Detection and characterization of mineralo-organic nanoparticles in human kidneys.

Ectopic calcification is associated with various human diseases, including atherosclerosis, cancer, chronic kidney disease, and diabetes mellitus. Although mineral nanoparticles have been detected in calcified blood vessels, the nature and role of these particles in the human body remain unclear. Here we show for the first time that human kidney tissues obtained from end-stage chronic kidney disease or renal cancer patients contain round, multilamellar mineral particles of 50 to 1,500 nm, whereas no particles are observed in healthy controls. The mineral particles are found mainly in the extracellular matrix surrounding the convoluted tubules, collecting ducts and loops of Henle as well as within the cytoplasm of tubule-delineating cells, and consist of polycrystalline calcium phosphate similar to the mineral found in bones and ectopic calcifications. The kidney mineral nanoparticles contain several serum proteins that inhibit ectopic calcification in body fluids, including albumin, fetuin-A, and apolipoprotein A1. Since the mineralo-organic nanoparticles are found not only within calcified deposits but also in areas devoid of microscopic calcifications, our observations indicate that the nanoparticles may represent precursors of calcification and renal stones in humans.

Acute appendicitis mimicking intestinal obstruction in a patient with cystic fibrosis.

Cystic fibrosis (CF) is an inherited disease of the secretory glands caused by mutations of the cystic fibrosis transmembrane regulator (CFTR) gene. The clinical manifestations of CF are repetitive lung infections, biliary cirrhosis, pancreatic abnormalities, and gastrointestinal disorders. We report a 21-year-old Taiwanese man with CF who had abdominal pain for 2 days. The diagnosis of CF had been confirmed by peripheral blood analysis of the CFTR gene 5 years before admission. He presented to the emergency department with nausea, vomiting, abdominal distension, and crampy abdominal pain, which is atypical for acute appendicitis. The physical examination and a series of studies revealed intestinal obstruction, but acute appendicitis could not be ruled out. After conservative treatment, together with empiric antibiotics, the refractory abdominal pain and leukocytosis with a left-shift warranted surgical intervention. A diagnostic laparoscopy revealed a swollen, hyperemic appendix, a severely distended small intestine, and serous ascites. The laparoscopic procedure was converted to a laparotomy for open disimpaction and appendectomy. He was discharged on the eighth postoperative day. The histologic examination of the appendix was consistent with early appendicitis. In conclusion, acute abdominal pain in adult CF patients is often associated with intestinal obstruction syndrome. The presentation of concurrent appendicitis may be indolent and lead not only to diagnostic difficulties, but also a number of therapeutic choices.

Glyoxalase-I is a novel prognosis factor associated with gastric cancer progression.

Glyoxalase I (GLO1), a methylglyoxal detoxification enzyme, is implicated in the progression of human malignancies. The role of GLO1 in gastric cancer development or progression is currently unclear. The expression of GLO1 was determined in primary gastric cancer specimens using quantitative polymerase chain reaction, immunohistochemistry (IHC), and western blotting analyses. GLO1 expression was higher in gastric cancer tissues, compared with that in adjacent noncancerous tissues. Elevated expression of GLO1 was significantly associated with gastric wall invasion, lymph node metastasis, and pathological stage, suggesting a novel role of GLO1 in gastric cancer development and progression. The 5-year survival rate of the lower GLO1 expression groups was significantly greater than that of the higher expression groups (log rank P = 0.0373) in IHC experiments. Over-expression of GLO1 in gastric cancer cell lines increases cell proliferation, migration and invasiveness. Conversely, down-regulation of GLO1 with shRNA led to a marked reduction in the migration and invasion abilities. Our data strongly suggest that high expression of GLO1 in gastric cancer enhances the metastasis ability of tumor cells in vitro and in vivo, and support its efficacy as a potential marker for the detection and prognosis of gastric cancer.

Overexpression of ADP-ribosylation factor 1 in human gastric carcinoma and its clinicopathological significance.

Gastric cancer is the sixth leading cause of cancer-related death in Taiwan, and the identification of related factors is essential to increase patient survival. ADP-ribosylation factor 1 (ARF1) was initially identified using 2-D electrophoresis combined with MALDI-time-of-flight mass spectrometry. ADP-ribosylation factor 1 belongs to the Ras superfamily or GTP-binding protein family and has been shown to enhance cell proliferation. In the current study, we evaluated the potential of ARF1 as a biomarker for gastric cancer detection. ADP-ribosylation factor 1 mRNA was upregulated in tumor tissues (compared with adjacent non-tumor tissues, n = 55) in approximately 67.2% of gastric cancer patients. Expression of ARF1 protein was additionally observed using Western blot and immunohistochemistry (IHC) analyses. The clinicopathological correlations of ARF1 were further evaluated. Elevated ARF1 expression was strongly correlated with lymph node metastasis (P = 0.008), serosal invasion (P = 0.046), lymphatic invasion (P = 0.035), and pathological staging (P = 0.010). Moreover, the 5-year survival rate for the lower ARF1 expression group (n = 50; IHC score < 90) was higher than that of the higher expression group (n = 60; IHC score ≥ 90) (P = 0.0228, log-rank test). To establish the specific function of ARF1 in human gastric cancer, isogenic ARF1-overexpressing cell lines were prepared. Our results showed that ARF1-overexpressing clones display enhanced cell proliferation, migration, and invasion. Furthermore, ARF1-overexpression might contribute to poor prognosis of patients. These findings collectively support the utility of ARF1 as a novel prognostic marker for gastric cancer and its role in cell invasion.

Combined epidermal-connective tissue nevus of proteoglycan (a type of mucinous nevus): a case report and literature review.

Mucinous nevus is a rare entity with only 11 cases reported previously. It may be divided into two histopathologic types: connective tissue nevus of the proteoglycan (CTNP) and combined epidermal-CTNP. We describe a boy with asymptomatic grouped brown papuloplaques on the lower back since birth. A diagnosis of mucinous nevus of the combined epidermal-CTNP type was made after a biopsy. We vaporized two lesions with carbon dioxide laser, and the wounds healed satisfactorily. We present a literature review indicating a striking preponderance of male patients (M : F = 5 : 1) for mucinous nevus. In half of the cases, mucinous nevus did not appear until childhood, adolescence or early adulthood. The predominantly affected site was the trunk. Half of the cases can be assigned to the CTNP type and the other half to the combined epidermal-CTNP type. We propose that carbon dioxide laser vaporization may be a treatment option for mucinous nevus of the combined epidermal-CTNP type with multiple lesions but not for the CTNP type.

Overexpression of a secretory leukocyte protease inhibitor in human gastric cancer.

Complementary DNA microarrays have identified aberrantly expressed genes in patients with gastric cancer. One that encodes secretory leukocyte protease inhibitor (SLPI) is among the aberrantly expressed genes and is associated with metastasis in gastric cancers. We evaluated the potential of SLPI expression as a helpful biomarker for detection of gastric cancer. Tumor tissue and matching noncancerous mucosa were obtained from 60 patients immediately after gastric resection. SLPI expression levels were determined by Northern and Western blot tests and quantitative-reverse transcriptase-polymerase chain reaction (Q-RT-PCR). Paraffin-fixed tumor tissues were used for immunohistochemistry study in 119 patients. A consistent result was obtained between all examinations except plasma SLPI. SLPI mRNA transcripts and protein were overexpressed in gastric cancer cells, and the depth of wall invasion was significantly greater in serosa-invading (T3 and T4) cancers compared to the serosa-free (T1 and T2) cancers. These enhanced expressions were significantly associated with lymph node metastasis, and were significantly higher in stages III and IV, and higher than those in stages I and II. Five-year survival of patients with lower expression of the SLPI gene was significantly better than among patients with a higher expression. To better understand the function of SLPI in human gastric cancer cells, isogenic SLPI overexpressing cell lines (AZ521) were prepared. The migratory and invasive abilities were increased 4.4-fold to 6.9-fold, or 3.0-fold to 4.1-fold, respectively, in SLPI-overexpressing cell lines. The results point to SLPI as a potential prognostic marker for gastric cancer and its function in cell invasion.

Endoscopic submucosal dissection for early gastric cancers: experience from a new endoscopic center in Taiwan.

GOAL: To evaluate the efficacy of endoscopic submucosal dissection (ESD) for early gastric cancers (EGCs) at a new endoscopic center. BACKGROUND: ESD is a novel technique that can facilitate en-bloc resection of EGCs, but seldom reported outside Japan. STUDY: A total of 25 consecutive patients (25 lesions) underwent ESD from June 2004 to March 2006. Patients were divided into 2 groups: group A underwent ESD from June 2004 to May 2005 (introduction stage) and group B from June 2005 to March 2006. The following data were obtained: tumor size, tumor location, operative time, and major complication. RESULTS: The complete resection was achieved in 20 lesions (success rate 80%). Four out of 10 lesions from group A were removed by conventional endoscopic mucosal resection (EMR) piecemeally after ESD failure. Conversely, 14 patients from group B (n=15) were resected by ESD en-bloc (success rate 93.3%). One patient with microscopic residual tumor after ESD was further treated by surgical resection. The time required for resection was significantly longer in group A when compared with group B (130.5 min vs. 81.5 min, P<0.05). Postoperative complication rate between the 2 groups were similar. One patient with piecemeal EMR recurred in follow-up, and was further treated successfully by EMR. CONCLUSIONS: ESD is an ideal method for EGC treatment, but it may result in a risk of complication. The complete resection rate can be improved by endoscopist's experience. Sophisticated endoscopic hemostasis and clipping skills are essential prior ESD procedures. Conventional EMR techniques are also obligatory during the beginning period.

Iatrogenic femoral neuropathy following pelvic surgery: a rare and often overlooked complication--four case reports and literature review.

Femoral neuropathy can result from diverse etiologies following abdominal surgery. We describe four cases of postoperative femoral neuropathy after proctological procedures that were carried out at our hospital. The related symptoms developed occultly but eventually impaired patient motor or sensory functions in the lower extremities. When the patient fails to address associated suffering, it is easy for clinicians to neglect this type of morbidity. All patients recovered from neuropathy following timely detection of the disease entity confirmed by electromyography and nerve conduction studies, followed by adequate rehabilitation management. We hypothesize that postoperative femoral neuropathy may be closely related to unsuitable applications of self-retaining retractors, rather than being associated with other factors, such as gender, age, surgery time or body mass index (BMI). Furthermore, we used a literature review to examine the pathophysiology, diagnoses and treatment modalities of femoral neuropathy resulting from inappropriate placement of self-retaining retractors. Based on a thorough comprehension of the femoral nerves anatomical course and meticulous placement of retractor blades, these types of iatrogenic complications may be prevented.

Metastatic Merkel cell carcinoma in the rectum: report of a case.

Merkel cell carcinoma is a rare, aggressive skin malignancy of neuroendocrine origin with predominant occurrence in the elderly males. Approximately 50 percent of patients with Merkel cell carcinoma develop distant metastasis at some point during the disease course; hence, Merkel cell carcinoma always has a poor prognosis. Distant metastasis has never been disclosed in the rectum to the best of our knowledge. We present a 76-year-old male with clinical manifestation of massive hematochezia and final diagnosis of metastatic Merkel cell carcinoma in the rectum. We conclude that radical resection of rectal metastatic Merkel cell carcinoma is important in the management strategy of a patient with recurrence and lymph node metastases.

Stapled hemorrhoidopexy for prolapsed hemorrhoids in patients with liver cirrhosis; a preliminary outcome for 8-case experience.

PURPOSE: To investigate the efficacy and safety of stapled hemorrhoidopexy in treating prolapsed hemorrhoids in patients with liver cirrhosis. PATIENTS AND METHODS: Eight consecutive cases of patients with prolapsed hemorrhoids comorbid with liver cirrhosis, who had intractable response to other interventions, were enrolled in this retrospective study between January 2002 and June 2006 at our institute. Six patients (75%) had Child-Pugh class A liver cirrhosis, whereas only two patients (25%) had class B disease. Rectal varices were identified in three patients (37.5%), and esophageal varices were identified in six patients (75%). Concurrent rectal and esophageal varices existed in three patients (37.5%). The patients underwent stapled hemorrhoidopexy with Proximate PPH-03 in a lithotomy position under spinal/intravenous general anesthesia. RESULTS: There was no procedure-related mortality or major complications except hemorrhage. Two patients (25%) were complicated with postoperative staple-line bleeding, which was managed with conservative treatment without reoperation. There were no leading symptoms of relapsing during a follow-up period of at least 6 months. CONCLUSIONS: This study may prove that stapled hemorrhoidopexy is a feasible and safe approach for prolapsed hemorrhoids concurrent with liver cirrhosis.

Randomized comparison between stapled hemorrhoidopexy and Ferguson hemorrhoidectomy for grade III hemorrhoids in Taiwan: a prospective study.

PURPOSE: Short-term and mid-term outcomes of stapled hemorrhoidopexy (SH) were compared with those for Ferguson hemorrhoidectomy (FH) for treating hemorrhoids. MATERIALS AND METHODS: Patients with prolapsed hemorrhoids were randomized into two groups treated with SH (N = 300) and FH (N = 296) at Chang Gung Memorial Hospital at Chiayi in Taiwan between January 2002 and December 2004. The outcomes of the procedures were evaluated postoperatively (short-term, i.e., intra-/postoperative conditions, hospital stay, pain intensity scoring, time off work, and procedure-related morbidity) and over a follow-up period of minimum 18 months (mid-term, i.e., relapse of prolapse and/or bleeding, anal stricture, anal sepsis, and the acceptability of the procedures to the patients). RESULTS: SH was superior to FH in operative time, intraoperative blood loss, postoperative pain intensity, and return to work. Based on telephone interviews over the follow-up period, most patients who received SH appreciated the procedure better than those with FH. CONCLUSIONS: This study confirms that SH generates less postoperative suffering, less time off work, and more complete resolution of primary symptoms associated with hemorrhoids in the mid-term follow-up than FH.

Synchronous prostate stromal sarcoma and gastrointestinal stromal tumor of rectum: case report and review of the literature.

We report a case of prostate stromal sarcoma with initial presentation of obstructive voiding symptoms. The synchronous rectal gastrointestinal stromal tumor was also finally discovered. The patient underwent pelvic exenteration as the choice of treatment. Synchronous prostate stromal sarcoma and rectal gastrointestinal stromal tumor is an extremely rare disease in the literature view.

Impact of the cyclin D1 A870G polymorphism on susceptibility to sporadic colorectal cancer in Taiwan.

PURPOSE: Cyclin D1 is a regulatory protein involved in the cell cycle of both normal and neoplastic cells. Polymorphism of this gene at codon 242 in exon 4 has impacts on risk of the early-age onset in several malignant neoplasms, including colorectal cancer. This investigation was designed to evaluate the effect of cyclin D1 gene polymorphism on the risk of colorectal cancer in Chinese migrants of the Taiwanese population. METHODS: We enrolled 831 primary sporadic colorectal cancer patients as the study group and 1,052 age-gender matched healthy individuals as the control group (1,883 total cases) for present study. Cyclin D1 genotypes (AA, AG, GG) were determined using PCR-RFLP analysis on genomic DNA. RESULTS: The frequency of G allele was 39.89 percent and 40.96 percent in the study group and the control group, respectively (P = 0.02). The patients were divided into three age groups for statistical analysis. The younger male patients had a higher frequency of AA/AG genotype compared with the controls (odds ratio, 2.75; 95 percent confidence interval, 1-7.9). The effect of AA/AG genotype on colorectal cancer risk was statistically significant for male patients (odds ratio, 1.34; 95 percent confidence interval, 1.04-1.72), but such phenomenon was not observed in female patients. CONCLUSIONS: Our study suggests that the effect of cyclin D1 gene polymorphism on colorectal cancer risk is only observed in males and AA/AG genotype of cyclin D1 gene is associated with a higher risk of colorectal cancer in the younger patients within the Taiwanese population.

Delayed ischemic gangrene change of distal limb despite optimal decompressed colostomy constructed in obstructed sigmoid colon cancer: a case report.

Creating blow-hole colostomy for decompression could provide a time-saving and efficient surgical procedure for a severely debilitated case with a completely obstructed colorectal cancer. Complications are reported as prolapse, retraction, and paracolostomal abscess. However, complication with an ischemic distal limb has not been reported. We report a case of critical intra-abdominal disease after decompressed colostomy for relieving malignant sigmoid colon obstruction; a potential fatal condition should be alerted. A 76-year-old male visited our emergency department for symptoms related to obstructed sigmoid colon tumor with foul-odor vomitus containing fecal-like materials. An emergent blow-hole colostomy proximal to an obstructed sigmoid lesion was created, and resolution of complete colon obstruction was pursued. Unfortunately, extensive abdominal painful distention with board-like abdomen and sudden onset of high fever with leukocytopenia developed subsequently. Such surgical abdomen rendered a secondary laparotomy with resection of the sigmoid tumor along with an ischemic colon segment located proximally up to the previously created colostomy. Eventually, the patient had an uneventful postoperative hospital stay. In the present article, we have described an emergent condition of sudden onset of distal limb ischemia after blow-hole colostomy and concluded that despite the decompressed colostomy would resolve acute malignant colon obstruction efficiently; impending ischemic bowel may progress with a possible irreversible peritonitis. Any patient, who undergoes a decompressed colostomy without resection of the obstructed lesion, should be monitored with leukocyte count and abdominal condition survey frequently.

Management of patients with stercoral perforation of the sigmoid colon: report of five cases.

To our knowledge, stercoral perforation of the colon is rarely seen with fewer than 90 cases reported in the literature till date. We explored the principles of management to prevent impending mortality in five patients with this condition. Five patients, two males and three females, whose median age was 64 years, had sustained stercoral perforation of the sigmoid colon. Chronic constipation was the common symptom among these patients. Three patients underwent a Hartmannos procedure and another two were treated with segmental colectomy with anastomosis and diverting colostomy. There was one surgical mortality and the other patients had an uneventful hospital stay. Timely intervention to prevent and/or treat any associated sepsis along with extensive peritoneal lavage and surgical intervention to remove diseased colonic tissue at the primary stercoral ulceration site coupled with aggressive therapy for peritonitis are key treatment modalities in salvaging patients presenting with stercoral perforation of the colon.

Attenuation of apoptosis and enhancement of proteoglycan synthesis in rabbit cartilage defects by hyperbaric oxygen treatment are related to the suppression of nitric oxide production.

Proinflammatory cytokine, nitric oxide (NO) and localized hypoxia-induced apoptosis and proteoglycan (PG) degradation are thought to be correlated to the degree of cartilage injury. This study evaluated hyperbaric oxygen (HBO)-induced changes in joint cavity oxygen tension, antigenickeratan sulfate (KS) content, inducible nitric oxide synthase (iNOS) expression, PG synthesis, and cell apoptosis in full-thickness defects of rabbit cartilage. The HBO group was exposed to 100% oxygen at 2.5 atm for 2 h daily, 5 days per week. Meanwhile, the control group was kept in housing cages with normal air. The joint cavity oxygen tension was determined with an oxygen sensor. Blood serum KS was quantified by competitive indirect enzyme-linked immunosorbent assay (ELISA). After sacrifice, specimen sections were sent for histological and histochemical examination with a standardized scoring system. In situ analysis of iNOs expression and apoptosis detection were performed using immunostaining and TUNEL staining, respectively and quantified by a computerized imagine analysis system. This study demonstrated that HBO treatment increased joint cavity oxygen tension but decreased blood KS content. Histological and histochemical score results showed that HBO treatment significantly increased the cartilage repair. Moreover, immunostaining and TUNEL staining showed that HBO treatment suppressed the iNOs expression and apoptosis of chondrocytes, respectively. Accordingly, HBO offers a potential treatment method for cartilage injury.