Risk factors for the recurrence of stage II perforated colorectal cancer: A retrospective observational study.

BACKGROUND: Patients with perforated colorectal cancer (PCRC) experience higher recurrence rates than those with non-perforated tissue. We identified the promoting factors of stage II PCRC recurrence after R0 surgery. METHOD: This retrospective observational study included patients treated for colorectal cancer at a single facility between 2007 and 2016, and compared the clinicopathological features of patients with perforating versus non-perforating stage II tumors who underwent R0 resection, while focusing on recurrences. RESULTS: Thirty-two and 112 patients (predominantly men) with perforating and non-perforating tumors, respectively, were included. The perforated group had significantly higher proportions of T4 tumors than the non-perforated group (44% vs. 15%). The perforated group had significantly lower numbers of resected lymph nodes than the non-perforated group (6 vs. 17). Seven of 17 patients with follow-up data in the perforated group experienced recurrence (41%), versus 19 of 104 in the non-perforated group (18%). In the non-perforated group, male sex (89% vs. 60%, p = 0.030), T4 stage (32% vs. 9%, p = 0.029), and fewer resected lymph nodes (12.5 vs. 18.6, p = 0.003) were significantly associated with recurrence; however, no such influences on recurrence were observed in the perforated group. The recurrence sites in the perforated group were mostly local (6 patients, 86%). Conversely, recurrences in the non-perforated group were mostly distant; 8 of 19 patients (42%) had liver metastasis and 1 (5%) had lung metastasis. CONCLUSION: Patients with stage II PCRC experienced higher recurrence rates regardless of clinicopathological features and had high local recurrence rates indicating possible local tumor cell dispersal owing to perforation.

Mesh penetrating the cecum and bladder following inguinal hernia surgery: a case report.

BACKGROUND: Tension-free repair using mesh is a common inguinal hernia surgical procedure. However, various complications such as mesh-related infection and recurrence may develop as a result. Moreover, although rare, there are also reports of intestinal obstruction caused by adhesion of the mesh to the intestinal wall and cases of mesh migration into various organs. Here, we report our experience with a patient in whom mesh extraction was performed due to migration of mesh into the intestinal tract following inguinal hernia surgery and formation of a fistula with the bladder. CASE PRESENTATION: Our patient was a 63-year-old Japanese man who had a history of operative treatment for right inguinal hernia during early childhood. Because a relapse subsequently occurred, he was diagnosed as having recurrent right inguinal hernia at the age of 56 years for which operative treatment (the Kugel method) was performed. He presented to our hospital 6 years later with the chief complaint of lower abdominal pain. Computed tomography findings revealed a mass shadow in contact with his bladder and cecal walls, and enteric bacteria were detected in his urine. Furthermore, because lower gastrointestinal endoscopic findings confirmed mesh in the cecum, we performed operative treatment. The mesh had migrated into the cecum and a fistula with his bladder had formed. We removed the mesh through ileocecal resection and partial cystectomy. CONCLUSIONS: It appeared that a peritoneal defect occurred when the mesh was placed, allowing the mesh to migrate into our patient's intestinal tract. Because contact between the mesh and the cecum resulted in inflammation, a fistula formed in his bladder. It is important to completely close the peritoneum when placing the mesh.

A case of myasthenia gravis and myositis induced by nivolumab.

A 74-year-old woman, who developed advanced colon cancer with focal recurrence, received two courses of a low dose of nivolumab. Five days after the second course she noticed bilateral ptosis. Her symptoms rapidly progressed to generalized manifestations including limb and neck weakness, dyspnea, and myalgia within the following two weeks. Neurological and laboratory findings supported the diagnosis of myasthenia gravis and myositis induced by nivolumab. The combination immunotherapy including oral prednisolone, intravenous immunoglobulin and plasma exchange with noninvasive positive-pressure ventilation successfully avoid tracheal intubation. Nivolumab, one of the immune checkpoint inhibitors, is the anti-programmed cell death-1 (PD-1) protein monoclonal antibody, which is effective for various cancers. Since the immune checkpoint inhibitors are going to be used widely, it is important to recognize the specific subtype of myasthenia gravis for neurologists.

Volume and Characteristics of Intracerebral Hemorrhage with Direct Oral Anticoagulants in Comparison with Warfarin
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BACKGROUND: Patients undergoing anticoagulation therapy often experience intracerebral hemorrhages (ICHs), and warfarin in particular is known to increase hematoma expansion in ICHs, which results in a poor outcome. Recent studies reported that, in comparison with warfarin, direct oral anticoagulants (DOACs) cause fewer ICHs with better functional outcome. However, since it is still unknown whether DOACs are associated with a smaller hematoma volume of ICHs, we aimed to compare the volume, hematoma expansion, and outcomes associated with ICHs treated with DOACs and warfarin. METHODS: We performed a prospective multicenter cross-sectional study. The subjects included patients with acute ICHs who received either DOACs or warfarin. We evaluated the clinical characteristics, and measured initial and follow-up ICH volumes. The volume of ICHs and hematoma expansion were compared between the DOAC and warfarin groups. Mortality and modified Rankin score at discharge were evaluated as outcomes. RESULTS: There were 18 patients in the DOAC group and 71 in the warfarin group. The baseline characteristics were similar between the 2 groups. Initial median hematoma volume of ICHs in the DOAC group was significantly lower than that in the warfarin group (6.2 vs. 24.2 mL, respectively; p = 0.04). In cases involving follow-up computed tomography scanning, the median hematoma volume of ICHs at follow-up was lower in the DOAC group than in the warfarin group (initial: DOACs 4.4 vs. warfarin 13.5 mL; follow-up: 5.0 vs. 18.4 mL, respectively; p = 0.05). Further, the hematoma in ICHs associated with DOACs did not expand. Although the mortality of ICHs associated with DOACs (11%) was lower than that associated with warfarin (24%), this difference was not statistically significant. The univariate analysis showed that the anticoagulant type (DOACs vs. warfarin) and sex (male vs. female) were associated with ICH volume. The multivariable linear regression showed that the use of DOACs (compared to warfarin; ß: -0.23, p = 0.03) and female sex (compared to male; ß: -0.25, p = 0.02) were associated with a small hematoma volume. CONCLUSIONS: Based on the results of the present study, in terms of the risks associated with ICHs, the use of DOACs appears to be safer than warfarin for anticoagulation therapy. Further studies are required to validate these findings.
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The Japan Statin Treatment Against Recurrent Stroke (J-STARS): A Multicenter, Randomized, Open-label, Parallel-group Study.

BACKGROUND: Although statin therapy is beneficial for the prevention of initial stroke, the benefit for recurrent stroke and its subtypes remains to be determined in Asian, in whom stroke profiles are different from Caucasian. This study examined whether treatment with low-dose pravastatin prevents stroke recurrence in ischemic stroke patients. METHODS: This is a multicenter, randomized, open-label, blinded-endpoint, parallel-group study of patients who experienced non-cardioembolic ischemic stroke. All patients had a total cholesterol level between 4.65 and 6.21 mmol/L at enrollment, without the use of statins. The pravastatin group patients received 10 mg of pravastatin/day; the control group patients received no statins. The primary endpoint was the occurrence of stroke and transient ischemic attack (TIA), with the onset of each stroke subtype set to be one of the secondary endpoints. FINDING: Although 3000 patients were targeted, 1578 patients (491 female, age 66.2 years) were recruited and randomly assigned to pravastatin group or control group. During the follow-up of 4.9 ± 1.4 years, although total stroke and TIA similarly occurred in both groups (2.56 vs. 2.65%/year), onset of atherothrombotic infarction was less frequent in pravastatin group (0.21 vs. 0.64%/year, p = 0.0047, adjusted hazard ratio 0.33 [95%CI 0.15 to 0.74]). No significant intergroup difference was found for the onset of other stroke subtypes, and for the occurrence of adverse events. INTERPRETATION: Although whether low-dose pravastatin prevents recurrence of total stroke or TIA still needs to be examined in Asian, this study has generated a hypothesis that it may reduce occurrence of stroke due to larger artery atherosclerosis. FUNDING: This study was initially supported by a grant from the Ministry of Health, Labour and Welfare, Japan. After the governmental support expired, it was conducted in collaboration between Hiroshima University and the Foundation for Biomedical Research and Innovation.

The Impact of Diagnosing Branch Atheromatous Disease for Predicting Prognosis.

BACKGROUND: We had reported that, in the acute phase of the brain penetrating artery infarction, patients with branch atheromatous disease (BAD) tended to be worsened compared with the lacunar infarction (LI). Because no prospective study has been reported, we composed a multicenter study (Japan Branch Atheromatous Disease [J-BAD] Registry) in which patients of penetrating artery infarction were prospectively enrolled for exploring the clinical features of BAD. METHODS: From the associated 9 hospitals, acute ischemic stroke patients were asked to be enrolled in the J-BAD Registry and classified into the lenticulostriate arterial (LSA) infarction (n = 124) and the pontine penetrating arterial (PPA) infarction (n = 42) groups. The clinical courses and the repeated magnetic resonance imaging findings were investigated. RESULTS: Neurologic worsening was observed at a significantly higher rate in BAD compared with the LI patients in both the LSA and PPA groups (P < .01, 45.1% versus 22.6% and 46.7% versus 0%, respectively). In the LSA group, the enlargement of the ischemic lesion was significantly more frequent in BAD compared with the LI patients (P < .01, 66.2% and 34.0%, respectively). There was a significant relation between the enlargement of the lesion and the worsening of neurologic deficits (P < .001). Moreover, the clinical features, which predict the lesion enlargement, were BAD and older age. CONCLUSIONS: LSA infarction of BAD diagnosis or older age patients might show an increase of lesion size and a tendency of neurologic worsening. It could be important to discriminate BAD from other ischemic stroke subtypes, in regard to the prediction of prognosis.

Final Results of Cilostazol-Aspirin Therapy against Recurrent Stroke with Intracranial Artery Stenosis (CATHARSIS).

PURPOSE: To compare the effect of cilostazol plus aspirin versus aspirin alone on the progression of intracranial arterial stenosis (IAS), and to compare ischemic and hemorrhagic events in patients with symptomatic IAS, an investigator-driven, nationwide multicenter cooperative randomized controlled trial (CATHARSIS; ClinicalTrials.gov Identifier 00333164) was conducted. METHODS: 165 noncardioembolic ischemic stroke patients with >50% stenosis in the responsible intracranial artery after 2 weeks to 6 months from the onset were randomly allocated to receive either cilostazol 200 mg/day plus aspirin 100 mg/day (n = 83, CA group) or aspirin 100 mg/day alone (n = 82, A group). The primary endpoint was the progression of IAS on magnetic resonance angiography at 2 years after randomization. Secondary endpoints were any vascular events, any cause of death, serious adverse events, new silent brain infarcts, and worsening of the modified Rankin Scale score. RESULTS: Progression of IAS was observed in 9.6% of the CA group patients and in 5.6% of the A group patients, with no significant intergroup difference (p = 0.53). The incidence of the secondary endpoints tended to be lower in the CA group compared with the A group, although the differences were not significant. By using exploratory logistic regression analysis adjusted for patient background characteristics, it was shown that the risk for certain combinations of secondary endpoints was lower in the CA group than in the A group [all vascular events and silent brain infarcts: odds ratio (OR) = 0.37, p = 0.04; stroke and silent brain infarcts: OR = 0.34, p = 0.04; all vascular events, worsening of modified Rankin Scale scores and silent brain infracts: OR = 0.41, p = 0.03]. Major hemorrhage was observed in 4 patients of the CA group and in 3 of the A group. CONCLUSION: Progression of IAS during the 2-year observation period appears to be less frequent than previously reported in stroke patients on antiplatelet agents after the acute phase, which could be due to the adequate control of risk factors, and because patients with stroke within 2 weeks after the onset were excluded. The results of the CATHARSIS trial suggest a potential utility of pharmacotherapies with cilostazol plus aspirin as well as of strict control of risk factors for the management of symptomatic IAS. Larger studies with higher statistical power are required to obtain conclusive results.

Subsequent vascular events after ischemic stroke: the Japan Statin Treatment Against Recurrent Stroke-Longitudinal.

BACKGROUND: We undertook a multicenter cohort observational study to investigate the frequency and type of subsequent vascular events after an ischemic stroke and to compare the rates of vascular events between patients with and without hyperlipidemia. METHODS: This nationwide study was conducted in 19 hospitals participating in the Japan Standard Stroke Registry Study. We enrolled ischemic stroke patients, including those with a transient ischemic attack, who had not experienced any vascular events before enrollment after their ischemic stroke events. Each subject was observed prospectively from September 1, 2003, to October 1, 2005, or until a primary end point or death. Primary end points included subsequent fatal or nonfatal vascular events: stroke, angina pectoris, acute myocardial infarction, aortic aneurysm, or arteriosclerosis obliterans. RESULTS: A total of 449 patients (mean age, 67.6 years; 64.8% men) were enrolled in this study. Of the 41 vascular events observed during follow-up, 40 were stroke. The median observation period was 568 days. We found that patients with hyperlipidemia had a significantly higher rate of vascular events compared with those without hyperlipidemia according to the Kaplan-Meier method and the log-rank test (P = .013). Hyperlipidemia significantly increased the risk of vascular events (hazard ratio, 2.169 [1.125-4.312]; P = .021) according to the Cox proportional hazard model after adjusting for confounding factors (age, sex, days from ischemic stroke until enrollment, smoking habits, and daily drinking habits). CONCLUSIONS: This study demonstrated that stroke was the most common subsequent vascular event after ischemic stroke; the study also indicated that hyperlipidemia could be a risk factor for subsequent vascular events after ischemic stroke.

Therapeutic Suggestions for Chronic Subdural Hematoma Associated with Idiopathic Thrombocytopenic Purpura: A Case Report and Literature Review.

A 66-year-old woman who was previously diagnosed with idiopathic thrombocytopenic purpura (ITP) presented with mild right-sided hemiparesis and drowsiness. Head computed tomography (CT) imaging demonstrated a massive left chronic subdural hematoma (CSDH) with a midline shift. Because initial laboratory data showed a significantly decreased blood platelet count (0.3 × 104/mm3), medical treatments such as platelet transfusion, intravenous immunoglobulin (IVIG), and high-dose corticosteroid therapy, were initiated. She clinically and radiologically responded well to these treatments without any surgical intervention. In addition to presenting our case, we searched the PubMed and Ichushi Web databases to comprehensively illustrate clinical characteristics and treatment outcomes of similar cases. Including the present case, we found 19 reports and 23 cases of CSDH associated with ITP in the literature, and assessed 17 reports and 21 cases that were written in English and Japanese. None or mild neurological symptom were seen in 13 cases, and severe, such as coma and hemiparesis, were described in the younger 8 cases with significant difference. All except one were first treated with medical therapies. Most cases of the former group responded well to conservative therapy. On the other hand, most in the latter eventually needed surgical treatment in addition except recent two cases including the present case. CSDH associated with ITP is rarely described, and its management remains controversial. However, this report highlights multiple continuous medical treatments under strict observation and general care might be a useful alternative to avoid surgery in cases presenting with severe neurological deficits and extremely low platelet counts.

Pyogenic granuloma of the ileum diagnosed by double-balloon enteroscopy.

A pyogenic granuloma (PG) is a capillary hemangioma that usually occurs on the skin or in the oral cavity; it is rarely observed in the gastrointestinal tract. We herein describe a case of a 86-year-old woman who presented with anemia. Esophagogastroduodenoscopy and colonoscopy did not reveal any significant bleeding focus, but capsule endoscopy revealed a bleeding focus in the small intestine. We performed double-balloon enteroscopy and identified a 7-mm-diameter, reddish, subpedunculated, hemispheric polyp with a smooth surface in the small intestine, approximately 100 cm from the ileocecal valve. The polyp was surgically removed, and the histological findings were consistent with a diagnosis of PG.

Critical ventriculo-peritoneal shunt failure due to peritoneal tuberculosis: Case report and diagnostic suggestions for abdominal pseudocyst.

BACKGROUND: Tuberculous peritonitis (TBP) is a well-known complication of ventriculo-peritoneal (VP) shunt treatment for hydrocephalus resulting from tuberculous meningitis (TBM). However, a case of hydrocephalus unrelated to TBM resulting from VP shunt malfunction due to TBP has not been reported. CASE DESCRIPTION: A 21-year-old male presented with nausea, abdominal pain, and headache. VP and cysto-peritoneal (CP) shunts had been inserted to treat hydrocephalus due to a suprasellar arachnoid cyst, replaced the VP and removed the CP in his childhood. Computed tomography demonstrated acute hydrocephalus and an abdominal pseudocyst surrounding the distal end of the peritoneal tube. Initial laboratory data showed elevated white blood cell count and C-reactive protein level, but no causative pathogen was identified. External drainage of cerebrospinal fluid (CSF) and of the fluid in the peritoneal cyst was established, and empirical antibiotic therapy was initiated. Bacterial cultures eventually revealed Mycobacterium tuberculosis infection, and TBP was diagnosed. The patient responded well to antituberculosis (anti-TB) agents and insertion of a ventriculo-pleural shunt. CONCLUSION: This case highlights the possibility of CSF shunt failure and concomitant neurological sequelae from TB infection even when the pathogen has not invaded the central nervous system, as in TBM. Moreover, TBP is rare in developed countries and therefore may be misdiagnosed because of nonspecific clinical features and low sensitivity of common TB screening methods.

Rationale, design, and baseline features of a randomized controlled trial to assess the effects of statin for the secondary prevention of stroke: the Japan Statin Treatment Against Recurrent Stroke (J-STARS).

BACKGROUND: Although statin therapy is beneficial for preventing first strokes, the benefit for recurrent stroke and its sub-types remains unknown in Asian populations. The aim of this study is to examine the role of pravastatin in the secondary prevention of stroke in Japanese patients. METHODS: This is a multicenter, randomized, open-label, parallel group study of patients with noncardioembolic ischemic stroke (atherothrombotic infarction, lacunar infarction, and infarction of undetermined etiology). All patients were diagnosed with hyperlipidemia and with a total cholesterol level between 180 and 240 mg/dl at enrollment. Patients in the treatment group receive 10 mg/day of pravastatin, and those in the control group receive no statin treatment. The primary end-point is the recurrence of stroke, including transient ischemic attack. The secondary end-points include the onset of respective stroke sub-types and functional outcomes related to stroke. The patients were enrolled for five-years and will be followed up for five-years. RESULTS: A total of 1578 eligible patients (age: 66·2 years, men: 68·8%), including 64·2% with lacunar infarction, 25·4% with atherothrombotic infarction, and 10·4% with infarction of undetermined etiology were included in this study. Lipid levels were generally well controlled (total cholesterol: 210·0 mg/dl, low density lipoprotein cholesterol: 129·5 mg/dl) at baseline. In addition, the disability of patients was relatively mild, and cognitive function was preserved in the majority of patients. CONCLUSION: This article reports the rationale, design, and baseline features of a randomized controlled trial to assess the effects of statin for the secondary prevention of stroke. Follow-ups of patients are in progress and will end in 2014.

[Branch atheromatous disease: how do we analyze its pathophysiology and treat it to prevent the progression of neurological symptoms?].

Branch atheromatous disease (BAD) has been recognized as one of the types of stroke which is often associated with clinical deterioration. Coagulation and platelet activation should play an important role in early neurological progression of BAD, which include complicated aspects for understanding the pathophysiology and the treatment. It has been suggested that multidrug combination therapy involving antiplatelet and anticoagulation could not prevent worsening of symptoms in the acute stage of BAD: nevertheless it should be important to improve prognosis of patients in the chronic stage. Further investigation including randomized controlled study will be needed for the accumulation of various evidences.

Electrocatalytic oxidation of dihydronicotineamide adenine dinucleotide on gold electrode modified with catechol-terminated alkanethiol self-assembly.

Synthesis of a mercaptoundecaneamide derivative having a terminus of catechol is described. FT-IR spectroscopic characterization showed that the new molecular entry simply undergoes molecular self-assembly on Au substrate surfaces promoting intra- and intermolecular hydrogen bonds to form well-packed monolayers. Cyclic voltammetric (CV) measurements on the monolayer-modified Au electrode revealed that the surface adlayer possesses specific electrochemical activity due to the reversible catechol/o-quinone redox reaction having characteristics of a surface process and also pH-dependence in its formal potential (59 mV per pH). Detailed analysis of CVs gave fundamental electrochemical parameters including the electroactive surface coverage (0.20-0.24 nmol cm(-2)), the transfer coefficients (0.24 in oxidation and 0.81 in reduction), and also the electron transfer rate constant (1.10-2.76 s(-1)). These data were almost consistent to those seen in literature. We have also found that the catechol monolayer modified electrode exhibits an electrocatalytic function in NADH oxidation. That is, the faradaic current appeared reinforcingly at around the same potential where catechol function is oxidized in the monolayer and increased with an increase in the NADH concentration from 1 to 5 mM, and then reached to a plateau indicating a catalyzed reaction pathway. Detailed analyses revealed that the present system could be characterized by its weak stability of the intermediate compound formed and prompt reaction rate compared with the previously reported chemically modified electrode (CME) systems. We think this type of achievement should be important for the basics of biosensors that rely on dehydrogenase enzymes.

Study of interleukin-6 in the spread of colorectal cancer: the diagnostic significance of IL-6.

We investigated the diagnostic significance of IL-6 for lymph node metastasis and/or hepatic metastasis from colorectal cancer in 65 patients and evaluated the contributions of 8 factors (IL-6, HGF, IL-1beta, TNF-alpha, TGF-beta1, ELAM-1, ICAM-1, VCAM-1) toward Dukes.s classification of 53 patients. We also examined IL-6 expression in tumor tissue. From the receiver operating characteristic (ROC) curve analysis, an optimal cutoff value of 5.8 pg/ml was determined to classify lymph node and/or hepatic metastasis, and that of 6.3 pg/ml was determined to classify hepatic metastasis. These values indicated sensitivities of 55.0% and 71.4%, and specifi cities of 100% and 88.6%, respectively. IL-6, HGF, and ELAM-1 were very useful for distinguishing among Dukes.s A/B group, C group, and D group. In all cases with high IL-6 values (more than 25.0 pg/ml), immunohistochemical staining was positive for IL-6 in the cytoplasm of cancer cells. IL-6 is strongly suspected to be involved in lymph node and/or hepatic metastasis by promoting it through HGF, and serum IL-6 value (pg/ml) would be useful diagnostically to estimate whether or not there is a high risk of lymph node and/or hepatic metastasis.

Metal ion-directed cooperative DNA binding of small molecules.

Compound (1), which consists of an oxine and a pyridinium group, was synthesized as a metal-responsive DNA binding ligand. Two 1s coordinate to a Cu(II) to form a stable dimer (1(2)-Cu), even in the presence of DNA. The binding of 1 with sonicated calf thymus DNA was enhanced by ca. 10(3) times after forming the dimer; the binding constants were estimated to be 3.2 x 10(4)M(-1) and 2.4 x 10(7)M(-1) in the absence and the presence, respectively, of a half mole of Cu(II). The enormous acceleration of the binding is partly attributed to the generation of a dicationic charge by the formation of the dimer. High cooperativity between dimers could be also responsible; dimers would gather along the duplex as a template to form 1D spiral aggregates.