Modified endoscopic submucosal tunnel dissection for large esophageal submucosal gland duct adenoma: A case report.

BACKGROUND: With the recent improvement of endoscopic techniques, endoscopic ultrasound-guided fine needle aspiration and endoscopic submucosal tunnel dissection (ESTD) have been widely used for accurate diagnosis and dissection acceleration of esophageal tumors. CASE SUMMARY: We used a modified submucosal tunnel technique during endoscopic en bloc resection in a 58-year-old man with large esophageal submucosal gland duct adenoma (ESGDA). During modified ESTD, the oral end of the involved mucosa was cut transversely, followed by a submucosal tunnel created from the proximal to the distal end, and the anal end of the involved mucosa blocked by the tumor was incised. As a result of retaining submucosal injection solutions using the submucosal tunnel technique, it was possible to reduce the amount of injection required and increase the efficiency and safety of dissection. CONCLUSION: Modified ESTD is an effective treatment strategy for large ESGDAs. Single-tunnel ESTD appears to be a time-saving procedure compared with conventional endoscopic submucosal dissection.

Deep learning driven colorectal lesion detection in gastrointestinal endoscopic and pathological imaging.

Colorectal cancer has the second highest incidence of malignant tumors and is the fourth leading cause of cancer deaths in China. Early diagnosis and treatment of colorectal cancer will lead to an improvement in the 5-year survival rate, which will reduce medical costs. The current diagnostic methods for early colorectal cancer include excreta, blood, endoscopy, and computer-aided endoscopy. In this paper, research on image analysis and prediction of colorectal cancer lesions based on deep learning is reviewed with the goal of providing a reference for the early diagnosis of colorectal cancer lesions by combining computer technology, 3D modeling, 5G remote technology, endoscopic robot technology, and surgical navigation technology. The findings will supplement the research and provide insights to improve the cure rate and reduce the mortality of colorectal cancer.

Peroral traction-assisted natural orifice trans-anal flexible endoscopic rectosigmoidectomy followed by intracorporeal colorectal anastomosis in a live porcine model.

BACKGROUND: Compared to traditional open surgery, laparoscopic surgery has become a standard approach for colorectal cancer due to its great superiorities including less postoperative pain, a shorter hospital stay, and better quality of life. In 2007, Whiteford et al reported the first natural orifice trans-anal endoscopic surgery (NOTES) sigmoidectomy using transanal endoscopic microsurgery. To date, all cases of NOTES colorectal resection have included a hybrid laparoscopic approach with the use of established rigid platforms. AIM: To introduce a novel technique of peroral external traction-assisted transanal NOTES rectosigmoidectomy followed by intracorporeal colorectal end-to-end anastomosis by using only currently available and flexible endoscopic instrumentation in a live porcine model. METHODS: Three female pigs weighing 25-30 kg underwent NOTES rectosigmoid resection. After preoperative work-up and bowel preparation, general anesthesia combined with endotracheal intubation was achieved. One dual-channel therapeutic endoscope was used. Carbon dioxide insufflation was performed during the operation. The procedure of trans-anal NOTES rectosigmoidectomy included the following eight steps: (1) The rectosigmoid colon was tattooed with India ink by submucosal injection; (2) Creation of gastrostomy by directed submucosal tunneling; (3) Peroral external traction using endoloop ligation; (4) Creation of rectostomy on the anterior rectal wall by directed 3 cm submucosal tunneling; (5) Peroral external traction-assisted dissection of the left side of the colon; (6) Trans-anal rectosigmoid specimen transection, where an anvil was inserted into the proximal segment after purse-string suturing; (7) Intracorporeal colorectal end-to-end anastomosis using a circular stapler by a single stapling technique; and (8) Closure of gastrostomy using endoscopic clips. All animals were euthanized immediately after the procedure, abdominal exploration was performed, and the air-under-water leak test was carried out. RESULTS: The procedure was completed in all three animals, with the operation time ranging from 193 min to 259 min. Neither major intraoperative complications nor hemodynamic instability occurred during the operation. The length of the resected specimen ranged from 7 cm to 13 cm. With the assistance of a trans-umbilical rigid grasper, intracorporeal colorectal, tension-free, end-to-end anastomosis was achieved in the three animals. CONCLUSION: Peroral traction-assisted transanal NOTES rectosigmoidectomy followed by intracorporeal colorectal end-to-end anastomosis is technically feasible and reproducible in an animal model and is worthy of further improvements.

Percutaneous transgastric endoscopic tube ileostomy in a porcine survival model.

AIM: To introduce natural orifice transgastric endoscopic surgery (NOTES) tube ileostomy using pelvis-directed submucosal tunneling endoscopic gastrostomy and endoscopic tube ileostomy. METHODS: Six live pigs (three each in the non-survival and survival groups) were used. A double-channeled therapeutic endoscope was introduced perorally into the stomach. A gastrostomy was made using a 2-cm transversal mucosal incision following the creation of a 5-cm longitudinal pelvis-directed submucosal tunnel. The pneumoperitoneum was established via the endoscope. In the initial three operations of the series, a laparoscope was transumbilically inserted for guiding the tunnel direction, intraperitoneal spatial orientation and distal ileum identification. Endoscopic tube ileostomy was conducted by adopting an introducer method and using a Percutaneous Endoscopic Gastrostomy Catheter Kit equipped with the Loop Fixture. The distal tip of the 15 Fr catheter was placed toward the proximal limb of the ileum to optimize intestinal content drainage. Finally, the tunnel entrance of the gastrostomy was closed using nylon endoloops with the aid of a twin grasper. The gross and histopathological integrity of gastrostomy closure and the abdominal wall-ileum stoma tract formation were assessed 1 wk after the operation. RESULTS: Transgastric endoscopic tube ileostomy was successful in all six pigs, without major bleeding. The mean operating time was 71 min (range: 60-110 min). There were no intraoperative complications or hemodynamic instability. The post-mortem, which was conducted 1-wk postoperatively, showed complete healing of the gastrostomy and adequate stoma tract formation of ileostomy. CONCLUSION: Transgastric endoscopic tube ileostomy is technically feasible and reproducible in an animal model, and this technique is worthy of further improvement.

Colossolactone H, a new Ganoderma triterpenoid exhibits cytotoxicity and potentiates drug efficacy of gefitinib in lung cancer.

Three pentacyclic triterpene dilactones were isolated from the fruiting bodies of Ganoderma colossum, a medicinal mushroom. Colossolactone H (colo H) as a new compound and the most cytotoxic among the isolates was studied for its anticancer mechanism and the potential use in cancer therapy. Gene expression profiling analysis indicated that treatment of lung cancer cells with colo H caused upregulation of 252 genes and downregulation of 398 genes. Gene ontology enrichment analysis indicated that the downregulated genes were the most significantly enriched in cell cycle progression, and the upregulated genes were significantly enriched in metabolic process, cellular response to stimulus, and oxidation reduction. Accordingly, colo H was found to halt cell growth and induce cell apoptosis via the elevation of cellular reactive oxygen species to cause DNA damage and the increase of tumor suppressor p53 protein. These events facilitate additive cytotoxicity of colo H and gefitinib for gefitinib-resistant H1650 lung cancer cells. Furthermore, combination of colo H and gefitinib effectively inhibited the growth of tumor xenografts in athymic mice. In addition to the efficacy in adjunctive cancer therapy, we have also demonstrated the isolation of colo H from cultivated G. colossum. Thus it is feasible to use colo H or Ganoderma colossum for cancer therapy.

Raman spectroscopy for early real-time endoscopic optical diagnosis based on biochemical changes during the carcinogenesis of Barrett's esophagus.

Raman spectroscopy is a spectroscopic technique based on the inelastic scattering of monochromatic light that represents the molecular composition of the interrogated volume to provide a direct molecular fingerprint. Several investigations have revealed that confocal Raman spectroscopy can differentiate non-dysplastic Barrett's esophagus from esophageal high-grade dysplasia and adenocarcinoma with high sensitivity and specificity. An automated on-line Raman spectral diagnostic system has made it possible to use Raman spectroscopy to guide accurate target biopsy instead of multiple random forceps-biopsies, this novel system is expected to improve in vivo precancerous diagnosis and tissue characterization of Barrett's esophagus.

Transgastric endoscopic gastrojejunostomy using holing followed by interrupted suture technique in a porcine model.

AIM: To demonstrate the feasibility and reproducibility of a pure natural orifice transluminal endoscopic surgery (NOTES) gastrojejunostomy using holing followed by interrupted suture technique using a single endoloop matched with a pair of clips in a non-survival porcine model. METHODS: NOTES gastrojejunostomy was performed on three female domestic pigs as follows: Gastrostomy, selection and retrieval of a free-floating loop of the small bowel into the stomach pouch, hold and exposure of the loop in the gastric cavity using a submucosal inflation technique, execution of a gastro-jejunal mucosal-seromuscular layer approximation using holing followed by interrupted suture technique with endoloop/clips, and full-thickness incision of the loop with a Dual knife. RESULTS: Pure NOTES side-to-side gastrojejunostomy was successfully performed in all three animals. No leakage was identified via methylene blue evaluation following surgery. CONCLUSION: This novel technique for preforming a gastrointestinal anastomosis exclusively by NOTES is technically feasible and reproducible in an animal model but warrants further improvement.

ALDH-positive lung cancer stem cells confer resistance to epidermal growth factor receptor tyrosine kinase inhibitors.

Molecular targeting therapeutics, such as EGFR tyrosine kinase inhibitors (TKIs), are important treatment strategies for lung cancer. Currently, the major challenge confronting targeted cancer therapies is the development of resistance. Cancer stem cells (CSCs) represent a rare population of undifferentiated tumorigenic cells responsible for tumor initiation, maintenance and spreading. Resistance to conventional chemotherapeutic drugs is a common characteristic of CSCs. However, the issue of whether CSCs contribute to EGFR TKI resistance in lung cancer is yet to be established. In the current study, we explored the association of ALDH1A1 expression with EGFR TKI resistance in lung cancer stem cells. ALDH1A1-positive lung cancer cells displayed resistance to gefitinib, compared to ALDH1A1-negative lung cancer cells. Moreover, PC9/gef cells (gefitinib-resistant lung cancer cells) presented a higher proportion of ALDH1A1-positive cells, compared to PC9 cells (gefitinib-sensitive lung cancer cells). Clinical sample studies were consistent with results from cell culture model systems showing that lung cancer cells with resistance to EGFR TKI and chemotherapy drugs contain significantly increased proportions of ALDH1A1-positive cells. These findings collectively suggest that ALDH1A1 positivity in cancer stem cells confers resistance to EGFR TKI in lung cancer.

Small bowel preparations for capsule endoscopy with mannitol and simethicone: a prospective, randomized, clinical trial.

BACKGROUND AND OBJECTIVE: There is no consensus concerning small bowel preparation before capsule endoscopy (CE). This study evaluated the effects of 4 regimens on small bowel cleansing and diagnostic yield. METHODS: Patients were randomly divided into 4 groups. Group A consumed a clear liquid diet after lunch on the day before CE, followed by overnight fasting. Group B took 250 mL 20% mannitol and 1 L 0.9% saline orally at 05:00 hours on the day of the procedure. In group C, the same regimen was taken at 20:00 hours on the day before and at 05:00 hours on the day of CE. In group D, in addition to the group C regimen, 20 mL oral simethicone was taken 30 minutes before CE. RESULTS: Two hundred patients were prospectively enrolled, and 7 were excluded from the final analysis because of incomplete small bowel transit. No significant difference was noted among the 4 groups for small bowel transit time. Bowel preparation in group D was significantly better than for the other regimens for overall cleansing of the proximal small bowel, and showed improved overall cleansing of the distal small bowel when compared with 10-hours overnight fasting. Pathological lesions of the proximal and distal small bowel were, respectively, achieved in 82 and 74 patients, mostly distributed in group D. CONCLUSIONS: Small bowel preparation that involves split-dose oral mannitol plus single-dose simethicone for CE can improve mucosal visualization and subsequent diagnostic yield when compared with 10-hours overnight fasting.

Arachidin-1, a peanut stilbenoid, induces programmed cell death in human leukemia HL-60 cells.

The stilbenoids, arachidin-1 (Ara-1), arachidin-3, isopentadienylresveratrol, and resveratrol, have been isolated from germinating peanut kernels and characterized as antioxidant and anti-inflammatory agents. Resveratrol possesses anticancer activity, and studies have indicated that it induces programmed cell death (PCD) in human leukemia HL-60 cells. In this study, the anticancer activity of these stilbenoids was determined in HL-60 cells. Ara-1 had the highest efficacy in inducing PCD in HL-60 cells, with an approximately 4-fold lower EC50 than resveratrol. Ara-1 treatment caused mitochondrial membrane damage, activation of caspases, and nuclear translocation of apoptosis-inducing factor, resulting in chromosome degradation and cell death. Therefore, Ara-1 induces PCD in HL-60 cells through caspase-dependent and caspase-independent pathways. Ara-1 demonstrates its efficacy as an anticancer agent by inducing caspase-independent cell death, which is an alternative death pathway of cancer cells with mutations in key apoptotic genes. These findings indicate the merits of screening other peanut stilbenoids for anticancer activity.

SUMO4 M55V variant is associated with diabetic nephropathy in type 2 diabetes.

OBJECTIVE-SUMO4 mRNA was recently found to be mainly expressed in the kidney, and the methionine-to-valine substitution at codon 55 (M55V) variant of SUMO4 may induce higher nuclear factor-kappaB (NF-kappaB) activity. Because NF-kappaB is known to mediate the development of diabetic nephropathy, we examined the association between the SUMO4 M55V variant and the severity of diabetic nephropathy. RESEARCH DESIGN AND METHODS-We recruited a total of 430 patients with type 2 diabetes. The M55V (rs237025, 163A-->G) polymorphism of SUMO4 was genotyped by real-time PCR, and urine albumin concentration was measured by radioimmunoassay. RESULTS-The frequencies of SUMO4 AA, GA, and GG were 52.6, 40.7, and 6.7%, respectively, in the normoalbuminuric group; 45.5, 47.3, and 7.1% in the microalbuminuric group; and 36.9, 46.2, and 16.9% in the macroalbuminuric group. We detected a significant linear trend for SUMO4 genotype between the macroalbuminuric and normoalbuminuric groups. The mean urine albumin-to-creatinine ratio (42.3 +/- 108.82 mg/mmol) in the GG group was significantly higher than in the AA (14.9 +/- 51.49 mg/mmol) and GA (17.0 +/- 43.74 mg/mmol) groups. Multivariate logistic regression analysis showed the SUMO4 M55V variant to be independently associated with the severity of diabetic nephropathy. CONCLUSIONS-This study indicates that the SUMO4 gene M55V variant is associated with severity of diabetic nephropathy in patients with type 2 diabetes.

Primary aldosteronism caused by unilateral adrenal hyperplasia: rethinking the accuracy of imaging studies.

A rare type of aldosteronism, known as unilateral adrenal hyperplasia (UAH), is difficult to diagnose, not only because it fails to conform to the typical common subtypes, but also because imaging results are unreliable. We report 2 Taiwanese patients with UAH. Case 1 was a 44-year-old man with 2 episodes of hypokalemic paralysis. Hypertension and suppressed plasma renin activity (PRA) with elevated plasma aldosterone concentration (PAC) were observed. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) showed a right adrenal mass, but adrenal scintigraphy revealed no definite laterality. The patient underwent a laparoscopic right adrenalectomy. Adrenal cortical hyperplasia was discovered from results of the histologic analysis. Case 2 was a 33-year-old woman referred for hypokalemia, hypertension, and a left adrenal mass found on a CT scan. However, MRI revealed normal adrenal glands. The adrenal vein sampling for PAC showed overproduction of PAC from the left adrenal gland. A laparoscopic left adrenalectomy was done. Pathology results revealed micronodular cortical hyperplasia with central hemorrhage. Blood pressure, plasma potassium, aldosterone, and renin activity levels returned to normal after operation in both cases. Both patients have been well for 3 years and 16 months, respectively, after surgery. We review the literature and discuss the limitations of imaging studies.

Klinefelter's syndrome with seizure, pseudohypoparathyroidism type Ib and multiple endocrine dysfunctions.

Klinefelter's syndrome is rarely associated with hypocalcemia, especially pseudohypoparathyroidism (PHP) type Ib. We describe a case of Klinefelter's syndrome associated with seizure, PHP type Ib and multiple endocrine dysfunctions. A 19-year-old Taiwanese male was admitted due to seizures with loss of consciousness. He had been diagnosed with Klinefelter's syndrome with seizure disorder and hypocalcemia 3 months previously. Physical examination revealed eunuchoidism but no osteodystrophy, while laboratory data revealed severe hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone. Chromosomal study showed 47,XXY. Osteoporosis was found on chest and abdominal radiography. Dense calcification in the cerebrum and cerebellum was shown on brain computed tomography and magnetic resonance imaging. Elevation of the patient's serum calcium level was noted after vitamin D and calcium carbonate supplements were given. Klinefelter's syndrome is rarely associated with PHP type Ib; our patient's hypocalcemia improved after long-term aggressive treatment.

Recurrent pulmonary embolism in an elderly patient with Cushing's syndrome, adrenocortical adenoma, pheochromocytoma and prostate adenocarcinoma.

Pulmonary embolism (PE) is a major health problem. Mortality in untreated PE is high, but with adequate (anticoagulant) treatment, can be reduced. Multiple primary and secondary risk factors are responsible for PE. But there is rare association of mixed adrenal tumor with PE. Here, we report a case of adrenocortical adenoma with Cushing's syndrome coexistent with pheochromocytoma with recurrent PE in an elderly patient with prostate adenocarcinoma. A 78-year-old Taiwanese retired veteran was admitted in July, 2002 with the presentation of syncope. Three years before, he was diagnosed with prostate adenocarcinoma and had received Androcur therapy since then. Five months later, he was admitted with Cushingoid appearance and hypertension. Abdominal imaging studies revealed a left adrenal tumor. Laparoscopic adrenalectomy revealed an adrenocortical adenoma. Two years later, a recurrent left adrenal tumor was found. Repeated laparoscopic adrenalectomy revealed pheochromocytoma. One month after the repeat laparoscopic surgery, the patient was admitted due to syncope. Chest X-ray revealed cardiomegaly with pulmonary venous congestion. Echocardiogram showed impaired right ventricle global systolic function. Perfusion lung scan showed a high probability of PE. Heparin and coumadin were given but stopped 5 weeks later due to the development of severe skin ecchymosis. In December 2002, the patient was admitted again with consciousness disturbance. Chest computed tomography (CT) revealed bilateral PE, and he died 5 hours later due to cardiogenic shock. In conclusion, in elderly patients with Cushing's syndrome with pheochromocytoma and prostate carcinoma, there is probability of pulmonary embolism.