Radiotherapy is not indicated in patients with vulvar squamous cell carcinoma and only one occult intracapsular groin node metastasis

ObjectiveMost guidelines advise no adjuvant radiotherapy in vulvar squamous cell carcinoma and a single occult intracapsular lymph node metastasis. However, several recent studies have questioned the validity of this recommendation. The aim of this study was to analyze the groin recurrence rate in patients with a single intracapsular positive lymph node treated without adjuvant radiotherapy.MethodsPatients with a single clinically occult intracapsular lymph node metastasis, treated without adjuvant radiotherapy, formed the basis for this study. Groin recurrences, and the risk of death, were analyzed in relation to the size of the metastasis in the lymph node and the lymph node ratio. Data were analyzed using SPSS, version 26.0 for Windows.ResultsAfter a median follow-up of 64 months, one of 96 patients (1%) was diagnosed with an isolated groin recurrence and another two (2.1%) were diagnosed with a combination of a local and a groin recurrence. The only isolated groin recurrence occurred in a contralateral lymph node negative groin. Size of the metastasis and lymph node ratio had no impact on the groin recurrence risk, nor on survival. The 5-year actuarial disease-specific and overall survivals were 79% and 62.5% respectively. The 5-year actuarial groin recurrence-free survival was 97%.ConclusionBecause of the low risk of groin recurrence and the excellent groin recurrence-free survival, we recommend that adjuvant radiotherapy to the groin in patients with vulvar squamous cell carcinoma and a single occult intracapsular lymph node metastasis can be safely omitted to prevent unnecessary toxicity and morbidity.     

Validation of tissue microarray technology in endometrioid cancer of the endometrium

AIM: To validate tissue microarray (TMA) for endometrial cancer by comparing immunohistochemical staining results of triplicate core biopsies on TMA with the results of full-section analysis. METHODS: The study material consisted of slides and selected tissue blocks of 41 patients with endometrioid cancer of the endometrium. A TMA was constructed. Both the TMA and the slides were stained with the same antibodies against progesterone receptor (PR), oestrogen receptor, p53 and epithelial membrane antigen (EMA). Concordance between results was expressed as the kappa statistic. RESULTS: Concordance between the staining results of TMA and whole slides was good for PR (kappa = 0.69), oestrogen receptor (kappa = 0.78), p53 (kappa = 0.81) and EMA (kappa = 0.72). Concordance between the results on TMA and slides depends on the number of assessable cores per tumour. Three assessable cores per case result in outcomes that are at least 94% similar to those achieved using conventional tissue sections with a two-class scoring system. This is independent of focal or diffuse staining patterns. CONCLUSION: TMA is a useful tool for further analysis of the molecular pathways in endometrial cancer. The effect of selection has to be taken into account when the prognostic value of protein expression on TMA is determined.     

Immunomodulatory role of endogenous interleukin-18 in gamma interferon-mediated resolution of replicative Legionella pneumophila lung infection

The in vivo role of endogenous interleukin-18 (IL-18) in modulating gamma interferon (IFN-gamma)-mediated resolution of replicative Legionella pneumophila lung infection was assessed using a murine model of Legionnaires' disease. Intratracheal inoculation of A/J mice with virulent bacteria (10(6) L. pneumophila organisms per mouse) resulted in induction of IL-18 protein in bronchoalveolar lavage fluid (BALF) and intrapulmonary expression of IL-18 mRNA. Real-time quantitative RT-PCR analysis of infected lung tissue demonstrated that induction of IL-18 in BALF preceded induction of IL-12 and IFN-gamma mRNAs in the lung. Blocking intrapulmonary IL-18 activity by administration of a monoclonal antibody (MAb) to the IL-18 receptor (anti-IL-18R MAb) prior to L. pneumophila infection inhibited induction of intrapulmonary IFN-gamma production but did not significantly alter resolution of replicative L. pneumophila lung infection. In contrast, blocking endogenous IL-12 activity by administration of anti-IL-12 MAb) alone or in combination with anti-IL-18R MAb inhibited induction of intrapulmonary IFN-gamma and resulted in enhanced intrapulmonary growth of the bacteria within 5 days postinfection. Taken together, these results demonstrate that IL-18 plays a key role in modulating induction of IFN-gamma in the lung in response to L. pneumophila and that together with IL-12, IL-18 regulates intrapulmonary growth of the bacteria.     

Sexual transmission of the [Het-S] prion leads to meiotic drive in Podospora anserina

In the filamentous fungus Podospora anserina, two phenomena are associated with polymorphism at the het-s locus, vegetative incompatibility and ascospore abortion. Two het-s alleles occur naturally, het-s and het-S. The het-s encoded protein is a prion propagating as a self-perpetuating amyloid aggregate. When prion-infected [Het-s] hyphae fuse with [Het-S] hyphae, the resulting heterokaryotic cells necrotize. [Het-s] and [Het-S] strains are sexually compatible. When, however, a female [Het-s] crosses with [Het-S], a significant percentage of het-S spores abort, in a way similar to spore killing in Neurospora and Podospora. We report here that sexual transmission of the [Het-s] prion after nonisogamous mating in the reproductive cycle of Podospora is responsible for the killing of het-S spores. Progeny of crosses between isogenic strains with distinct wild-type or introduced, ectopic het-s/S alleles were cytologically and genetically analyzed. The effect of het-s/S overexpression, ectopic het-s/S expression, absence of het-s expression, loss of [Het-s] prion infection, and the distribution patterns of HET-s/S-GFP proteins were categorized during meiosis and ascospore formation. This study unveiled a het-S spore-killing system that is governed by dosage of and interaction between the [Het-s] prion and the HET-S protein. Due to this property of the [Het-s] prion, the het-s allele acts as a meiotic drive element favoring maintenance of the prion-forming allele in natural populations.     

Coamplification of DAD-R, SOX5, and EKI1 in human testicular seminomas, with specific overexpression of DAD-R, correlates with reduced levels of apoptosis and earlier clinical manifestation

Seminomas and nonseminomas represent the invasive stages of testicular (TGCTs) of adolescents and adults. Although TGCTs are characterized by extra copies of the short arm of chromosome 12, the genetic basis for gain of 12p in the pathogenesis of this cancer is not yet understood. We have demonstrated that gain of 12p is related to invasive growth and that amplification of specific 12p sequences, i.e., 12p11.2-p12.1, correlates with reduced apoptosis in the tumors. Here we show that three known genes map within the newly determined shortest region of overlap of amplification (SROA): DAD-R, SOX5, and EKI1. Whereas EKI1 maps close to the telomeric region of the SROA, DAD-R is the first gene at the centromeric region within the 12p amplicon. Although all three genes are amplified to the same level within the SROA, expression of DAD-R is significantly up-regulated in seminomas with the restricted 12p amplification compared with seminomas without this amplicon. DAD-R is also highly expressed in nonseminomas of various histologies and derived cell lines, both lacking such amplification. This finding is of particular interest because seminomas with the restricted 12p amplification and nonseminomas are manifested clinically in the third decade of life and show a low degree of apoptosis. In contrast, seminomas lacking a restricted 12p amplification, showing significantly lower levels of DAD-R with pronounced apoptosis, manifest clinically in the fourth decade of life. A low level of DAD-R expression is also observed in normal testicular parenchyma and in parenchyma containing the precursor cells of this cancer, i.e., carcinoma in situ. Therefore, elevated DAD-R expression in seminomas and nonseminomas correlates with invasive growth and a reduced level of apoptosis associated with an earlier clinical presentation. These data implicate DAD-R as a candidate gene responsible in part for the pathological effects resulting from gain of 12p sequences in TGCTs. In addition, our results also imply differences in expression regulation of DAD-R between seminomas and nonseminomas.     

Failure in the detection of the sentinel lymph node with a combined technique of radioactive tracer and blue dye in a patient with cancer of the vulva and a single positive lymph node

BACKGROUND: In early stage vulvar cancer, the sentinel lymph node procedure with a radioactive tracer appears to be a promising new diagnostic tool to predict lymph node status. No detection failures have been published so far in vulvar cancer. We recently experienced failure in the detection of the sentinel lymph node in a patient with a positive lymph node. CASE: A 75-year-old patient with a clinical T2N0M0 squamous cell carcinoma replacing the clitoris underwent a sentinel node procedure. A sentinel node was detected only at one groin. An exploration of the other groin showed a positive lymph node totally replaced by tumor. CONCLUSION: In the case we present, stasis of the lymph flow might be the leading cause of the failure of the sentinel lymph node procedure.     

The treatment of drooling by ultrasound-guided intraglandular injections of botulinum toxin type A into the salivary glands

OBJECTIVE: The aim of the study was to present the background, procedure, and technique of bilateral ultrasound-guided, single-dose injections of botulinum toxin type A (BTX) into the salivary glands in patients with severe drooling. STUDY DESIGN: Clinical trial. METHODS: Initially, an in vitro study was performed to determine the volume of the dilution of BTX required for optimal spreading and to gain insight in the spreading pattern of the fluid in the submandibular gland. Subsequently, patients with severe drooling were included in a clinical study. Salivary flow was measured under standardized conditions, and BTX was injected into the submandibular glands with the patient under general anesthesia and with ultrasound guidance as an outpatient procedure or during a short stay at the daytime care unit. RESULTS: BTX for each gland should be diluted in a volume of 1 to 1.5 mL saline to achieve adequate spreading within the gland and to diminish the risk of diffusion into surrounding structures. With ultrasound guidance, separate structures surrounding the glands and structures within the glandular parenchyma are well recognized and injection errors can be avoided. CONCLUSIONS: With the procedure described, it is possible to accurately inject BTX directly into the glandular parenchyma and to visualize spreading of the fluid in the glandular parenchyma. It is found to be a safe method that guarantees an optimal clinical effect and avoids potentially harmful side effects. We recommend ultrasound guidance if injections of BTX into the salivary glands are considered.