Unwillingness to cooperate with COVID-19 contact tracing in Japan.

OBJECTIVES: Contact tracing for COVID-19 relies heavily on the cooperation of individuals with authorities to provide information of contact persons. However, few studies have clarified willingness to cooperate and motivation to provide information for contact tracing. This study sought to describe willingness to cooperate and motivation to report contact persons for COVID-19 contact tracing among citizens in Japan, and to assess any associated sociodemographic factors. STUDY DESIGN: Cross-sectional study. METHODS: This was an online-based survey using quota sampling. Participants were asked about their willingness to cooperate in reporting contacts for COVID-19 contact tracing if they tested positive. Participants also responded to questions regarding their reasons for cooperating or not cooperating and provided sociodemographic data. Multiple logistic regression analysis was performed to clarify associations between sociodemographic factors and willingness to cooperate. RESULTS: This study included 2844 participants. The proportion of participants who were not willing to cooperate in reporting contacts was 27.6%, with their main reasons being concerns about causing trouble for the other person and being criticised for revealing their names. Willingness to cooperate was lower among men, young adults and those with an educational level less than a university degree. CONCLUSIONS: To improve the effectiveness of contact tracing, educational campaigns, such as reducing the fear and stigma associated with COVID-19, may be important. Furthermore, it is essential to understand that individuals may have contacts whom they do not wish to disclose to others and to be considerate when handling such situations.

Neoadjuvant chemotherapy with S-1 and cisplatin followed by D2 gastrectomy with para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis.

BACKGROUND: Locally advanced gastric cancer with extensive regional and/or para-aortic lymph node (PAN) metastases is typically unresectable and associated with poor outcomes. This study investigated the safety and efficacy of S-1 plus cisplatin followed by extended surgery with PAN dissection for gastric cancer with extensive lymph node metastasis. METHODS: Patients with gastric cancer with bulky lymph node metastasis along the coeliac artery and its branches and/or PAN metastasis received two or three 28-day cycles of S-1 plus cisplatin, followed by gastrectomy with D2 plus PAN dissection. The primary endpoint was the percentage of complete resections with clear margins in the primary tumour (R0 resection). A target sample size of 50 with one-sided α of 0.105 and ß of approximately 0.2 corresponded to an expected R0 rate of 65 per cent and a threshold of 50 per cent. RESULTS: Between February 2005 and June 2007, 53 patients were enrolled, of whom 51 were eligible. The R0 resection rate was 82 per cent. Clinical and pathological response rates were 65 and 51 per cent respectively. The 3- and 5-year overall survival rates were 59 and 53 per cent respectively. During chemotherapy, grade 3/4 neutropenia occurred in 19 per cent and grade 3/4 non-haematological adverse events in 15.4 per cent. The incidence of grade 3/4 adverse events related to surgery was 12 per cent. There were no reoperations or treatment-related deaths. CONCLUSION: For locally advanced gastric cancer with extensive lymph node metastasis, 4-weekly S-1 plus cisplatin followed by surgery including PAN dissection was safe and effective for some patients. Further investigation of this treatment strategy is warranted.

Current status of organ transplantation in Japan.

To overcome severe donor shortage, Japanese doctors over the years have developed innovative strategies to maximize organs transplanted per brain death donor and expanded the donor pool using living donors. They also used living and marginal organs and drastically improved living donor lung, liver, pancreas and kidney transplantations. Moreover, they initiated ABO blood type incompatible liver transplantation advancements and succeeded in overcoming the blood type barrier in kidney and liver transplantations. Similar efforts are underway for pancreas transplantation. Furthermore, Japanese doctors have developed a nonaggressive step to achieve immunosuppression following organ transplantation by carefully monitoring donor-specific hyporesponsiveness and infectious immunostatus. However, the institution of amendments to allocation systems and the intensification of efforts to decrease living donor morbidity and to increase the number of brain death donors have remained important issues needing attention. Overall, the strategies Japan has adopted to overcome donor shortage can provide useful insights on how to increase organ transplantations.

Retrospective and prospective studies of hepatitis B virus reactivation in malignant lymphoma with occult HBV carrier.

BACKGROUND: In surface antigen of hepatitis B virus (HBsAg)-positive carrier for anticancer treatment of malignant lymphoma, it is well recognized that reactivation of hepatitis B virus (HBV) occasionally occurs. However, there have been only a few studies of HBV reactivation in serum HBsAg-negative and hepatitis B core antigen (HBcAb)-positive occult HBV carriers. We looked at both retrospective and prospective studies to determine the prevalence, clinical course and risk factor of HBV reactivation during chemotherapy in lymphoma patients. PATIENTS AND METHODS: Forty-eight of 127 (37.8%) lymphoma patients were HBsAg negative and HBcAb positive, and 24 of these patients were then given liver function tests and HBsAg tests monthly and serum HBV DNA every 3 months. RESULTS: HBV reactivation was observed in two patients (4.1%) who had received intensive chemotherapy including steroid and rituximab. Immediate administration of entecavir therapy after elevation of HBV DNA level was conducted, and this resulted in reduction of it and improvement of liver function test. CONCLUSIONS: Rituximab plus steroid-containing regimens may increase the risk of HBV reactivation in HBsAg-negative and HBcAb-positive lymphoma patients. More ambitious prospective studies are required to establish clinically useful or cost-effective follow-up methods for control of HBV reactivation in lymphoma patients with occult HBV infection.

Phase II study of neoadjuvant chemotherapy and extended surgery for locally advanced gastric cancer.

BACKGROUND: Locally advanced gastric cancer with extensive lymph node metastasis is usually considered unresectable and so treated by chemotherapy. This trial explored the safety and efficacy of preoperative chemotherapy followed by extended surgery in the management of locally advanced gastric adenocarcinoma. METHODS: Patients with gastric cancer with extensive lymph node metastasis received two or three 28-day cycles of induction chemotherapy with irinotecan (70 mg/m(2) on days 1 and 15) and cisplatin (80 mg/m(2) on day 1), and then underwent gastrectomy with curative intent with D2 plus para-aortic lymphadenectomy. Primary endpoints were 3-year overall survival and incidence of treatment-related death. RESULTS: The study was terminated because of three treatment-related deaths when 55 patients had been enrolled (mortality rate above 5 per cent). Two deaths were due to myelosuppression and one to postoperative complications. Clinical response and R0 resection rates were 55 and 65 per cent respectively. The pathological response rate was 15 per cent. Median overall survival was 14.6 months and the 3-year survival rate 27 per cent. CONCLUSION: This multimodal treatment of locally advanced gastric cancer provides reasonable 3-year survival compared with historical data, but at a considerable cost in terms of morbidity and mortality.

Strategies for maximizing heart and lung transplantation opportunities in Japan.

INTRODUCTION: Because the donor shortage is extremely severe in Japan because of a strict organ transplantation law, special strategies must be established to maximize heart transplantation (HTx) and lung transplantation (LTx) opportunities. The purpose of this study was to review our strategies to identify and manage heart and lung donors. METHOD: Transplantation doctors themselves assessed their own donor heart and lung function before starting the procurement operation; skillful staff surgeons harvested the organs. Since November 2002, a special transplantation consultant doctor assessed donor organ function to identify useful organs and intensively cared for the donor to improve cardiac and lung function. RESULTS: Only 63 brain-dead donors have been available in Japan. However, 49 HTx (77.7%) and 39 LTx (19 bilateral and 20 single) were performed from 36 donors (57.1%). Thirty-six HTx donors were marginal, requiring sustained high doses of inotropes (n = 26), low left ventricular ejection fraction (n = 5), cardiopulmonary resuscitation (n = 15), and age older than 55 years (n = 6). Twenty LTx donors had infected sputa or showed pneumonia using chest X-ray. None of 49 HTx recipients died of primary graft failure (PGF). Patient survival at 3 years after HTx was 98.0%. Although 5/39 LTx died early, including 2 of PGF, patient survival rate at 3 years was 66.9%. CONCLUSION: Although the number of cases was still small, the availability of hearts and lungs has been high and the transplantation outcomes were acceptable. These strategies may be useful to maximize HTx/LTx opportunities.

Clinical Outcomes of Patients With the HeartMate II Left Ventricular Assist Device: A Single-center Experience From Japan.

BACKGROUND: Left ventricular assist device (LVAD) therapy is the "gold standard" alternative therapy for patients with advanced heart failure. However, LVAD therapy is still uncommon in the Asia-Pacific region. Therefore, we aimed to elucidate the clinical outcomes of patients from Japan supported with the HeartMate II (HM-II) LVAD at our institution. METHODS: Ninety-two patients (mean 44.3 ± 12.1 years, 68 men, average body mass index 1.65 ± 0.28 m2; 81 with nonischemic cardiomyopathy) who underwent HM-II implantation for bridge to transplantation (n = 91) or for destination therapy in a clinical study (n = 1) at the National Cerebral and Cardiovascular Center between April 2013 and October 2017 were enrolled in this analysis. Preoperatively, most patients (n = 73, 79%) had an INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profile of between level 2 and 4. Postoperatively, the average pump speed was 8602 ± 258 rpm and the hemodynamics were well compensated. RESULTS: Adverse events consisted of 38 (41.3%) hemolysis, 30 (32.6%) major infection, 27 (29.3%) major bleeding (6 [6.5%] with gastrointestinal bleeding), and 18 (19.6%) neurologic dysfunction events. Eighteen patients underwent heart transplantation (HTx) after an average of 32.9 ± 8.9 months of VAD support, and overall survival at both 6 months and 3 years was 96.3%. CONCLUSION: Clinical outcome among patients with HM-II at our institution is satisfactory for both survival and adverse events. The HM-II can provide effective hemodynamic support during the extremely long waiting period for HTx in Japan.

Terminal Ileac Ulcers Mimicked Post-transplantation Lymphoproliferative Disorder in a Heart Recipient Treated With Everolimus: A Case Report.

Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized and potentially fatal complication of cardiac transplantation that commonly involves the gastrointestinal tract. Herein, we report a case of life-threatening gastrointestinal bleeding from recurrent terminal ileac ulcers mimicking PTLD in a heart recipient treated with everolimus (EVL). A 40-year-old man underwent heart transplantation for dilated cardiomyopathy 3 years prior to the current admission and was treated with tacrolimus and EVL. He was admitted to a local hospital because of fever, abdominal pain, and diarrhea. His symptoms persisted and, 3 weeks later, hematochezia occurred; thus, he was transferred to our hospital. As computed tomography and 18F-fluorodeoxyglucose positron emission tomography showed bowel-wall thickening of the terminal ileum, gastrointestinal PTLD was initially suspected. However, although colonoscopy- performed after switching EVL to mycophenolate mofetil (MMF)-showed terminal ileac ulcers, the histologic examination revealed no findings corresponding to PTLD. As EVL may delay ulcer healing, MMF was maintained for 3 months. After repeated colonoscopy showed ulcer healing, MMF was switched back to EVL for cardiac allograft vasculopathy prevention. Three weeks later, he was emergently admitted to a local hospital for life-threatening gastrointestinal bleeding from a recurrent terminal ileal ulcer, which required hemostatic forceps hemostasis. As EVL is suspected to be associated with recurrent ileal ulcers, EVL was again switched back to MMF. The ileal ulcers resolved, without recurrence in 3 months of clinical follow-up. This case demonstrates that cases of life-threatening gastrointestinal bleeding from recurrent terminal ileac ulcers can mimic PTLD in a heart recipient treated with EVL.

Paradoxical Reaction of Tuberculosis in a Heart Transplant Recipient During Antituberculosis Therapy: A Case Report.

INTRODUCTION: Tuberculous paradoxical reactions (PRs) are excessive immune reactions occurring after antituberculosis (TB) treatment and are commonly observed in immunocompromised hosts such as patients infected with the human immunodeficiency virus. CASE REPORT: We recently encountered a 63-year-old male heart transplant recipient who developed tuberculous PR after treatment for miliary TB. The patient had been receiving immunosuppressive therapy with cyclosporine and mycophenolate mofetil for over 15 years. The diagnosis of miliary TB was made based on the presence of intermittent fever and fatigue; thus, anti-TB treatments (isoniazid, levofloxacin, ethambutol, and pyrazinamide) were started, which led to rapid defervescence and regression of the granular shadow and pleural effusion. However, a new persistent fever and confused state developed 1 month after the anti-TB therapy was started. After excluding possible etiologies of the patient's symptom, a PR was suspected, and anti-TB drugs were continued; corticosteroids were added as anti-inflammatory agents. After that, he has shown a favorable course with long-term anti-TB chemotherapy. CONCLUSION: A PR should always be considered when the patients' symptoms of tuberculosis re-exacerbate after an appropriate anti-TB therapy. A PR commonly occurs in patients with various immunologic conditions including heart transplant recipients.

Metastasis in para-aortic lymph nodes in patients with advanced gastric cancer, treated with extended lymphadenectomy.

BACKGROUND/AIMS: Lymph node dissection is an essential component of curative resection for advanced gastric cancer. To improve the survival of N2 patients, Asian surgeons have been performing D2+para-aortic lymph node dissection. The current study presents the results of lymph node status from multicenter trial of D2 and D2 + para-aortic nodal (No.16) dissection (D4 dissection). METHODOLOGY: Patients enrolled in the study had potentially curable gastric adenocarcinoma in an advanced stage, T2, T3 or T4/N1 or N2. Patients were randomized to undergo either D2 or D4 gastrectomy. RESULTS: Two hundred and seventy patients were registered and 136 and 134 patients were allocated into the D2 or D4 group, respectively. The average nodal yield of No.16 in D4 group was 18.4 +/- 14.1, ranging from 2 to 84. No.16 metastasis was detected in 12 (9.0%) of 134 D4 patients. One, 9 and 2 patients had simultaneous involvement in N1, N2, and N3 (No.8p, 12, 13 or 14). Namely, in 39 patients who were diagnosed as N2 from the lymph node status in N1 and N2 levels, nine (23.0%) patients had No.16 metastasis. The stage migration by D4 was found in 10 (7.5%). Logistic regression analysis revealed that the stations of No.7 and No.8 were the significant predictors of No.16 involvement. CONCLUSIONS: The present study may strongly suggest that prophylactic D4 dissection may be indicated for patients with N2 involvement, and that No.7 and No.8 are the junctional nodes for D4 dissection.

The GTPase effector domain sequence of the Dnm1p GTPase regulates self-assembly and controls a rate-limiting step in mitochondrial fission.

Dnm1p belongs to a family of dynamin-related GTPases required to remodel different cellular membranes. In budding yeast, Dnm1p-containing complexes assemble on the cytoplasmic surface of the outer mitochondrial membrane at sites where mitochondrial tubules divide. Our previous genetic studies suggested that Dnm1p's GTPase activity was required for mitochondrial fission and that Dnm1p interacted with itself. In this study, we show that bacterially expressed Dnm1p can bind and hydrolyze GTP in vitro. Coimmunoprecipitation studies and yeast two-hybrid analysis suggest that Dnm1p oligomerizes in vivo. With the use of the yeast two-hybrid system, we show that this Dnm1p oligomerization is mediated, in part, by a C-terminal sequence related to the GTPase effector domain (GED) in dynamin. The Dnm1p interactions characterized here are similar to those reported for dynamin and dynamin-related proteins that form higher order structures in vivo, suggesting that Dnm1p assembles to form rings or collars that surround mitochondrial tubules. Based on previous findings, a K705A mutation in the Dnm1p GED is predicted to interfere with GTP hydrolysis, stabilize active Dnm1p-GTP, and stimulate a rate-limiting step in fission. Here we show that expression of the Dnm1 K705A protein in yeast enhances mitochondrial fission. Our results provide evidence that the GED region of a dynamin-related protein modulates a rate-limiting step in membrane fission.

Percutaneous Coronary Intervention and Coronary Artery Bypass Grafting in Heart Transplant Recipients With Transplant Coronary Arterial Vasculopathy.

BACKGROUND: Transplant coronary arterial vasculopathy (TCAV) is a major cause of death after heart transplantation (HTx). Palliative coronary revascularization has been attempted in patients with severe TCAV; however, the outcome has not been fully elucidated. METHODS: Ninety-six patients who were treated after HTx at our institute between 1999 and 2015 were screened for TCAV. TCAV was defined as >70% stenosis on coronary angiography (CAG) or a maximal intimal thickness of >0.5 mm in the right or left coronary arteries on intracoronary ultrasonography (IVUS). In the present study, the outcomes of patients with severe TCAV who underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) were investigated. RESULTS: TCAV containing donor-transmitted atherosclerosis was cumulatively found in 69 patients (71.9% of the total; mean age, 34.6 ± 13.1 years; 52 men; mean follow-up duration, 83.0 ± 60.4 months). Five (7.2%) and 64 (92.8%) of the 69 patients were diagnosed as having TCAV by use of CAG and IVUS, respectively. All 5 patients diagnosed by with the use of CAG underwent coronary revascularization between 1 and 236 months after HTx. Three patients underwent PCI with drug-eluting stents, with a primary success rate of 100%. No angiographic restenosis occurred in 2 patients at 31 and 36 months after PCI, respectively. Meanwhile, 2 patients underwent CABG. No peri-operative complications occurred, and all grafts were patent as assessed by use of CAG at 34 and 5 months after CABG. CONCLUSIONS: Coronary revascularization was feasible and effective for severe TCAV with middle-term follow-up.

Reversible Cerebral Vasoconstriction Syndrome After Heart Transplantation: A Case Report.

BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) is a transient cerebrovascular disorder putatively caused by some immunosuppressive agents. CASE REPORT: We recently encountered a 47-year-old female patient diagnosed with dilated cardiomyopathy who developed RCVS after heart transplantation. A triple-drug regimen consisting of tacrolimus, mycophenolate mofetil, and a corticosteroid was started after surgery. On postoperative day (POD) 11, the patient developed a severe headache, although computed tomography of the head demonstrated no signs of hemorrhage or infarction. At first, both a painkiller and migraine drugs were regularly administered to the patient. On POD 21, however, she developed an unbearable headache with a visual field defect and mild hemiparesis of the right hand. Magnetic resonance imaging (MRI) of the brain revealed a cerebral infarction in the left occipital lobe with diffuse vasoconstriction of both the middle and posterior cerebral arteries. A diagnosis of RCVS was made and tacrolimus, a drug suspected to cause RCVS, was discontinued. In its place, two doses of basiliximab followed by everolimus, both of which are alternatives for tacrolimus, were given. The corticosteroid dose was also increased. Furthermore, to release vasoconstriction, both verapamil and diltiazem were administered. On POD 27, cerebrovascular constrictions were shown to be relieved on brain MRI and the patient's neurological symptoms subsequently almost completely diminished. CONCLUSION: RCVS should always be considered as a cause of headache in heart transplant recipients because tacrolimus, an immunosuppressive agent, may trigger RCVS. This will allow rapid intervention that is essential for avoiding irreversible neurological deficits.

Circadian clock molecules CLOCK and CRYs modulate fibrinolytic activity by regulating the PAI-1 gene expression.

Disruptions of circadian rhythms are associated with the development of many disorders. However, whether a disruption of the circadian clock can cause anomalies of the hemostatic balance remains unknown. The present study examines coagulation and fibrinolytic activities in circadian clock mutants, a homozygous Clock mutant and Cry1/Cry2 double knockout (Cry1/2-deficient) mice. The euglobulin clot lysis time (ELT) showed circadian variations that peaked at 21:00 (early night) in wild-type mice, suggesting that fibrinolytic activity is lowest at this time. The ELT was continuously reduced in Clock mutants, while the ELT was significantly increased and did not differ between day and night (9:00 and 21:00) in Cry1/2-deficient mice. The prothrombin time (PT) and activated partial prothrombin time (APTT) were constant in all genotypes. To identify which factors cause the loss of ELT rhythm, we measured fibrinolytic parameters in Clock mutant and Cry1/2-deficient mice. The robust circadian fluctuation of plasma plasminogen activator inhibitor 1 (PAI-1) that peaked at early night was damped to trough levels in Clock mutant mice. On the other hand, PAI-1 levels in Cry1/2-deficient mice remained equivalent to the peak levels of those in wild-type mice at both 9:00 and 21:00. Circadian changes in plasma PAI-1 levels seemed to be regulated at the level of gene expression, because the plasma PAI-1 levels in Clock mutant and Cry1/2-deficient mice were closely correlated with the level of PAI-1 mRNA transcript in these mice. Plasma plasminogen and hepatic mRNA levels were not rhythmic in wild-type mice, and continuously higher in Clock mutant than in wild-type or Cry1/2-deficient mice. In contrast, the activity and mRNA levels of tissue type plasminogen activator (t-PA), plasma levels and mRNA levels of plasminogen, and plasma levels of alpha2 plasmin inhibitor (alpha2PI) in all genotypes were constant throughout the day. Coagulation parameters such as factor VII, factor X, prothrombin and fibrinogen remained constant throughout the day, and were not affected by clock gene mutations. These results suggest that circadian clock molecules play an important role in hemostatic balance by regulating the fibrinolytic systems.

Effects of hypoglossal and facial nerve injuries on milk-suckling.

Functional roles of the perioral anatomical structures involved in breastfeeding were examined in newborn rat pups in which the hypoglossal (XII) and facial (VII) nerves had been resected at the neonatal stage. The XII nerve controls tongue movement and is comprised of two functionally distinct branches: the medial branch related to protrusion of the tongue and the lateral branch related to its retraction. Newborn rat pups with bilateral resection of either of the XII nerve components (main trunk: XII-trunk; medial branch: XII-med; lateral branch: XII-lat) failed to suckle milk and did not survive. Unilateral XII nerve-resected neonates showed different milk-suckling capabilities, which thus resulted in differences in survival rate (XII-trunk: 38%; XII-med: 24%; XII-lat: 92%) and postnatal growth during the postnatal 3 weeks until P21. Unilateral and bilateral resections of the VII nerve innervating the buccolabial musculature produced lowered suckling capabilities and retarded postnatal growth, although all pups showed 100% survival. The results indicate a crucial role of the tongue, especially of protruding muscular elements innervated by the XII-med nerve, in breastfeeding. The results also indicate differential effects of the VII and XII nerve components on suckling capability, survival, and postnatal growth of newborn rat pups.

Differential effects of hypoglossal and facial nerve injuries on survival and growth of rats at different developmental stages.

The hypoglossal (XII) nerve is made up of functionally different nerve branches: the medial branch related to protrusion of the tongue and the lateral branch related to its retraction. The present study was performed to determine the effects of facial (VII) and XII nerve injuries on the survival and growth of rats in which the unilateral or bilateral VII and XII nerve components (main trunk, XII-trunk; medial branch, XII-med; lateral branch, XII-lat) had been resected at different developmental stages. In the suckling period, unilateral as well as bilateral injuries in the XII-trunk or XII-med nerve produced disturbed milk intake, lower survival rates and growth retardation in the nerve-injured rats. In the transition and mastication periods, only bilateral injury in the XII-trunk or XII-med nerve produced disturbed food intake followed by lower survival rates and growth retardation in those animals. The unilateral XII-lat nerve injury did not have significant effects on milk and food intake, whereas the bilateral injury caused disturbance in milk intake especially at the early neonatal stage. The unilateral VII nerve injury at the early neonatal stage caused deteriorating effects on food intake resulting in lower survival rate and severe growth retardation in the nerve-injured rats. The results indicate that the survival and growth of XII and VII nerve-resected rats differ considerably depending on the nerves injured and the developmental ages of the animals at the time of nerve insult.

Operative morbidity and mortality after D2 and D4 extended dissection for advanced gastric cancer: a prospective randomized trial conducted by Asian surgeons.

BACKGROUND/AIMS: A randomized study was performed to evaluate morbidity and mortality after D2 (level 1 and 2 lymphadenectomy) and D4 (D2 plus lymphadenectomy of para-aortic lymph nodes) dissection for advanced gastric cancer. METHODOLOGY: Two hundred and fifty-six patients with advanced gastric adenocarcinoma were enrolled (128 to each group). Patients were randomly allocated into D2 (N = 128) or D4 (N = 128) group. The first and second tiers of lymph nodes are removed in D2 dissection. In D4 gastrectomy, the paraaortic lymph nodes were additionally removed. RESULTS: There was no indication of significant distribution bias with regard to age, sex, T-grade, and N-grade between the two groups. Operation time of D4 gastrectomy (369 +/- 120 min) was significantly longer than that of D2 gastrectomy (273 +/- 1103 min), and blood loss of the D4 group (872 +/- 683 mL) was significantly greater than that of the D2 group 571 +/- 527 mL (P < 0.001). Five (4%) and two (2%) medical complications developed in the D2 and D4 groups, respectively. Surgical complications developed in 28 (22%) and 48 patients (38%) after D2 and D4 gastrectomy. The most common complications were anastomotic leakage, pancreatic fistula, and abdominal abscess. Pancreatic fistula developed in 6 (19%) of 32 patients after D4 plus pancreatosplenectomy, but the incidence of pancreatic fistula after D2 gastrectomy plus pancreatosplenectomy was low (6%, 1/16). Two patients died within 30 days of operation (0.8%, 2/256), and each patient belonged to the D2 and D4 group. CONCLUSIONS: Although there is a significantly higher surgical complication rate in D4 dissection, D4 dissection can be done safely as D2 dissection when performed by well-trained surgeons.

Regional Survey of Tissue Donation Among the General Public and Medical Staffs Around Osaka, Japan.

BACKGROUND: Because tissue transplantation (TTx) has not been familiar to the general public or even to medical staffs in Japan, awareness of TTx is very important to increase tissue donation. Our primary aim was to describe the current status of awareness of TTx in medical staffs and in the general public around Osaka. METHODS: Between July 2014 and February 2015, 1015 general public citizens, 203 medical staff members working in emergency hospitals, and 168 cardiothoracic surgeons were invited to complete a letter or web-based survey through the use of a self-designed questionnaire. RESULTS: In the general public citizens, only 25.1% knew about TTx, whereas 54.7% knew about organ transplantation (OTx); 25.4% agreed to donate their organs or tissues and 17.3% disagreed to donate their organs or tissues. In medical staff members working in emergency hospitals, 58.7% knew about TTx; 82.3% agreed to support organ or tissue procurement and 10.8% disagreed to do so. Among cardiothoracic surgeons, 78.7% knew about TTx; 33.2% had used valve or vascular homografts and 57.4% wanted to use them if possible. CONCLUSIONS: According to these surveys, public awareness of TTx has been less than that of OTx, but willingness to donate tissue was not different from that of donating organs. Awareness of TTx in medical staffs in emergency hospitals was higher but still not satisfactory. To increase tissue donation in Japan, the East and West Japan Tissue Transplant Network, in collaboration with cardiothoracic surgeons, should make more effort to carry out dissemination and awareness regarding TTx to the general public and to medical staffs.

Regulation of Schwann cell morphology and adhesion by receptor-mediated lysophosphatidic acid signaling.

In peripheral nerves, Schwann cells (SCs) form contacts with axons, other SCs, and extracellular matrix components that are critical for their migration, differentiation, and response to injury. Here, we report that lysophosphatidic acid (LPA), an extracellular signaling phospholipid, regulates the morphology and adhesion of cultured SCs. Treatment with LPA induces f-actin rearrangements resulting in a "wreath"-like structure, with actin loops bundled peripherally by short orthogonal filaments. The latter appear to anchor the SC to a laminin substrate, because they colocalize with the focal adhesion proteins, paxillin and vinculin. SCs also respond to LPA treatment by forming extensive cell-cell junctions containing N-cadherin, resulting in cell clustering. Pharmacological blocking experiments indicate that LPA-induced actin rearrangements and focal adhesion assembly involve Rho pathway activation via a pertussis toxin-insensitive G-protein. The transcript encoding LP(A1), the canonical G-protein-coupled receptor for LPA, is upregulated after sciatic nerve transection, and SCs cultured from lp(A1)-null mice exhibit greatly diminished morphological responses to LPA. Cultured SCs can release an LPA-like factor implicating SCs as a potential source of endogenous, signaling LPA. These data, together with the previous demonstration of LPA-mediated SC survival, implicate endogenous receptor-mediated LPA signaling in the control of SC development and function.