Metagenomic Analysis of Bacterial Microflora in Dental and Atherosclerotic Plaques of Patients With Internal Carotid Artery Stenosis.

Background: Internal carotid artery stenosis is primarily attributed to atherosclerosis in the carotid artery bifurcation. Previous studies have detected oral bacteria in atherosclerotic lesions, suggesting an association between oral bacteria and atherosclerosis. In this study, we compared the bacterial flora of the atherosclerotic plaque in the carotid artery and dental plaque of patients with internal carotid artery stenosis using 16S ribosomal RNA (16S rRNA) metagenomic sequencing. Methods: Fifty-four patients who underwent internal carotid endarterectomy for internal carotid artery stenosis at the Showa University Hospital between April 2016 and February 2018 were included. Polymerase chain reaction targeting the 16S rRNA gene detected bacterial DNA in the carotid plaques of 11 cases, of which only 5 could be further analyzed. Thereafter, DNA extracted from the carotid and oral plaques of these 5 cases were analyzed using metagenomic sequencing targeting 16S rRNA. In addition, their general condition and oral conditions were evaluated. The patients were classified into symptomatic and asymptomatic groups based on the presence or absence of symptoms of transient ischemic attack, and their bacterial flora was evaluated. Results: The results demonstrated that the microflora of carotid plaques (n = 5) contained bacterial species from 55 families and 78 genera. In addition, 86.5% of the bacteria detected in the carotid plaques were also detected in oral plaques. Cariogenic and periodontopathic bacteria accounted for 27.7% and 4.7% of the bacteria in the carotid plaques, respectively. Conclusions: These results suggest that oral bacteria are directly or indirectly involved in the pathogenesis of atherosclerosis. More extensive studies of oral commensal bacteria detected in extra-oral lesions are warranted to comprehensively investigate the role of oral bacteria in the pathogenesis of systemic diseases.

Single-Center Case Series of Simple Proximal Clipping for Large Thrombosed Vertebral Artery Aneurysms: Preservation of Perforating Arteries and Long-Term Outcomes.

BACKGROUND: Surgical proximal parent artery occlusion (PAO) is one of the treatments for partially thrombosed vertebral artery aneurysms (PTVAs). However, whether long-term changes in size and perforating arteries through the blind end can be truly preserved remain unknown. OBJECTIVE: To evaluate the efficacy and safety of surgical proximal PAO for PTVAs, focusing on the transition in size and preservation of perforating arteries. METHODS: We retrospectively reviewed 14 consecutive cases of unruptured large PTVAs. The cases were treated with surgical proximal PAO without trapping or thrombectomy. Preservation of the perforating arteries was confirmed through intraoperative indocyanine green video angiography. The aneurysm size was evaluated by measuring the maximum diameter on axial T2-weighted magnetic resonance images. Post-treatment outcomes were assessed using the modified Rankin Scale at the last follow-up examination. RESULTS: Thirteen patients (excluding 1 with morbidity) had a mean follow-up time of 33.2 months (range, 12-60 months) and a mean reduction rate of 71% (range, 32%-95%). Only 1 patient (7.2%) experienced postoperative stroke, and 13 patients (92.8%) showed no worsening of the modified Rankin Scale score at the final follow-up examination. The symptoms were improved in 5 of the 6 symptomatic patients (83.3%). In 10 patients (71.4%), a perforating branch that could not be identified on preoperative imaging was identified intraoperatively. CONCLUSION: Surgical proximal PAO without trapping or thrombectomy for PTVAs allows long-term reduction of aneurysm size and improves treatment safety by preserving the perforating artery, especially in cases wherein direct reconstruction is not feasible.

Peritoneal adenomatoid (microcystic) mesothelioma.

There are several reports of pleural adenomatoid (microcystic) mesothelioma, but peritoneal adenomatoid mesothelioma is extremely rare. A 64-year-old Japanese woman presented with no symptoms and no asbestos exposure history. An abdominal computed tomography scan revealed multiple hypervascular masses on the liver surface, pelvic cavity and anterior peritoneum. Over 10 pieces of the multiple resected tumors showed numerous microcysts composed of a bland mesothelial cell background with rich capillary vessels. Focally, atypical cells with bizarre nuclei with prominent nucleoli were observed. Adenomatoid mesothelioma was suspected based on histochemical, immunohistochemical and fluorescence in situ hybridization findings. The tumors relapsed 4 years later and metastasized to the lung, but the patient remains alive 7 years after the first tumor resection surgery. Although the prognosis of adenomatoid mesothelioma of pleural origin is poor, the progression of this peritoneal case is slow.

An Experimental Clamping and Cutting Study of Carotid and Intracranial Stents: Preparation for Surgical Rescue in Stent Complications.

OBJECTIVE: To carry out surgery safely in vessels with stents, it is essential to have knowledge of what would happen if the stents were clamped or cut. Using all stents that are permitted in Japan, we recorded with a surgical microscope the behavior of stents when they were clamped or cut and discussed the morphologic changes along with image findings. METHODS: We classified carotid artery and intracranial stents as group 1A and 1B or group 2A and 2B according to the structure of stent eye: laser cut or blade. Each stent was clamped using a Yasargil aneurysm clip, bulldog forceps, and vascular forceps. Degree of closure and presence or absence of stent deformation after declamping were recorded using a surgical microscope. Furthermore, we performed morphologic evaluations using high-resolution cone-beam computed tomography. Lastly, each stent was cut; the behavior of the cut stent was recorded, and differences between stents were examined. RESULTS: Complete clamping was confirmed both visually and based on image evaluations with bulldog forceps and vascular forceps in the groups of carotid artery stents, with the Yasargil aneurysm clip in the intracranial stents. In the blade-type stents, we found that the stents elongated during clamping, and the component wire scattered at the time of stent cutting. Furthermore, the stents could be easily separated by holding with forceps. CONCLUSIONS: Knowing the properties of each stent is essential to conduct safe surgery in response to complications. Special care must be taken when clamping and cutting blade-type stents.

Distance Between the Falciform Ligament and Distal Dural Ring as a Surgical Landmark for the Treatment of Paraclinoid Aneurysms.

OBJECTIVE: It is difficult to completely comprehend the anatomy of the structures surrounding the paraclinoid region before aneurysm and tumor treatment therein. When treating paraclinoid aneurysms, it is important to determine the location of the aneurysm as intradural or extradural. Thus, accurate prediction of the position of the distal dural ring (DDR) is necessary. To this end, we focused on the falciform ligament (FL), which is easily visualized on images based on its anatomic features. We measured the distance between the FL and the DDR in patients undergoing paraclinoid aneurysm operations. METHODS: Between January 2017 and July 2018, 15 patients who underwent clipping for paraclinoid aneurysm treatment were retrospectively identified. The distance between the FL and the DDR was measured using a microscale at the time of the operation. RESULTS: The patients comprised 14 women and 1 man. The mean aneurysm diameter was 7.29 ± 2.21 mm and the median size was 6.5 mm. Eleven of the aneurysms were on the left and 4 were on the right side. The mean distance between the FL and the DDR was 3.50 ± 0.17 mm and the median distance was 3.50 mm. The distance between the FL and the DDR was almost the same across cases (3.5 mm). CONCLUSIONS: The position of the FL can be easily predicted using preoperative three-dimensional computed tomography angiography based on its anatomic features. In this study, the DDR was located 3.5 mm proximal to the FL along the internal carotid artery. This information is useful for predicting the position of the DDR.

Is surgical parent artery occlusion effective for intracranial aneurysms measuring over 10 mm in size? Result from long-term follow-up of size changes and outcomes.

BACKGROUND: There have been no long-term follow-up reports pertaining to chronological size changes in large or giant unruptured intracranial aneurysms treated with surgical parent artery occlusion (PAO). The object of this study is to investigate the utility and safety of surgical PAO by conducting a long-term follow-up of chronological aneurysm size changes and outcomes. METHODS: A retrospective study of 21 unruptured intracranial aneurysms measuring over 10 mm (20 patients) treated with surgical PAO in the period 2012-2017 was conducted. For aneurysms presenting with anterior circulation, high/low flow bypass was chosen and carried out concomitantly on the basis of preoperative balloon occlusion test results. Aneurysm size before and after surgery was evaluated chronologically using maximum diameter measurements taken from the same slice of MRI T2-weighted images. Moreover, post-surgery outcomes were evaluated according to a modified Rankin scale (mRS) at discharge. RESULTS: PAO aiming for blind-alley formation was performed in 20 of 21 aneurysms (95.2%). Aneurysm size reduction was confirmed in 20 aneurysms (95.2%) after proper PAO, with an average reduction rate of 63.1% (range, 28-95%), during an average follow-up period of 27 months (range, 4-54 months). Eighteen (90.4%) of the 20 patients with 21 aneurysms returned to previous life with mRS score 0-2. With regard to preoperative symptoms, diplopia and visual impairment had improved in three patients (50%) and one patient (100%), respectively. Ischemic complications had occurred in five patients, two (9.6%) of whom were symptomatic and three (14.3%) were asymptomatic. The mortality rate in this study was 0%. CONCLUSIONS: Surgical PAO for unruptured intracranial aneurysms measuring over 10 mm has been shown to be an effective method of treatment, eliciting a reduction in aneurysm size.

Three-dimensional Fusion Imaging without Contrast Medium for Carotid Endarterectomy.

Carotid endarterectomy (CEA) is a popular surgical procedure for patients with carotid artery stenosis. Before performing CEA, radiologic information about carotid artery stenosis must be obtained using three-dimensional (3D) computed tomography angiography (CTA). However, it is difficult to perform 3D-CTA in patients with renal dysfunction and an allergy to contrast medium. To solve this problem, 3D fusion images (3D-FI) with magnetic resonance angiography and 3D computed tomography are created. In this report, we describe the utility of 3D-FI.

A novel surgical technique for bleeding duodenal varices after failure of balloon-occluded retrograde transvenous obliteration: a case report.

BACKGROUND: Duodenal varices are a low-frequency cause of gastrointestinal bleeding; however, greater than 40 % mortality has been reported after the initial bleeding episode. CASE PRESENTATION: This report describes a 72-year-old woman with bleeding duodenal varices treated by surgery after failure of balloon-occluded retrograde transvenous obliteration (B-RTO). The patient presented with profuse melena. Emergent upper endoscopy was immediately performed, and bleeding duodenal varices in the second portion of the duodenum were seen. Endoscopic band ligation was attempted first followed by B-RTO; however, the combined procedures failed. Laparotomy under general anesthesia was then performed, and the venous collaterals were cannulated using an 18-gauge needle. Following intraoperative angiography, the venous collateral was ligated on the peripheral side of the needle entry point, and ethanolamine oleate was injected into the afferent collateral vessel. Endoscopic examination on postoperative day 4 showed embolization of the duodenal varices. The patient was discharged on postoperative day 11. CONCLUSIONS: This technique is simple and effective, and we believe it is a potential alternative surgical treatment for duodenal varices with portal hypertension.

Assessment of aggressiveness of rectal cancer using 3-T MRI: correlation between the apparent diffusion coefficient as a potential imaging biomarker and histologic prognostic factors.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DW-MRI) permits non-invasive assessment of tumor characteristics. PURPOSE: To assess the value of DW-MRI as a potential non-invasive marker of tumor aggressiveness in rectal cancer by analyzing the relationship between tumoral apparent diffusion coefficient (ADC) values of MRI and histopathologic prognostic parameters that are not affected by preoperative chemoradiation therapy. MATERIAL AND METHODS: Forty patients with rectal cancer were assessed with primary staging 3-T MRI, including DWI, before undergoing surgical therapy. In all patients, surgery was performed without neoadjuvant therapy. Mean tumor ADC was measured and compared between subgroups based on pretreatment carcinoembryonic antigen (CEA) levels, MRI parameters (e.g. postoperative local recurrence), and histopathologic parameters, including A (invasive distance: A1, T-stage; A2, mesorectal fascia [MRF] status), B (differentiation grade: B1, poorly differentiated; B2, moderately differentiated; B3, well differentiated), C (others: C1, N-stage; C2, lymphangiovascular invasion). RESULTS: Mean tumor ADCs were different when comparing groups stratified by histologic differentiation grades (P=0.0192). There was no significant difference in mean ADCs when stratifying patients according to CEA levels, T-stage, N-stage, MRF status, presence of lymphangiovascular invasion, or the presence of local recurrence. CONCLUSION: Significant correlations were found between mean ADC values and differentiation grade. ADC may be useful as an imaging biomarker of tumor aggressiveness, but it cannot serve as an independent biomarker of advanced rectal cancer.

Primary squamous cell carcinoma of the liver concomitant with primary colon cancer: report of a case.

A 55-year-old Japanese female was admitted to our hospital to treat colon cancer. Computed tomography revealed a 2.6 × 2.0 cm liver mass considered to be liver metastasis. She synchronously underwent right colectomy with D3 lymph node dissection and subsegmentectomy 8 under the diagnosis of advanced colon cancer with liver metastasis. The pathology examination revealed the liver nodule was pure squamous cell carcinoma (SCC), whereas histology of colon cancer was a well differentiated tubular adenocarcinoma containing no squamous component. The patient underwent intensive checkup by imaging for a primary site of SCC. However, no lesion considered as possible primary site of SCC was found. Therefore, the liver nodule was finally diagnosed as a primary hepatic SCC. Primary SCC of the liver is a rare and high-grade malignant tumor. Recurrent multiple liver nodule was found at 13 months after surgery and the patient died of cancer 17 months after surgery.

Effects of reduced dose intensity of modified FOLFOX6 in patients with metastatic or recurrent colorectal cancer.

The current study was conducted to retrospectively investigate the effects of reducing average relative dose intensity (ARDI) in response to adverse events on time to treatment failure (TTF) and overall survival (OS) in patients with metastatic or recurrent colorectal cancer receiving modified FOLFOX6 (mFOLFOX6) therapy between January 2006 and May 2010. Patients were divided into two groups based on ARDI: those with an ARDI of 85% or more (ARDI maintained; n = 12) and those with an ARDI of less than 85% (ARDI reduced; n = 37). In the ARDI-reduced group, out of a total of 402 treatment courses conducted, 25.9% involved treatment delays and 8.2% involved dose reductions, and the incidence rate of treatment delay was significantly higher than that of dose reduction (p < 0.001). Hematological toxicity was the main reason for both treatment delays and dose reductions. Reduced ARDI by dose reduction effectively prevented any increase in the severity of neutropenia and the treatment delays in the next courses, suggesting that the dose reductions were appropriately performed. Median TTF in the ARDI-maintained and ARDI-reduced groups was 5.2 and 5.8 months, respectively (p = 0.225). Median OS was 15.5 months and 33.9 months in the ARDI-maintained and ARDI-reduced groups, respectively (p = 0.347). These findings suggested that reductions in ARDI of mFOLFOX6 therapy for metastatic or recurrent colorectal cancer due to treatment delays and dose reductions in response to adverse events do not necessarily lead to shortened TTF and OS.

Clinical significance of CEA and CA19-9 in postoperative follow-up of colorectal cancer.

BACKGROUND: We evaluated the efficiency of CEA and CA19-9 as tools for diagnosing recurrence in the postoperative surveillance of colorectal cancer. MATERIALS AND METHODS: A total of 227 patients who underwent curative resection for colorectal cancer between 1999 and 2003 at our hospital received complete follow-up according to the schedule determined prospectively. Using receiver operating characteristic (ROC) analysis, performance of postoperative values of CEA or CA19-9 for detecting recurrence was assessed. RESULTS: The sensitivity (1.000) and specificity (0.978) of the postoperative values of CEA in the high preoperative CEA group were very high. Even in the normal preoperative CEA group, the area under the curve (AUC) of the ROC curve of CEA (0.740, 95% confidence interval [95% CI], 0.628-0.852) was significantly larger than 0.5 (P < 0.001). The postoperative values of CA19-9 showed high sensitivity (0.833) and specificity (0.900) in the high preoperative CA19-9 group, while the AUC of the ROC curve of the normal preoperative group was as small as 0.510 (95% CI, 0.376-0.644). In the high preoperative CA19-9 group, however, there was no significant difference between the AUC of CA19-9 (0.904, 95% CI, 0.786-1.000) and that of CEA (0.869, 95% CI, 0.744-0.994) (P = 0.334). CONCLUSIONS: The measurement of CEA is an efficient way to detect recurrence. The efficiency of measuring CA19-9 for the purpose of detecting recurrence is low, especially in patients with a normal level of preoperative CA19-9. Even in patients with a high preoperative level of CA19-9, CEA might be able to fill the role of CA19-9.

[Three cases of serious abdominal tuberculosis associated with pulmonary tuberculosis].

Case 1) A 21-year-old Thai woman, and Case 2) a 22-year-old Indonesian woman, were each given a diagnosis of pulmonary tuberculosis. Immediately after starting medication, peritonitis symptoms appeared. Colonoscopies detected multiple rings and zonal ulcers. Abdominal tuberculosis was diagnosed, and anti-tubercular therapy was effective. Case 3) A 23-year-old man was given a diagnosis of pulmonary tuberculosis. The day after starting anti-tubercular therapy, he complained of abdominal pain that increased with muscular defense. He was given a diagnosis of perforation of the digestive tract, underwent emergency surgery, and recovered. Pathological examinations revealed granuloma with caseous necrosis and Mycobacterium tuberculosis. Physicians should be aware that tuberculosis can be a potential source of acute abdomen in young adults who do not take proper care of their health.

[Diagnostic efficacy and pitfalls of a 64-raw multislice computed tomography scan for mild head injuries in children].

The aim of this study is to analyze the usefulness of 64-raw multislice computed tomography (CT) scans and bone images of three-dimensional CT (3D-CT) scans for evaluation of mild head injuries in children. Thirteen children (9 boys and 4 girls, less than or equal to 15 years old) with mild head injury were included in the study. Head CT scans obtained within 24 hours after injury. All children had no episodes of loss of consciousness, amnesia, epilepsy, vomiting, and no neurological abnormality on arrival at hospital. We detected 9 positive findings on CT scans, which looked like fracture lines at the frontal bone in 7 cases. The bone images of CT axial views revealed a true fracture in one case in which a skull X-ray could not demonstrate a fracture line, but, other positive findings turned out to be a diploic vein surrounded by a thin bone cortex. All false positive findings were detected in the patients under the age of 6. By the 3D-reconstructive CT scan, it is easier to detect not only the intracranial lesions but also the cranial fracture. But, the diploic vein is apt to be misdiagnosed as the fracture line, especially in patients under the age of 6.

CpG island methylation of BNIP3 predicts resistance against S-1/CPT-11 combined therapy in colorectal cancer patients.

Aberrant gene methylation is frequently observed in various cancers and plays an important role in carcinogenesis, cancer progression and drug responsiveness. The aim of this study is to identify colorectal cancer specific gene methylation determining chemosensitivity to S-1/CPT-11 therapy. The gene methylation of CHFR, p16, RUNX3, E-cadherin, MGMT, hMLH1, ABCG2, UGT1A1 and BNIP3 genes were analyzed in 27 colorectal cancer tissues by quantitative methylation-specific PCR (q-MSP). All 27 patients were postoperatively treated by S-1/CPT-11 therapy targeting the metastatic lesion and the recurrent tumor. Thereafter, the patients were divided into a responder group (RG) or a non-responder group (NRG) according to the effect of the chemotherapy. There were 13 cases of RG (48.1%) and 14 cases of NRG (51.9%). The methylation level in CHFR, RUNX3 and BNIP3 was significantly higher in cancer lesions in comparison to the non-cancerous lesion. Only methylation of the BNIP3 gene was significantly higher in primary cancer tissue of the NRG than the RG. The correlation between the BNIP3 methylation status and time to progression (TTP) suggested that the low methylation group (n=16) resulted in a significantly longer TTP, in comparison to the high methylation group (n=11; P=0.004). The methylation level of BNIP3 showed a significant inverse correlation with the mRNA expression suggesting the DNA methylation suppressed BNIP3 expression (r=-0.466, P=0.021). In conclusion, BNIP3 gene methylation is a possible marker predicting a poor response to the S-1/CPT-11 combined therapy in colorectal cancer.

[A case of advanced gastric cancer with peritoneal dissemination effectively treated with fourth-line chemotherapy of S-1 alone].

The patient was a 42-year-old female diagnosed with unresectable highly advanced gastric cancer complicated by peritoneal dissemination. We performed systemic chemotherapy with MTX+5-FU as the first-line treatment, which stabilized the disease. Since the patient initially wished a radical resection, we tried chemotherapy with weekly PTX as a second-line treatment. Her therapeutic response remained between a partial response and a stable disease for about five months, followed, however, by progressive disease. The result of the third-line treatment with CPT-11+CDDP was again a progressive disease, so we switched her regimen to single-agent S-1 as a fourth-line treatment. The ascites disappeared three months after the change in regimen. As of March 2006, the patient had survived for 17 months since diagnosis (8 months since the ongoing S-1 therapy started) and the disease is currently stabilized, and preserving a favorable performance status. However, in June 2006, the patient died of pneumonia 20 months after the diagnosis.

[Two cases of gastric cancer with multiple liver metastases responding to TS-1 with hepatic arterial infusion of CDDP following low-dose 5-FU and CDDP chemotherapy].

Case 1: A 77-year-old man was revealed to have type 3 gastric cancer with synchronous liver metastases. He underwent total gastrectomy with lymphatic dissection of D1+a and tubing of the hepatic artery. After surgery, two courses of hepatic arterial infusion of low-dose 5-FU plus CDDP were performed. The patient was discharged, and TS-1 (60 mg/day) was administered from day 1 to 14 followed by 7 days rest as one course. CDDP (10 mg/ body) was infused in the hepatic artery bolus on day 8 and 15 as outpatient treatment. After 8 months, the CEA was decreased from 3,098 ng/dl to 5.4 ng/dl, hepatic metastases were decreased by 85% assessed as a partial response. Case 2: A 71-year-old man was diagnosed with multiple liver metastases 10 months after distal gastrectomy for early gastric cancer. After tubing of the hepatic artery, three courses of hepatic arterial infusion of low-dose 5-FU plus CDDP were performed. TS-1 with hepatic arterial infusion of CDDP was administered using the same regimen as an outpatient. After 4 months, hepatic metastases decreased by 73%. These cases suggest that TS-1 with hepatic arterial infusion of CDDP in an outpatient may be an effective treatment with low toxicities and no damage to QOL in gastric cancer patients with multiple liver metastases.

Loss of estrogen receptor beta expression at cancer front correlates with tumor progression and poor prognosis of gallbladder cancer.

Gallbladder carcinoma is a relatively rare malignancy with an extremely poor patient prognosis. This malignancy occurs more frequently in women than men, yet expression of the estrogen receptor (ER) family has not been studied. We applied an immunohistochemical technique to examine the expression of ERalpha and ERbeta in gallbladder carcinoma tissues and then compared their expression status with several clinicopathological factors. We examined 26 gallbladder adenocarcinoma specimens and 11 non-cancerous regions using ERalpha and ERbeta antibodies. Expression of the ER isoforms in the cancer specimens was further evaluated at the central area and at the invasive front. ERbeta was expressed in most specimens including cancer and normal region, however ERbeta expression significantly differed between non-cancerous and cancerous regions. Moreover, negative expression of ERbeta at the invasive front was significantly associated with malignant properties of the primary tumor such as lymph node metastasis, advanced stage, lower differentiation of histologic type, lymphatic invasion and a poor prognosis of the patients. In conclusion, evaluation of ERbeta expression at cancer front may be an important factor in identifying a highly malignant group of gallbladder carcinoma.

Gallbladder cancers rarely overexpress HER-2/neu, demonstrated by Hercep test.

c-erbB-2, proto-oncogene is amplified and overexpressed in a number of human adenocarcinomas. Overexpression of c-erbB-2 is indicated as a worse prognostic factor and associated with neoplastic progression in various organs. To investigate the therapeutic effect of Trastuzumab in gallbladder cancer, we studied HER-2/neu expression in 43 primary tumors, 12 metastatic lymph nodes and two liver metastasis, using the Hercep test. Among primary tumors, strong (3+) immunohistochemical intensity was found in two cases (4.7%), weak (2+) in two (4.7%) and negative (1+) (2.3%) in one case. This positivity rate was distinctly lower than those in previous reports. There was no tendency between clinicopathologic characteristics and HER-2 positivity in the primary gallbladder. Among 12 metastatic lymph nodes, only one specimen showed 2+ positivity where the primary lesion revealed 3+ intensity of HER-2. In two liver metastatic lesions, the expression of HER-2 was not found. Our study implied that Trastzumab may not contribute to improvement in treatment of gallbladder cancer. However, there may be a therapeutic possibility for cases with lymph node recurrence overexpressing c-erbB-2.