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.

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.

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.

Preoperative evaluation of tumor ploidy in endometrial carcinoma: An accurate tool to identify patients at risk for extrauterine disease and recurrence.

BACKGROUND: Tumor ploidy is a strong prognostic factor in patients with endometrial carcinoma, but generally is evaluated only after surgery. The availability of a simple and reliable method to determine tumor ploidy before any treatment is initiated could be helpful in the selection of patients at high risk for advanced primary disease and subsequent recurrence, with several possible benefits. The objectives of the current study were: 1) to test the accuracy of flow cytometric determination of tumor ploidy from preoperative outpatient endometrial biopsies compared with standard postoperative evaluation from the surgical specimen and 2) to correlate this preoperative parameter with the local recurrence and extrauterine tumor spread. METHODS: Tumor ploidy from both preoperative biopsy material and the macroscopic surgical specimens was evaluated prospectively in 50 consecutive patients with endometrial carcinoma. DNA analyses were performed in a blind fashion. Patients were followed for a median of 26 months (range, 16-46 months). RESULTS: In 9 of 50 cases (18%) an aneuploid tumor was found by the standard postoperative analysis. All 9 aneuploid tumors (100%) also were identified correctly by the preoperative test on biopsy material. Occult extrauterine tumor spread was found in 10 patients (20%). The incidence rate of aneuploidy among these tumors was 50% compared with 10% in surgical International Federation of Gynecology and Obstetrics Stage I tumors (P = 0.01). The recurrence rate was 55.5% (5 of 9 tumors) in the aneuploid group and 2.4% (1 of 41 tumors) in the diploid group (P < 0.001). The disease free survival rates of patients with diploid and aneuploid tumors were 97.5% and 44.4%, respectively (P < 0.0001). CONCLUSIONS: Preoperative tumor ploidy determination based on outpatient endometrial biopsy is as accurate as the standard postoperative evaluation in patients with endometrial carcinoma. Tumor aneuploidy confirms the usefulness of this method in selecting patients at risk for occult extrauterine tumor diffusion and recurrence.

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.

Three classes of radical vaginal hysterectomy for treatment of endometrial and cervical cancer.

OBJECTIVES: The aims of this study were to (1) describe three types of extended vaginal hysterectomy with different degree of radicality, (2) to identify possible indications for each one of them, and (3) to encourage individualization of the treatment, with special reference to the reevaluation of the role of vaginal surgery in gynecologic oncology. STUDY DESIGN: The surgical-anatomic principles of radical vaginal surgery and the techniques of three increasingly extended vaginal hysterectomies are illustrated. Possible indications are pointed out on the basis of our personal experience from previously published retrospective studies. RESULTS: Class I extended vaginal hysterectomy allows the "en bloc" dissection of the uterus along with the upper third of vagina and both the adnexa. The parametria are not removed. This procedure has proved to be of value for treatment of stage I endometrial cancer. In the class II extended vaginal hysterectomy the distal tract of the anterior and posterior parametria are preserved, whereas the cardinal ligament is entirely removed. This operation has shown promising results for treatment of stage IB-IIA cervical cancer of small volume while reducing the incidence of bladder and rectal dysfunctions. The class III procedure includes the complete removal of the parametria (anterior, lateral, and posterior). This operation has been shown to provide a high rate of cure for stage IB-IIA cervical cancer. CONCLUSIONS: In view of the several advantages of vaginal surgery, this approach should be considered in the individualized treatment of selected cases of endometrial and cervical cancers. The three classes of radical vaginal hysterectomy allow tailoring the type of vaginal operation to the clinical and physical characteristics of the patients. The combined use of extraperitoneal or laparoscopic lymphadenectomy would considerably extend the indications for radical vaginal operations.

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.

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.

Intravenous immune globulin therapy of lupus nephritis: use of pathogenic anti-DNA-reactive IgG.

The authors have recently shown that antibodies with anti-idiotype (Id) specificity to pathogenic Ids of lupus nephritis may occasionally occur in several intravenous immune globulin (IVIG) preparations because they are present in healthy donors and the healthy relatives of SLE patients. In the present study, the authors purified these anti-Ids and treated two SLE patients with nephritis in parallel with conventional high-dose IVIG management with a commercial preparation (IVIG 6) in three controls for two months. Because pathogenic Ids of anti-DNA molecules, such as both 8.12 and F4 Ids, show a cationic mobility in isoelectric focusing, a commercial preparation of IVIG (11) was absorbed on a Sepharose column coupled with DC-305-39 myeloma protein, namely an 8.12+ and F4+ cationic IgG. Infusion of the eluate (EL-11) induced a prompt resolution of proteinuria levels and an evident decrease of serum levels of anti-DNA antibodies in both patients, whereas in the three controls, proteinuria and anti-DNA antibodies were scarcely reduced. In addition, plasma levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha were also significantly influenced by both treatments. The mean values of both cytokines increased significantly after 1 h and then progressively declined over the next 48 h. It was of interest, however, that the increased TNF-alpha in the two EL-11-treated patients was significantly lower than in the three controls. The data suggest that reduction of active lupus nephritis by enriched specific anti-Id molecules is the result of two (or perhaps more) mechanisms: suppression of pathogenic idiotypes at the cellular level and improvement in the mesangium of the secretion of anti-inflammatory cytokines, such as IL-6, whose defective function is related to the autoimmune disorder.

Vaginal hysterectomy versus abdominal hysterectomy for the treatment of stage I endometrial adenocarcinoma.

OBJECTIVE: The aims of the current study were to (1) determine the effectiveness of vaginal hysterectomy for the treatment of stage I endometrial cancer and (2) analyze which clinical pathologic parameters were independent predictors of clinical outcome. STUDY DESIGN: In a retrospective analysis, 5- and 10-year results of vaginal hysterectomy were compared with those of abdominal hysterectomy in 327 cases of stage I adenocarcinoma. No preoperative irradiation was given. Overall, 180 patients underwent vaginal hysterectomy, whereas 147 patients had abdominal hysterectomy (106 cases with lymphadenectomy). The log-rank test was used for evaluation of survival differences. RESULTS: The 5- and 10-year survival rates (Kaplan-Meier method) were, respectively, 90% and 87% in the vaginal hysterectomy group and 91% and 90% in the abdominal hysterectomy group (difference not significant). The grade of differentiation, depth of myometrial invasion, and age were significantly correlated with survival, whereas histologic type, mode of surgery, lymphadenectomy, and adjuvant radiotherapy were not. In a multivariate analysis (Cox proportional hazards), grade of differentiation and age were independent predictors of clinical outcome, whereas depth of myometrial invasion lost significance. CONCLUSIONS: Vaginal hysterectomy showed a high rate of cure in stage I endometrial cancer. Therefore it can be used as an alternative to the abdominal operation in obese and poor surgical risk patients and, possibly, in selected low-risk cases.

Epithelial ovarian tumors in the reproductive age group: age is not an independent prognostic factor.

BACKGROUND: While ovarian carcinoma is rare in the reproductive age group, these younger patients are known to fare better than the older patients. To determine whether age is an independent prognostic factor, as well as to investigate the clinicopathologic profile and survival rate of young women with ovarian carcinoma, a retrospective analysis in a series of patients aged 40 years or younger was performed. METHODS: We collected data on 74 patients with borderline or invasive ovarian carcinoma treated at the Department of Obstetrics and Gynecology at the University of Florence between 1969 and 1994. The median follow-up was 72 months (range, 11-288 months). To assess the clinicopathologic profile and survival differences according to age, the series was subdivided into "very young" (30 years or younger) and "young" (31-40 years) groups of 34 and 40 patients, respectively. Survival rates (Kaplan-Meier method) were compared by the log rank test. A multivariate analysis (Cox proportional hazards) was used to determine the independent effect of each variable on survival. RESULTS: The overall 5-year and 10-year survival rates were 58.2% and 46.1%, respectively. Several prognostic factors were found significant by univariate analysis, including stage (P < 0.001), grade (P < 0.001), residual disease (P < 0.001), histologic type (P < 0.05), and age (< or = 30 years vs. 31-40 years; P = 0.009). Five year survival rates for the patients age 30 years and younger and patients age 31-40 years were 71.3% and 47.1%, respectively. In the former group, low malignant potential tumors and well differentiated carcinomas were significantly more frequent (68.8% vs. 37.5%; P = 0.01). In the multivariate analysis, only stage (I vs. >I; P = 0.004), grade (0-1 vs. 2-3; P = 0.03) and residual disease (P = 0.02) were found to be significant independent prognostic factors, whereas age (< or = 30 years vs. 31-40 years) yielded no independent information (P = 0.36). CONCLUSIONS: Epithelial ovarian cancer patients age 30 years or younger have a more favorable prognosis because of a higher rate of early stage, low grade tumors. Patients aged 31-40 years also show a more favorable disease profile and clinical outcome, although to a lesser extent, than the average ovarian cancer population. Age does not emerge as an independent prognostic factor for ovarian carcinoma in women younger than 40 years.

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.

Immunomodulation of T and B cell functions in multiple myeloma patients treated with combined erythropoietin and alpha-interferon therapy.

T and B lymphocyte functions were investigated in the course of a long-term trial of recombinant human erythropoietin in patients with progressing multiple myeloma. Peripheral mononuclear cell as well as T and B lymphocyte cultures were established at the 1st, 13th, and last week of the 24-week protocol from 16 treated and 15 untreated patients. Control cultures from healthy individuals were also obtained. A suppression of phytohemagglutinin-induced proliferation of T cells was noted in all 1st-week cultures, whereas a variable increase of 3H-thymidine uptake was noted at the end of the trial in the cultures from erythropoietin-treated patients. A significant increase was observed, however, in cultures from 5 erythropoietin-treated patients who also received alpha-interferon when their cells were grown in the presence of the hormone. In contrast, the pokeweed mitogen-driven in vitro synthesis of immunoglobulins was not significantly influenced by the duration of erythropoietin treatment, nor by addition of the hormone. IgG secretion by Epstein-Barr virus-transformed B cells in cultures from 9 erythropoietin-treated and 6 untreated patients was enhanced in the presence of both recombinant human erythropoietin and alpha-interferon. These data suggest that synergy between the two cytokines may variably modulate certain immune functions in vitro. This effect might account for the increase of serum IgM levels noted in some patients who received alpha-interferon.

Crystallization and preliminary X-ray analysis of the river buffalo (Bubalus bubalis L.) BB phenotype carbonmonoxyhaemoglobin.

Ruminant haemoglobin (Hb) extracted from river buffalo (Bubalus bubalis) has been purified and crystallized. Two different Hb forms of the phenotype BB gave isomorphous crystals which diffracted to 2.8 A resolution and were not sensitive to radiation damage. Crystals of CO Hb have space group P2(1)2(1)2(1) with unit-cell parameters a = 54.8, b = 64.0, c = 158.6 A, and contain one Hb molecule per asymmetric unit.