[Long-Term Complete Response following Chemotherapy for Advanced Gastric Cancer in an Elderly Patient].

A 78-year-old man was diagnosed with HER2-positive advanced gastric cancer, cT3N2M1(LYM: #16a1, 16b1), cStage ⅣB, after being referred for anemia. The lesion was deemed unresectable, and first-line chemotherapy was initiated using S-1, cisplatin(CDDP), and trastuzumab(T-mab). After 2 courses of chemotherapy, the patient developed febrile neutropenia( Grade 3). At this point, the lesion showed partial response(PR), and chemotherapy was continued using oral S-1 as a single agent. After 3 months of S-1 monotherapy, the para-aortic lymph node metastases showed a complete response (CR). S-1 monotherapy was continued without major adverse events for 2 years, and the patient is presently alive and well 6 years after obtaining clinical CR. This may suggest that S-1 is a safe and effective treatment for unresectable advanced gastric cancer in elderly patients.

Occurrence of Focal Atrial Tachycardia During the Ablation Procedure Is Associated With Arrhythmia Recurrence After Termination of Persistent Atrial Fibrillation.

INTRODUCTION: Catheter ablation can terminate persistent atrial fibrillation (AF). However, atrial tachycardia (AT) often arises after termination of AF. METHODS AND RESULTS: Of 215 patients who underwent index stepwise ablation for persistent AF, 141 (66%) patients (64 ± 9 years) in whom AF terminated during the ablation procedure were studied. If AF converted into AT, ablation for AT was subsequently performed. ATs were categorized as focal or macroreentrant AT. We assessed whether type of AT occurring after conversion of AF during the ablation procedure was associated with freedom from atrial tachyarrhythmia (AF or AT) during follow-up. Sinus rhythm was directly restored from AF in 37 patients, while 34, 37, and 33 patients had focal AT alone, a mix of focal and macroreentrant AT, and macroreentrant AT alone after termination of AF, respectively. Arrhythmia-free survival rates at 1 year after the index procedure were 30%, 34%, 61%, and 59% in the patients with focal AT alone, a mix of focal AT and macroreentrant AT, macroreentrant AT alone, and direct restoration of sinus rhythm, respectively (P = 0.004). Type of AT occurring during the index procedure was associated with type of recurrent AT (P = 0.03), but the origin of focal AT occurring during the index ablation differed from that of the recurrent AT in 85% of patients. CONCLUSION: In patients who had AF termination by ablation, occurrence of focal AT during the ablation procedure was associated with worse clinical outcome than occurrence of macroreentrant AT, likely due to ATs arising from other foci during follow-up.

Malondialdehyde-Modified Low Density Lipoprotein as Oxidative-Stress Marker in Vasospastic Angina Patients.

Vasospastic angina (VSA) is caused by endothelial dysfunction and hypercontraction of vascular smooth muscle cells. Although oxidative-stress can induce endothelial dysfunction, the relationship of VSA and the oxidative-stress marker malondialdehyde-modified low density lipoprotein (MDA-LDL) remains unclear. PURPOSE: Serum MDA-LDL was evaluated in candidate VSA patients.The subjects were 84 patients admitted to our hospital because of chest pain at rest. We stratified the patients into 3 groups; definite VSA, suspected VSA, and unlikely VSA according to a Japanese Circulation Society (JCS) guideline. The patients classified as definite VSA or suspected VSA were considered as "clinical VSA".Forty cases were classified as definite VSA, 35 as suspected VSA, and 9 as unlikely VSA. Thus, clinical VSA was the diagnosis in 75 cases. The patient characteristics showed that the average age of the patients was 60.2 years old (men, 61%). The serum MDA-LDL level of the clinical VSA group (126.3 ± 38.0 U/L) was significantly higher than the unlikely VSA group (98.7 ± 31.1 U/L). Serum MDA-LDL was positively correlated with total cholesterol (T-Chol), lowdensity lipoprotein cholesterol (LDL-C), triglycerides, and fasting blood glucose. Multivariate analysis showed that serum MDA-LDL was the most predictive marker for making a diagnosis of clinical VSA (Odds ratio 1.064, 95% confidence interval 1.014-1.145, P = 0.008). In a population with positive or borderline ECG change, the positive rate in the acetylcholine provocation test was significantly higher in the MDA-LDL higher group compared to the MDA-LDL lower group (81% versus 37%, P = 0.032).: Serum MDA-LDL might be a useful biomarker of VSA and have additional value for the diagnosis of clinical VSA.

Mechanisms of Diuresis for Acute Decompensated Heart Failure by Tolvaptan.

Tolvaptan, a vasopressin type 2 receptor antagonist, does not affect kidney circulation or cause worsening of renal function (WRF) in patients with acute decompensated heart failure (ADHF). Bioelectrical impedance analysis (BIA) can be used to evaluate intravascular volume by calculating the ratio of extracellular water (ECW) to intracellular water (ICW). There have been no reports examining the mechanisms of tolvaptan-induced diuresis using BIA. We investigated whether tolvaptan decreases excess volume while maintaining intravascular volume in ADHF patients.Study patients included 29 ADHF patients (age 48-95, men 69%) diagnosed between April 2013 and May 2016 and who underwent BIA before and after treatment. Fifteen patients were treated with tolvaptan in addition to conventional diuresis therapy (tolvaptan group), and 14 patients were treated with conventional diuresis therapy only (control group). In the control group, the numerical value of serum creatinine (Cre) significantly increased from 0.89 ± 0.22 mg/ dL to 1.07 ± 0.29 mg/dL (P = 0.004), and the ECW/ICW significantly decreased from 0.696 ± 0.036 to 0.673 ± 0.032 (P = 0.004). These values were not significantly different from those obtained for the tolvaptan group. Furthermore, regression analysis showed a negative correlation between ΔCre and ΔECW/ICW, which are the differences between values before and after treatment (ΔCre = -0.002-5.668 × ΔECW/ICW, r2 = 0.306, P = 0.002).Our findings suggest that WRF is caused by a reduction in intravascular volume and that tolvaptan treatment can decrease the excess volume while maintaining intravascular volume.

[A Case of Severe Bradycardia Induced by Combination Chemotherapy with Cisplatin and 5-Fluorouracil].

A 78-year-old man with Stage III esophageal cancer was referred to our hospital. Combination chemotherapy with cisplatin (CDDP) and 5-fluorouracil (5-FU) was initiated. The patient experienced bradycardia episodes after starting the cisplatin infusion on day 1; he was otherwise asymptomatic. Therefore, combination chemotherapy was continued. However, on day 4, his heart rate dropped to 22 beats/min, with no other symptoms; however, treatment was stopped. After treatment was stopped, the patient's heart rate improved gradually and returned to normal in a few days. Combination chemotherapy with CDDP and 5-FU is a useful treatment for esophageal cancer, but it may induce severe bradycardia. Therefore, we must perform infusion therapy with caution.

Prognostic implications of chronic kidney disease and anemia after percutaneous coronary intervention in acute myocardial infarction patients.

Anemia is a common complication of chronic kidney disease (CKD), and a few studies suggest that both CKD and anemia have a marked impact on the prognosis of patients with cardiovascular disease. We retrospectively analyzed the prevalence of CKD and anemia in 312 patients with acute myocardial infarction (AMI). The patients were divided into four groups according to the presence of CKD and anemia. Chronic kidney disease was defined as estimated glomerular filtration rate <60 ml/min/1.73 m(2), and anemia was defined according to the World Health Organization definition. Of 312 AMI patients, 166 (53.2%) had CKD and 87 (27.8%) had anemia. A powerful relationship was observed between both CKD and anemia and major adverse cardiac and cerebrovascular events (MACCE) or death by any cause. After adjustment for comorbidities, the hazard ratio (HR) for MACCE was significantly higher in the anemia-only group (HR 5.42, 95% confidence interval (CI) 1.38-21.27, P = 0.015), the CKD-only group (HR 6.4, 95% CI 2.09-19.58, P = 0.001), and the CKD and anemia group (HR 11.61, 95% CI 3.65-36.89, P < 0.001). With respect to death by any cause, the HR was significantly higher in the CKD-only group (HR 2.68, 95% CI 1.02-7.02, P = 0.045) and the CKD and anemia group (HR 4.40, 95% CI 1.56-12.43, P = 0.005). One-half of the patients with AMI had CKD as well. Furthermore, when anemia coexisted with CKD, these conditions had a multiplicative amplification effect on the risk of MACCE and death by any cause in patients with AMI.

Long-term Survival after Treatment of Synchronous Isolated Right External Iliac Lymph Node Metastasis from Ascending Colon Cancer: A Case Report.

BACKGROUND: Synchronous isolated external iliac lymph node metastasis of ascending colon cancer is extremely rare, and its treatment strategy has not been established. In this report, we present a case of long-term survival after surgical resection and adjuvant chemotherapy for ascending colon cancer with synchronous isolated right external iliac lymph node metastasis. CLINICAL CASE: A 65-year-old woman with anorexia and anemia was referred to our hospital. Colonoscopy and computed tomography revealed a three-quarter circumferential type 2 tumor from the cecum to the ascending colon, along with regional and right external iliac lymph node swelling. We diagnosed ascending colon cancer with right external iliac artery lymph node metastasis. An open right hemicolectomy with D3 and right external iliac lymph node dissections were performed. Results of histopathological examination showed that both lymph nodes were metastasized from ascending colon cancer. The patient received eight courses of capecitabine and oxaliplatin therapy as adjuvant chemotherapy. At 60 months after surgery, the woman has not had a recurrence. CONCLUSIONS: Surgical resection and adjuvant chemotherapy may be an effective treatment strategy for synchronous isolated right external iliac lymph node metastases from ascending colon cancer.

Standardized laparoscopy-assisted distal gastrectomy with a novel surgical technique for lifting the liver.

BACKGROUND/AIMS: It is very important to achieve a sufficient field and space in laparoscopic assisted distal gastrectomy (LADG) for a less-experienced surgeon. In this study, the usefulness of a novel surgical technique to lift the liver was evaluated in LADG. METHODOLOGY: Fifty-four patients who underwent standardized LADG for gastric cancer using the novel technique of lifting the liver were retrospectively evaluated based on video records. Patient characteristics, the time required to lift the liver and for gastrectomy, total operation time, blood loss and complications were analyzed. RESULTS: The mean time necessary to lift the liver using this novel technique was 240.1±86.1 seconds and that for gastrectomy was 167.6±50.4 minutes. Blood loss was 72.5±59.6mL. The morbidity rate was 4/54 (7.4%). CONCLUSIONS: Standardized LADG using this novel technique is feasible and possible in a period of time.

Current state of symptomatic aortic valve stenosis in the Japanese elderly.

BACKGROUND: There have been few reports regarding treatment selection and prognosis of symptomatic aortic valve stenosis (AS) in the elderly in Japan. METHODS AND RESULTS: Sixty-one patients hospitalized between January 2000 and December 2007 for symptomatic severe AS were investigated. The average observation period was 27 months. Thirty-seven patients (61%) were diagnosed with AS for the first time on hospitalization. Thirty-six patients had onset of symptoms within 1 month before admission. Thirty-six patients received aortic valve replacement (group S) and 25 received medical therapy (group M). The patients in group M were older than those in group S (84.1 ± 5.3 years vs. 74.2 ± 4.6 years, P<0.001). Maximum flow velocity measured by echocardiography was lower in group M (4.5 ± 0.3 m/s vs. 4.9 ± 0.5 m/s, P<0 .01), but there was no difference in valve area between the 2 groups (0.62 ± 0.19 cm² vs. 0.57 ± 0.15 cm², P=0.12). One-year mortality rate derived from the Kaplan-Meier curve was higher in group M than group S (53.1% vs. 6.4%, respectively). On multivariate analysis, the only independent favorable prognostic factor was aortic valve replacement (HR: 0.02, 95%CI: 0.01-0.15, P<0.01). CONCLUSIONS: Medical therapy is often selected for treatment of symptomatic AS in the elderly, but the prognosis is very poor. Symptomatic severe aortic stenosis should be treated surgically, or with transcatheter aortic valve implantation in cases with high surgical risk.

Prevalence and prognostic implications of pre-diabetic state in patients with heart failure.

BACKGROUND: Diabetes mellitus (DM) is a risk factor of poor prognosis in patients with heart failure (HF). The prevalence and prognostic impact of the pre-diabetic state, however, are not well understood. METHODS AND RESULTS: One hundred and thirty-six consecutive patients admitted due to HF were included in this prospective study. The 75-g oral glucose tolerance test (OGTT) was performed in all patients without known DM, and patients were classified into normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and DM groups. Forty-two of the 136 patients had previously been diagnosed with diabetes. Of the remaining 94 patients without known diabetes, 35 (37.2%) patients were classified as NGT, 9 (9.6%) as having IFG, 37 (39.4%) were classified as having IGT, and 13 (13.8%) were newly diagnosed with DM. During follow-up, patients with DM or IGT had significantly lower major adverse cardiac and cerebrovascular event (MACCE)-free rates than NGT patients (P=0.006, P=0.036, respectively). IFG, however, was not significantly related to increased MACCE risk. The presence of IGT (hazard ratio [HR], 4.51; P=0.011) and DM (HR, 4.74; P=0.005) were independent predictors of MACCE even after multivariate analysis. CONCLUSIONS: IGT and DM contribute to adverse prognosis in patients with HF. It is feasible to perform diabetes screening using OGTT in patients with HF for risk stratification.

A case of giant cell arteritis with massive pericardial effusion.

Giant cell arteritis (GCA) is a chronic inflammatory disease of the medium and large blood vessels. The early symptoms of this disease are nonspecific, and pericardial effusion is a rare manifestation of GCA. Recently, we investigated a case of GCA in which massive pericardial effusion was the initial symptom, and active aortitis was observed on positron emission tomography with fluorine-18 fluorodeoxyglucose. These observations indicated that pericardial effusion could occur in patients with GCA.

Multidetector computed tomography for preoperative identification of left gastric vein location in patients with gastric cancer.

BACKGROUND: The area near the left gastric vein (LGV) is a challenging site at which to perform dissection of the lymph nodes during gastrectomy. Therefore, knowledge of the precise location of the LGV is important. The objective of this study was to examine the usefulness of multidetector computed tomography (MDCT) for the identification of the LGV. METHODS: Eighty-one patients with gastric cancer underwent MDCT, which was performed with contrast media in 76 patients and without contrast media in 5 patients. A 5-mm thin slice of the frontal image was reconstructed. These images were examined preoperatively to detect the location of the LGV. Upon gastrectomy, the LGV was identified and its location compared to that determined by MDCT. RESULTS: The LGV was identified by MDCT in 76 of the 81 patients (93.8%). The LGV was subsequently located during the operation in all 81 patients. The LGV was located dorsal to the common hepatic artery in 40 patients (49.4%), ventral to the common hepatic artery in 18 patients (22.2%), ventral to the splenic artery in 17 patients (21.0%), dorsal to the splenic artery in 2 patients (2.5%) and in other positions in 4 patients (4.9%). In all patients, the location of the LGV detected using MDCT was consistent with that identified during gastrectomy. In the 4 patients with relatively unusual locations of the LGV, these 4 LGV variants were identified preoperatively by MDCT. CONCLUSION: MDCT was useful for identifying the location of the LGV prior to gastrectomy.

Effect of Endovascular Treatment on Systemic Vascular Resistance in Patients with Lower-Limb Peripheral Artery Disease.

Objective: Endovascular treatment (EVT) for lower-limb peripheral artery disease patients reduces blood pressure (BP) and improves prognosis. This study retrospectively examined hemodynamics during EVT to clarify the mechanism. Materials and Methods: Systemic vascular resistance (SVR) was measured using a noninvasive continuous cardiac output monitoring system during EVT. Furthermore, ankle brachial index was measured before and after EVT. Results: The study included 88 lesions of 56 patients (hypertension in 98%). SVR significantly decreased from 2409.1±746.8 dynes·s·cm-5 to 2033.7±635.0 dynes·s·cm-5 (p<0.0001). The difference in SVR before and after EVT was significantly greater in the Fontaine IV group than in the Fontaine IIa group (554.7±406.6 dynes·s·cm-5 vs. 312.9±245.7 dynes·s·cm-5, p=0.0151). The change in SVR was correlated with a change in mean BP in the upper limb (p=0.0026). When the change in pressure gradient between the upper limb and the diseased lower limb was large, mean BP of the upper limb significantly decreased (p=0.0022). Conclusion: EVT can reduce SVR and BP by canceling the pressure gradient between central BP and diseased lower-limb BP.

Anomalous origin of the coronary artery coursing between the great vessels presenting with a cardiovascular event (J-CONOMALY Registry).

AIMS: Anomalous origin of the coronary artery (AOCA) with an inter-arterial course (IAC) between the great vessels poses a risk for a life-threatening cardiovascular event. We assessed, in a registry-based study, the clinical features, treatment strategies, and prognoses of life-threatening cardiovascular events ensuant to AOCA. METHODS AND RESULTS: Included were 65 AOCA patients (48 men/17 women, aged 41 ± 23 years) from 40 clinical centres who had experienced sudden cardiac arrest (SCA) (n = 30), acute myocardial infarction (AMI) (n = 5), angina (n = 23), or syncope (n = 7). The anomalous vessel was the right coronary artery in 72% of patients and left coronary artery in 28%; the ostium was slit-like in 42%. Coronary luminal narrowing ≥75% was absent in patients with SCA or syncope (86% and 57%, respectively), but occlusion or narrowing was seen in those with AMI (100%) or angina (52%). Age ≤40 years, male sex, sporting activity, absence of prodromal symptoms, acutely angled (≤30°) take-off from the aorta, and absence of luminal narrowing of the IAC segment were associated with SCA in this patient group. Coronary vasospasm was inducible in 12 of 17 patients without coronary narrowing. Management included surgical revascularization (n = 26) percutaneous coronary intervention (n = 9), and medical treatment (n = 26). Four SCA patients died while hospitalized; no others died during the median 5.0 (range, 1.8-7.0)-year follow-up period. CONCLUSIONS: In patients with AOCA, age ≤40 years, male sex, sporting activity, and an acute take-off angle appear to be risk factors for SCA. Appropriate management can be beneficial. Confirmation in a large-scale study is warranted.

[A case of curatively resected biliary tract cancer with peritoneal dissemination through effective response to chemotherapy of S-1].

The patient is a 55-year-old woman who has biliary tract cancer with peritoneal dissemination (T3N1P2M0, Stage IV b). Since a curative operation was deemed impossible, we conducted chemotherapy using S-1. S-1 (120 mg/day) was administered for 2 weeks and then chemotherapy was discontinued for 1 week, which was regarded as one course. After 2 courses of the chemotherapy, CT scan showed that the metastatic lymph node and tumor of peritoneal dissemination were reduced in size, and that there was no ascites. Left lobectomy of the liver, cholecystectomy, and partial resection of omentum were carried out. The pathological diagnosis was also curative (pT1, pN0, pP0, Stage I). We think this case shows the possibility of S-1 for patients with unresectable biliary tract cancer.

[A successfully resected case of rectal cancer with liver metastases treated with mFOLFOX6 and bevacizumab].

A sixties-man had complained of melena. Colonoscopy revealed type 2 tumor at rectum. Computed tomography (CT)demonstrated lymph node metastasis in front of sacrum and two low density areas which were suspected metastases in the liver. The patient was diagnosed stageIV rectal cancer and resected primary focus and lymph node metastasis.[ Ra-RS, ant, type 2, moderately differentiated adenocarcinoma, ly1, v3, pSE, pN2, sH1(Grade C), sP0, pM1(No. 270)]without liver resection. It was due to high level of CEA and remote lymph node metastasis. The patient was treated with mFOLFOX6 and bevacizumab after the operation. The level of CEA decreased to normal level and CT revealed a partial response after 4 cycles of systemic chemotherapy. Liver resection was performed safely. Histological response was Grade 2 at liver metastases.

Anti-tumor effect of angiogenesis inhibitor TNP-470 and 5-FU combined therapy on human gastric cancer xenograft.

BACKGROUND/AIMS: TNP-470, an angiogenesis inhibitor, has already been used in combination with chemotherapy to enhance its antitumor activity. The mechanism of enhanced antitumor activity in combination therapy has not been clarified, however, and few studies have described the combined effect of TNP-470 and 5-fluorouracil (5-FU) on gastric cancer. The present study was conducted to investigate the effect of TNP-470 + 5-FU on gastric cancer cell line MKN-45 in vivo and in vitro. METHODOLOGY: MKN-45 cells were subcutaneously injected into mice that were divided into 4 groups: a control group, a 5-FU treated group, a TNP-470 treated group, and a 5-FU + TNP-470 treated group. After the inoculation, the volume of subcutaneous tumors was measured. Blood and lymphatic vessels were also analyzed for the assessment of lymphangiogenesis. RESULTS: Compared with 5-FU or TNP-470 alone, the combined effect of TNP-470 and 5-FU significantly inhibited and suppressed tumor growth in a synergistic fashion. The combined therapy significantly suppressed both angiogenesis and lymphagenesis. CONCLUSIONS: The study suggests that the combined therapy provides an enhanced antitumor effect on human gastric cancer. The enhanced antitumor activity is explained mainly by the stronger inhibition of angiogenesis.

Intratumoral heterogeneous expression of thymidylate synthase in gastric cancer.

BACKGROUND/AIMS: Thymidylate synthase (TS) is reported to be a predictive factor of survival in gastric cancer patients. Its heterogeneous expression has been observed in various cancerous lesions but has not been assessed intratumorally. The aim of this study was to determine the most pertinent site for investigating intratumoral TS expression for the prediction of survival. METHODOLOGY: TS staining grade was evaluated at the center (CT), the horizontal edge (HT) and the vertical edge (VT) of the tumor, and TS protein level was determined by ELISA at CT and HT. Proliferating cell nuclear antigen (PCNA) was examined for proliferation markers in all tumor samples. RESULTS: TS expression at HT and VT was significantly higher than at CT. A positive correlation was observed between TS protein level and PCNA-Labeling Index at HT, but not at CT. The survival rate of the high TS group was poor compared with the low TS group at HT and VT, but not at CT. CONCLUSIONS: The horizontal edge of the tumor (HT) is the most pertinent site for the evaluation of TS expression in gastric cancer; it could prove especially useful in the presurgical estimation of prognosis through biopsy samples.

Paget's disease of the male breast: a case report.

The patient was a 91-year-old man with change in nipple appearance, itching and redness, and a palpable breast mass. At presentation, mammary Paget's disease (PD) was clinically suspected. Skin biopsy was performed and showed epidermis invaded by Paget cells, characterized by hyperchromatic nuclei and abundant pale-staining cytoplasm. Computed tomography and mammary ultrasonography confirmed the absence of an underlying invasive carcinoma, and the patient underwent right mastectomy and sentinel lymph node biopsy (SLNB). Both sentinel lymph nodes were found to be negative perioperatively, and further axillary dissection was not performed. Pathological results revealed no malignancy under the nipple, yet the Paget cells were more widely spread than expected. The patient was followed up without the need of postoperative chemotherapy. Male mammary PD is an extremely rare breast cancer, and there is no standard preoperative assessment or operative procedure. Mammography is many times unable to detect possible underlying breast carcinoma in female patients with mammary PD, and previous studies have reported that the detection rate was less than 50 %. However, some researchers reported that magnetic resonance imaging (MRI) might be more detectable to confirm the extent of the cancer. The extent of the skin change around the nipple is often different from the actual perimeter of Paget cells. In extra-mammary PD, mapping biopsy is known to be useful to determine areas free of cancer. The benefits of SLNB have also been demonstrated for the management of less invasive breast cancers, and previous reports have shown that the use of SLNB is reasonable for treatment of mammary PD without underlying invasive cancer. MRI, mapping biopsy, and SLNB are all less invasive procedures and thus may be suitable for treatment of male mammary PD.