antigen levels remains unclear. We evaluated the feasibility and oncological outcomes of radical prostatectomy in non-metastatic prostate cancer patients with prostate-specific antigen levels of 50 ng/ml or higher. METHODS: This retrospective study included 31 patients who were diagnosed as very high-risk prostate cancer (clinical stage of any T, N0-1 M0 and PSA levels ≥50 ng/ml) and underwent radical prostatectomy either as a monotherapy or as a component of multimodal therapy (RP group). Surgery-related complications were investigated. Time to castration-resistant prostate cancer, cancer-specific survival, and overall survival were estimated using the Kaplan-Meier method. A total of 47 patients with very high-risk prostate cancer who were treated with androgen deprivation therapy without local therapy served as a control group (ADT group). Survivals were compared between RP group and ADT group in exploratory analyses. RESULTS: The median pretreatment prostate-specific antigen was 87 ng/ml and 100 ng/ml in the RP and ADT groups, respectively (P = 0.67). Surgical complications of Clavien-Dindo Grade 3 were documented in nine patients (29%). Ten-year castration-resistant prostate cancer-free, cancer-specific and overall survivals were 78%, 81% and 77% in RP group, respectively, and they were significantly better than those of ADT group (54%, P = 0.006; 54%, P = 0.006 and 38%, P < 0.001). Exploratory multivariate analysis identified radical prostatectomy as the only significant factor associated with a better cancer-specific survival (hazard ratio: 0.25, P = 0.006). CONCLUSIONS: Radical prostatectomy is feasible for non-metastatic prostate cancer patients with prostate-specific antigen levels of 50 ng/ml or higher. Radical prostatectomy is a viable option for select patients with non-metastatic, very high-risk prostate cancer.

Dopamine-Secreting Paraganglioma in the Retroperitoneum.

Pheochromocytomas and paragangliomas, which exclusively produce dopamine, are very rare. Herein, we report for the first time a Japanese case of an exclusively dopamine-producing paraganglioma accompanied by detailed immunohistochemical analyses. A 70-year-old Japanese woman was referred to our hospital for functional examination of her left retroperitoneal mass. Her adrenal functions were normal, except for excessive dopamine secretion. After the tumorectomy, her dopamine level normalized. The histopathological diagnosis of the tumor was paraganglioma; this was confirmed by positive immunostaining of chromogranin A (CgA), tyrosine hydroxylase (TH), dopamine ß-hydroxylase (DBH), and succinate dehydrogenase gene subunit B (SDHB). However, the immunostaining of CgA in the tumor cells showed peculiar dot-like staining located corresponding to Golgi complex in the perinuclear area, rather than the diffuse cytoplasmic staining usually observed in epinephrine- or norepinephrine-producing functional pheochromocytomas and paragangliomas. The immunohistochemical results suggested that the tumor cells had sparse neuroendocrine granules in the cytoplasm, resulting in inhibition of catecholamine synthesis from dopamine to norepinephrine in neurosecretory granules. This may be the mechanism responsible for exclusive dopamine secretion in the present case.

Diffusion-weighted magnetic resonance imaging to differentiate malignant from benign gallbladder disorders.

PURPOSE: To retrospectively evaluate the utility of apparent diffusion coefficient (ADC) and lesion to spinal cord ratio (LSR) in diffusion-weighted magnetic resonance (MR) imaging (DWI) as compared with morphological assessment alone, for differentiating malignant from benign gallbladder disorders. METHODS: This study was approved by the ethics committee, and written informed consent was waived. Ninety-one patients (13 malignancy and 78 benignancy) were reviewed. ADC was calculated using two DW images with different motion-probing gradient strengths (b=0, 1000s/mm(2)). LSR was measured by dividing the signal intensity of a thickened gallbladder wall by the maximum signal intensity of the lumbar enlargement of the spinal cord. In addition, the morphology of the gallbladders was assessed with conventional MR imaging. RESULTS: In receiver operating characteristic curve analysis, the areas under the curves for ADC and LSR were 0.861 and 0.906, respectively. Three morphological findings were considered: a massive formation, a disrupted mucosal line, and the absence of a two-layered pattern. When a combination of two or more of these morphological findings was positive for malignancy, the sensitivity, specificity, and accuracy were 76.9%, 84.0%, and 83.0%, respectively. When a combination of three or more of the above morphological findings together with ADC of less than 1.2 × 10(-3)mm(2)/s or LSR of more than 0.48 were positive for malignancy, these values were 73.0%, 96.2%, and 92.9%, respectively. There were significant differences in specificity and accuracy. CONCLUSION: Use of ADC and LSR in DWI can improve diagnostic performance for differentiating malignant from benign gallbladder disorders.

Ectopic ACTH syndrome caused by desmopressin-responsive thymic neuroendocrine tumor.

A 32-year-old Chinese woman with rapid weight gain and progressive edema was found to have typical Cushingoid features. Her endocrine data were consistent with a diagnosis of ACTH-dependent Cushing's syndrome. To differentiate ectopic ACTH syndrome (EAS) from Cushing's disease (CD), various dynamic endocrine and imaging tests were performed. Her ACTH response was negative to corticotropin-releasing hormone (CRH) and positive to desmopressin. Magnetic resonance imaging of the pituitary showed no mass lesion. Computed tomography scan of the chest revealed a large mass (21 × 15 mm) in the anterior mediastinum, where positron emission tomography showed accumulation of [(18)F] fluorodeoxyglucose. Selective venous sampling showed marked step-up in ACTH level in the internal thoracic vein but not in the cavernous sinus after CRH stimulation. These data are compatible with the diagnosis of EAS. The resected tumor was pathologically consistent with thymic neuroendocrine tumor (NET) positive for ACTH by immunohistochemistry and abundant V1b receptor gene expression by RT-PCR. Postoperatively, her circulating ACTH/cortisol levels became normalized, and responded to stimulation with CRH but not with desmopressin. Her Cushingoid appearance gradually disappeared, and she was free from recurrence 5 years after surgery. This is a rare case of desmopressin-responsive EAS caused by thymic NET with predominant V1b gene expression, which was successfully localized by imaging modalities combined with selective venous sampling.

[Myelofibrosis ameliorated after treatment for nontuberculous mycobacterial infection].

A 42-year-old female was admitted to our hospital because of continuous fever, anemia, and immature myeloid cells in peripheral blood. Bone marrow biopsy revealed severe myelofibrosis (MF). We performed computed tomography and identified several swollen mediastinal lymph nodes and nodules in the right upper lung. Lymph node biopsy showed an infection with Mycobacterium intracellulare (M. intracellulare), a nontuberculous mycobacterium (NTM). Antituberculosis drugs led to remission of the NTM infection. Bone marrow biopsy revealed marked improvement in MF and red blood cell infusion was not required after therapy. No prior cases of concomitant NTM with M. intracellulare and MF have been reported. This is thus the first reported case showing improvement of myelofibrosis after NTM treatment. This case report offers valuable insights into the pathology of MF.

Role of methylation of the hMLH1 gene promoter in the development of gastric and colorectal carcinoma in the elderly.

The occurrence of malignant neoplasms increases with advancing age. Although aging and carcinogenesis are basically different processes, they share phenomena such as the accumulation of DNA damage and abnormal proteins. Recent advances in molecular biology have shown an accumulation of genetic and epigenetic changes in both aging and carcinogenesis, as well as the alteration of metabolism, immunosenescence and shortened telomeres. DNA methylation is a representative epigenetic phenomenon and is frequently involved in controlling gene functions during development and tumorigenesis. We herein focused on methylation of genes in the development of gastrointestinal carcinomas in the elderly. The proportion of gastric and colorectal carcinomas with hypermethylation of the hMLH1 promoter increases with age, reaching 25-30% of all carcinomas of the stomach and large intestine in elderly patients. These tumors have clinicopathological and molecular characteristics such as loss of hMLH1 expression, microsatellite instability, poorly differentiated histology, peritumoral inflammatory cell infiltration, low incidence of lymph node metastasis and favorable prognosis. However, methylation-related carcinogenesis accounts for up to approximately one-third of tumors, and other mechanisms; for example chromosomal instability as a result of telomere dysfunction, are responsible for the development of most carcinomas in the elderly.

Microsatellite-unstable mucinous colorectal carcinoma occurring in the elderly: comparison with medullary type poorly differentiated adenocarcinoma.

Mucinous carcinoma and poorly differentiated adenocarcinoma of the large intestine have a high frequency of microsatellite instability, and their occurrence increases gradually with age. To elucidate the clinicopathological and immunohistochemical features of microsatellite-unstable mucinous carcinoma and compare the tumor with medullary type poorly differentiated adenocarcinoma, the clinicopathological status and expression of mucin core and hMLH1 proteins were studied in 15 microsatellite-unstable and 20 microsatellite-stable mucinous colorectal carcinomas occurring in elderly patients, and compared with 23 cases of medullary type poorly differentiated adenocarcinoma in which 21 cases were microsatellite-unstable. Thirteen (87%) of 15 microsatellite-unstable carcinomas exhibited absent hMLH1 expression compared with three (15%) of 20 microsatellite-stable carcinomas (P < 0.01). The proportion (87%) of positive MUC5AC expression in microsatellite-unstable mucinous carcinoma was significantly higher than that (45%) in microsatellite-stable mucinous carcinoma (P = 0.01). Compared with microsatellite-stable mucinous carcinoma, microsatellite-unstable mucinous carcinomas were significantly associated with a proximal location, intra- and peritumoral inflammatory cell infiltration, frequent MUC5AC expression, a low incidence of lymph node metastasis and absent hMLH1 protein expression, which is not different to medullary type poorly differentiated adenocarcinoma except for MUC2 expression and age-related occurrence. These results suggest that microsatellite-unstable mucinous carcinoma occurring in the elderly shares clinicopathological and molecular features with medullary type poorly differentiated adenocarcinoma and that microsatellite instability with absent hMLH1 expression plays an important role in the development of these two carcinomas.

Age-related alteration in the association of microsatellite instability with absent hMLH1 expression and histological types of colorectal carcinoma.

Microsatellite instability (MSI) is present in approximately 15-20% of sporadic colorectal cancers. However, despite the increased prevalence of absent hMLH1 expression and MSI in colorectal cancer in the elderly, few attempts have been made to define it in detail. The aim of the present paper was to correlate age-related alterations in absent hMLH1 expression and MSI with various histological types of colorectal carcinoma. hMLH1 expression and microsatellite status were studied in 184 colorectal carcinomas (49 well-differentiated, 49 moderately differentiated, 49 poorly differentiated adenocarcinomas, and 37 mucinous carcinomas). The prevalence of absent hMLH1 expression was higher in poorly differentiated adenocarcinoma (63%) and mucinous carcinoma (43%) than in well- (8%) and moderately (12%) differentiated adenocarcinomas. MSI was found more frequently in poorly differentiated adenocarcinoma (69%) and mucinous carcinoma (41%) than in well- and moderately differentiated adenocarcinomas (8% and 6%, respectively). Age-related differences in absent hMLH1 expression and MSI were found only in poorly differentiated adenocarcinoma, in which the prevalence of medullary-type carcinoma increased with advancing age. These results indicate that an age-related increase of medullary-type tumors in poorly differentiated adenocarcinoma may play an important role in the increase of absent hMLH1 expression and MSI in colorectal carcinoma.

Standard organ weights among elderly Japanese who died in hospital, including 50 centenarians.

The present study was conducted to determine standard organ weights among the elderly, because little has been reported on this subject. To analyze the human aging process in terms of organ weights, age-associated changes and correlations among organ weights and the contributions of age and nutrition to organ weights were also examined. The subjects included 1615 consecutive autopsy cases of patients aged 60-99 years who died between 1995 and 2003, and cases of 50 centenarians who died between 1973 and 2005. The weights of nine organs were measured before formalin fixation. If affected by serious diseases, such as cancer, the organs were excluded from the study. Values beyond 99% of the bilateral measurement limits were also excluded. In this manner the standard organ weights were obtained. The organ weights decreased significantly according to age in all organs except for the heart in men and the lungs in both genders. Undernutrition strongly contributed to organ weight except for the hypophysis, and was especially apparent in the heart and liver. In conclusion, the standard organ weights of elderly patients who died while hospitalized were determined. Undernutrition contributed significantly to a reduction in organ weights.

Sustained progression and loss of the gender-related difference in atherosclerosis in the very old: a pathological study of 1074 consecutive autopsy cases.

INTRODUCTION: Epidemiological surveys show decrease or reversal of male predominance in cardiovascular mortality in the very old, but the actual condition of atherosclerosis in the very old is largely unknown. The objective of this paper is to reveal whether the atherosclerosis continues to progress, or the gender-related difference exists in the very old. METHODS: The subjects were 1074 consecutive autopsy cases of in-hospital death. The male:female ratio was 1.1:1 and the average age was 80 years. Macroscopic evaluation was performed on the degree of atherosclerosis in 10 arteries including the intracranial arteries, carotid artery, aorta, coronary artery, and femoral artery. RESULTS: The severity of atherosclerosis differed greatly among arteries. The age-related increase of the atherosclerotic degree was evident, even after 80 years of age. The atherosclerosis was more severe in males than in females in their 60s, but this male predominance decreased with ageing and finally disappeared in their 90s. CONCLUSION: The sustained progression of atherosclerosis and loss of the gender-related difference probably account for the increase of cardiovascular mortality in very old females. They also suggest that the prevention of the atherosclerotic progression is still important in the seventh and eighth decade of life.

Pathologic characteristics of gastric cancer in the elderly: a retrospective study of 994 surgical patients.

BACKGROUND: The clinicopathologic features of gastric carcinoma in elderly people have been reported previously. The present study examined the patterns and distribution of gastric carcinomas in the elderly, especially in patients aged 85 and older. METHODS: A retrospective study of 994 consecutive Japanese patients aged 65 years or older was performed. In this group, a total of 1,147 lesions were analyzed. Pathological findings in the very old group (older than 85 years; n = 126) were compared with those in younger groups (65-74 years [young-old group]; n = 356) and (75-84 years [middle-old group]; n = 512). RESULTS: While the male-to-female ratio significantly decreased with advancing age, the relative odds of gastric cancer in men were higher than those in women in all age groups. In the very old group, cancer of the lower third of the stomach tended to increase with advancing age, and accounted for 43.7% of cases. In the population overall, differentiated-type adenocarcinoma accounted for 89.6% in the early cancers and 50.3% in the advanced cancers. The proportion of cases involving differentiated-type carcinoma significantly increased with advancing age in early cancer and female advanced cancer cases, whereas no significant change was found in male advanced-cancer patients. In the very old group, lymph node metastasis was found in 5.4% of early cancers and 72.7% in advanced cancers. Multiple cancers significantly increased with advancing age ( P < 0.05; 10.7% in the younger-old group, 12.7% in the middle-old group, and 19.0% in the very old group). CONCLUSION: These results indicate that, in the very old group, gastric cancers showed a distal shift with predominantly differentiated-type carcinoma in the early stages and increased undifferentiated-type carcinomas in advanced stages. These results suggest increased histologic diversity with tumor growth. These findings have important implications for the screening and diagnosis of gastric cancer in the elderly.

Developments of geriatric autopsy database and Internet-based database of Japanese single nucleotide polymorphisms for geriatric research (JG-SNP).

To facilitate geriatric research on the roles of genetic polymorphisms of candidate genes, two databases were developed based on data obtained from autopsy examinations of elderly subjects: the geriatric autopsy database (GEAD) and the Japanese single nucleotide polymorphisms (SNP) database for geriatric research (JG-SNP) which is accessible on the Internet (http://www.tmgh.metro.tokyo.jp/jg-snp/english/E_top.html). The data for the GEAD were derived from 1074 consecutive autopsy cases (565 male and 509 female cases) with an average age of 80 years. The GEAD was installed on a stand-alone Windows 2000 server using Oracle 8i as the database application. The GEAD contains clinical diagnoses of 26 geriatric diseases, histories of smoking and alcohol consumption, pathological findings (720 items), severity of atherosclerosis, genetic polymorphism data, etc. On the JG-SNP website, case distribution corresponding to a specified SNP or disease can be searched or downloaded. Although there are several Internet-based SNP databases such as dbSNP, no databases are available at present on the web that contain both SNP data and phenotypic data. As autopsy studies can provide large amounts of accurate medical information, including the presence of undiagnosed diseases such as latent cancers, the GEAD is a unique and excellent database for research on genetic polymorphisms.

Differentiation between completely hyalinized uterine leiomyomas and ordinary leiomyomas: three-phase dynamic magnetic resonance imaging (MRI) vs. diffusion-weighted MRI with very small b-factors.

PURPOSE: To assess the possibility of differentiating between completely hyalinized leiomyomas and ordinary leiomyomas by using diffusion-weighted (DW) magnetic resonance imaging (MRI) (DWI) employing very small b-factors (b = 1.51 and 55.3 seconds/mm(2)) in comparison with three-phase dynamic MRI. MATERIALS AND METHODS: The subjects were 25 patients with 52 histopathologically confirmed uterine leiomyomas. All leiomyomas were divided into two histopathologic subtypes (5 completely hyalinized leiomyomas and 47 ordinary leiomyomas). For each leiomyoma, the enhancement index (EI) at three-phase dynamic MRI and apparent diffusion coefficient (ADC) were obtained and then compared. RESULTS: The EIs at second and third dynamic phases clearly differentiated the two types of leiomyomas without overlap of values. ADCs also clearly differentiated the two types of leiomyomas without overlap of values. Moreover, there were significant positive correlations between ADCs and EIs at all dynamic phases (r = 0.41-0.50, P < 0.01). CONCLUSION: Not only three-phase dynamic MRI but also DWI with very small b-factors could be useful for differentiating completely hyalinized leiomyomas from ordinary leiomyomas.

Triple-phase dynamic MRI of intratumoral vessel density and hyalinization grade in uterine leiomyomas.

OBJECTIVE: Our purpose was to clarify the relationship between the tissue vascularity shown on triple-phase dynamic MRI and the number of intratumoral vessels and degree of hyalinization, which are two histopathologic changes in leiomyoma. SUBJECTS AND METHODS. The subjects were 10 premenopausal patients with 20 leiomyomas who had undergone surgery without preoperative gonadotropin-releasing hormone analogue treatment. Intratumoral vessel density was determined by the mean number of intratumoral vessels with at least one smooth-muscle layer in the optic fields magnified 100 times. Hyalinization grade was determined by the severity of hyalinization, histopathologically classified in three grades. The enhancement index (EI) of the leiomyoma was calculated using the formula EI(t) = [S(t) - S(0)] / S(0), where S(0) is the signal intensity on pre-enhanced T1-weighted images and S(t) is the signal intensity on each dynamic phase image (t = 20, 60, and 180 sec) [corrected]. The histopathologic parameters of intratumoral vessel density and hyalinization grade were compared with the enhancement indexes obtained from the triple-phase dynamic MRI. RESULTS: We found positive correlations between intratumoral vessel density and EI(60) and between intratumoral vessel density and EI(180) (in both cases, p = 0.0028 and r = 0.69). We found significant differences among the mean enhancement indexes for each hyalinization grade at all dynamic phases (p < 0.01). The leiomyomas with lower intratumoral vessel densities tended to show greater hyalinization. CONCLUSION: Our results showed that leiomyomas with only slight hyalinization or with abundant vessels were well enhanced, but the leiomyomas with severe hyalinization enhanced poorly.

[An autopsied case of chronic active Epstein-Barr virus infection complicated in systemic lupus erythematosus and antiphospholipid antibody syndrome].

We have experienced a case of chronic active Epstein-Barr virus infection (CAEBV) complicated in systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APS). A 35-year-old woman was admitted to our hospital with complaints of fever and dyspnea on exertion. She was diagnosed as having SLE on the basis of arthritis, oropharyngeal ulcer, lymphopenia, and positive autoantibodies against DNA, RNP and SSA. The diagnosis of APS was also made because of positive anti-cardiolipin IgG antibodies and the existence of multiple pulmonary infarction with pulmonary hypertension. The administration of 30 mg/day of prednisolone and anti-coagulation significantly improved clinical symptoms. However, she was again admitted to the hospital four months later because of progressive liver damage and pancytopenia. Increment of prednisolone did not improve the clinical situation and she expired because of pulmonary hemorrhage. At autopsy, there were a significant increase of histiocytes with hemophagocytosis and a dense infiltration of atypical lymphocytes in the liver, spleen, lymph nodes and bone marrow. Infiltrated lymphocytes were positive for CD 3 and EBER 1 in immunohistochemical staining and EBVmRNA was detected by in situ hybridization. Final pathological diagnosis was CAEBV with hemophagocytic syndrome in association with lupus nephritis, pulmonary hemorrhage and pulmonary infarction.