Involvement of transient receptor potential vanilloid 2 in intra-oral incisional pain.

OBJECTIVE: To examine whether transient receptor potential vanilloid 2 (TRPV2) contributes to the changes in intra-oral thermal and mechanical sensitivity following the incision of buccal mucosa. MATERIALS AND METHODS: Buccal mucosal pain threshold was measured after the incision. Changes in the number of TRPV2-immunoreactive (IR) trigeminal ganglion (TG) neurons which innervate the whisker pad skin and buccal mucosa, changes in the number of isolectin B4-negative/isolectin B4-positive TRPV2-IR TG neurons which innervate the whisker pad skin and the buccal mucosa, and the effect of peripheral TRPV2 antagonism on the pain threshold of incisional whisker pad skin and buccal mucosa were examined after these injuries. RESULTS: Buccal mucosal pain hypersensitivities were induced on day 3 following the incision. The total number of TRPV2-IR TG neurons and the number of isolectin B4-negative TRPV2-IR TG neurons which innervate the whisker pad skin and buccal mucosa were increased. Buccal mucosal TRPV2 antagonism completely suppressed the heat and mechanical hypersensitivities, but not cold hypersensitivity. TRPV2 antagonist administration to the incisional whisker pad skin only partially suppressed pain hypersensitivities. CONCLUSION: The increased expression of TRPV2 in peptidergic TG neurons innervating the incisional buccal mucosa is predominantly involved in buccal mucosal heat hyperalgesia and mechanical allodynia following buccal mucosal incision.

Feeding catheter gastrostomy with the round ligament of the liver prevents mechanical bowel obstruction after esophagectomy.

Jejunostomy, which requires the fixation of the jejunum to the abdominal wall, is commonly used as an enteral feeding access after esophagectomy. However, this procedure sometimes causes severe complications, such as mechanical bowel obstruction. In 2009, we developed a modified approach to insert an enteral feeding tube through the reconstructed gastric tube using the round ligament of the liver. The aim of this study is to investigate the usefulness of this approach as compared to the approach through jejunostomy. Between January 2005 and March 2015, 420 patients with thoracic esophageal cancer underwent esophagectomy via thoracotomy and laparotomy. Of these, 214 underwent feeding jejunostomy (FJ group) and 206 patients underwent feeding via gastric tube with round ligament of the liver (FG group). Catheter-related complications, other postoperative complications, and mortality were compared between the two groups. The incidence of catheter site infection during catheterization in the FG group was significantly lower (n = 1/206, 0.5%) compared to the FJ group (n = 11/214, 5.1%) (P < 0.01). The postoperative bowel obstruction did not occur in the FG group, while it occurred in eight patients (3.7%) in the FJ group (P < 0.01). The incidences of other catheter-related and postoperative complications were similar between the two groups. Feeding catheter gastrostomy with the round ligament of the liver can be a useful enteral feeding access after esophagectomy, because the incidence rate of severe catheter-related complications, such as surgical site infection and mechanical obstruction tend to be lower with this technique compare to jejunostomy.

Risk factors for mortality in patients with non-traumatic pontine hemorrhage.

OBJECTIVES: For patients with non-traumatic pontine hemorrhage (PH) who will survive, determining prognosis is vital for appropriate therapeutic planning in the acute stage. This study aimed to determine reliable prognostic factors of mortality in patients with PH. MATERIALS AND METHODS: The cases of a total of 118 consecutive PH patients were reviewed. We compared clinical and radiological characteristics between patients who died and survivors by the log-rank test and performed multivariate analysis by the Cox proportional hazards model using variables that were marginally or significantly associated with PH-related death on the log-rank test (P < 0.20). RESULTS: The median length of follow-up was 51 days (interquartile range: 7-742 days). Sixty-six patients (56%) died and 52 (44%) survived during follow-up period. Multivariate analysis showed that Glasgow Coma Scale score <9, hyperthermia (a core temperature of ≥39°C), maximum hematoma diameter more than 27 mm, and hematoma extension to midbrain and/or thalamus were significantly related to PH-related death. The Kaplan-Meier method showed that patients without these four factors had successively longer period at PH-related death (21 patients without factors: mean 2900 days; 97 patients with at least one of four factors: mean 820 days). CONCLUSIONS: Promptly identifying PH patients who are most likely die is important. The decision to stop life support in patients with PH is difficult, but factors, which are shown in this study, may be used to determine the level of care.

Arterial stiffness as a risk factor for cerebral aneurysm.

OBJECTIVES: A low ankle-brachial index (ABI) is associated with increased mortality and risk of myocardial infarction and stroke in the general population. Arterial stiffness can be assessed non-invasively by the measurement of brachial-ankle pulse wave velocity (PWV), a simple and reproducible method. Because the importance of ABI and baPWV in the pathogenesis of cerebral aneurysms remains uncertain, we aimed to measure ABI and baPWV in patients with intracranial saccular and dissecting aneurysms to clarify whether these aneurysms are associated with arterial stiffness and atherosclerosis. MATERIALS AND METHODS: We prospectively investigated 78 patients diagnosed with intracranial saccular (n = 66) and dissecting (n = 12) aneurysms. The control group consisted of an age- and gender-matched normal population. We compared the clinical characteristics in patients with intracranial saccular aneurysms and controls, those with intracranial dissecting aneurysms and controls, and those who had cerebral aneurysms with and without subarachnoid hemorrhage. We also compared ABI and baPWV among saccular aneurysm locations and evaluated the correlation between the number of saccular aneurysms and ABI and baPWV. RESULTS: Multivariate logistic regression analysis shows that hypertension and higher baPWV (>1400 cm/s) are significantly associated with saccular aneurysms. Simple regression analysis revealed no correlation between the number of saccular aneurysms and ABI (r = -0.064, P = 0.611), and baPWV (r = 0.007, P = 0.956). CONCLUSIONS: The baPWV was associated with intracranial saccular aneurysms even after adjustment of hypertension and smoking. Assessment of the baPWV may aid the evaluation of the intracranial saccular aneurysm and the development of strategies for screening patients with intracranial saccular aneurysms.

Hemoadsorption of high-mobility group box chromosomal protein 1 using a column for large animals.

BACKGROUND: High-mobility group box chromosomal protein 1 (HMGB1) has recently been identified as an important mediator of various kinds of acute and chronic inflammation. A method for efficiently removing HMGB1 from the systemic circulation could be a promising therapy for HMGB1-mediated inflammatory diseases. MATERIALS AND METHODS: In this study, we produced a new adsorbent material by chemically treating polystyrene fiber. We first determined whether the adsorbent material efficiently adsorbed HMGB1 in vitro using a bovine HMGB1 solution and a plasma sample from a swine model of acute liver failure. We then constructed a column by embedding fabric sheets of the newly developed fibers into a cartridge and tested the ability of the column to reduce plasma HMGB1 levels during a 4-hour extracorporeal hemoperfusion in a swine model of acute liver failure. RESULTS: The in vitro adsorption test of the new fiber showed high performance for HMGB1 adsorption (96% adsorption in the bovine HMGB1 solution and 94% in the acute liver failure swine plasma, 2 h incubation at 37°C; p < 0.05 vs. incubation with no adsorbent). In the in vivo study, the ratio of the HMGB1 concentration at the outlet versus the inlet of the column was significantly lower in swine hemoperfused with the newly developed column (53 and 61% at the beginning and end of perfusion, respectively) than in those animals hemoperfused with the control column (94 and 93% at the beginning and end of perfusion, respectively; p < 0.05). Moreover, the normalized plasma level of HMGB1 was significantly lower during perfusion with the new column than with the control column (p < 0.05 at 1, 2, and 3 h after initiation of perfusion). CONCLUSION: These data suggest that the newly developed column has the potential to effectively adsorb HMGB1 during hemoperfusion in swine.

Factors associated with lobar vs. non-lobar intracerebral hemorrhage.

OBJECTIVES: The relationship between body mass index (BMI) and stroke subtypes has received more research attention than that between BMI and location of intracerebral hemorrhage (ICH). Lobar hemorrhage (LH) differs from non-LH primarily in terms of etiology, i.e. cerebral amyloid angiopathy is the main cause of LH. This study aimed to determine the relationship between BMI and ICH. MATERIALS AND METHODS: In this retrospective study involving 460 consecutive patients with ICH, BMI was significantly lower in LH than for other ICH locations. BMI categories were underweight (BMI < 18.5 kg/m(2)), normal weight (18.5-23.0 kg/m(2)), overweight (23.0-27.5 kg/m(2)), or obesity (≥27.5 kg/m(2)). Outcome at 1 year was evaluated by the modified Rankin Scale (mRS). We investigated the relationship of BMI and other clinical characteristics with LH and non-LH. RESULTS: LH was associated with age (>70 years), underweight, unfavorable outcome (mRS ≥3), and daily alcohol consumption. Hypertension and intraventricular bleeding were significantly less common in patients with LH than those with non-LH. CONCLUSIONS: Alongside risk factors conventionally thought to be related to LH, underweight may also be a LH-related factor, specifically in the elderly.

Increased plasma levels of high mobility group box 1 in patients with acute liver failure.

BACKGROUND: High-mobility group box 1 (HMGB1) is a monocyte-derived late-acting inflammatory mediator, which is released in conditions such as shock, tissue injury and endotoxin-induced lethality. In this study, we determined the plasma and hepatic tissue levels of HMGB1 in patients with acute liver failure (ALF). PATIENTS AND METHODS: We determined the plasma levels of HMGB1 and aspartate aminotransferase (AST) in 7 healthy volunteers (HVs), 40 patients with liver cirrhosis (LC), 37 patients with chronic hepatitis (CH), 18 patients with severe acute hepatitis (AH), and 14 patients with fulminant hepatitis (FH). The 14 patients with FH were divided into two subgroups depending upon the history of plasma exchange (PE) before their plasma sample collection. The hepatic levels of HMGB1 were measured in tissue samples from 3 patients with FH who underwent living-donor liver transplantation and from 3 healthy living donors. Hepatic tissue samples were also subjected to immunohistochemical examination for HMGB1. RESULTS: The plasma levels of HMGB1 (ng/ml) were higher in patients with liver diseases, especially in FH patients with no history of PE, than in HVs (0.3 ± 0.3 in HVs, 4.0 ± 2.0 in LC, 5.2 ± 2.6 in CH, 8.6 ± 4.8 in severe AH, 7.8 ± 2.7 in FH with a history of PE, and 12.5 ± 2.6 in FH with no history of PE, p < 0.05 in each comparison). There was a strong and statistically significant relationship between the mean plasma HMGB1 level and the logarithm of the mean AST level (R = 0.900, p < 0.05). The hepatic tissue levels of HMGB1 (ng/mg tissue protein) were lower in patients with FH than in healthy donors (539 ± 116 in FH vs. 874 ± 81 in healthy donors, p < 0.05). Immunohistochemical staining for HMGB1 was strong and clear in the nuclei of hepatocytes in liver sections from healthy donors, but little staining in either nuclei or cytoplasm was evident in specimens from patients with FH. CONCLUSION: We confirmed that plasma HMGB1 levels were increased in patients with ALF. Based on a comparison between HMGB1 contents in normal and ALF livers, it is very likely that HMGB1 is released from injured liver tissue.

Epstein-Barr virus-associated inflammatory pseudotumor variant of follicular dendritic cell sarcoma of the liver: a case report and review of the literature.

BACKGROUND: Follicular dendritic cell sarcoma is a rare stromal tumor with no standard treatment. However, some reports have revealed that follicular dendritic cell sarcoma has an inflammatory pseudotumor variant associated with Epstein-Barr virus infection that has a relatively good prognosis. In this report, we present a case of a resected inflammatory pseudotumor variant of follicular dendritic cell sarcoma of the liver, and have reviewed the literature on the clinicopathological, molecular, and genomic features of this tumor. CASE PRESENTATION: The inflammatory pseudotumor variant of follicular dendritic cell sarcoma originates only in the liver or spleen, causes no symptoms, and is more common in middle-aged Asian women. It has no characteristic imaging features, which partially explains why the inflammatory pseudotumor variant of follicular dendritic cell sarcoma is difficult to diagnose. Pathologically, the inflammatory pseudotumor variant of follicular dendritic cell sarcoma has spindle cells mixed with inflammatory cells and is variably positive for follicular dendritic cell markers (CD21, CD23, and CD35) and Epstein-Barr virus-encoded RNA. On genetic analysis, patients with this tumor high levels of latent membrane protein 1 gene expression and extremely low levels of host C-X-C Chemokine Receptor type 7 gene expression, indicating that the inflammatory pseudotumor variant of follicular dendritic cell sarcoma has a latent Epstein-Barr virus type 2 infection. CONCLUSIONS: The inflammatory pseudotumor variant of follicular dendritic cell sarcoma is an Epstein-Barr virus-associated tumor and a favorable prognosis by surgical resection, similar to Epstein-Barr virus-associated gastric cancer.

Modulation of visceral hypersensitivity by glial cell line-derived neurotrophic factor family receptor α-3 in colorectal afferents.

Irritable bowel syndrome is characterized by colorectal hypersensitivity and contributed to by sensitized mechanosensitive primary afferents and recruitment of mechanoinsensitive (silent) afferents. Neurotrophic factors are well known to orchestrate dynamic changes in the properties of sensory neurons. Although pain modulation by proteins in the glial cell line-derived neurotrophic factor (GDNF) family has been documented in various pathophysiological states, their role in colorectal hypersensitivity remains unexplored. Therefore, we investigated the involvement of the GDNF family receptor α-3 (GFRα3) signaling in visceral hypersensitivity by quantifying visceromotor responses (VMR) to colorectal distension before and after intracolonic treatment with 2,4,6-trinitrobenzene sulfonic acid (TNBS). Baseline responses to colorectal distension did not differ between C57BL/6 and GFRα3 knockout (KO) mice. Relative to intracolonic saline treatment, TNBS significantly enhanced the VMR to colorectal distension in C57BL/6 mice 2, 7, 10, and 14 days posttreatment, whereas TNBS-induced visceral hypersensitivity was significantly suppressed in GFRα3 KO mice. The proportion of GFRα3 immunopositive thoracolumbar and lumbosacral colorectal dorsal root ganglion neurons was significantly elevated 2 days after TNBS treatment. In single fiber recordings, responses to circumferential stretch of colorectal afferent endings in C57BL/6 mice were significantly increased (sensitized) after exposure to an inflammatory soup, whereas responses to stretch did not sensitize in GFRα3 KO mice. These findings suggest that enhanced GFRα3 signaling in visceral afferents may contribute to development of colorectal hypersensitivity.

A phase II multi-center study of triple therapy with paclitaxel, S-1 and cisplatin in patients with advanced gastric cancer.

OBJECTIVES: To carry out a phase II multi-center study on the efficacy and safety of triple combination therapy with paclitaxel, S-1, and cisplatin in patients with unresectable/metastatic gastric cancer. METHODS: A total of 63 patients from 8 institutions were included in this study. Paclitaxel (160 mg/m²) was administered by infusion for 3 h on the first day. S-1 (70 mg/m²/day) was administered orally for 14 consecutive days from the first day. Cisplatin (60 mg/m²) was administered intravenously over 24 h on day 14 of every 28-day cycle. RESULTS: All 63 patients were assessed for clinical efficacy and safety. A total of 259 cycles of treatment were administered (median 4, range 1-10). Grade 3-4 toxicities included neutropenia in 30.2%, thrombocytopenia in 12.7%, and anemia in 11.1%. There was no grade 3-4 non-hematological toxicity or treatment-related death. Complete response was observed in 6 patients and partial response in 34 patients. The overall response rate was 63.5%. The median progression-free survival and response duration were 8.0 and 8.8 months, respectively, and median survival time was 15 months. CONCLUSIONS: Triple combination therapy with paclitaxel, S-1, and cisplatin showed promising safety and efficacy profiles with the potential to become a standard regimen for unresectable/metastatic gastric cancer.

A new mutation of GCH1 in triplets family with dopa-responsive dystonia.

BACKGROUND: Dopa-responsive dystonia (DRD) is associated with mutations of the GCH1. We first report four female siblings with DRD from one family, including three monozygotic triplets patients clinically and genetically. METHODS: We performed GCH1 analysis by direct sequencing of PCR product amplified with primers designed to cover the entire exons of GCH1 in those four patients and their mother. RESULTS: In all four patients with DRD, a new frameshift mutation (c.729delG; p.A190fsX191) was identified in the exon 5 of GCH1. CONCLUSIONS: The frameshift mutation results in truncated GCH1 protein which is suspected to result in loss of function of the catalytic GTP-cyclohydrol domain.

Role of Necl-5 in the pathophysiology of colorectal lesions induced by dimethylhydrazine and/or dextran sodium sulphate.

Necl-5 is an immunoglobulin-like molecule that was originally identified as a poliovirus receptor. Although Necl-5 expression is often up-regulated in cancer cells, its pathophysiological significance in the development of cancer remains unclear. We investigated the roles of Necl-5 in the development of colitis-associated neoplasia. Necl-5-deficient mice were generated and treated with dimethylhydrazine (DMH) and/or dextran sodium sulphate (DSS) to induce colitis and its associated neoplasias. Colon tissues were examined for histology, Ki-67 expression by immunohistochemistry and K-ras gene mutation. Colon tumours occurred significantly less frequently in heterozygous (Necl-5(+/-)) or homozygous Necl-5-deficient (Necl-5(-/-)) mice than in wild-type (WT) mice with DMH/DSS treatment. Total ulcer index and inflammatory cell infiltration were significantly lower in Necl-5(-/-) mice than in WT mice with DSS alone or DMH/DSS treatment. Colon tumours in both WT and Necl-5(-/-) mice showed high cell proliferation ability but lacked K-ras mutation. The total Ki-67 labelling index in non-neoplastic colon epithelium was significantly higher in WT (45.9 +/- 0.94) than in Necl-5(+/-) (34.3 +/- 1.40) or Necl-5(-/-) (27.7 +/- 1.15) mice with DMH/DSS treatment (p < 0.001). Necl-5 plays a role in the development of colitis-associated cancer by up-regulating colonic mucosal cell proliferation.

Outcome of laparoscopic living donor nephrectomy in 2007: national survey of transplantation centers in Japan.

Laparoscopic nephrectomy (LN) has been accepted for a donor in living donor kidney transplantation. However, the current status of LN in living donors is not yet clarified in Japan. In this study, we surveyed 138 Japanese kidney transplantation centers to investigate the outcomes of living donor LN in 2007. Of 138 centers, 107 responded, and 48 performed LN. These centers performed 840 living donor nephrectomies, including 623 LN and 217 open nephrectomies. Among 47 centers, 23 performed hand-assisted (HA) LN, 18 non-HA (pure laparoscopic), 3 both HA and non-HA, and 3 laparoscope-assisted. Seventeen centers utilized a peritoneal approach, 26 a retroperitoneal approach, and 4 both approaches. Among 623 LN donors, the 2 who had the life-threatening complications of bleeding and intestinal injury both survived. Blood transfusions were performed in 5 donors (0.8%). There were 8 (1.3%) open conversions from LN. Minor complications not requiring a longer hospital stay were reported in 10. There was no donor mortality after LN. However, among the recipients, there was 1 case of primary nonfunction. Thirteen recipients (2.0%) required hemodialysis after transplantation because of delayed graft function. Urinary tract complications were noted in 13 recipients (2.0%). This survey presented the current status of this procedure among donors who provided informed consent.

Outcome of laparoscopic living donor nephrectomy: current status and trends in Japan.

Laparoscopic nephrectomy (LN) has been accepted for donors in living donor kidney transplantation. But the current status of LN in living donors is not clarified yet in Japan. In this study, we surveyed 124 Japanese kidney transplantation centers to investigate the outcomes of living donor LN in 2006. Of 124 centers, 100 responded, and 52 performed LN. These centers performed 831 living donor nephrectomies, including 589 LN, and 242 open procedures. In 52 centers, 20 were performed as hand-assisted (HA) LNs, 23 non-HA (pure laparoscopic), five both HA and non-HA, and four laparoscope-assisted. Eighteen centers used a peritoneal approach, 31 used a retroperitoneal approach and three, both. Among 589 LN donors, three experienced life-threatening complications of bleedings and intestinal injury, but all of them survived. Blood transfusions were performed in nine donors (1.5%), and open conversions of LN in 33 (5.6%). Minor complications not requiring a long hospital stay were reported in 45. The mortality of LN was 0. Among the 589 recipients, there was one case of primary nonfunction after venous injury at the operation. Twenty eight recipients (4.8%) needed hemodialysis after transplantation because of delayed graft function. Urinary tract complications were noted in 11 recipients (2.5%). This survey presented the current status of LN in Japan.

Role of Neuron-Glial Interaction Mediated by IL-1ß in Ectopic Tooth Pain.

Although many reports have demonstrated that ectopic pain develops in the orofacial region following tooth pulp inflammation, which often causes misdiagnosis and inappropriate treatment for patients with pulpitis, the precise mechanism remains unknown. In the present study, we hypothesized that the functional interaction between satellite glial cells and neurons mediated by interleukin 1ß (IL-1ß) in the trigeminal ganglion (TG) is involved in ectopic orofacial pain associated with tooth pulp inflammation. The digastric muscle electromyogram (D-EMG) activity elicited by capsaicin administration into the maxillary second molar tooth pulp was analyzed to evaluate the noxious reflex and was significantly increased in rats with inflammation of the maxillary first molar (M1) versus rats injected with saline. A significant increase in the expression of connexin43 (Cx43), a gap junction containing protein, was observed in activated satellite glial cells surrounding second molar-innervating neurons in the TG after M1 pulpitis. Daily administration of Gap26, a Cx43 mimetic peptide and inhibitor, in the TG significantly suppressed the enhancement of capsaicin-induced D-EMG activity and the percentage of Fluoro-Gold (FG)-labeled cells encircled by glial fibrillary acid protein-immunoreactive (IR) + Cx43-IR cells after M1 pulp inflammation ( P < 0.01). The percentage of FG-labeled cells encircled by glial fibrillary acid protein-IR + IL-1ß-IR cells, IL-1 type I receptor-IR cells labeled with FG, and TRPV1-IR cells labeled with FG significantly increased after M1 pulp inflammation ( P < 0.01). Daily administration of IL-1ra, an IL-1 receptor antagonist, into the TG significantly reduced the enhancement of capsaicin-induced D-EMG activity and the percentage of TRPV1-IR neurons labeled with FG after M1 pulp inflammation ( P < 0.01). The present findings suggest that satellite glial cell is activated in the TG via activated gap junctions composed of Cx43 following tooth pulp inflammation, which leads to the hyperactivation of remote neurons via IL-1ß mechanisms and results in ectopic tooth pulp pain in the adjacent tooth.

Decreased Incidence of Acute Cellular Rejection in Low-Muscle-Mass Recipients After Living-donor Liver Transplantation.

BACKGROUND: Sarcopenia has recently been studied as a potential risk factor for mortality and complications after liver transplantation. We investigated the impact of low muscle mass on postoperative outcomes after living-donor liver transplantation. METHODS: Our study population consisted of 100 adult recipients who underwent living-donor liver transplantation in our department between 2005 and 2017. Recipients were divided into a low-muscle-mass group (L group) and a normal-muscle-mass group (N group) based on skeletal muscle index (SMI) values, and postoperative outcomes were compared between the groups. Regarding factors that were significantly different between the groups, multivariate analyses were performed to identify predictive factors. RESULTS: Based on the SMI definition, 47 and 53 of the recipients were categorized as having low muscle mass (L group) and normal muscle mass (N group), respectively. Comparison between the groups revealed a significantly reduced incidence of rejection (10.6% in L group vs 30.2% in N group, P = .017) and increased incidences of bacterial infection (61.7% in L group vs 37.7% in N group, P = .017) in the L group compared with the N group. The survival rate did not differ significantly between the groups. Multivariate analyses indicated that muscle mass was a significant predictive factor for both rejection and bacterial infection. CONCLUSION: It is important to recognize that muscle mass has an impact not only on bacterial infection but also on rejection in recipients with low muscle mass in the postoperative course of living-donor liver transplantation.

A Report on the Positive Response to an Outdoor Nature Challenge of a Snow Camp for Young Liver Transplant Patients.

OBJECTIVES: More than two decades have passed since the first living donor liver transplantation was performed in Japan in 1989. There are many reports about problems in adherence to taking medication and medical follow-ups in children who received liver transplants, because there is no transition strategy for those children and parents or guardians. The objective of this study is to measure the effect of nature and outdoor activity to improve children's medical adherence. METHODS: We recruited participants from 9-year-old children who are attending the outpatient liver transplant clinic in a stable condition (no event such as rejection or surgical procedure within 6 months). We took participants to a snow camp and measured its effect by using the IKIRU CHIKARA (IKR) tool, which contain 28 items divided into 3 categories: psychosocial ability, moral fitness, and physical ability. Children were tested on three occasions, before, just after, and 1 month after the camp. RESULTS: Eight patients participated in the snow camp and 7 patients were eligible for the study. The average age was 12.6 with a range 10 to 17 years. There were 3 girls and 4 boys. The average IKR scores before, just after, and 1 month after the camp were 127.9, 131.5, and 126.6, respectively. CONCLUSION: An outdoor activity such as a snow camp can be safely conducted, and it is an acceptable option to incorporate within a pediatric liver transplant program. There were no significant changes in IKR scores during this short observation. Longer observation is needed to measure the effect of nature and outdoor activities.

Outcome of laparoscopic live donor nephrectomy in 2005: National survey of Japanese transplantation centers.

The increased acceptance of laparoscopic nephrectomy (LN) has been a driving force for live donor kidney transplantation. However, the outcomes of LN in live donors has not yet been clarified in Japan. In this study, we surveyed 125 Japanese kidney transplantation centers to investigate the current status of live donor LN. Of 125 centers, the 98 that responded had performed 695 live donor nephrectomies. Among these centers, 43 had performed LN. Among the 695 nephrectomies, 441 donors had undergone LN and 254, open nephrectomies. In 43 centers, 16 were performed as hand-assisted (HA) LN; 20, non-HA; 3, both HA and non-HA; and 5 laparoscope-assisted. Ten centers used a peritoneal approach; 30, a retroperitoneal; and 3, both. In 441 LN donors, 1 had a life-threatening complication of deep venous thrombosis and survived. Blood transfusions were performed in 7 donors. Open conversions from LN were necessary in 24. Minor complications not requiring prolonged hospital stay were reported in 52. The mortality of LN was zero. In contrast, among the 441 recipients, 1 case was reported as primary nonfunction after venous misadventure in the operation and 30 recipients needed hemodialysis after transplantation because of delayed graft function. Urinary tract complications were noted in 11 recipients. This survey presented the current status of the procedure, providing a base for informed consent from potential donors.

Clinical implications of p53 autoantibodies in the sera of patients with non-small-cell lung cancer.

BACKGROUND: The presence of autoantibodies to p53 protein has been associated with the presence of p53 (also known as TP53) gene mutations in primary tumors and with poor prognosis. This study was undertaken to determine the clinical significance of p53 autoantibodies in patients with non-small-cell lung cancer (NSCLC). METHODS: We studied 188 consecutive patients with NSCLC who underwent pulmonary resection and for whom preoperative serum was available. The presence of p53 autoantibodies, detected by use of two amino-terminal and two carboxy-terminal peptides (20-30 mers) as antigens and an enzyme-linked immunosorbent assay, was related to various clinicopathologic parameters and to overexpression of p53 protein in the primary tumor. For 22 patients who had p53 autoantibodies before surgery, we also examined sera taken during postoperative follow-up. Reported P values are two-sided. RESULTS: Autoantibodies to p53 protein were detected in 38 patients. Patients with squamous cell carcinoma, those with more advanced disease (stage III-IV), and those with tumors that overexpressed p53 had a significantly higher incidence of p53 autoantibodies (P = .05,.0079, and .02, respectively). In all but one of the patients with postoperative serum samples, the antibody titer declined after surgery; however, there was no relationship between clinical course and this change in antibody titer. In addition, there was no relationship between the presence of p53 autoantibodies and overall survival in 171 patients who underwent potentially curative resection (P = .28); however, 13 patients with autoantibodies to amino-terminal peptides had a worse overall survival (P = .02). CONCLUSIONS: In NSCLC, the incidence of p53 autoantibodies is associated with histologic type, stage, and p53 overexpression--but not with patient survival. Our data do not support the clinical utility of p53 autoantibodies as diagnostic or prognostic markers in patients with NSCLC.

Lymph node metastasis is associated with allelic loss on chromosome 13q12-13 in esophageal squamous cell carcinoma.

Allelotype analysis of whole chromosomes showed that loss of heterozygosity (LOH) on 13q was exclusively associated with lymph node metastasis and poor prognosis in esophageal squamous cell carcinoma (ESC). To identify a locus responsible for lymph node metastasis, we performed fine deletion mapping on 13q by analyzing 60 ESCs with 18 polymorphic markers. Allelic loss was observed with at least one marker in 34 tumors (56.7%), and lymph node metastasis was significantly correlated with LOH (P = 0.0053). We found frequent loss at D13S260 (43.7%), D13S171 (38.6%), and D13S267 (43.6%) on 13q12-13. Among these markers, LOH at D13S171 showed a significant correlation with lymph node metastasis (P = 0.0441). Because these markers flank the BRCA2 gene, we intensively examined a mutation of the gene through all coding exons and exon-intron junctions by PCR-single-strand conformational polymorphism analysis under two different assays. We found only seven nucleotide substitutions as normal polymorphic changes; tumor-specific mutations were not detected, and loss of expression was not observed, indicating that the BRCA2 gene might not be a target of allelic loss in this region. Relatively frequent LOH was also found at the RB1 locus (34.7%), but a significant correlation with lymph node metastasis was not observed (P = 0.7430). Protein expression of RB1 was examined in 31 ESC cell lines, and loss of expression was infrequent (6.5%), indicating that inactivation of the RB1 gene might not be responsible for lymph node metastasis. Taken together, allelic loss at 13q12-13 of the primary ESC was closely associated with lymph node metastasis, and unidentified tumor suppressor gene(s) in this region might be involved.