Successful treatment of multiplex alopecia areata using transactional analysis: a case report.

The patient was a 13-year-old female. Six years previously, she developed alopecia areata when her parents divorced. One year after that, the bald area drastically expanded when her mother remarried. She was treated at her local hospital; however, no improvement was observed. She then visited our hospital for examination. A bald patch was covering >80% of her head. Self Grow-Up Egogram indicated the basic interpersonal relationship stance of 'I am not OK, You are OK'. We therefore implemented a transactional analysis approach to increase the patient's score on the Free Child subscale. New hair growth was observed after 6 months and the bald patch disappeared after 2 years. Our results suggest that this method could also be easily applied in a clinical setting by dermatologists.

[A case of primary gastric choriocarcinoma treated by curative operation after neoadjuvant chemotherapy with S-1/CDDP].

We experienced a case of primary gastric choriocarcinoma(PGC)treated by curative operation after neoadjuvant chemotherapy with S-1/CDDP. Gastric endoscopy was carried out on this 43-year-old woman with epigastric discomfort and revealed an ulcerative lesion in her stomach. Choriocarcinoma in the gastric lesion was pathologically shown by endoscopic biopsy, so we diagnosed the patient without another primary lesion as PGC. The patient was initially treated by five courses of neoadjuvant chemotherapy with S-1/CDDP due to the metastases of Virchow and intraabdominal lymph nodes, and then a curative operation could be performed because of disappearance of the lymph node metastases by neoadjuvant chemotherapy. The patient was continuously treated by S-1 after gastrectomy but was dead due to the multiple metastases of the liver and adrenals, and the multiple recurrences of lymph nodes four months after the surgery. Further therapeutic strategy by chemotherapies against PGC is needed to ameliorate the prognosis.

Intraoperative fluorescent imaging using indocyanine green for liver mapping and cholangiography.

BACKGROUND: Preoperative imaging is widely used and extremely helpful in hepatobiliary surgery. However, transfer of preoperative data to a intraoperative situation is very difficult. Surgeons need intraoperative anatomical information using imaging data for safe and precise operation in the field of hepatobiliary surgery. We have developed a new system for mapping liver segments and cholangiograms using intraoperative indocyanine green (ICG) fluorescence under infrared light observation. METHOD: The imaging technique for mapping liver segments and cholangiogram based on ICG fluorescence used an infrared-based navigation system. Eighty one patients with liver tumors underwent hepatectomy from 2006, January to 2009, March. In liver surgery, 1 ml of ICG was injected via the portal vein under observation by the fluorescent imaging system. Fourteen patients were underwent laparoscopic cholecystectomy for chronic cholecystitis with gallstones. In laparoscopic cholecystectomy, 5 ml of ICG was administered intravenously just before operation and the bile duct was observed using the infrared-based navigation system. RESULT: This new technique successfully identified stained subsegments and segments of the liver in 73 of 81 patients (90.1%). Moreover, clear mapping of liver segments was obtained even against a background of liver cirrhosis. Fluorescent cholangiography clearly showed the common bile duct and cystic duct in 10 of 14 patients (71.4%). No adverse reactions to the ICG were encountered. CONCLUSION: Application of this technique allows intraoperative identification of anatomical landmark in hepatobiliary surgery.

Natural course of the remnant hepatic functional reserve as estimated by technetium-99m-galactosyl human serum albumin scintigraphy after a hepatectomy.

BACKGROUND: Technetium-99m-galactosyl human serum albumin (GSA) scintigraphy provides an accurate estimation of the hepatic functional reserve but is not applied after a hepatectomy. The aim of this study was to elucidate the natural course of the remnant hepatic functional reserve (RHFR) after hepatectomy by GSA scintigraphy. METHODS: Eighty-six patients (partial hepatic resection, Hr0 = 46; sectionectomy, Hr1 = 21; bisectionectomy, Hr2 = 19) classified as Child-Pugh class A before the hepatectomy were enrolled, and GSA scintigraphy to detect HH15 (uptake ratio of the heart at 15 min to that at 3 min) and LHL15 (uptake ratio of the liver at 15 min to the liver plus the heart at 15 min) was performed periodically before and after the hepatectomy. HH15, LHL15, and the percentages of patients that recovered to the preoperative levels of these entities were estimated. In addition, hematobiochemical tests and the remnant liver volume were also periodically monitored. RESULTS: HH15 and LHL15 levels deteriorated until 2 months postoperatively (PO) after the procedure and subsequently recovered to the preoperative levels at 6 months PO in Hr0 patients. In Hr1 patients, but not in Hr2 patients, these levels also deteriorated until 3 months PO and had improved by 6 months after the surgery. Only 40% of the patients showed recovery to the preoperative levels by 6 months PO in the Hr0 group; furthermore, the percentage of patients who showed recovery to the preoperative levels by 6 months PO was under 40% in the Hr1 group and around 10% in the Hr2 group. However, the results of hematobiochemical tests and the remnant liver volume in all types of hepatectomies were rapidly normalized after the hepatectomy. CONCLUSIONS: Remnant hepatic functional reserve estimated by GSA scintigraphy revealed that a larger resected liver volume induced both more serious and continued remnant hepatic dysfunction in comparison to results shown by hematobiochemical tests, while the functional regeneration was also appreciably slower and more gradual in comparison to the volume regeneration.

Cold preservation of the liver with oxygenation by a two-layer method.

BACKGROUND: The two-layer method (TLM) has recently been found to be superior to simple cold storage in University of Wisconsin (UW) solution as a means of pancreas preservation for islet transplantation. In this study, we investigated whether TLM would result in better hepatocyte function over UW cold storage and if it could be applied to hepatocyte transplantation. MATERIALS AND METHODS: Hepatocytes from male Sprague Dawley rat livers were isolated and divided into three groups: a non-preservation group (group 1), a 10-h preservation group (group 2), and a 24-h preservation group (group 3). Groups 2 and 3 were then divided into three subgroups: a group preserved by the TLM (subgroup a), a group preserved in UW solution (subgroup b), and a group preserved in water (subgroup c). Isolated hepatocytes were evaluated for cell yield, viability, and adenosine triphosphate level after preservation. Hepatocytes were either cultured or transplanted. RESULTS: Although no differences in cell yield or morphological findings were observed between any of the groups, TLM significantly improved hepatocyte viability and adenosine triphosphate levels in comparison with UW cold storage. Albumin production or urea synthesis were significantly higher in subgroup 3a than in subgroup 3b at almost all time points. Surprisingly, after hepatocyte transplantation, the serum albumin level in subgroup 2a was significantly higher than in subgroup 2b at every time point. CONCLUSIONS: The results of this study demonstrated that liver preservation by the TLM before hepatocyte isolation might be beneficial and will be useful in the field of hepatotocyte transplantation.

Image-guided liver mapping using fluorescence navigation system with indocyanine green for anatomical hepatic resection.

BACKGROUND: In malignant hepatic neoplasm, anatomic resection could improve survival and limit complications from hepatectomy. Our purpose was to develop an intraoperative method for identifying segment and subsegment of the liver with high-sensitivity near-infrared fluorescence imaging. METHODS: The subjects were 35 patients with hepatic malignant liver disease who received hepatectomy in 2006. The segments of liver method of identification that used infrared observation camera system termed Photo Dynamic Eye-2 (PDE-2) with indocianine green (ICG) for the patient with malignant liver tumor (hepatocellular carcinoma: 13 cases; metastatic liver cancer: 18 cases; intrahepatic cholangio carcinoma: 4 cases) were performed before liver resection. RESULTS: Although greenish stain of the liver surface after the injection of ICG via portal vein is not visible clearly without infrared observation camera system PDE-2, 1 minute after injection of ICG with fluorescent using infrared observation camera system PDE-2, demarcation of liver segment and subsegment was clearly detected. Ten minutes after injection of ICG with fluorescent using infrared observation camera system PDE-2, fluorescence of liver subsegment remained. Stained subsegment and segment of liver were identifiable in 33 (94.3%) of the 35 patients. There were no complications or side-effects related to the injection of patent blue dye. CONCLUSION: We demonstrated here that near-infrared fluorescence imaging system is a novel and reliable intraoperative technique to identify hepatic segment and subsegment for anatomical hepatic resection.

Impact of MDM2 single nucleotide polymorphism on tumor onset in head and neck squamous cell carcinoma.

CONCLUSIONS: The GG genotype of MDM2 SNP309 is associated with an earlier onset of head and neck squamous cell carcinoma (HNSCC) in the Japanese population. SNP309 may be a key factor in the tumorigenesis of HNSCC as well as other hereditary or sporadic tumors. OBJECTIVE: This study was designed to evaluate the association between the single nucleotide polymorphism (SNP) 309 in the MDM2 gene with HNSCC. An MDM2 protein down-regulates the p53 pathway. Recently, an important SNP was discovered in the MDM2 promoter region, which could affect the tumorigenesis of HNSCC by attenuation of the p53 pathway. PATIENTS AND METHODS: Patients with 103 HNSCCs were genotyped using direct sequencing and real-time PCR. The relationship between the SNP309 genotypes and the clinicopathological features was statistically analyzed. RESULTS: The number of patients genotyped to TT, TG, and GG was 29 (28%), 46 (44.7%), and 28 (27.2%), respectively. The average age at tumor onset was 65.6 years for TT, 62.9 years for TG, and 56.7 years for GG. The patients with the GG genotype had a significantly earlier tumor onset in comparison to those with the TT genotype (p=0.032).

Treatment of locally recurrent Epstein-Barr virus-associated nasopharyngeal carcinoma using the anti-viral agent cidofovir.

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV) associated malignant tumor. Recently, cidofovir, an anti-viral drug which is an acyclic nucleoside analogue, has been reported to have an anti-tumor potential. Two patients with NPC, who had previously received multi-round therapy, were treated with cidofovir. Cidofovir was topically injected in and around the tumor once every 3 weeks (originally 75 mg/ml sulution, diluted to 15 mg/ml just before injection, 37.5 mg of cidofovir at a time). Tumor growth was suppressed for several months around the injection site in each patient. EBV-encoded RNAs in situ hybridization revealed the reduction of the tumor cell population; however, the EBER expression was still maintained in the NPC tumor cells. Although the anti-tumor mechanism remains unclear, these results suggest that cidofovir is actually an effective and safe agent for the treatment of NPC.

A single nucleotide polymorphism in the matrix metalloproteinase-1 and interleukin-8 gene promoter predicts poor prognosis in tongue cancer.

OBJECTIVE: Matrix metalloproteinase-1 (MMP-1) and interleukin-8 (IL-8) play an important role in cancer development and metastasis. There is a single nucleotide polymorphism (SNP) located in the promoter region of MMP-1 and IL-8 that regulates gene expression. MMP-1 -1607 2G/2G and IL-8 -251 A/A genotypes enhance transcriptional activity and may be associated with increased risk in malignant tumors. We therefore evaluated the impact of these SNPs in tongue squamous cell carcinoma (SCC). METHODS: In this study, we genotyped 69 tongue SCC patients. The expression of MMP-1 and IL-8 in tongue SCC patients was analyzed by immunohistochemistry. RESULTS: We found a significant difference in IL-8 A/A genotypes with nodal recurrence (P=0.0068). An analysis of disease-free survival rates showed that the presence of both MMP-1 2G/2G and IL-8 A/A genotypes was associated with a particularly poor prognosis (P=0.0032) and was an independent prognostic factor (P=0.001). The expression of MMP-1 was significantly correlated with the frequency of MMP-1 2G/2G genotypes (P=0.049). CONCLUSION: These results suggest that SNP in the promoter region of MMP-1 and IL-8 plays an important role in tumor progression and recurrence through its expression in tongue SCC.

Microencapsule technique protects hepatocytes from cryoinjury.

AIM: Hepatocyte transplantation is a potential alternative to whole organ liver transplantation. To realize this procedure, a hepatocyte bank system capable of supplying large numbers of hepatocytes must be established. We previously reported an easy method for cryopreserving hepatocytes using a microencapsulation technique. Here, we investigated how cryoinjury to microencapsulated hepatocytes could be avoided during cryopreservation. METHODS: Hepatocytes from Sprague-Dawley rats were harvested in situ using a two-step ethylenediaminetetraacetic acid (EDTA)/collagenase digestion protocol. The cells were microencapsulated using alginate-poly L-lysine. The microencapsulated hepatocytes were put into vials and immediately immersed in liquid nitrogen. The growth of ice crystals in the vials containing the microencapsulated hepatocytes was observed using cryomicroscopy. The microencapsulated hepatocytes were sectioned for ultrastructural examination to investigate their intracellular conditions. Finally, total RNA was isolated from the cryopreserved microencapsulated hepatocytes and analyzed for hepatocyte nuclear factor (HNF) using reverse transcriptase polymerase chain reaction (RT-PCR) analysis. RESULTS: Cryomicroscopy showed that the alginate microencapsulation technique protected the hepatocytes from physical damage caused by the growth of extracellular ice crystals. Ultrastructural examination revealed that the intracellular environment of the microencapsulated hepatocytes was maintained. The RT-PCR analysis additionally suggested that the alginate gel also maintained the HNF level. CONCLUSION: Our microencapsulation technique protects hepatocytes from cryoinjury. This novel technique could be utilized by hepatocyte banks.

Intra-arterial chemotherapy less intensive than RADPLAT with concurrent radiotherapy for resectable advanced head and neck squamous cell carcinoma: a prospective study.

OBJECTIVES: This study was designed to evaluate the efficacy and feasibility of our intra-arterial chemotherapy protocol with a lower amount and frequency of cisplatin delivery than in RADPLAT for the treatment of resectable advanced head and neck cancer. METHODS: Fifty-one patients with advanced squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx were included in this prospective study. The patients were treated with 3 courses of cisplatin (100 mg at 1 treatment, intra-arterial) and sodium thiosulfate (28 g at 1 treatment, intravenous) once every 2 weeks during concurrent radiotherapy (66 to 70 Gy, 2 Gy per fraction, daily for 5 days over 7 weeks). Nodal metastases larger than 3 cm in diameter were treated with an additional 50 mg of cisplatin. The patients with less than 50% tumor reduction after 40 Gy and 2 courses of chemotherapy were treated with surgery. RESULTS: The protocol was completed for 49 patients. All living patients had a minimum follow-up period of 2 years. Including the 3 patients with salvage surgery, local disease-free control was achieved in 39 patients (80%). For 36 patients (73.5%), disease-free primary organs were preserved at 2 years after treatment. Locoregional disease-free control for 2 years was obtained for 38 patients (77.6%), in 30 of them without salvage surgery. The patients treated with surgery had an overall survival rate similar to that of the patients with a complete response (80% and 84.6%, respectively). The patients with a partial response had a worse prognosis (40%; p = .0069). CONCLUSIONS: This treatment regimen is feasible and effective for advanced resectable head and neck cancer.

Hepatocyte transplantation from steatotic liver in a rat model.

BACKGROUND: Hepatocyte transplantation (HTx) has progressed significantly, but widespread application remains slow because of the shortage of donor hepatocytes. Many sources of hepatic cells have been proposed as alternatives to isolated hepatocytes, but primary isolated hepatocytes continue to be the best source for liver cell-based therapy. To expand the donor pool, we focused on steatotic liver as a new cell source for HTx because numerous steatotic livers are discarded as unsuitable for orthotopic liver transplantation. This study investigated the efficacy of steatotic hepatocyte transplantation (SHTx) using steatotic liver in a rat model. MATERIALS AND METHODS: Hepatocytes were isolated from obese and lean Zucker rats. Hepatocytes from each group were cultured to analyze the function of steatotic hepatocytes. Hepatocytes from each group were also transplanted into the spleens of Nagase analbuminemic rats (NARs) to investigate the efficacy of SHTx. RESULTS: In the in vitro experiment, a real-time reverse-transcription polymerase chain reaction assay showed that albumin and several hepatocyte nuclear factors were highly expressed in both groups. Morphologically, the steatotic hepatocytes were positive for albumin, and an enzyme-linked immunosorbent assay showed no significant differences between the two groups except for albumin production after 5 d of culture. In the in vivo experiment, the transplanted steatotic hepatocytes in the spleens of Nagase analbuminemic rats were positive for albumin and periodic acid-Schiff staining. Surprisingly, an enzyme-linked immunosorbent assay showed no significant differences in the serum albumin levels between the two groups throughout the study period. CONCLUSIONS: We have demonstrated that steatotic hepatocytes are a potential new cell source for HTx therapy.

Long-term maintenance of the drug transport activity in cryopreservation of microencapsulated rat hepatocytes.

Transplantation of isolated hepatocytes has been proposed to compensate for essential functions lacking in liver failure or for genetic defects that alter a specific liver metabolic pathway. Hepatocyte utilization for these purposes would be facilitated with a reliable, reproducible, and effective method of long-term hepatocyte storage. We have recently developed a simple new system for cryopreservation of hepatocytes that encapsulates alginate microspheres and maintains liver-specific function. The aim of this study was to elucidate the transport and drug-metabolizing enzyme activities of cryopreserved microencapsulated hepatocytes stored for a long time. Morphological examinations showed there is no apparent injury of the hepatocytes during cryopreservation processes. A drug-metabolizing enzyme (testosterone 6beta-hydroxylase, a specific probe for CYP3A2) and drug transport activities [salicylate, allopurinol, and prostaglandin E2 (PGE2), typical substrates of rOat2] in cryopreserved microencapsulated hepatocytes were maintained up to 120 days. Our results thus demonstrate for the first time that cryopreservation of primary rat hepatocytes by the encapsulation technique allows long-term retention of drug metabolism and drug transport activities.

Cyst wall resection and ablation by hand-assisted laparoscopic surgery combined with argon plasma coagulator for huge hepatic cysts.

Six cases of deroofing of giant liver cysts by hand-assisted laparoscopic surgery (HALS) and safe and definitive cyst wall ablation with argon plasma coagulation (APC), which was verified by pathological examination of the resected cyst wall, were shown.

Pathological dynamics of activated microglia following medial forebrain bundle transection.

To elucidate the role and pathological dynamics of activated microglia, this study assessed the phagocytic, immunophenotypic, morphological, and migratory properties of activated microglia in the medial forebrain bundle (MFB) axotomized rat brain. Activated microglia were identified using two different monoclonal antibodies: ED1 for phagocytic activity and OX6 for major histocompatibility complex (MHC) class II. Phagocytic microglia, characterized by ED1-immunoreactivity or ED1- and OX6-immunoreactivity, appeared in the MFB and substantia nigra (SN) as early as 1-3 days post-lesion (dpl), when there was no apparent loss of SN dopamine (DA) neurons. Thereafter, a great number of activated microglia selectively adhered to degenerating axons, dendrites and DA neuronal somas of the SN. This was followed by significant loss of these fibers and nigral DA neurons. Activation of microglia into phagocytic stage was most pronounced between 14 approximately 28 dpl and gradually subsided, but phagocytic microglia persisted until 70 dpl, the last time point examined. ED1 expression preceded MHC II expression in phagocytic microglia. All phagocytic microglia sticking to DA neurons showed activated but ramified form with enlarged somas and thickened processes. They were recruited to the SNc from cranial, dorsal and ventral aspects along various structures and finally stuck to DA neurons of the SNc. Characteristic rod-shaped microglia in the white matter were thought to migrate a long distance. The present study strongly suggests that neurons undergoing delayed neurodegeneration may be phagocytosed by numerous phagocytic, ramified microglia at various sites where specific surface signals are exposed or diffusible molecules are released.

Development of hepatocellular carcinoma following treatment with 6-mercaptopurine for ulcerative colitis: investigation of chromosomal aberration by comparative genomic hybridization.

In a 64-year-old man who had been treated with prednisolone (PSL) and 6-mercaptopurine (6MP) for a long period, for ulcerative colitis (UC), hepatocellular carcinoma (HCC) was detected incidentally. The UC was in remission with these medications. After he had been taking these medications for about 8 years, HCC was detected by computed tomography (CT), done for the evaluation of an other disease. Blood chemistry examination results were normal, except that the protein induced by vitamin K antagonist (PIVKA)-II level was 7940 AU/ml. We performed resection of liver segment V. With comparative genomic hybridization, chromosomal aberrations were recognized; these were gains of 1q, 3ptel-21, 8p12, and 22q11.23-22q13.1. Generally, HCC is associated with hepatitis virus infection in most cases, but in this patient, the HCC was not related to hepatitis C virus (HCV) or HBV. It is presumed that this case was related to the immunosuppressive therapy for UC and was associated with the gains of 1q, 3p, and 8p.

Hepatocyte growth factor is constitutively produced by donor-derived bone marrow cells and promotes regeneration of pancreatic beta-cells.

Recent studies have demonstrated that the transplantation of bone marrow cells following diabetes induced by streptozotocin can support the recovery of pancreatic b-cell mass and a partial reversal of hyperglycemia. To address this issue, we examined whether the c-Met/hepatocyte growth factor (HGF) signaling pathway was involved in the recovery of b-cell injury after bone marrow transplantation (BMT). In this model, donor-derived bone marrow cells were positive for HGF immunoreactivity in the recipient spleen, liver, lung, and pancreas as well as in the host hepatocytes. Indeed, plasma HGF levels were maintained at a high value.The frequency of c-Met expression and its proliferative activity and differentiative response in the pancreatic ductal cells in the BMT group were greater than those in the PBS-treated group, resulting in an elevated number of endogenous insulin-producing cells. The induction of the c-Met/HGF signaling pathway following BMT promotes pancreatic regeneration in diabetic rats.

Psychosomatic analysis of atopic dermatitis using a psychological test.

In patients with atopic dermatitis (AD), psychosomatic factors are important elements in treating the condition. In this study, we surveyed 51 outpatients with AD who consulted the Department of Dermatology of Fujita Health University Hospital using a questionnaire involving present illness/treatment history regarding AD to analyze psychosomatic factors. The severity of AD was evaluated using the severity classification described by Yoshiike et al. Four psychological tests were used to examine depression, anxiety, personality, and upbringing experiences during childhood. Beck Depression Inventory (BDI) was used as a scale for depression, Self-rating Anxiety Scale (SAS) as a scale for anxiety, the Temperament and Character Inventory (TCI) as a scale for the personality tendency, and the Parental Bonding Instrument (PBI) as a scale for upbringing experiences during childhood. The BDI and SAS scores were high in the severe AD group. Among patients with the same grade of AD, the BDI and SAS scores were higher in the low IgE RIST group. In the patients with AD, the BDI scores were significantly higher than those in the healthy controls (P<0.05). In clinical practice, the treatment of AD should include psychosomatic approaches.