Successful photodynamic therapy for biliary papillomatosis： A case report

Papillomatosis of the bile duct is a rare disease with a high risk of malignant transformation. Therapeutical options include partial hepatectomy and liver trans- plantation. A previously healthy 65-years old male developed jaundice and right upper abdominal quadrant pain in 1996. A villous adenoma of the distal bile duct was diagnosed. A Whipple procedure was performed. In 2002 the patient turned symptomatic again. An- other adenoma was found in the right hepatic duct resulting in a right hepatectomy. Two years later the patient again developed cholestasis. Alter drainage of the left hepatic duct with a percutaneous transhepatic cholangial drainage （PTCD） catheter, a recurrent biliary adenomatosis was diagnosed by cholangioscopy. As there was no surgical option left, the patient received photodynamic therapy （PDT） for the recurrent biliary papillomatosis. Three mo alter he received further photodynamic therapies, the bile duct epithelium appeared normal and the patient had no signs of adenomatosis, both macroscopically and histologically. The follow-up cholangioscopy in late 2005 revealed only a small papil-loma without the need for intervention. In early 2006, the patient died of multi organ failure without signs of extrahepatic cholestasis or cholangitis at the age of 75, 10 years after the diagnosis of biliary papillomatosis was established. The patient exceeded the average life expectancy of patients with biliary papillomatosis by far. Thus, PDT might be a sufficient therapeutic option for recurrent papillomatosis patients with no significant side effects.     

Secondary haematological neoplasm after treatment of adult acute lymphoblastic leukaemia: analysis of 1170 adult ALL patients enrolled in the GIMEMA trials

Between 1983 and 1994 the incidence of secondary haematological neoplasms (SHM) was evaluated in 1170 new cases of ALL enrolled in the GIMEMA trials. Of the 942 patients who achieved complete remission (CR); seven developed a SHM: four AMLs and three NHLs.
The median latency from onset of ALL and of secondary haematological neoplasm was 69 months for AML and 61 months for NHL. Three out of four patients with secondary AML were unresponsive to the new chemotherapy and died, whereas the fourth patient achieved a new CR. Among the three NHL cases, two patients are presently alive in CR, whereas the third patient was refractory to chemotherapy and died.
The relative risk of haematological malignancy among the GIMEMA trials population, as compared to that of the Italian Cancer Registries, was 15.25-fold higher, and the actuarial estimated cumulative proportion of ALL patients with a secondary haematological neoplasm at 5 and 10 years were 0.59% and 3.63% respectively.
The incidence of adult ALL who developed a SHM, although apparently lower than in the paediatric ALL series, was higher when compared to the normal population. The difference between paediatric and adult ALL is probably due to the lack of craniospinal radiotherapy and to the lower doses of epipodoxiphyllotoxins used in adult trials. The higher percentage of childhood ALL with a prolonged event-free survival could result in an increase of secondary neoplasms in these cases, which suggests that secondary haematological neoplasms in adult ALL patients are real, although rare, events.     

Cyclosporine A, FK-506, 40-O-[2-hydroxyethyl]rapamycin and mycophenolate mofetil inhibit proliferation of human intrahepatic biliary epithelial cells in vitro

AIM: To investigate the effect of cyclosporine A (CsA),FK-506, and mycophenolate mofetil (MMF) and 40-0-[2-hydroxyethyl]rapamycin (RAD) on proliferation of human intrahepatic biliary epithelial cells (BECs)in vitro.METHODS: BECs were isolated from six human liver tissuespecimens with the immunomagnetic separation method and treated with different concentrations of CsA, FK-506, RAD, and MMF in vitro. Proliferation of the cells was measured by MTT assay at 24 and 48 h after treatment, respectively. One-way analysis of variance was used to analyze the results. Expression of CK 19in BECs was monitored by flow cytometry and Western blot.RESULTS: Six lines of BECs were established. They survived for 4-18 wk in vitro. Flow cytometry analysis showed that these cells always expressed CK19. CsA,FK-506, RAD, and MMF inhibited proliferation of BECs in a dose-dependent manner. The lowest concentration of CsA, FK-506, RAD, and MMF to inhibit proliferation of BECs (P＜0.05) was 500, 100, 0.25, and 100 μg/L,respectively. However, the expression of CK19 by BECs was not changed.CONCLUSION: CsA, FK-506, RAD, and MMF have an antiproliferative effect on human intrahepatic BECs in vitro, while RAD has the strongest growth-inhibitory effect. Their possible effects on liver regeneration and bile duct injury in transplant patients should be further investigated.     

Low frequency of germline mutations in the RET proto-oncogene in patients with apparently sporadic medullary thyroid carcinoma

BACKGROUND AND OBJECTIVES Medullary thyroid carcinoma (MTC) occurs both sporadically and In the autosomal domlnantly inherited multiple endocrine neoplasia (MEN) type 2 syndromes. The distinction between true sporadic MTC and a new mutation familial case is important for future clinical managment of both the patient and family. The susceptibility gene for MEN 2 is theRET proto-oncogene. Systematic analysis for germ-line mutations of theRET proto-oncogene was performed in a series of 67 patients with apparently sporadic MTC to determine whether they were true sporadic cases or unsuspected de novo MEN 2 cases. DESIGN AND PATIENTS Sixty-seven unselected patients with sporadic MTC were randomly ascertained from clinic patients from four centres. The diagnosis of MTC was confirmed by hlstopathology. Germline DNA was extracted from peripheral blood leucocytes or from paraffin-embedded tissue and subsequently used for polymerase chain reaction amplification. MEASUREMENTS Polymerase chain reaction basedRET mutation analysis was performed by direct double-stranded cycle sequencing of axons 10, 11, 13 and 16, within which the majority ofMEN2 mutations have been shown to occur. RESULTS In this series, there was one proven case of germline mutation InRET codon 620, which previously has been shown to be responsible for MEN 2, thus Indicating heritable disease. No germline mutation in codon 918, typical of MEN 2B, was found. CONCLUSIONS A figure of 1.5% germline mutations In 67 apparently sporadic MTC Is lower than the incidence of familial disease reported in previous series Involving clinical and biochemical screening. The presence of a germline mutation in theRET proto-oncogene in a patient with MTC indicates heritable disease. The absence of germlineRET exon 10,11,13 or 16 mutation appears to rule out MEN 2A to a high probability, although the presence of a familial form of MTC other than classical MEN 2A cannot be excluded conclusively.     

Report: workshop on mediastinal grey zone lymphoma

Abstract:  There are several indications that classical Hodgkin lymphoma (cHL) and at least a proportion of cases of Primary Mediastinal B cell Lymphoma (PMBL) are derived from B cells at similar stages of differentiation and share common pathogenic mechanisms. The first indication was the existence of mediastinal grey zone lymphomas as identified in the 4th International Symposium on HL, with clinical, histological and immunohistochemical features intermediate between cHL and PMBL. Second, both tumor types resemble a cell that is developmentally situated in-between the germinal center reaction and a plasma cell. Third, cHL and PMBL were found to have similar gene expression profiles, including the lack of immunoglobulin expression and low levels of B cell receptor signalling molecules, and the secretion of molecules like the chemokine TARC and the prominent expression of IL-13 receptors. Fourth, both entities were found to have common genomic aberrancies, notably in 2p15 and 9p24, the sites of the REL oncogene and the tyrosine kinase gene JAK2, respectively. Further comparison of both lymphoma types may provide further insight in the pathogenic mechanisms and allow the design of diagnostic algorithms to sort out the small number of so-called mediastinal grey zone lymphomas, that appear to be intermediate between PMBL and cHL.     

Risk factors of neonatal respiratory distress following vaginal delivery and caesarean section in the German population

Background: The incidence of caesarean section (CS) is steadily rising world-wide. In particular, CS on maternal demand is performed more frequently. In parts, this might be due to insufficient information of pregnant women about neonatal risks of CS. We sought to specify neonatal outcomes following different modes of delivery, i.e. vaginal delivery, primary CS and secondary CS and to define risk factors for respiratory morbidity and hospitalization.
Methods: We analysed 2073 births (gestational age > 35 weeks) during a two-year period at a tertiary obstetric and neonatal centre in Germany. Statistical analyses were performed for single parameters by SPSS as well as by logistic regression to account for possible confounders. Furthermore, extensive model calculation was done.
Results: Respiratory morbidity was increased following primary and secondary CS (p = 0.001). By multiple logistic regression, the strongest effect on respiratory symptoms was seen with gestational age, each week more in utero reducing the risk by an odds ratio (OR) of 0.69 (95% CI: [0.61; 0.79]; p = 1.9 × 10⁻⁸). Furthermore, a significant interaction between mode of delivery and gestational age was found for the risk of respiratory symptoms (p = 0.0035).
Conclusion: For every eight newborns delivered by primary CS one more than expected with vaginal delivery is hospitalized. It is highly relevant to recognize that each week of gestational age reduces the risk of respiratory symptoms, especially if primary CS is performed. The higher rate of respiratory morbidity and neonatal admission following CS should be clearly recognized in counselling of pregnant women.