Innovative method of alopecia treatment by autologous adipose-derived SVF.

BACKGROUND: Alopecia refers to a condition developed by gradual reduction of hair loss by various abnormal causes such as endocrine system, genetic factors, and stress. Stromal vascular fraction (SVF) isolated from the fat is one of the latest innovative solutions in the field of regeneration therapy. We focused on presenting effectiveness of clinical cases to improve AGA through transplantation of autologous SVF into the scalp. OBJECTIVE: To confirm the efficacy of the autologous SVF usage to the patients with AGA. METHODS: Nine patients (age range 43-64 years; 4 men, grade IV to V and 5 women, grade I to III), who are suffering from androgenic alopecia (AGA), were treated with single transplantation of autologous SVF in the upper scalp. Autologous SVF was isolated and characterized prior to the injection of live 7-9 × 106 cells into the patients' treatment site. The hair loss improvement effect was assessed by three test criteria: hair skin quality, hair thickness and hair density 3 and 6 months after post-injection compared to pre-injection status. RESULTS: Hair density of SVF-treated side was significantly increased after 3 and 6 months of transplantation compared to non-treated side (P = 0.01 and P = 0.009 per each). And significant improvement in the score of the keratin on the scalp was seen in the injected area as compared to the non-injected area 6 months after transplantation (P = 0.032). Although thickness increase was observed at 3 and 6 months after transplantation, there was no statistical significance (P = 0.142 and 0.155, respectively). CONCLUSIONS: One transplantation of autologous SVF for the AGA patients, hair density and score for the keratin were significantly increased within 6 months. This study shows that SVF is a very effective way to treat hair loss and most of subjects are satisfied with the result after treatment.

Endoscopic enucleation for gastric subepithelial tumors originating in the muscularis propria layer.

BACKGROUND: Subepithelial tumors (SETs) of the stomach are considered benign. However, they have the potential for malignant transformation, especially if they originate in the muscularis propria layer. This study aimed to determine the feasibility of endoscopic enucleation (EEN) for SETs in the muscularis propria layer and to evaluate the diagnostic efficacy and safety of EEN for SETs. METHODS: A total of 65 lesions in 64 patients were eligible for inclusion in the study during the period between June 2006 and September 2009. En bloc enucleation using an insulated-tip knife and snare was attempted for removal of gastric SETs from the muscularis propria. RESULTS: A total of 60 tumors were successfully resected by EEN (success rate, 92.3%). The mean tumor size, determined by endoscopic ultrasound, was 13.8 mm (range, 5-30 mm). A histologic diagnosis was obtained for 63 tumors (diagnostic yield, 96.9%), which was leiomyoma for 32 lesions, gastrointestinal stromal tumor for 26 tumors, and other for 5 tumors. The rate for complete resection in relation to the location of the lesion in the stomach was higher for the cardia, the mid/lower body (100%), and the high body (96%) than for the fundus (75%) or the antrum (50%, p=0.006). The rate of perforation was significantly higher for the fundus (50%) than for other locations (0% for the cardia and 4% for the high body) (p<0.001). CONCLUSIONS: Endoscopic enucleation of gastric SETs originating in the muscularis propria layer was a safe and effective method for the histologic diagnosis and removal of small gastric SETs, especially those located in the cardia and the high body of the stomach.

Successful outcomes of endoscopic resection for gastric adenomas and early cancers located on the pyloric ring (with video).

BACKGROUND: Endoscopic resection is difficult to perform in patients who have gastric neoplasms located on the pyloric ring, especially for lesions that extend from the pyloric area to the duodenal bulb, where it is difficult to retroflex the endoscope, and the risk of perforation is increased. OBJECTIVE: To assess the results of endoscopic resection of early gastric neoplasms located on the pyloric ring. DESIGN: Case series. SETTING: Tertiary-care referral center. PATIENTS: This study involved 16 patients with 5 gastric adenomas and 11 early cancers that were located on the pyloric ring. INTERVENTIONS: After a retroflexion trial within the duodenum for evaluation of tumor extension from the pyloric area to the duodenal bulb, en bloc resection was attempted. Endoscopic submucosal dissection was attempted at the duodenal bulb with an endoscope retroflexed for cases of duodenal invasion. MAIN OUTCOME MEASUREMENTS: The curative resection rate, en bloc resection rate, and complications were determined. RESULTS: The success rate of retroflexion within the duodenum was 88% (14 of 16). The curative resection rate was 81.3% (13 of 16), and the en bloc resection rate was 75% (12 of 16). En bloc resection was possible for 3 of 4 (75%) cases of duodenal bulb extension. Major procedure-related complications were not encountered. LIMITATIONS: Small number of patients. CONCLUSION: Endoscopic resection appears to be a feasible and effective treatment for early gastric neoplasms located on the pyloric ring, including lesions that extend from the pyloric area to the duodenal bulb.

Is pancreatic core biopsy sufficient to diagnose autoimmune chronic pancreatitis?

OBJECTIVES: This study aimed to evaluate the adequacy of pancreatic core biopsy in histological diagnosis of autoimmune chronic pancreatitis (AIP). METHODS: Histopathologic study as well as immunohistochemical staining using anti-IgG4 antibody was done with pancreatic tissue specimens of 26 AIP patients (19 transabdominal ultrasound (US)-guided core biopsies, 3 intraoperative wedge biopsies, and 4 surgical resections). Eight patients with alcoholic chronic pancreatitis and 10 patients with pancreatic cancer served as controls. RESULTS: Lymphoplasmacytic sclerosing pancreatitis (LPSP) histology was observed in 26% (5/19) of US-guided core biopsy specimens, 33% (1/3) of open biopsy specimens, and all 4 resection specimens in AIP patients. None of the patients in the control group showed the full spectrum of changes of LPSP. Abundant IgG4-positive cells (>10 cells/high-power field) in the pancreas were observed in 21% (4/19) of AIP patients with US-guided core biopsy specimen. Abundant IgG4-positive cells in the pancreas were also observed in 2 of 8 patients with chronic alcoholic pancreatitis and 1 of 10 patients with pancreatic cancer. CONCLUSIONS: Transabdominal US-guided pancreatic core biopsy may not provide enough tissue to evaluate characteristic histopathologic features of AIP that include LPSP or abundant IgG4-positive cell infiltration. The LPSP histology may be specific to AIP, but abundant IgG4-positive cells in the pancreas may not.

Reactive oxygen species-dependent EndoG release mediates cisplatin-induced caspase-independent apoptosis in human head and neck squamous carcinoma cells.

Cisplatin is a chemotherapeutic agent that is widely used to treat cancers such as head and neck squamous cell carcinoma (HNSCC). Previously, we have reported that cisplatin induced an early caspase-dependent apoptosis (8 hr) in a HNSCC cell, HN4. In this study, we examined a late caspase-independent apoptosis as well as an early caspase-dependent apoptosis in cisplatin-treated HN4 cells. While z-VAD-fmk, a pan-caspase inhibitor, blocked the caspase activities and protected cells from the early apoptosis, it did not provide protection against delayed apoptosis occurring after extended exposure (16 hr) to cisplatin, suggesting that the delayed apoptotic response in the presence of z-VAD-fmk was caspase-independent. Cisplatin treatment induced reactive oxygen species (ROS) generation, loss of the mitochondrial membrane potential (MMP) and nuclear translocation of endonuclease G (EndoG). Small interfering RNA mediated-knockdown of EndoG significantly protected cells from the delayed apoptosis induced by cisplatin in the presence of z-VAD-fmk. Overexpression of Bcl-2 in HN4 cells prevented loss of MMP, nuclear translocation of EndoG and protected cells from the delayed apoptosis induced by cisplatin in the presence of z-VAD-fmk. Pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger, prevented both ROS generation, loss of the MMP and nuclear translocation of EndoG. Together, our data indicate that cisplatin treatment induced ROS-mediated loss of the MMP, and, then, the nuclear translocation of EndoG, which played a crucial role in caspase-independent apoptosis of HN4 cells in the presence of z-VAD-fmk. This is the first report about the involvement of EndoG in cisplatin-induced caspase-independent apoptosis of cells.

Allelic alterations in well-differentiated neuroendocrine tumors (carcinoid tumors) identified by genome-wide single nucleotide polymorphism analysis and comparison with pancreatic endocrine tumors.

Well-differentiated neuroendocrine tumors (WDNT, carcinoid tumors) are uncommon indolent neoplasms. The genetic alterations of these tumors are not well characterized. We used genome-wide high-density single nucleotide polymorphism (SNP) array analysis to detect copy number alterations in 29 WDNTs, including seven lung, seven nonileal gastrointestinal, and 15 ileal tumors, and compared with allelic imbalances in 15 pancreatic endocrine tumors (PETs). Most frequent allelic imbalances in WDNTs were losses of chromosome 18 in 10 tumors (34%), chromosome 21 or 21q in six (21%), chromosome 13 or 13q in five (17%) and chromosome 16 or 16q in four (14%) tumors, and amplification of chromosome 20 or 20p in seven (24%) tumors. We also found one tumor with loss of heterozygosity of chromosomes 10 and 15 without copy number loss. These allelic imbalances were associated with primary site of tumor: loss of chromosome 18 was present exclusively in ileal WDNTs (P = 0.001), and loss of chromosome 21 or 21q was more frequent in nonileal gastrointestinal WDNTs (P = 0.02). The tumors with loss of chromosome 21 were larger compared to tumors without loss (P = 0.03). Chromosomal aberrations were less common in WDNTs from lung and gastrointestinal tract compared to PETs (P = 0.001). Our study shows that genome-wide allelotyping using SNP array is a powerful new tool for the analysis of allelic imbalances in WDNTs, and some of these alterations are tumor site-dependent and are different than in PETs.

[Hemobilia from pancreatic arteriovenous malformation: successful treatment with transportal coil embolization of draining veins].

Pancreatic arteriovenous malformations (AVM) are extremely rare diseases frequently complicated by gastrointestinal hemorrhage. While surgical resection of affected lesion is preferred for the treatment of pancreatic AVM, angiographic intervention can be used as an alternative treatment, especially in surgically high-risk patients. We experienced a patient with pancreatic AVM manifested by hemobilia and biliary sepsis. Superior mesenteric and common hepatic arteriography showed pancreaticoduodenal AVM composed of nidus supplied by numerous fine feeding arteries and of draining veins encircling the common bile duct (CBD). Hemobilia was controlled by transportal coil embolization of draining veins of AVM around the CBD. Herein, we report this case with the review of literatures.

Allelic alterations in pancreatic endocrine tumors identified by genome-wide single nucleotide polymorphism analysis.

Pancreatic endocrine tumors (PETs) are uncommon and the genetic alterations in these indolent tumors are not well characterized. Chromosomal imbalances are frequent in tumors but PETs have not been studied by high-density single nucleotide polymorphism (SNP) array. We used genome-wide high-density SNP array analysis to detect copy number alterations using matched tumor and non-neoplastic tissue samples from 15 patients with PETs. In our study, whole or partial loss of chromosomes 1, 3, 11, 22 was present in 40, 47, 53, 40% of tumors respectively, and gain of chromosomes 5, 7, 12, 14, 17, and 20 was present in 47, 60, 47, 53, 53, and 47% of tumors respectively. One tumor had loss of heterozygosity of chromosome 3 and another of chromosome 22 without copy number alterations, suggesting uniparental disomy due to non-disjunction and deletion or to chromosomal recombination. Chromosomal aberrations of the autosomal chromosomes were correlated with chromosomal loss or gain of other chromosomes (r>0.5, P<0.5). About 60% of PETs had high allelic imbalances (AI) defined by more than four chromosomal aberrations, and 40% of tumors had low AI. The PETs with high AI were larger: the mean tumor size with high AI was 5.4 +/- 3.1 cm compared with 2.3 +/- 1.3 cm for low AI (P = 0.03). Our study shows that genome-wide allelotyping is a powerful new tool for the analysis of AI in PETs.

A gastrointestinal stromal tumor of the duodenum masquerading as a pancreatic head tumor.

Gastrointestinal stromal tumor (GIST) represents the most common kind of mesenchymal tumor that arises from the alimentary tract. GIST is currently defined as a gastrointestinal tract mesenchymal tumor showing CD117 (c-kit protein) positivity at immunohistochemistry. Throughout the whole length of the gastrointestinal tract, GIST arises most commonly from the stomach followed by the small intestine, the colorectum, and the esophagus. Only 3%-5% of GISTs occur in the duodenum, and especially, if GIST arises from the C loop of the duodenum, it can be difficult to differentiate from the pancreas head mass because of its anatomical proximity. Here, we report a case of duodenal GIST, which was assessed as a pancreatic head tumor preoperatively.

Hypomethylation of LINE-1 and Alu in well-differentiated neuroendocrine tumors (pancreatic endocrine tumors and carcinoid tumors).

Neuroendocrine tumors including carcinoid tumors and pancreatic endocrine tumors are uncommon, and the genetic alterations in these indolent tumors are not well characterized. We studied global hypomethylation by analyzing long interspersed nucleotide elements (LINE)-1 and Alu methylation using pyrosequencing in 35 neuroendocrine tumors and corresponding normal tissue. The tumor samples were less methylated than normal tissue at LINE-1 (P=0.04) and Alu (P=0.001). The mean relative tumor hypomethylation (difference in methylation between normal tissue and in tumor) was 11.5+/-10.0 for LINE-1 and 5.8+/-6.4 for Alu, and were correlated with each other (correlation coefficient 0.6, P=0.001). Relative tumor hypomethylation of LINE-1 was higher in ileal carcinoid tumors than in non-ileal carcinoid tumors and pancreatic endocrine tumors (P=0.047), and tumors with lymph node metastasis (P=0.02), chromosome 18 loss (P=0.001) and RAS-association domain family 1, isoform A gene methylation (P=0.02). Alu methylation in tumors was inversely correlated with methylation of O(6)-methyl-guanine methyltransferase gene (P=0.02). Our study shows that hypomethylation is more common in carcinoid tumors than in pancreatic endocrine tumors and is associated with clinicopathologic features, and genetic and epigenetic alterations in these tumors, including lymph node metastasis.

Metastasis of hepatocellular carcinoma to the small bowel manifested by intussusception.

Hepatocellular carcinoma (HCC) is a highly invasive tumor that metastasizes hematogenously and lymphogenously to distant site. Frequent sites are lung, regional lymph node, bone, and adrenal gland. But metastasis to the gastrointestinal (GI) tract is rare, and most common site is stomach. Metastasis to the small intestine is extremely rare. Moreover, metastatic HCC of the small bowel causing intussusception has not been reported until now. Here, we report a case of metastasis of HCC to the small bowel manifested by intussusception.

A phase II study of docetaxel and cisplatin in patients with gastric cancer recurring after or progressing during 5-FU/platinum treatment.

BACKGROUND: Docetaxel plus cisplatin (DP) is a combination chemotherapy regimen that is active against untreated advanced gastric cancer. We evaluated the feasibility of DP treatment in patients with recurring or metastatic gastric cancer who had been previously treated with other chemotherapy regimens. PATIENTS AND METHODS: The DP regimen consisted of docetaxel (75 mg/m(2) i.v.) and cisplatin (60 mg/m(2) i.v.) over 1 h on Day 1 every 4 weeks for a maximum of nine cycles. RESULTS: Thirty-seven patients (28 men, 9 women; median age, 53 years; range 28-71 years) received a total of 128 cycles of therapy (median, 3; range 1-9). Twenty-six patients had recurrent disease and 11 had metastatic tumors. The objective response rate was 32.4% (95% confidence interval = 16.6-48.3%), including 1 complete response and 11 partial responses. Eleven had stable disease, whereas 12 had progressive disease. The median duration of response was 70.5 days (range 30-392 days). Grade 3/4 toxicities included anemia (10.8%), leukopenia (27.0%), neutropenia (51.4%), thrombocytopenia (2.7%), nausea/vomiting (5.4%) and oral mucositis (13.5%). Median time to progression was 136 days and median overall survival was 235 days. CONCLUSION: The DP combination was well tolerated and effective for patients with metastatic gastric cancer treated previously with 5-fluorouracil/platinum chemotherapy.

Santorinicele containing a pancreatic duct stone in a patient with incomplete pancreas divisum.

Santorinicele, a focal cystic dilatation of the distal duct of Santorini, has been suggested as a possible cause of the relative stenosis of the accessory papilla, is associated with complete pancreas divisum, which results in acute episodes of pancreatitis or pain. This report describes a case of a santorinicele, which was initially detected by upper gastrointestinal endoscopy as a polypoid mass, in a patient with recurrent abdominal pain. The mass was subsequently proved to be a santorinicele containing a pancreatic duct stone associated with incomplete pancreas divisum on endoscopic retrograde pancreatography. To the best of our knowledge this is believed to be the first description of a santorinicele associated with these characteristic findings.

Duodenal duplicated cyst manifested by acute pancreatitis and obstructive jaundice in an elderly man.

A duodenal duplication cyst is an uncommon congenital anomaly that is usually encountered during infancy or in early childhood. Duodenal duplication cysts generally appear on the first or second portion of the duodenum and may cause duodenal obstruction, hemorrhage or pancreatitis. Here, we report a case of a duodenal duplication cyst on the second and third portion of the duodenum in an old aged man with obstructive jaundice and acute pancreatitis, which was treated successfully by a surgical excision.

Combination chemotherapy with 5-fluorouracil and heptaplatin as first-line treatment in patients with advanced gastric cancer.

Heptaplatin is a recently developed platinum derivative. This agent has been reported to have a response rate of 17% as a single agent, and tolerable toxicity in the treatment of advanced gastric cancer. The aim of this study was to evaluate the efficacy and toxicity of a combination of 5-fluorouracil (5-FU) and heptaplatin in patients with advanced gastric cancer. Forty-seven chemotherapy-naive patients with advanced or recurred gastric cancer were recruited. 5-FU was administered over 120 hr by continuous intravenous infusion from day 1 to 5, at a daily dose of 1,000 mg/m2 and heptaplatin was administered over 1 hr by intravenous infusion on day 1 at 400 mg/m2, and this cycle was repeated every 4 weeks. The response rate was 21%, median progression-free survival was 1.9 months (95% CI, 1.6 to 2.2 months). Median overall survival was 6.2 months (95% CI, 4 to 8.4 months) and the 1-yr survival rate was 29% for all patients. The most frequent toxicity was proteinuria. Toxicities were generally mild and reversible. This study demonstrates that the combination of 5-FU/heptaplatin combination is less active but tolerated in patients with advance gastric cancer.

The role of bile carcinoembryonic antigen in diagnosing bile duct cancer.

It is known that the fluids bathing tumors might contain a higher level of the carcinoembryonic antigen (CEA) than those found in the blood. Therefore, we evaluated the role of bile CEA in diagnosing bile duct cancer. One hundred and thirty two patients were prospectively studied. The patients were divided into 3 groups: the bile duct cancer (n=32), pancreatic cancer (n=16), and benign biliary diseases (n=84) groups. Bile samples were obtained on the next day of the biliary drainage procedures. The mean bile CEA level in those with bile duct cancer (120.6 +/- 156.9 ng/mL) was significantly higher than those with pancreatic cancer and benign biliary diseases (32.0 +/- 28.5 ng/mL, 29.3 +/- 56.3 ng/mL). Using the level of 20 ng/mL, the sensitivity and specificity of bile CEA in the diagnosis of bile duct cancer from benign biliary diseases were 65.6% and 66.7%, respectively. Both the bile CEA and total bilirubin level were found to be an independent factor linked to bile duct cancer. This study result suggests that bile CEA level is a useful supplementary test for diagnosing bile duct cancer.

[Diagnostic usefulness of intradermal test for clonorchiasis in patients with pancreatobiliary diseases].

BACKGROUND/AIMS: The diagnosis of clonorchiasis is based on demonstrating eggs in stool or bile. It is believed that bile examination is the most precise method for detecting eggs. We evaluated diagnostic usefulness of intradermal test (IDT) by comparing it with the result of bile examination. METHODS: For 88 patients with pancreatobiliary diseases, we examined Clonorchis sinensis eggs in bile and performed IDT for clonorchiasis. The bile was obtained from endoscopic nasobiliary or percutaneous transhepatic biliary drainage tubes. RESULTS: We calculated ROC curve to decide the cut-off value of IDT in determining diagnostic accuracy on the basis of bile examination. We chose a value of 40 mm2, which significantly improved the sensitivity, without reducing the specificity. With a cut-off value of 40 mm2, the sensitivity, specificity, positive and negative predictive values of IDT were 81.5%, 67.2%, 52.4%, and 89.1%, respectively. The value of IDT was not affected by age and showed no difference between benign and malignant diseases. However, in egg-positive patients, the mean value was lower in malignant diseases than in benign diseases. CONCLUSIONS: In patients with pancreatobiliary diseases, IDT with a cut-off value of 40 mm2 seems to be a valuable supplementary diagnostic test for clonorchiasis in view of its high sensitivity.

A case of simultaneous xanthogranulomatous cholecystitis and carcinoma of the gallbladder.

Xanthogranulomatous cholecystitis (XGC) is a rare inflammatory disease of the gallbladder. Not only does XGC occasionally present as a mass formation with adjacent organ invasion like a malignant neoplasm, it can also infrequently be associated with gallbladder cancer. In the situation, it is difficult to make a differential diagnosis between the diseases. Here, we describe a case of a simultaneous XGC and a carcinoma of the gallbladder in a 61-year-old woman. To the best of our knowledge, there are only a small number of reports on this combination of diseases.