Low-Volume Metastases in Apparent Early-Stage Endometrial Cancer: Prevalence, Clinical Significance, and Future Perspectives.

Endometrial cancer (EC) is the most diagnosed gynecologic malignancy, and its incidence and mortality are increasing. The prognosis is highly dependent on the disease spread. Surgical staging includes retroperitoneal evaluation to detect potential lymph node metastases. In recent years, systematic lymphadenectomy has been replaced by sentinel lymph node (SLN) biopsy and ultrastaging, allowing for the detection of macrometastases, micrometastases, and isolated tumor cells (ITCs). Micrometastases and ITCs have been grouped as low-volume metastases (LVM). The reported prevalence of LVM in studies enrolling more than one thousand patients with apparent early-stage EC ranges from 1.9% to 10.2%. Different rates of LVM are observed when patients are stratified according to disease characteristics and their risk of recurrence. Patients with EC at low risk for recurrence have low rates of LVM, while intermediate- and high-risk patients have a higher likelihood of being diagnosed with nodal metastases, including LVM. Macro- and micrometastases increase the risk of recurrence and cause upstaging, while the clinical significance of ITCs is still uncertain. A recent meta-analysis found that patients with LVM have a higher relative risk of recurrence [1.34 (95% CI: 1.07-1.67)], regardless of adjuvant treatment. In a retrospective study on patients with low-risk EC and no adjuvant treatment, those with ITCs had worse recurrence-free survival compared to node-negative patients (85.1%; CI 95% 73.8-98.2 versus 90.2%; CI 95% 84.9-95.8). However, a difference was no longer observed after the exclusion of cases with lymphovascular space invasion. There is no consensus on adjuvant treatment in ITC patients at otherwise low risk, and their recurrence rate is low. Multi-institutional, prospective studies are warranted to evaluate the clinical significance of ITCs in low-risk patients. Further stratification of patients, considering histopathological and molecular features of the disease, may clarify the role of LVM and especially ITCs in specific contexts.

Incidence of sentinel lymph node metastases in apparent early-stage endometrial cancer: a multicenter observational study.

OBJECTIVE: Ultrastaging is accurate in detecting nodal metastases, but increases costs and may not be necessary in certain low-risk subgroups. In this study we examined the risk of nodal involvement detected by sentinel lymph node (SLN) biopsy in a large population of apparent early-stage endometrial cancer and stratified by histopathologic characteristics. Furthermore, we aimed to identify a subgroup in which ultrastaging may be omitted. METHODS: We retrospectively included patients who underwent SLN (with bilateral mapping and no empty nodal packets on final pathology) ± systematic lymphadenectomy for apparent early-stage endometrial cancer at two referral cancer centers. Lymph node status was determined by SLN only, regardless of non-SLN findings. The incidence of macrometastasis, micrometastasis, and isolated tumor cells (ITC) was measured in the overall population and after stratification by histotype (endometrioid vs serous), myometrial invasion (none, <50%, ≥50%), and grade (G1, G2, G3). RESULTS: Bilateral SLN mapping was accomplished in 1570 patients: 1359 endometrioid and 211 non-endometrioid, of which 117 were serous. The incidence of macrometastasis, micrometastasis, and ITC was 3.8%, 3.4%, and 4.8%, respectively. In patients with endometrioid histology (n=1359) there were 2.9% macrometastases, 3.2% micrometastases, and 5.3% ITC. No macro/micrometastases and only one ITC were found in a subset of 274 patients with low-grade (G1-G2) endometrioid endometrial cancer without myometrial invasion (all <1%). The incidence of micro/macrometastasis was higher, 2.8%, in 708 patients with low-grade endometrioid endometrial cancer invading <50% of the myometrium. In patients with serous histology (n=117), the incidence of macrometastases, micrometastasis, and ITC was 11.1%, 6.0%, and 1.7%, respectively. For serous carcinoma without myometrial invasion (n=36), two patients had micrometastases for an incidence of 5.6%. CONCLUSIONS: Ultrastaging may be safely omitted in patients with low-grade endometrioid endometrial cancer without myometrial invasion. No other subgroups with a risk of nodal metastasis of less than 1% have been identified.

General practitioners' management of symptomatic uncomplicated diverticular disease of the colon by using rifaximin, a non-adsorbable antibiotic.

OBJECTIVE: Symptomatic uncomplicated diverticular disease of the colon (SUDD) is generally managed by gastroenterologists rather than General Practitioners (GPs). The aim of this study was to assess the efficacy of the treatment of SUDD with rifaximin, a non-absorbable antibiotic, in a primary care setting by GPs. PATIENTS AND METHODS: This retrospective, observational study investigated the use of rifaximin at a dose of 400 mg b.i.d. for 5, 7 or 10 days monthly, up to 3 months. The symptoms were reported by the patients using a visual analogic scale (VAS) of 0-10. RESULTS: 286 SUDD patients were enrolled (44.4% of men, average age 70.92±10.98). Respectively, 15 (5.2%) patients received the treatment for 5 days, 205 (71.7%) for 7 days and 66 (23.1%) for 10 days. After three months, a significant reduction of VAS score was observed in almost all symptoms assessed: 135 (47.2%) patients reported no abdominal pain (p<0.001) and 23 (8.1%) reported no symptom. Adverse events related to the treatment were recorded in 3 (1.04%) patients, all of them mild and not requiring interruption of the treatment. Acute diverticulitis occurred in 9 (3.1%) patients, but only 2 of them [0.7% (n=2)] underwent surgery due to complicated diverticulitis. Analysis within the different treatment groups (5, 7 and 10 days) shows that rifaximin treatment is effective in reducing the severity of symptoms in almost all groups except for the constipation in the 5-day group. CONCLUSIONS: Rifaximin can be effectively used by GPs in real-life for the management of SUDD.

Comparing the use of a novel antibiotic-free film-forming topical wound dressing versus a topical triple antibiotic in dermatologic surgical procedures including Mohs micrographic surgery.

BACKGROUND: There is no universally accepted protocol of topical wound care after cutaneous surgical procedures. The current practice is to use petrolatum-based products, commonly containing topical antibiotics. The rise in antibiotic-resistant bacteria and increased risk of allergic and contact dermatitis due to the use of topical antibiotics is well established. OBJECTIVE: To compare the prevalence of contact dermatitis, the infection rate and the subjective measures of healing of a novel, antibiotic-free, film-forming silicone-based wound dressing to a topical triple antibiotic petrolatum-based ointment in patients undergoing invasive dermatological interventions in two arms: (1) Mohs micrographic surgery (MMS) and (2) a combination of various routine dermatologic surgical procedures. DESIGN: The 231 patients were enrolled in this open-label, randomized, single-blinded study. Patients applied the products immediately after surgery and daily afterwards. Clinicians evaluated the surgical site for infection or contact dermatitis at all follow-up visits. Acute wound healing progression was assessed using a rating scale against clinical experience and expected results from -4 (much worse) to +4 (much better). RESULTS: Contact dermatitis was significantly decreased in the wound dressing group compared to the topical antibiotic group (0 vs 15.9%, P < 0.001). There was no difference between the study arms (Mohs vs. non-Mohs, P = 0.242). Infection rate was not significantly different between the groups (P > 0.05) and between the study arms (P > 0.05). Assessor-rated secondary outcomes like healing time, healing quality, erythema and new tissue quality were significantly better in the wound dressing group, while comfort and perceived overall satisfaction were better in the antibiotic group. Patient-rated outcomes did not show any difference between groups and between study arms. CONCLUSION: The wound dressing used in this study is a topical silicone gel preparation and presents a viable alternative to topical antibiotics for postoperative wound care without enhancing the risk of infection.

Spreading of COVID-19 in Italy as the spreading of a wave packet.

We find that the spreading of the COVID-19 pandemic in Italy can be described as the propagation of a wave packet in a dispersive medium where the effect of lockdown is simulated by the dispersion relation of the medium. We start expanding a previous statistical analysis based on the official data provided by the Italian Civil Protection during 100 days, from March 2nd to June 9th. As the total number of people infected with the virus is uncertain, we have considered the trend of ICU patients and the sum of hospitalized patients and the deceased. Both the corresponding curves are well approximated by the same function depending on four free parameters. The model allows to predict the short-term behavior of the pandemic and to estimate the benefits due to lockdown measures.

Partial repair in irreparable rotator cuff tear: our experience in long-term follow-up.

AIM OF THE WORK: Massive rotator cuff tears are a common source of shoulder pain and dysfunction, especially in middle age patient; these lesions represent about 20% of all rotator cuff tears and 80% of recurrent tears. Some lesions are not repairable or should not be repaired: in this case, a rotator cuff partial repair should be recommended. The aim of the study is to evaluate the outcome of rotator cuff partial repair in irreparable rotator cuff massive tear at medium and long-term follow-up. MATERIALS AND METHOD: We have evaluated 74 consecutive patients treated with functional repair of rotator cuff by the same surgeon between 2006 and 2014. We divided patients into 2 groups, obtaining 2 average follow-up: at about 6,5 (group A) and 3 years (group B). In December 2015, we evaluated in every patient ROM and Constant Score. We analyzed difference between pre-operatory data and the 2 groups.  Results: We found statistical significant difference in ROM and in Constant Score between pre-operatory data and group A and group B. Between group A and group B there is relevant difference in Constant Score but not in ROM. CONCLUSIONS: Partial repair can give good results in a medium follow-up, in terms of pain relief and improvement of ROM, as well as in quality of life. Difference in ROM and Constant Score between group A and group B may indicate the begin of partial repair failure; according to our data, 6-7 years may be the time limit for this surgery technique.

Characterization of endocrine features and genotype-phenotypes correlations in blepharophimosis-ptosis-epicanthus inversus syndrome type 1.

OBJECTIVE: Blepharophimosis syndrome (BPES) is an autosomal dominant genetic condition resulting from heterozygous mutations in the FOXL2 gene and clinically characterized by an eyelid malformation associated (type I) or not (type II) with premature ovarian failure. The distinction between the two forms is critical for female patients, as it may allow to predict fertility and to plan an appropriate therapy. Identifying an underlying causative mutation is not always predictive of the clinical type of BPES since genotype-phenotype correlations are not yet fully delineated. Here, we describe the clinical and hormonal phenotypes of three female patients with BPES type 1 from two novel families, correlate their phenotypes with identified mutations, and investigate the effects of hormone replacement therapy (HRT). METHODS: Clinical, biochemical, and genetic evaluation were undertaken in all the patients and genotype-phenotype correlation was analyzed. The effects of substitutive hormonal therapy on secondary sexual characteristics development and induction of menarche were evaluated. RESULTS: All patients presented with primary amenorrhea or other signs of ovarian dysfunction. Two distinct mutations, a missense p.H104R change and an in-frame p.A222_A231dup10 duplication in the FOXL2 gene were identified. Observed phenotypes were not in accordance with the prediction based on the current genotype-phenotype correlations. HRT significantly improved secondary sexual characteristics development, as well as the induction of menarche. CONCLUSIONS: This study highlights the importance of early recognition of BPES and emphasizes the need of personalized therapy and follow-up in female patients carrying distinct FOXL2 mutations.

[Detection of HTLV-1 DNA in biopsies of Chilean patients with cutaneous T-cell lymphoma]. / Búsqueda del ADN del virus HTLV-1 en biopsias de pacientes con linfoma cutáneo de células T.

BACKGROUND: Human T-lymphotropic virus-1 (HTLV-1) infection has been associated with the pathogenesis of cutaneous T cell lymphomas (CTCL). AIM: To search for HTLV-1 DNA in skin biopsies of patients with CTCL. MATERIAL AND METHODS: A retrospective study was conducted using 25 biopsies of patients with CTCL. DNA was extracted from lymphoid tissue by microdissection. A nested PCR was conducted to detect HTLV-1 genome using primers for the tax region. As negative controls, four cases of superficial perivascular dermatitis were chosen. As positive controls, five cases of T-cell leukemia/lymphoma (ATCL) were studied. RESULTS: A positive reaction was found in 3 of 25 cases. These biopsies corresponded to a case of Mycosis Fungoides, a case of CD30 (-) T-cell lymphoma and a case of lymphomatoid papulosis. Search was negative in the four cases of superficial perivascular dermatitis and positive in four cases of adult T-cell leukemia/lymphoma (ATCL). CONCLUSIONS: HTLV-1 DNA search in tissues is a useful tool recommended to study T-cell lymphomas. HTLV-1 infection only occurs in sporadic cases but may contribute to tumor aggressiveness and prognosis.

Búsqueda del ADN del virus HTLV-1 en biopsias de pacientes con linfoma cutáneo de células T / Detection of HTLV-1 DNA in biopsies of Chilean patients with cutaneous T-cell lymphoma

Background: Human T-lymphotropic virus-1 (HTLV-1) infection has been associated with the pathogenesis of cutaneous T cell lymphomas (CTCL). Aim: To search for HTLV-1 DNA in skin biopsies of patients with CTCL. Material and Methods: A retrospective study was conducted using 25 biopsies of patients with CTCL. DNA was extracted from lymphoid tissue by microdissection. A nested PCR was conducted to detect HTLV-1 genome using primers for the tax region. As negative controls, four cases of superficial perivascular dermatitis were chosen. As positive controls, five cases of T-cell leukemia/lymphoma (ATCL) were studied. Results: A positive reaction was found in 3 of 25 cases. These biopsies corresponded to a case of Mycosis Fungoides, a case of CD30 (-) T-cell lymphoma and a case of lymphomatoid papulosis. Search was negative in the four cases of superficial perivascular dermatitis and positive in four cases of adult T-cell leukemia/lymphoma (ATCL). Conclusions: HTLV-1 DNA search in tissues is a useful tool recommended to study T-cell lymphomas. HTLV-1 infection only occurs in sporadic cases but may contribute to tumor aggressiveness and prognosis.

Eritema elevatum diutinum: reporte de dos casos y revisión de la literatura / Erythema elevatum diutinum: report of two cases and literature review

Eritema elevatum diutinum es una enfermedad cutánea poco frecuente y de curso crónico recurrente. Se caracteriza por pápulas, placas y nódulos de color rojo-violáceo de distribución acral y simétrica sobre las superficies extensoras. Un hallazgo histopatológico característico es la vasculitis leucacitoclástica. El tratamiento de elección es la dapsona, A continuación se describen dos casos de Eritema Elevatum Diutinum, el primero en un paciente adulto y el segundo en una niña de 15 años, ambos con estudio histopatológico compatible y buena respuesta al uso de difenildiazona (dapsona).

Erithema elevatum diutinum is a rare cutaneous disease. It usually has a chronic course and is characterized by purple red papules, plaques o nodules with an acral and symmetrical distribution. The main histological feature is o leucocytoclostic vasculitis. Treatment of choice is dapsone. We describe two cases of erithema elevatum diutinum, a male adult patient and a 15 year old girl. Both cases present characteristic histological findings and good response to dapsone.

Vasculopatía livedoide: reporte de dos casos / Livedoid vasculopathy: a two case report

Vasculopatía livedoide es una enfermedad poco frecuente que se presenta principalmente en mujeres de edad media de la vida, antes de los cuarenta años. Es llamado también atrofia blanca, livedo reticular con ulceración de verano, vasculitis hialinizante segmentaria, o PURPLE (úlceras purpúricas dolorosas con patrón reticular de extremidades inferiores). Generalmente afecta los tobillos y se exacerba en primavera y verano. Su etiología es aún desconocida, pero se puede clasificar en formas primarias (sin ninguna patología asociada) y secundarias, ambos con un componente trombótico. A continuación se describen dos casos de vasculopatía livedoide: una mujer de 22 años con úlcera en pierna izquierda y púrpura retiforme en ambas extremidades. El estudio demostró que el cuadro estaba asociado o síndrome antifosfolípidos. El segundo caso es de una mujer de 47 años con uno vasculopatía livedoide secundaria o lupus eritematoso sistémico.

Livedoid vasculitis is a rare disease that occurs mainly in women under 40 years of age. It has also be ennamed atrofia blanche, hyaline segmentary vasculitis or PURPLE (purpuric ulcers with reticular pattem in low legs). It usually affects ankles and has an exacerbation during Spring and Summer seasons. It has an unknown etiology, and it has been classified as primary (or idiopathic) or secondary (associated to another disease). We describe two cases of livedoid vasculopathy: the first case is o 22-year-old women with ulcers and retiform purpura associated to antiphospholipid syndrome. The second case is o 47-year-old women with livedoid vasculopathy associated to systemic lupus erythematosus.

Metástasis cutáneas en cáncer de ovario: [revisión] / Skin metastases of ovarian cancer: [review]

El cáncer de ovario es la segunda neoplasia maligna ginecológica más común, pero la principal causa de muerte entre las mujeres que padecen algún cáncer ginecológico. El hallazgo de metástasis a distancia en cáncer de ovario tanto en el diagnostico como durante el seguimiento, se encuentra en cerca del 18 por ciento de las pacientes. Las metástasis en piel se han reportado en cifras menores a un 4 por ciento. El compromiso cutáneo se ha descrito como un fenómeno tardío en la historia natural de la, enfermedad, reportándose una sobrevida promedio de 4 meses, posterior al hallazgo de la metástasis en piel. En éste trabajo se reporta el caso de una paciente con éste tipo de diseminación metastásica en piel, junto con una revisión bibliográfica del tema.

Ovarian carcinoma is the second most common gynecologic neoplasm, but it is still the main cause of death among the gynecologic tumors in women. Distant metastases are found in 18 percent of the patients with ovarian carcinoma. Skin metastases of ovarian carcinoma are very rare. It has been reported in almost 4 percent and in some cases as the first manifestation of the disease. Skin metastases have been described as a late manifestation during the natural history of the disease, reporting an average of 4 month survival after the finding of skin lesions. In this paper a case of a patient with this type of metastatic dissemination on skin is reported, including a bibliographic review of the literature.

Dependence of the electron-cloud instability on the beam energy.

The electron cloud (EC) can be formed in the beam pipe of a circular accelerator if the secondary emission yield (SEY) of the inner surface is larger than 1, and it can detrimentally affect the circulating beam. Understanding the underlying physics and defining the scaling laws of this effect is indispensable to steer the upgrade plans of the existing machines and the design of new ones. The single bunch EC instability (ECI) is shown to be strongly affected by the transverse beam size. Transversely, smaller beams going through an electron cloud generate higher electron peak densities and lower the intensity threshold to make the beam unstable. In particular, since higher energy beams have smaller transverse sizes (for equal normalized transverse emittances), the scaling of the ECI threshold with the beam energy turns out to be surprisingly unfavorable.

Incoherent effects of electron clouds in proton storage rings.

Electron clouds in the beam pipe of high-energy proton or positron storage rings can give rise to significant incoherent emittance growth, at densities far below the coherent-instability threshold. We identify two responsible mechanisms: namely, (1) a beam particle periodically crosses a resonance and (2) a beam particle periodically crosses a region of the bunch where its motion is linearly unstable. Formation of halo or beam-core blow up, respectively, are the result. Key ingredients for both processes are synchrotron motion and electron-induced tune shift. The mechanisms considered provide a possible explanation for reduced beam lifetime and emittance growth observed at several operating accelerators. Similar phenomena are likely to occur in other two-stream systems.

Telangiectasia macularis eruptiva perstans: reporte de un caso y revisión de la literatura / Telangiectasia macularis eruptiva perstans: a case report and literature review

Mastocitosis es una enfermedad poco frecuente, caracterizada por incremento en el número de células cebadas en diferentes tejidos y órganos. El sitio más frecuentemente comprometido en cualquier variedad de mastocitosis es la piel. Dentro de las mastocitosis cutáneas se encuentran: uticaria pigmentosa, mastocitoma solitario, mastocitosis cutánea difusa y telangiectasia macularis eruptiva perstans. Telangiectasia macularis eruptiva perstans es una entidad poco frecuente dentro de las mastocitosis cutáneas. Se caracteriza por múltiples placas confluentes color rojizo o café, ubicadas frecuentemente en el tórax, aunque también en cara. Ocurre principalmente en adultos de mediana edad, y la mayoría de los paciente con esta enfermedad sólo presentan compromisos cutáneo. El pronóstico en general es favorable, con episodios de urticaria o síntomas constitucionales. Sin embargo, también se ha descrito asociación con enfermedades sistémicas. Se presenta el caso de una paciente de 67 años con máculas café y telangiectasias en tórax anterior, espalda y brazos, acompañada de hiperpigmentación. Las lesiones desaparecieron después de maniobras de comprensión y el signo de Darier fue negativo. La biopsia demostró la epidermis con leve espongiosis y la dermis con infiltración perivascular e intersticial significativa de mastocitos que se tiñen con Giemsa. No se observaron ni granulomas ni vasculitis. Se confirma el diagnóstico de telangiectasia macularis eruptiva perstans. Se discuten características clínicas, diagnósticas y terapéuticas de rara condición.