Recurrent Fever and Failure to Thrive in an 11-Year-Old Boy.

Recurrent fever is frequent among children and mostly associated with viral infections inoculated via social contacts with others of the same age. Rarely, severe conditions such as hematological malignancies, pediatric rheumatoid diseases, chronic infections, or inherited recurrent fever syndromes are causative. Herein, we present the case of an 11-year-old boy with frequently recurring high-fever episodes since early childhood, failure to thrive, and iron deficiency who was found to have classical celiac disease (CD) with highly elevated tissue transglutaminase and anti-gliadin antibodies and marked duodenal villous atrophy. Upon implementation of a gluten-free diet, the boy ceased to have fevers, antibodies decreased markedly, his iron status improved, and he significantly gained weight. Although infrequent, recurrent fever should be included into the polymorphic clinical picture of CD, and the threshold of testing for diagnostic antibodies should be low in such patients.

New laser soldering-based closures: a promising method in natural orifice transluminal endoscopic surgery.

BACKGROUND: Complete closure of gastrotomy is the linchpin of safe natural orifice transgastric endoscopic surgery. OBJECTIVE: To evaluate feasibility and efficacy of a new method of gastrotomy closure by using a sutureless laser tissue-soldering (LTS) technique in an ex vivo porcine stomach. DESIGN: In vitro experiment. SETTING: Experimental laboratory. INTERVENTIONS: Histological analysis and internal and external liquid pressure with and without hydrochloric acid exposure were determined comparing gastrotomy closure with LTS and with hand-sewn surgical sutures. MAIN OUTCOME MEASUREMENTS: Comparison of LTS and hand-sewn surgical gastrotomy closure. The primary outcome parameter was the internal leak pressure. Secondary parameters were the difference between internal and external leak pressures, the impact of an acid environment on the device, histological changes, and feasibility of endoscopic placement. RESULTS: The internal liquid leak pressure after LTS was almost twice as high as after hand-sewn surgical closure (416 ± 53 mm Hg vs 229 ± 99 mm Hg; P = .01). The internal leak pressure (416 ± 53 mm Hg) after LTS was higher than the external leak pressure (154 ± 46 mm Hg; P < .0001). An acidic environment did not affect leak pressure after LTS. Endoscopic LTS closure was feasible in all experiments. Histopathology revealed only slight alterations beneath the soldering plug. LIMITATIONS: In vitro experiments. CONCLUSIONS: Leak pressure after LTS closure of gastrotomy is higher than after hand-sewn surgical closure. LTS is a promising technique for closure of gastrotomies and iatrogenic perforations. Further experiments, in particular survival studies, are mandatory.

Photodynamic therapy for cholangiocarcinoma.

The only hope for cure in patients with cholangiocarcinoma is curative surgical resection. Unfortunately it can only performed in less than half of the patients. In the palliative setting endoprostheses insertion improves cholestasis. Survival time is not prolonged. The most promising conventional antitumoral therapy is chemotherapy with cisplatin and gemcitabine. However, randomized trials showing a clear survival advantage of chemo- or radiotherapy are missing. Photodynamic therapy utilizing photo-physical properties of light-absorbing drugs to efficiently generate reactive cytotoxic oxygen species has shown efficacy in several pilot studies, retrospective comparative studies and two prospective, randomized studies. Here, we review mechanism of action, technique, and efficacy of photodynamic therapy for cholangiocarcinoma.

Time-gated fluorescence spectroscopy improves endoscopic detection of low-grade dysplasia in ulcerative colitis.

BACKGROUND: Dysplasia in ulcerative colitis is frequently missed with 4-quadrant biopsies. An experimental setup recording delayed fluorescence spectra simultaneously with white light endoscopy was recently developed. OBJECTIVE: We compared detection of invisible flat intraepithelial neoplasia with protoporphyrin IX fluorescence and standard 4-quadrant biopsies. DESIGN: Prospective, crossover design without randomization of the order of procedures. SETTING: Gastroenterology Department, Humboldt University, Charité, Berlin, Germany. PATIENTS: Forty-two patients with extensive ulcerative colitis of more than 10 years' duration were included. INTERVENTIONS: Colonoscopy with 4-quadrant biopsies and targeted biopsies of macroscopic lesions and time-gated fluorescence-guided colonoscopy were performed 2 weeks apart by 2 blinded endoscopists. Three independent pathologists examined the biopsy specimens. MAIN OUTCOME MEASUREMENTS: The primary outcome criterion was detection rate of invisible flat intraepithelial neoplasia. RESULTS: Invisible flat intraepithelial neoplasia was detected in 3 (7%) patients by white light 4-quadrant biopsies and in 10 (24%) patients by fluorescence-guided endoscopy (P = .02). The sensitivity and specificity for differentiating patients with and without dysplasia were 100% and 81%, respectively. Dysplastic and nondysplastic mucosa could be discriminated with a sensitivity and specificity of 73% and 81%, respectively. LIMITATIONS: The trial was not randomized. CONCLUSION: The detection rate of intraepithelial neoplasia in patients with ulcerative colitis can be improved by fluorescence-guided colonoscopy.

Photodynamic therapy for cholangiocarcinoma: overview and new developments.

PURPOSE OF REVIEW: Photodynamic therapy (PDT) with hematoporphyrins has emerged as promising treatment for nonresectable cholangiocarcinoma in several prospective observational studies and two randomized studies. This review describes the mechanism of action of PDT, gives an overview of clinical experience in cholangiocarcinoma and summarizes the results published in 2007 and 2008. RECENT FINDINGS: The mechanism of action of PDT has been further elucidated. PDT induces an apoptotic, antiangiogenic as well as an immunomodulatory response. Interleukin-6, a bile duct epithelium growth factor correlating with tumor burden, decreases after PDT. The efficacy of PDT was confirmed in a comparative study in the United States. Patients with no visible mass on imaging studies, high serum albumin levels and treatment immediately after diagnosis seem to benefit most from PDT. Although it is recommended to perform PDT in bile ducts without stents in place, illumination through metal stents is possible if the light dose is adjusted. Meso-tetrahydroxyphenyl chlorine is a new potent photosensitizer for PDT of cholangiocarcinoma. SUMMARY: In advanced nonresectable cholangiocarcinoma, PDT is the only evidence-based treatment that improves survival when compared with stenting. Therefore, PDT should be offered to those who are unsuitable for surgery.

[Chronic pancreatitis]. / Pancréatite chronique.

New insights in the pathogenesis, classification and the identification of novel risk factors and novel mutations involved in pancreas divisum and in idiopathic pancreatitis have been introduced. Despite novel diagnosis methods, the identification of early pancreatitis, of pancreatitis with minimal morphological changes and the differential diagnosis between chronic pancreatitis and pancreatic carcinoma remain challenges. Treatment of pain associated with pancreatitis remains also difficult; evidence for endoscopic and surgical approaches is still missing. These new discoveries in pathogenesis, etiology and diagnosis methods did not yet lead to improved diagnosis and treatment of chronic pancreatitis.

Technology insight: Photodynamic therapy for cholangiocarcinoma.

Cholangiocarcinoma is, in most cases, rapidly fatal. Curative resection can only be offered to approximately 10% of patients. Even after seemingly curative resection, recurrence frequently occurs. Adjuvant chemotherapy and/or radiotherapy do not reduce the recurrence rate after resection. In the palliative setting, endoscopic or percutaneous biliary drainage is performed to relieve jaundice; however, poor results have been obtained in patients with tumors involving the intrahepatic bile ducts. Biliary drainage alleviates jaundice, but there is no evidence that it prolongs life. Palliative chemotherapy and/or radiotherapy have not been proven to prolong life and relieve jaundice. Photodynamic therapy (PDT) is a relatively new local, minimally invasive procedure that can be used to treat cholangiocarcinoma. PDT uses the physical properties of light-absorbing molecules, so-called photosensitizers, which accumulate within proliferating cells. Activation of the photosensitizer by a non-thermal laser leads to selective photochemical destruction of tumors. In a randomized trial of patients with nonresectable cholangiocarcinoma, PDT prolonged survival time, improved cholestasis and quality of life considerably, and had a favorable side-effect profile. A second randomized trial confirmed the beneficial effect of PDT. For the time being, PDT is recommended for patients with nonresectable disease. The role of PDT before and after surgical resection needs to be assessed.

Photodynamic therapy in cholangiocarcinomas.

Symptoms occur late in cholangiocarcinoma and therefore only about half of the patients at the time of diagnosis are candidates for curative surgery. In patients with advanced non-resectable cholangiocarcinoma palliative treatment options are limited. Until now, insertion of endoprostheses for the treatment of cholestasis has been the method of choice. However, tumour growth cannot be influenced and so that prognosis is dismal. Although radiotherapy and chemotherapy are frequently used, prospective, randomized trials showing an improvement in survival time are missing. Encouraging results from prospective, single-arm phase II trials and a randomized trial using photodynamic therapy (PDT) in non-resectable cholangiocarcinoma indicate considerable benefit on survival with a good quality of life. Furthermore, PDT is well tolerated, with only few specific side-effects. This is of great importance in patients with short life expectancy. PDT should therefore be offered to all patients with non-resectable cholangiocarcinoma. However, before initiating PDT or any other palliative measure, a proper staging and a surgical consultation is necessary to avoid missing a curative surgical option.

Photodynamic therapy in cholangiocarcinoma: an overview.

Cholangiocarcinoma is a challenge to manage; mortality rate is nearly as high as the incidence. Unless curative resection is performed, these tumours are rapidly fatal because they respond poorly to current therapies. Symptoms occur late in cholangiocarcinoma and curative resection can be performed in less than half of the patients. In non-resectable disease, endoprostheses insertion can relieve jaundice and improve quality of life, provided that tumour extension does not lead to diffuse intrahepatic stenoses of ductal system. However, tumour growth cannot be influenced and therefore, prognosis remains dismal. Despite the fact, that radiotherapy and chemotherapy could reduce tumour volume and growth, no survival advantage has yet been shown. Photodynamic therapy has been evaluated as an new additional, palliative option. A randomised trial comparing photodynamic therapy plus endoprostheses insertion versus endoprostheses insertion alone, indicates a considerably benefit on survival time, cholestasis and quality of life in large, advanced cholangiocarcinoma. Furthermore, few specific side effects occurred. Since photodynamic therapy is the first approach leading to an improvement of prognosis, it should be offered to patients with non-resectable cholangiocarcinoma.

Endoscopic interventions for preneoplastic and neoplastic lesions: mucosectomy, argon plasma coagulation, and photodynamic therapy.

The classical treatment of neoplastic lesions is surgical resection. Improved detection of early lesions has offered new therapeutic strategies. Thus, for the last 20 years it has been increasingly attempted to undertake endoscopic resection of such tumors. While there is no doubt that morbidity and mortality are lower than after surgery, it was assumed that the long-term prognosis is not as good as with surgery. Surprisingly, however, the 5-year survival rates are excellent. Therefore, in local mucosal lesions of colon, stomach, and esophagus, endoscopic removal has become standard treatment. In Barrett's esophagus, the treatment modality it is still discussed controversially, despite encouraging results. Since we are yet not able to completely eliminate the premalignant specialized intestinal epithelium of the esophagus, it is still uncertain whether eradication of the malignant or dysplastic lesion is sufficient.