Proof-of-Principle Experiment on the Dynamic Shell Formation for Inertial Confinement Fusion.

In the dynamic-shell (DS) concept [V. N. Goncharov et al., Novel Hot-Spot Ignition Designs for Inertial Confinement Fusion with Liquid-Deuterium-Tritium Spheres, Phys. Rev. Lett. 125, 065001 (2020).PRLTAO0031-900710.1103/PhysRevLett.125.065001] for laser-driven inertial confinement fusion the deuterium-tritium fuel is initially in the form of a homogeneous liquid inside a wetted-foam spherical shell. This fuel is ignited using a conventional implosion, which is preceded by a initial compression of the fuel followed by its expansion and dynamic formation of a high-density fuel shell with a low-density interior. This Letter reports on a scaled-down, proof-of-principle experiment on the OMEGA laser demonstrating, for the first time, the feasibility of DS formation. A shell is formed by convergent shocks launched by laser pulses at the edge of a plasma sphere, with the plasma itself formed as a result of laser-driven compression and relaxation of a surrogate plastic-foam ball target. Three x-ray diagnostics, namely, 1D spatially resolved self-emission streaked imaging, 2D self-emission framed imaging, and backlighting radiography, have shown good agreement with the predicted evolution of the DS and its stability to low Legendre mode perturbations introduced by laser irradiation and target asymmetries.

Circulating regulatory T cells in "clinical" monoclonal B-cell lymphocytosis.

Regulatory T-cells (Tregs) constitute a small subset of cells involved in antitumour immunity and are generally increased in patients with chronic lymphocytic leukemia (CLL). No data is available on Tregs in monoclonal B-cell lymphocytosis (MBL), a disease entity characterized by less than 5000/microL circulating clonal B-cells in absence of other features of lymphoproliferative disorders. We used multicolour flow cytometry to evaluate the number of circulating Tregs in 56 patients with "clinical" MBL, 74 patients with previously untreated CLL and 40 healthy subjects. MBL patients showed a lower absolute number of Tregs, compared to CLL patients, but slightly higher than controls. Moreover, the absolute cell number of Tregs directly correlated both with more advanced Rai/Binet clinical stages and peripheral blood B-cell lymphocytosis. Of note, the absolute number of Tregs was found lower in MBL patients than in CLL patients staged as 0/A Rai/Binet. The study showed that Treg increase gradually from normal subjects to "clinical" MBL patients and are significantly higher in CLL patients as compared to MBL patients. Moreover, a significant direct relationship was found between higher Treg values and a higher tumor burden expressed by B-lymphocytosis or more advanced clinical stages. In light of this data, MBL seems to be a preliminary phase preceding CLL. The progressive increase of Treg numbers might contribute both to the clinical evolution of MBL to overt CLL and to CLL progression.

Expression of the retinoblastoma-related gene Rb2/p130 correlates with clinical outcome in endometrial cancer.

PURPOSE: The retinoblastoma gene is the prototype of tumor-suppressor genes and has been shown to be involved in the pathogenesis and progression of several human malignancies. In this study, we determined the relation between the expression of a newly discovered retinoblastoma-related gene Rb2/p130 and outcome in patients with endometrial carcinoma. PATIENTS AND METHODS: pRb2/p130 expression was determined immunohistochemically in specimens of endometrial carcinoma (stages I to IV) from 100 patients who underwent surgery as the first treatment. The pRb2/p130 status was analyzed in relation to the length of disease-free survival and disease-specific survival. RESULTS: Decreased levels of pRb2/p130 in endometrial cancer cells was significantly associated with a decreased probability of remaining disease-free after treatment (P = .003) and with decreased probability of survival (P < .0001). In a multivariate analysis, pRb2/p130 status (P = .004), tumor stage (P = .009), and ploidy status (P = .02) were independent predictors of clinical outcome. The risk of dying of disease was increased substantially (risk ratio, 4.91; 95% confidence interval, 1.66 to 14.54) among patients with decreased levels of pRb2/p130 in tumor cells. CONCLUSION: In patients with endometrial carcinoma who did not receive radiotherapy or chemotherapy before surgery, the presence of decreased levels of pRb2/p130 in tumor cells is associated with a significantly increased risk of recurrence and death of disease, independent of tumor stage and ploidy status.

Management of benign adnexal masses by vaginal route.

Until recently, surgical treatment of a benign adnexal mass implied a laparotomy. In recent years, the development of laparoscopic surgery, as well as ultrasound-guided aspiration techniques, have significantly modified the treatment options for these patients. These procedures have shown considerable advantages. They have reduced surgical trauma and have shortened the hospital stay. We present the results of our experience on the feasibility of a trans-vaginal surgical approach for the removal of benign adnexal masses. This technique, using traditional and cheap surgical instruments, allows the surgeon to excise benign adnexal masses, by entering the peritoneum through the posterior vaginal fornix and thus avoids the trauma of laparotomy. Fifty-four patients were operated on by this technique at our Department. The mean age was 39 years (range 21-66). In all cases, the operation was completed by the trans-vaginal approach. The median operative time was 30 minutes (range 20-45), and no blood transfusion was needed. The pathological diagnoses were as follows: functional ovarian cyst; 19, endometriotic cyst; 18, dermoid cyst; 11, parovarian cyst; 4 and peduncolated fibroid of the uterine fundus; 2 cases. The diameter of the adnexal masses ranged from 3 to 10 cm (median of 6 cm). In 30 cases, a conservative surgery was done (including 2 myomectomies), whereas in 24 cases, the adnexectomy was needed. Median post-operative stay in hospital was 4 days (range 1-14). This study shows the feasibility of trans-vaginal surgical approach for benign adnexal masses. The advantages and limitations of this technique, as well as of the traditional and laparoscopic surgery are considered and discussed. We believe that the transvaginal approach could be useful and cost-effective for the treatment of selected cases of adnexal masses.

CD38 expression correlates with adverse biological features and predicts poor clinical outcome in B-cell chronic lymphocytic leukemia.

CD38 identifies a surface molecule with multi-functional activity. Its prognostic importance in B-cell chronic lymphocytic leukemia (B-CLL) is currently under investigation in view of the fact that two different groups have recently indicated that CD38 expression could be an independent prognostic marker in B-CLL. We analyzed the clinico-biological features of 61 immunologically typical (CD5+CD23+) B-CLL patients stratified according to the CD38 expression. Twenty-two (36%) patients expressed CD38 in more than 30% of CD19-positive cells and were considered as CD38-positive B-CLL. Atypical morphology (p 0.02), peripheral blood lymphocytosis (p 0.01) and diffuse histopathologic bone marrow pattern (p 0.003) were findings found to be closely associated with CD38 expression. On the other hand, A and B Binet stages (p 0.02) and interstitial bone marrow involvement (p 0.005) were more represented in the CD38-negative B-CLL group. Trisomy 12 was detected more frequently in the CD38-positive B-CLL group, while 13q14 deletions mainly occurred in CD38-negative group (p 0.005). Finally, median survival of CD38-positive B-CLL patients was 90 months, while it was not reached at 180 months in CD38-negative patients. Taken together, our data strongly suggest that the evaluation of CD38 expression may identify two groups patients with B-CLL greatly differing in their clinico-biological features.

Morphologically typical and atypical B-cell chronic lymphocytic leukemias display a different pattern of surface antigenic density.

Recent evidences suggest that B-cell chronic lymphocytic leukemia (B-CLL) may have heterogeneous biological and clinical features. Immunological phenotype may be useful for distinguishing these different forms of disease. We used a quantitative flow cytometric approach to analyze the expression of several membrane molecules (CD19, CD20, CD22, CD23, CD11c, CD5, CD79b) commonly used to diagnose and characterize B-CLL in a choort of 84 consecutive B-CLL patients diagnosed according to morphological and immunological findings. We found that morphologically so-called "atypical" B-CLL displayed a significantly higher number of CD20 and CD22 molecules than typical forms. On the other hand, CD19 was found to be more expressed in typical B-CLL, although without reaching statistical significance. Finally, no difference was detected with respect to CD23, CD79b, CD11c and CD5 number of molecules/per cell between typical and atypical B-CLL. Other clinico-biological features, such as surface membrane immunoglobulin density, percentage of CD79b and FMC7 expression, peripheral blood lymphocytosis, trisomy 12 and advanced clinical stages were also found to be more frequent in atypical B-CLL. In conclusion, our data confirm the hypothesis that atypical B-CLL is a disease sustained by more mature B-cells, closely related but, at the same time, clearly distincted from neoplastic cells of typical B-CLL.

Magnetic resonance imaging in the measurement of clinical stage IB cervical carcinoma.

MRI can accurately define the extension of cervical carcinoma to the parametria. However, in patients with cervical carcinoma clinical stage IB, the definition of the dimensions of the tumour, prior to surgery, and may also modify the treatment procedure. Recently pre-operative neoadjuvant chemotherapy has been proposed for patients with bulky tumours. Multiple factors may influence the prognosis of clinical stage IB and survival varies greatly among these patients. In particular the maximum dimensions of the tumour seem to have a prognostic relevance. The aim of this paper is to evaluate the potential of MRI to measure tumour size, in order to discriminate between patients needing surgery alone or pre-operative therapy followed by surgery. In 20 patients with clinical stage IB cervical carcinoma we performed MRI to measure the radius of the cervix, the radius of the tumour and their ratios. The measurements obtained have been compared with the corresponding data from histopathology of the operative specimens. The close correspondence between these linear measurements allows us to propose MRI as a reliable method to define tumour size in clinical stage IB patients before surgery.

GnRH analogs in gynecological oncology: a review.

Chronic GnRH analogs (GnRH-A) administration has proven to be effective for the control of some hormone-dependent tumors. GnRH-A are now in the standard treatment of prostatic cancer. In the present paper experimental and clinical data on the use of GnRH-A in gynecologic oncology are reviewed in order to identify a possible role in the therapy of breast, endometrial and ovarian cancer. Besides the indirect hormonal effect of GnRH-A, mediated by the suppression of gonadal steroidogenesis, in vitro evidence suggests a direct anti-proliferative action involving autocrine-paracrine regulation of cellular function. In advanced or recurrent breast cancer objective responses were observed in 157 out of 378 premenopausal patients (41%) and in 18 out of 166 postmenopausal women (10%). In ovarian cancer complete and partial responses were observed in 14 out of 121 (11%). At present, data on advanced endometrial carcinoma are limited: only 18 treated patients are reported, of whom 7 responded (38.8%). However, in general, most of the responses observed were transient. Thus, so far, the use of GnRH-A in gynecologic oncology has to be considered for palliation, after the failure of other better understood treatment modalities. The possible use of GnRH-A as an adjuvant is still under investigation.

Estradiol and progestin receptors, 17-beta-hydroxysteroid-dehydrogenase and histopathologic grade in endometrial carcinoma.

The possible correlation between steroid receptor systems, 17-beta-HSD and histopathologic examinations were investigated. The well-differentiated tumors showed higher steroid receptor and 17-beta-HSD values than undifferentiated carcinomas. The steroid receptors did not present a statistically significant correlation with 17-beta-HSD. Nevertheless, some neoplastic endometria (29%) show higher values of progestin receptors and 17-beta-HSD, with a progestin:estrogen receptor ratio greater than one.

Efficacy of biofiltration for intradialytic hypotension.

Biofiltration, a simplified variant of hemodiafiltration, relieved intradialytic hypotension and acidosis in three patients previously on conventional hemodialysis.

Role of vaginal surgery in the 1st stage endometrial cancer. Experience of the Florence School.

The role of vaginal surgery in first stage endometrial carcinoma is reviewed. Out of total of 231 patients with endometrial cancer, observed at the Gynecologic Clinic of Florence from 1977 to 1981, 187 were at Stage I and 180 of them were submitted to surgery. During the period 1977-1979, the treatment protocol recommended vaginal hysterectomy; since 1980 abdominal surgery has prevailed. Depending on risk factors, adjunctive radiotherapy was employed. No statistically significant difference was observed in the actuarial survival curves between different surgery routes. However, severe complications and operative mortality was significantly lower in patients operated by vaginal hysterectomy. The vaginal route may be considered an adequate alternative therapy for endometrial carcinoma Stage I.

Radical vaginal hysterectomy with extraperitoneal pelvic lymphadenectomy in cervical cancer.

OBJECTIVE: The aim of this work was to examine three types of radical vaginal hysterectomy with different degrees of radicality, performed in order to reduce surgical complications and sequelae in different indications, and to test the feasibility of a new simple and quick technique for extraperitoneal pelvic lymphadenectomy to be used in combination with radical vaginal hysterectomy for treatment of cervical cancer. In this way the advantages of vaginal surgery (e.g.: unnecessary general anaesthesia, reduced surgical trauma, applicability to obese and poor surgical risk patients, fast time-saving procedure) can be preserved. METHODS: We compared retrospectively the long-term results of radical vaginal and radical abdominal operations in a large series of stage IB-IIA cervical cancer patients treated at our institution in Florence from 1968 to 1983. Furthermore, we analysed the results of our experience from 1995 to 1998, when we performed extraperitoneal pelvic lymphadenectomy, followed by radical vaginal hysterectomy, on 48 patients affected by cervical cancer. Extraperitoneal pelvic lymphadenectomy was performed through two small abdominal incisions (6-7 cm). Twenty-two patients (45%) were obese (BMI>30 kg/m2) and 20 were poor surgical risks. FIGO stage was: IB1 in 18 cases, IB2 in eight, IIA in six, IIB in 12, IIIB in four. Neoadjuvant chemotherapy was given in 12 cases and preoperative irradiation was given in ten. General and regional anaesthesia were used in 30 (62.5%) and in 18 (37.5%) cases, respectively. RESULTS: As for past experience, in stage IB the five-year survival of 356 patients who underwent radical vaginal hysterectomy and that of 288 who had radical abdominal hysterectomy with pelvic lymphadenectomy were 81% and 75%, respectively (p<0.05). Surgical complications were fewer with no mortality in the first group. In stage IIA, survival rates were 68% for radical vaginal hysterectomy and 64% for radical abdominal hysterectomy, in 76 and 64 cases, respectively (p=n.s.). As for the more recent experience, median operative time for extraperitoneal pelvic lymphadenectomy was 20 minutes for each side (range 15-36). In each patient a median of 26 lymph nodes were removed (range 16-48). Positive nodes were found in 12 cases (25%). Median operative time for radical vaginal hysterectomy was 40 minutes (range 30-65). Extraperitoneal pelvic lymphadenectomy complications included: lymphocyst, five cases (10%) and retroperitoneal hematoma, one (2%); all occurred at the beginning of the experience. Radical vaginal hysterectomy complications included: ureteral stenosis, one (2%) and uretero-vaginal fistula, one (2%). All complications occurred in patients who received radiotherapy or chemotherapy preoperatively. Median hospital stay was ten days (range 6-20). CONCLUSIONS: The results of our work demonstrate that our technique for extraperitoneal pelvic lymphadenectomy shows a good applicability to cervical cancer patients submitted to radical vaginal hysterectomy, which has a high rate of cure for stage IB and IIA as shown by our past experience. The procedure of extraperitoneal pelvic lymphadenectomy was quick, easy, and safe, and its realization was not detrimental to the advantages of radical vaginal hysterectomy. Our experience supports the continued use of this combined extraperitoneal and vaginal approach in the treatment of cervical cancer. Moreover, the three classes of radical vaginal hysterectomy allow tailoring the type of the operation to the clinical and physical characteristics of the patients.

Clinico-pathological profile of endometrial carcinoma in young women (under 40 years of age).

Twenty primary endometrial carcinomas in 40 year-old or younger women were collected from a series of 845 carcinomas and newly re-evaluated. The typical histological profile was well-differentiated adenocarcinoma (30%) or adenoacanthoma (35%); however, a case of adenosquamous carcinoma and an exceptional malignant mixed mesodermal tumor were also observed. No tendency for myometrial infiltration (M0) was displayed by 11 (55%) of the cases, while 6 were M1 and 3 were M2 infiltrating neoplasias. Adenomatous hyperplasia was associated with cancer in 53% of the 15 assessable cases. Histopathological diagnostic problems were elicited in 5 cases only. Typical Stein-Leventhal syndrome occurred in 7 patients (35%), while polycystic ovaries were observed in 15 cases (75%). Usually, the patients were obese (40%) and nulligravida (65%). All but one case were stage I disease. Prognosis seems to be excellent following surgery.

Clinical stage IIb carcinoma of the uterine cervix: results in 122 patients.

122 patients affected by clinical stage IIb cervical carcinoma were referred to the Radiation Therapy Department and Obstetrics and Gynaecology Department of the University of Florence between 1977 and 1986 for either radiation therapy only (42 patients) or preoperative treatment followed by surgical resection (80 patients). Among the 42 patients receiving radiation therapy only 23 were treated with external beam therapy only (total dose ranging between 50 Gy and 70 Gy at the mid-plane of the pelvis) while 19 received an additional intracavitary boost (total dose ranging between 68 Gy and 98 Gy at Manchester point A). Higher doses of irradiation to point A were correlated with significantly improved survival (65% vs. 18.5%, p = 0.001) and lower incidence of pelvic failure (33% vs 78%). Following preoperative radiation therapy 80 patients underwent radical surgery. Reassessment of the pathologic specimens was possible in all the cases. Disease free survival was not influenced by involvement of parametria, type of surgery or dose to Manchester point A, but rather to nodal status and thickness of the residual tumour in the cervix.

The microcolposcopy in the management of the cervical intraepithelial neoplasia.

The authors report their experience with the microcolpohysteroscope of Hamou. This instrument allows a magnification from 0 to 150 times. Its fine caliber (4 mm) allows to work easily also in the interior of the cervical canal, without preventive dilatation. The instrument allows the in vivo vision of the cellular arrangement at the superficial level, after vital staining. The purpose of this research is the discussion of the potentiality of the microcolpohysteroscopy as complementary mean to colposcopy, citology and histology in the management of the Cervical Intraepithelial Neoplasia (CIN). The authors conclude showing the advantages of this technique underlining as this method does not interfere with the natural evolution of the pathologic process, allowing at the contrary to determine the nature and the extension of the lesion. Then, without opposing or to citology or to colposcopy or to histology, it is not only a valid complementary diagnostic mean, but in particularly it contributes to a more rational therapeutic decision.

Pre-neoplastic lesions of vulvar cancer.

The monitoring of potentially neoplastic lesions is based on the determination of the histopathologic characteristics of the lesion, which is done either by large surgical resection of the lesions "in toto" or by biopsy of the lesion. Chronic vulvar dystrophy may develop into carcinoma, the supposed likelihood varying according to the various Authors. The lesion which is histologically defined as atypical keratoacanthoma is the most frequent precursor of carcinoma. Most Authors agree in believing that lichen scleroatrophic does not often develop into carcinoma. It is, nevertheless, the most frequent precursor of leukoplakia which is, on the other hand, a risk lesion. However, any chronic vulvar irritation may increase the risk of cancer and must therefore be carefully monitored by multiple biopsies to be examined at regular intervals.

Usefulness of hysteroscopy in endometrial adenocarcinoma staging.

Endometrial carcinoma has an absolutely unfavourable prognosis when it involves the cervix. Clinical staging, which is essential to a correct therapeutical approach, has proven quite wrong when relying on endocervical curettage. This work deals with the use of Hamou's microhysteroscope to assess the endocervical diffusion of endometrial cancer. Thanks to its very high sensitivity (100%), high specificity (89%) and diagnostic accuracy (92%), this method has proven extremely reliable in the clinical staging of endometrial carcinoma.