Restricting Kidney Transplant Wait‐Listing for Obese Patients: Let's Stop Defending the Indefensible

The allocation of limited medical resources represents an ethical dilemma that continues to generate lively debates. While the allocation of allografts to wait‐listed patients is done in a transparent manner, with its rules open to public debate and prone to continuous improvement, the practice of wait‐listing is not centrally regulated, and its rules are often less scrutinized. Denial of kidney transplant wait‐listing to obese individuals has been a common practice by most transplant centers. On the face of it, this practice is justified by commonly accepted ethical standards, yet there is now mounting evidence that these justifications do not withstand closer scrutiny. A candid and open debate in the Nephrology and Transplant community is needed to examine the true motivations that underlie the practice of denying wait‐listing to obese individuals, and to find a solution that is truly in the best interest of our patients.     

Contralateral axillary silicone lymphadenopathy after modified radical mastectomy and reconstruction

We describe a 49-year-old female patient who was diagnosed with breast cancer in her left breast. The patient underwent a modified radical mastectomy and immediate reconstruction with the placement of an expander implant. Two years later, the patient suffered a minor trauma and began to feel the softening of her reconstructed breast, and a growing palpable mass appeared in the contralateral (right) axilla. Examinations revealed the intracapsular rupture of the expander implant. Aspiration cytology from the palpable axillary mass suggested silicone lymphadenopathy. We replaced the ruptured implant, and the lymph node from the contralateral axilla was removed. Silicone lymphadenomegaly in the right axilla was verified by a postoperative histopathological review. This case represents a rare manifestation of silicone lymphadenopathy caused by altered lymphatic drainage due to previous axillary lymphadenectomy. Level of Evidence: Level V, diagnostic study.     

Risk of recurrence in major central nervous system malformations between 1976 and 2005

OBJECTIVE: The goal of the current publication is to review isolated central nervous system malformations (CSMs) using a database in excess of 75 000 cases, with special regard to the risk of recurrence of these malformations alone or in combination. METHODS: In the period between 1 January 1976 and 31 December 2005, among the 75 320 documented cases, consultations were requested due to earlier isolated CSMs in the patients' histories in 3030 cases (4.2%). Processing the data we only considered disorders of genetic origin, and that was why we excluded the cases due to intrauterine infection. Monogenically inherited malformations were also excluded from the analysis. The diagnosis of the malformations was based on the prenatal diagnosis of ultrasonography as well as the findings of the foetopathological examination. RESULTS: In 65% of the cases, the couples sought counselling because of malformation in a previous pregnancy. In these cases, the risk of recurrence was thought to be 5.2%, while in the case of two affected children this figure stood at 21.9%. Analysing the values for the risk of recurrence in 5-year periods, neural tube defects (NTDs) (particularly anencephaly and spina bifida) showed a detectable decrease, which could be attributed to a growing use of folic acid supplementation around the time of conception and during pregnancy. CONCLUSION: There is a clear decrease of risk of recurrence of NTDs, while in the case of the other CSMs in this study, there is no noteworthy chronological change in their risk of recurrence.     

Effect of C2 ceramide on the inositol phospholipid metabolism (uptake of 32P, 3H-serine and 3H-palmitic acid) and apoptosis-related morphological changes in Tetrahymena

Sphingomyelin metabolites have significant role in the regulation of many life processes of mammalian cells. In the present experiments the influence of phospholipid turnover and apoptosis related morphologic signs by one of this metabolite, C2 ceramide was studied, and compared to the control, untreated cells, in the unicellular Tetrahymena. The incorporation of phospholipid head group components (serine, phosphorus) show a clear time-dependence; while the incorporation of fatty acid component (palmitic acid) is very fast: no significant alterations were found between 5- and 60-min incubations. C2 ceramide treatment didn't alter 3H-palmitic acid incorporation into phospholipids, however 3H-serine incorporation was mainly inhibited. The amount of total incorporated 32P was also decreased, on the other hand the lover concentration C2 ceramide (10 microM) elevated the synthesis of inositol phospholipids. The higher concentration of C2 ceramide (50 microM) had inhibitory effect on the synthesis of each phospholipids examined. This means that in the presence of the C2 ceramide the synthesis, recovery and turnover of phospholipids, participating in signal transduction, are altered. However these observations were based the uptake of labeled phospholipid precursors, which gives information on the dynamics of the process, without using lipid mass measurements. C2 ceramide also caused the rounding off the cells, DNA degradation and nuclear condensation. These latter observations point to morphological signs of apoptosis. The results call attention to the role of sphingomyelin metabolites on signalization of unicellulars, to the cross-talk between the inositol phospholipids and sphingomyelin metabolites, and the role of these molecules in the apoptotic processes at a low evolutionary level.     

Claudin-4 differentiates biliary tract cancers from hepatocellular carcinomas.

The recently identified claudins are dominant components of tight junctions, responsible for cell adhesion, polarity and paracellular permeability. Certain claudins have been shown to have relevance in tumor development, with some of them, especially claudin-4, even suggested as future therapeutic target. The aim of the present study was to analyze the expression of claudin-4 in the biliary tree, biliary tract cancers and hepatocellular carcinomas. A total of 107 cases were studied: 53 biliary tract cancers, 50 hepatocellular carcinomas, 10 normal liver and 10 normal extrahepatic biliary duct samples. Immunohistochemical analysis was performed on conventional specimens and on tissue microarrays as well. Claudin-4 was further investigated by Western blot analysis and real-time RT-PCR. Intense membranous immunolabeling was found for claudin-4 in all biliary tract cancers unrelated to the primary site of origin, namely intrahepatic, extrahepatic or gallbladder cancers. Normal biliary epithelium showed weak positivity for claudin-4. In contrast, normal hepatocytes and tumor cells of hepatocellular carcinomas did not express claudin-4. The results of Western immunoblot analysis and real-time RT-PCR were in correlation with the immunohistochemical findings. Cytokeratins, as CK7 (92%) and CK19 (83%) were mostly positive in biliary tract cancers, however, one-third of hepatocellular carcinomas also expressed CK7 (34%). HSA antibody (HepPar1) reacted with the majority of hepatocellular carcinomas (86%), while being positive in a low percentage of the biliary tract cancers (8%). In conclusion, this is the first report of a significantly increased claudin-4 expression in biliary tract cancers, which represents a novel feature of tumors of biliary tract origin. Claudin-4 expression seems to be a useful marker in differentiating biliary tract cancers from hepatocellular carcinomas and could well become a potential diagnostic tool.     

Lasting impact of a single benzpyrene treatment in pre-natal and growing age on the thymic glucocorticoid receptors of rats.

1. Rats exposed to benzpyrene in utero at 19 days of pre-natal life showed a relative decrease in the number of thymic glucocorticoid receptors at 6 weeks of age. 2. Primary exposure to benzpyrene at 6 weeks of age had a similar effect on females 4 weeks later, but did not change the glucocorticoid receptor number of males. 3. In utero exposure accounted for an increase in the fetal cytochrome P450 level within 1 day, whereas exposure at 6 weeks of age did not change it within 4 weeks. 4. It appears that exposure to benzpyrene gives rise to a faulty imprinting of the thymic glucocorticoid receptor in both fetal and growing age, to judge from a lasting change in the receptor number.     

Benzpyrene exposure at 15 days of prenatal life reduces the binding capacity of thymic glucocorticoid receptors in adulthood.

1. The offspring of female rats treated with a single dose of benzpyrene on day 15 of gestation showed in adulthood a significant relative decrease in the number of thymic glucocorticoid receptors, without an appreciable decrease in binding affinity. 2. There is experimental evidence that exposure to a hormone analogue in the early stage of organogenesis effects receptor development and the maternal organism fails to confer protection against that untoward influence.     

Congenital lung malformations in the second trimester: prenatal ultrasound diagnosis and pathologic findings

PURPOSE: To correlate prenatal sonographic diagnosis of cystic lung malformations with fetopathologic findings after termination of pregnancy. METHODS: We retrospectively analyzed the data of 16 terminated cases in which a cystic lung lesion was diagnosed pre- or postnatally. RESULTS: On average, prenatal diagnosis was established on the 21(st) gestational week (range, 19-26 weeks). The cause of termination was severe polyhydramnios in 4 cases, nonimmune fetal hydrops in 4 cases, other congenital malformation in 5 cases (renal malformation, 2 cases; congenital diaphragmatic hernia, 3 cases), and obstetrical conditions (intrauterine death, placental abruption, spontaneous abortion) in 3 cases. In 11 cases, congenital cystic adenomatoid malformation (CCAM) was the presumptive prenatal diagnosis. Autopsy confirmed the prenatal diagnosis in 6 of them, while in the other 5 cases, an enteric cyst, a laryngeal atresia, an unidentified tumor, a pulmonary hypoplasia, and an extralobar pulmonary sequestration were found on histologic examination. On the other hand, the autopsy revealed CCAM in those 5 cases in which other malformations were suggested prenatally. CONCLUSION: The prenatal sonographic diagnosis of CCAM is difficult. Our cases emphasize the important role of fetopathology even today in the verification of prenatal diagnosis based on sonographic examinations.     

Radiotherapy Confined to the Tumor Bed Following Breast Conserving Surgery

BACKGROUND: The standard technique of radiotherapy (RT) after breast conserving surgery (BCS) is to treat the entire breast up to a total dose of 45-50 Gy with or without tumor bed boost. The majority of local recurrences occur in close proximity to the tumor bed. Thus, the necessity of whole breast radiotherapy has been questioned, and several centers have evaluated the feasibility and efficacy of sole tumor bed irradiation. The aim of this study was to review the current status, controversies, and future prospects of tumor bed irradiation alone after breast conserving surgery. MATERIAL AND METHODS: Published prospective trials evaluating the feasibility and efficacy of radiotherapy confined to the tumor bed following breast conserving surgery were reviewed in order to analyze treatment results. RESULTS: In three earlier studies, using tumor bed radiotherapy for unselected patients, the incidence of intra-breast relapse was reported in the range of 15.6-37%. However, in nine prospective phase I-II trials, sole brachytherapy (BT) with different dose rates, strict patient selection, and meticulous quality assurance, resulted in 95.6-100% local control rates. To date, only one phase III protocol has been initiated comparing the efficacy of tumor bed brachytherapy alone with conventional whole breast radiotherapy. The ideal extend of the planning target volume (PTV) for tumor bed radiotherapy alone has not been established yet. In most series, PTV was defined as the excision cavity with generous (1-3 cm) safety margins. Minimal requirement for PTV localization is the use of titanium clips to mark the walls of the excision cavity intraoperatively, but the combination of clip demarcation and three-dimensional (3-D) visual information obtained from cross-sectional images seems to be the best method to determine the target volume. 3-D virtual brachytherapy is also a promising method to minimize the chance of geographic miss. Recently developed techniques, such as intraoperative radiotherapy (IORT), as well as accelerated 3-D conformal external beam radiation therapy (3-D-CRT) were also found to be feasible for tumor bed radiotherapy alone. CONCLUSIONS: In spite of the existing arguments against limiting radiotherapy to the tumor bed after breast conserving surgery, results of phase I-II studies suggest that tumor bed radiotherapy alone might be an appropriate treatment option for selected breast cancer patients. Whole breast radiotherapy remains the standard radiation modality used in the treatment of breast cancer, and brachytherapy as the sole modality should be considered as investigational. Further phase-III trials are suggested to determine the equivalence of sole tumor bed radiotherapy, compared with whole breast radiotherapy. Preliminary results with recently developed techniques (CT-image based conformal brachytherapy, 3-D virtual brachytherapy, IORT, 3-D-CRT) are promising. However, more experience is required to define whether these methods might improve outcome for patients treated with tumor bed radiotherapy alone.