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The development of vascular networks in microfluidic chips is crucial for the long-term culture of three-dimensional cell aggregates such as spheroids, organoids, tumoroids, or tissue explants. Despite rapid advancement in microvascular network systems and organoid technologies, vascularizing organoids-on-chips remains a challenge in tissue engineering. Most existing microfluidic devices poorly reflect the complexity of in vivo flows and require complex technical set-ups. Considering these constraints, we develop a platform to establish and monitor the formation of endothelial networks around mesenchymal and pancreatic islet spheroids, as well as blood vessel organoids generated from pluripotent stem cells, cultured for up to 30 days on-chip. We show that these networks establish functional connections with the endothelium-rich spheroids and vascular organoids, as they successfully provide intravascular perfusion to these structures. We find that organoid growth, maturation, and function are enhanced when cultured on-chip using our vascularization method. This microphysiological system represents a viable organ-on-chip model to vascularize diverse biological 3D tissues and sets the stage to establish organoid perfusions using advanced microfluidics., (© 2024. The Author(s).)

Advances in microphysiological systems have prompted the need for robust and reliable cell culture devices. While microfluidic technology has made significant progress, devices often lack user-friendliness and are not designed to be industrialized on a large scale. Pancreatic islets are often being studied using microfluidic platforms in which the monitoring of fluxes is generally very limited, especially because the integration of valves to direct the flow is difficult to achieve. Considering these constraints, we present a thermoplastic manufactured microfluidic chip with an automated control of fluxes for the stimulation and secretion collection of pancreatic islet. The islet was directed toward precise locations through passive hydrodynamic trapping and both dynamic glucose stimulation and insulin harvesting were done automatically via a network of large deformation valves, directing the reagents and the pancreatic islet toward different pathways. This device we developed enables monitoring of insulin secretion from a single islet and can be adapted for the study of a wide variety of biological tissues and secretomes., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Microencapsulation technologies have experienced much growth over the past decades and are commonly used for food, cosmetic, pharmaceutical and biomedical applications. Certain application fields impose stricter requirements on the polymer capsules. In many biomedical applications including bioencapsulation, cell therapy and drug delivery applications, capsules are required to have a controlled shape and size, as well as a defined mechanical stability and porosity. This data article reports the alginate capsule production using common centrifugal technology, which enables the production of microcapsules with highly viscous biopolymers. We describe the experimental data generated in a parametric study, where the main control parameters of the centrifugal encapsulation system (alginate viscosity, rotating speed, nozzle diameter, collecting distance) were varied. The geometric properties of the produced hydrogel capsules were analysed by microscope photography and image processing. The dataset presented here contains the experimental data, the raw capsule images, the analysis scripts, the analysed images, and tables with extracted geometric information. All extracted data was compiled into a table containing geometric properties of more than 50000 analysed capsules. These data allow (i) to reproduce quickly the encapsulation experiments and be able to choose in a straight-forward manner the combination of parameters needed in order to generate capsules with desired properties; (ii) to create more general phase diagrams of the centrifugal encapsulation technology which can be widely used for prediction and/or parameter selection; (iii) to analyse more thoroughly the sensitivity of capsule properties to given stages of the encapsulation process. The research article on these data [1] was published in the journal Colloids and Surfaces A: Physicochemical and Engineering Aspect, with the title: Three-dimensional phase diagram for the centrifugal Calcium-alginate microcapsules production technology., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier Inc.)

Purpose Prostate motion occurs during radiotherapy for localized prostate cancer. We evaluated the input of intraprostatic fiducials for image-guided radiation therapy and compared it with bony anatomy and skin marks. Methods Eleven patients were implanted with three fiducial markers in the prostate. Daily sets of orthogonal kV-kV images were compared with digitally reconstructed radiography. Data were recorded for skin marks, bony anatomy, and fiducial markers. The variations were analyzed along three principal axes (left-right: LR, superoinferior: SI, and anteroposterior: AP). Results A total of 2,417 measures were recorded over 38 fractions of radiotherapy (76 Gy). Fiducial marker movements from bony anatomy were ≤ 5 mm for 84.2% (confidence interval: CI 95%±1.5), 91.3% (CI 95%±1.1), and 99.5% (CI 95%±0.4) of the measures along the AP, SI, and LR axes, respectively. Ninety-five percent of the shifts between a fiducial marker and the bony anatomy were < 8 mm in the AP and SI axes, and < 3 mm in the LR axis. Fiducial marker movements from skin marks were ≤ 5 mm for 64.8% (CI 95%±1.9), 79.2% (CI 95%±1.6), and 87.2% (CI 95%±1.3) of the measures along the AP, SI, and LR axes, respectively. Bony anatomy movements from skin marks were ≤ 5 mm for 84% (CI 95%±1.4), 92% (CI 95%±1.1), and 87% (CI 95%±1.3) of the measurements along the AP, SI, and LR axes, respectively. Conclusion Using fiducial markers provides better accuracy of repositioning of the prostate than using bony anatomy and skin marks for image-guided radiotherapy of prostate cancer., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Intensity modulated radiotherapy for prostate cancer involves daily monitoring of the positioning of the prostate, possible with cone beam CT (CBCT). It allows increased accuracy compared to readjustments but induces an increase in the time dedicated to these medical checks. The aim of the study was to evaluate the possibility of delegation of this task to the radiation therapists by comparing their readjustments to the doctors., Patients and Methods: Five consecutive patients treated with radiation for prostate cancer (76Gy) were analysed. All had a daily CBCT for position control. The movements of the prostate relative to the bony part, the positional variations of the prostate measured by the radiation therapists and the doctors and medical time required to analyse imagery (filling of the rectum and bladder and perform a recalibration) were measured., Results: One hundred seventy-six CBCT were analysed or 980 steps in the three axes. The movements of the prostate relative to bony part were respectively at least 5mm in 19%, 7% and 3% in the anterior-posterior, upper-lower and right-left axes. Changes readjustments between radiation therapists and doctors were in 95% of cases at the most 4mm in the anterior-posterior and upper-lower axis, and 3mm in the left-right axis. The time for medical use of the CBCT averaged 8min 40 [4 to 22min]., Conclusion: The daily readjustment on the prostate using CBCT may be delegated to radiation therapists with acceptable concordance of less than 4mm for 95% of measurements. An initial and ongoing training will ensure treatment safety., (Copyright © 2017. Published by Elsevier SAS.)

Purpose: To evaluate the surgical possibility following concomitant chemoradiotherapy for inflammatory breast cancer, after unsucessful neoadjuvant chemotherapy., Patients and Methods: The data from ten patients with inflammatory breast cancer treated between 1996 and 2010 by concomitant chemoradiotherapy after unsucessful neoadjuvant chemotherapy were analysed. All patients had an invasive carcinoma. All patients received a neoadjuvant chemotherapy, including anthracyclin, six patients received taxan and one received trastuzumab. Radiotherapy was delivered to the breast and regional lymph nodes in all patients at a dose of 50Gy; a boost of 20Gy was delivered to one patient. Concomitant chemotherapy was based on weekly cisplatin for six patients, on cisplatin and 5-fluorouracil the first and last weeks of radiotherapy for four patients., Results: The median follow-up for all patients was 44 months. Mastectomy was performed in nine patients. Two- and 5-year overall survival rates were respectively 70 % and 60 %. Median local recurrence delay was 5 months; six patients died (all from cancer), seven developped metastasis. Grade 1 and 2 epithelite was respectively observed in six and two patients, grade 2 renal toxicity in three patients, grade 2 neutropenia in one patient., Conclusion: Concomitant chemoradiotherapy for inflammatory breast cancer after unsucessful neoadjuvant chemotherapy may control the disease in some patients and lead to mastectomy. These results have to be confirmed through a multicentric study with more patients., (Copyright © 2015. Published by Elsevier SAS.)

This paper presents a new method for solving analytically the axisymmetric swirling flow generated in a finite annular channel from a rotating end wall, with no-slip boundary conditions along stationary side walls and a slip condition along the free surface opposite the rotating floor. In this case, the end-driven swirling flow can be described from the coupling between an azimuthal shear flow and a two-dimensional meridional flow driven by the centrifugal force along the rotating floor. A regular asymptotic expansion based on a small but finite Reynolds number is used to calculate centrifugation-induced first-order correction to the azimuthal Stokes flow obtained as the solution at leading order. For solving the first-order problem, the use of an integral boundary condition for the vorticity is found to be a convenient way to attribute boundary conditions in excess for the stream function to the vorticity. The annular geometry is characterized by both vertical and horizontal aspect ratios, whose respective influences on flow patterns are investigated. The vertical aspect ratio is found to involve nontrivial changes in flow patterns essentially due to the role of corner eddies located on the left and right sides of the rotating floor. The present analytical method can be ultimately extended to cylindrical geometries, irrespective of the surface opposite the rotating floor: a wall or a free surface. It can also serve as an analytical tool for monitoring confined rotating flows in applications related to surface viscosimetry or crystal growth from the melt.

Purpose: This retrospective study evaluated the effectiveness of salivary gland radiotherapy for reducing sialorrhea in patients with amyotrophic lateral sclerosis (ALS)., Patients and Methods: From August 2001 to February 2008, 21 patients with amyotrophic lateral sclerosis (six men, 15 women; mean age 61.2 years, range 39-81) received external beam radiotherapy for sialorrhea (evaluation by the ALS Functional Rating Scale). All patients had previously received pharmacological treatments with unsatisfactory results or side effects. The mean dose was 19.1Gy (range 3-48), delivered in five fractions (range 1-16) on 17 days (range 1-77). Eight patients received 3D-conformal and 13 received 2D-conformal radiotherapy. Clinical target volumes included the parotids and submandibular glands (18 patients), submandibular glands and one parotid (one patient), or parotids (two patients). Thirteen patients were treated with 5.5-6MV photons and eight were treated with 6-15MeV electrons. A satisfactory salivary response was defined as complete or partial improvement. The median follow up was 10.4 months (range 0.4-26). One patient was lost to follow up., Results: A positive response was observed in 65% of patients during a mean of 7 months (range 1-23). Four patients (20%) treated with photons and no patients treated with electrons experienced acute toxicity. Half (50%) the patients treated with photons and 87.5% of patients treated with electrons responded positively (P=0.09). Positive responses were more common with a high total dose (≥16Gy; 78.6%) than a low total dose (<16Gy; 33%; P=0.07). No differences were observed in tolerance (P=0.27). Age and sex did not impact the response., Conclusion: Salivary gland radiotherapy effectively reduced sialorrhea in patients with amyotrophic lateral sclerosis. An adequate compromise between toxicity and efficiency was achieved with 3D-conformal radiotherapy delivered with electrons to parotids and submandibular glands in a total dose of 16Gy or more (mean: 20Gy in five fractions)., (Copyright © 2013 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: To evaluate the feasability of immediate breast reconstruction (IBR) following mastectomy after neoadjuvant chemotherapy (NACT) and radiation therapy (RT) for operable invasive breast cancer (OIBC), in terms of incidence of local complications, locoregional control and survival., Patients and Methods: From 1990 to 2008, 210 patients were treated by NACT, RT and mastectomy with IBR for OIBC. One hundred and seven patients underwent a latissimus dorsi flap with implant (LDI), 56 patients a transverse rectus abdominis musculocutaneous (TRAM) flap, 25 an autologous latissimus dorsi flap (ALD) and 22, a retropectoral implant (RI) reconstruction., Results: Forty-six (21.9%) early events were recorded: 20 necrosis, 9 surgical site infections and 6 haematomas, requiring further surgery in 23 patients. More necrosis were observed with TRAM flap reconstructions (p = 0.000004), requiring more surgical revision than LD reconstructions. Seromas represented 42% of early complications in LD reconstructions. Fifty-five patients presented with late complications (26.2%) with mainly implant complications (capsular contracture, infection, dislocation, deflation) (23.6%), requiring reintervention in 14 cases. There were more delayed surgical revisions in RI reconstructions (p = 0.0005). The 5 years overall and disease-free survival rates were respectively 86.7% and 75.6%. Sixty-four patients presented at least one recurrence (30.5%) with 5 local, 9 locoregional and 54 distant relapses., Conclusion: This therapeutic sequence does not seem to increase the IBR morbidity nor alter disease-free and overall survival., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Study Objective: To assess the surgical outcomes and long-term results of laparoscopic treatment of endometrial cancer in obese patients, and compare these results with those of nonobese women., Design: Retrospective cohort study (Canadian Task Force classification II-2)., Setting: Two referral cancer centers., Patients: Fifty-two obese and 155 nonobese women with clinical stage I endometrial cancer managed by laparoscopy from 1990-2005 in two referral centers., Interventions: Demographic, surgical, perioperative and pathological characteristics of obese women and nonobese women with endometrial cancer treated by laparoscopy were analyzed and then compared. Recurrence-free and overall survival was calculated by use of Kaplan-Meier method., Measurements and Main Results: Median BMI of the study population was 26.2 Kg/m(2). Median BMI among obese patients was 34.2 Kg/m(2). The conversion rate was independent from the BMI of the patient (3.8% vs 4.5%, p = .80). Neither mean operative time (187.5 vs 172 min, p = .11) neither hospital stay (5.2 vs 4.9 days, p = .44) were related with BMI. Lymphadenectomy was considered not feasible in 7 obese (17%) and 8 nonobese (7%) women (p = 0.09). Fewer lymph nodes were retrieved among obese women (8 versus 11, p <.0002). No differences were found between the groups in terms of perioperative complications. Median follow-up was 69 and 71 months for the obese and nonobese, respectively (p = .59). Overall and disease-free 5-year survival rates did not differ between obese and nonobese patients (90.3% and 87.5% versus 88.5% and 89.8%, respectively)., Conclusion: Despite some limitations, the laparoscopic approach seems to be particularly useful for obese patients with endometrial cancer, with similar survival and recurrence rates and without any more complications compared to the nonobese population., (Copyright © 2011 AAGL. Published by Elsevier Inc. All rights reserved.)

This paper presents promising microfluidic devices designed for continuous and passive extraction of plasma from whole human blood. These designs are based on red cells lateral migration and the resulting cell-free layer locally expanded by geometric singularities such as an enlargement of the channel or a cavity adjacent to the channel. After an explanation of flow patterns, different tests are described that confirm the advantages of both proposed singularities, providing a 1.5 and 2X increase in extraction yield compared to a reference device, for 1:20 diluted blood at 100 microL/min. Devices have also been successively optimized, with extraction yields up to 17.8%, and biologically validated for plasma extraction, with no protein loss or denaturation, no hemolysis and with excellent cell purity. Finally, the dilution effect has been experimentally investigated.

Objectives: Knowing the importance of sexuality items in the choice by the patient of the modality of treatment of localized prostate cancer, we aimed at reviewing and updating the effects of prostate radiotherapy and brachytherapy on sexual functions., Method: A PubMed search was done using the keywords: prostate cancer, erectile dysfunction, radiotherapy, brachytherapy, ejaculation and orgasm., Results: After both radiotherapy and brachytherapy, sexual troubles occur progressively, the onset of occurrence of erectile dysfunction being 12-18 months after both treatments. Even though the pathophysiological pathways by which radiotherapy and brachytherapy result in erectile dysfunction have not yet been fully clarified, arterial damage and exposure of neurovascular bundle to high levels of radiation seem to be two main causes of erectile dysfunction after radiotherapy and brachytherapy. The radiation dose received by the corpora cavernosa at the crurae of the penis may also be important in the etiology of erectile dysfunction. Another important factor following radiotherapy is the treatment modality. Not many data about ejaculation and orgasm after radiation treatments have been published yet. Recent data show that most of the population treated by brachytherapy conserves ejaculation and orgasm after treatment, even if a majority describe reduction of volume and deterioration of orgasm. Patients need to be correctly informed on the possible sequela of radiotherapy and brachytherapy on their sexual well-being while planning their treatment. Patients should also be informed about the possible treatment modalities for erectile dysfunction., (Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.)

Promising microfluidic devices are proposed herein to continuously and passively extract plasma from whole human blood. These designs are based on the red cells lateral migration and the resulting cell-free layer locally expanded by geometric singularities, such as an abrupt enlargement of the channel or a cavity adjacent to the channel. After an explanation of flow patterns, devices are experimentally and biologically validated for plasma extraction. They are also successively optimized with extraction yields up to 17.8% for a 1:20 blood injected at 100 microL/min.

Pathologic complete response (pCR) is linked to a better outcome, but its definition varies among working groups. We performed this study to validate different expressions of pCR as well as to determine the role of in situ and isolated tumor cell residues. A pathologic review was conducted on 710 operable patients with breast cancer to assess the residual disease in breast and in nodes according to the Chevallier (Ch) and Sataloff's (Sa) classifications. The pCR rate was 14.3% according to the Chevallier and 25.8% according to the Sataloff's classification. Overall survival and disease-free survival have been compared according to the pathologic response. There were significant differences between the pCR Ch(1+2) or Sa(A) and the non-pCR group. No significant difference was found between classes Ch(1) versus Ch(2) and between class Sa(A) without isolated cells versus class Sa(A) with isolated cells. Conversely, tumors histologically modified by chemotherapy were associated with a better prognosis than unmodified tumors. Finally, evidence of pCR in nodes was associated with a better prognosis. pCR should be defined as an absence of node invasion, and in the breast, either absence of tumor or tumor residue less than 5% of the tumor.

Purpose: To improve the outcome prediction of uterine cervical carcinoma by measuring the vascular permeability (k(ep)) and the extracellular volume fraction (v(e)) of the tumor from Dynamic T(1)- IRM Relaxometry., Materials and Methods: Twenty-six patients with proven cervical carcinoma were divided into good outcome and poor outcome groups. Classic tumor prognostic factors, the longest diameter L and the volume V of the tumor, were measured from morphologic MR images. The tumor parameters k(ep) and v(e) were determined from the relaxometry time-curve acquired during the contrast uptake after a bolus intravenous injection of an extracellular contrast agent., Results: All "small" tumors (L<35 mm or V<11 cm(3)) were good outcome with 100% sensitivity but a rather low specificity (36% and 43% for L and V, respectively). With regard to the physiopathological parameter k(ep), "large" tumors (L >or= 35 mm) can also be classified as good outcome on the condition that k(ep) >or= 2.2 min(-1) with 100% sensitivity and 89% specificity. Regarding the extracellular volume fraction (v(e)), no significant difference was observed between the two groups., Conclusion: Measurement of the tumor vascular permeability might be useful to predict prognostic, to evaluate the treatment efficacy, and to adapt a proper therapy schedule., ((c) 2008 Wiley-Liss, Inc.)

The aim of this study was to detect and analyze changes in hormone receptor (HR) status after treatment of operable breast cancer with neoadjuvant chemotherapy (NCT). Patients were treated from 1982 to 2004 with different NCT combinations, mainly in successive prospective phase II trials. HR status before and after NCT was retested and reviewed in a blinded fashion by two pathologists, for 420 patients from a database of 710 patients. Among these 420 tumors, 145 (35%) were HR negative and 275 (65%) were HR positive before NCT. The HR status had changed after treatment in 98 patients (23%): 61 patients (42%) initially HR negative became HR positive. This HR-positive switch was significantly correlated with better overall survival (OS), compared with patients with unchanged HR-negative tumors. Moreover, this HR-positive switch also had an effect on disease-free survival (DFS). Conversely, 37 patients (13%) initially HR positive became HR negative after NCT. However, this group of previously positive patients still had a survival advantage for OS, but not for DFS. The Allred score was evaluated before and after chemotherapy. An increase in Allred score after NCT was significantly correlated with better DFS but not OS. It was previously shown, for other tumor parameters, that residual disease after NCT, rather than parameters evaluated on the initial biopsy, must be considered for patient prognosis. In this work, NCT induced variations in HR status in 23% of patients. A positive switch in HR status after NCT could be an indicator of better prognosis for patient outcome.

Neoadjuvant chemotherapy in breast cancer corresponds to the use of a systemic treatment applied before loco-regional treatment (surgery and/or radiotherapy). Initiated in the seventies for treatment of the locally advanced and/or inflammatory breast cancers, induction chemotherapy has been extended in the beginning of eighties for cancers known as operable (size higher than 3 cm and/or in central position) in order to allow a more frequent conservating surgery. This objective is obtained in 75% of the cases approximately without increase in the risk of local relapse and without noxious effect on overall survival, in spite of the delay of the loco-regional treatment. Neo-adjuvant chemotherapy progressively moved with the advent of major drugs in breast cancer which are anthracyclins, vinorelbine and taxans. But to date, no protocol was essential like an uncontested standard. However, it seems that obtaining a complete clinical response is the best guarantor to avoid relapse. That seems to be observed only after 6 cycles, even 8 cycles of chemotherapy, each cycle combining the 2 major drugs for the treatment of breast cancer of which are anthracyclins and taxanes employed according a sequential scheme after a based-anthracyclins treatment, except any cardiac contra-indication. Moreover, the use of targeted therapeuticals like Herceptin, with a chemotherapy, seems to be promising and should be more studied. Finally, when a neoadjuvant chemotherapy is administered, the evaluation of the pre-treatment biopsy helps to establish key patient-management parameters such as tumour type, SBR grade and immunohistochemical parameters. This evaluation provides predictive parameters with regards to drug response (hormonal status, overexpression of Her2). The further studies realised in this way will permit to improve the results yet obtained.

Purpose: The purpose of this study was to contribute to the evaluation of long-term external beam radiation treatment in patients with subfoveal occult choroidal neovessels complicated with pigment epithelium detachment in age-related macular degeneration., Materials and Methods: This was a retrospective study of ten patients with a mean age of 75 years and a mean follow-up of 18.7 months. External beam radiation of 14.4 Gy was administered with a daily dose of 1.8 Gy. The efficacy of the treatment was assessed based on visual acuity, the size of the membrane and the persistence or not of neovascular activity., Results: We observed stabilization of visual acuity in 44% of the cases at 6 months but only in 20% at 19 and 30 months. The mean initial visual acuity was measured at 0.2 at presentation and 0.1 at the final evaluation. At the end of the study, 60% of patients attained the level of legal blindness; 90% of patients developed a disciform scar, with persistence of neovascular activity in 27% of the cases. On fluorescein angiography, the size of pigment epithelium detachment increased more than one optic disc diameter in 20% of the cases at 1 year. On the other hand, no radiation complication was observed., Discussion: The visual and anatomical results of our study are similar to the natural progression of occult neovascular membrane. External beam radiation at a dose of 14.4 Gy did not seem to provide a long-term benefit in the treatment of subfoveal occult neovessels associated with pigment epithelium detachment.

Docetaxel (Taxotere), alone or in combination with other anticancer agents, has proven efficacy in the first- and second-line treatment of metastatic breast cancer. This phase II study investigated the efficacy and tolerability of docetaxel as neoadjuvant chemotherapy in women with stage II-III primary operable breast cancer. Patients (n=88) were treated with six cycles of docetaxel at 100 mg m(-2) every 21 days, followed by definitive surgery and radiotherapy. After six cycles of docetaxel, the overall clinical response rate was 68.4% (CI 95%: 58.1-78.7%), including 19.0% complete remissions. Breast conservation was achieved in 72.4% of patients. A high pathological complete response (pCR) rate in breast was confirmed in 15 patients (19.8% (CI 95%: 10.8-28.8%)) on Chevallier's classification restricted to breast and in 27 patients (35.5% (CI 95%: 24.7-46.3%)) on Sataloff's classification. After a median follow-up of 30.8 months, 19 recurrences were documented with a median time to first recurrence of 17.3 months. Patients with stage III tumours had more recurrences than patients with stage II tumours (P=0.02). The principal toxicity of docetaxel is myelosuppression and 70.5% of patients developed grade III or IV neutropenia with 13.6% developing neutropenic sepsis. There was no case of severe cardiac toxicity, thrombocytopenia or any other serious adverse events. In conclusion, neoadjuvant docetaxel induces a high pCR and breast-conservation rate. Docetaxel monotherapy is a highly effective regimen that merits formal comparison with currently used combination regimens in a randomised phase III study.

Context: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Cancer Centers, and specialists from French Public Universities, General Hospitals and Private Clinics, and some specialists learned societies. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The SORs are developed using a methodology based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery., Objectives: To develop clinical practice guidelines for the management of patients with carcinoma of the endometrium according to the definitions of the Standards, Options and Recommendations project., Methods: Data were identified by searching Medline , web sites, and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 63 independent reviewers., Results: The main recommendations for the management of carcinoma of the endometrium are: 1) The diagnosis of carcinoma of the endometrium is based on biopsy and histological examination. However, as first intention, the first elements for diagnosis can be obtain from a hysterography, or particularly, a endovaginal ultrasound examination. Ultrasound allows locoregional metastases to be detected, the CT scan allows the lymph node involvement to be assessed and magnetic resonance imaging allows the myometrium invasion to be evaluated. 2) For the majority of patients, surgery is the initial treatment, both for localised and advanced-stage carcinomas. The excised sample can be used for pathological analysis and tumour staging, using the FIGO (Fédération internationale de gynécologie obstétrique) classification. Surgery for patients with stage I and II carcinomas involves total extrafascial hysterectomy with bilateral salpingo-oophorectomy., In patients with stage III and IV carcinomas radical surgery should be performed, when possible. If this is not possible, then surgery should be as complete as possible and be associated with a complementary treatment. In patients with the most advanced carcinomas, tumour reduction by surgery should be performed. 3) Complementary treatment includes external-beam radiotherapy and brachytherapy. The decision concerning the extent and type of irradiation should be taken taking into consideration the stage and the prognostic factors present. For patients with stage I and II carcinoma, complementary treatment with brachytherapy can be performed, if the myometrium invasion is not deep, or if the carcinoma is grade 2 or 3. Patients with stage III carcinomas can be treated with pelvic or abdominal-pelvic complementary irradiation. In patients that cannot undergo surgery, exclusive radiotherapy can be performed. 4) In the absence of any symptoms, surveillance should include a general clinical and gynaecological examination. All patients with symptoms should undergo an additional work-up.

Only a few papers have been published concerning the incidence and outcome of patients with a pathological complete response after cytotoxic treatment in breast cancer. The purpose of this retrospective study was to assess the outcome of patients found to have a pathological complete response in both the breast and axillary lymph nodes after neoadjuvant chemotherapy for operable breast cancer. Our goal was also to determine whether the residual pathological size of the tumour in breast could be correlated with pathological node status. Between 1982 and 2000, 451 consecutive patients were registered into five prospective phase II trials. After six cycles, 396 patients underwent surgery with axillary dissection for 277 patients (69.9%). Pathological response was evaluated according to the Chevallier's classification. At a median follow-up of 8 years, survival was analysed as a function of pathological response. A pathological complete response rate was obtained in 60 patients (15.2%) after induction chemotherapy. Breast tumour persistence was significantly related to positive axillary nodes (P=5.10(-6)). At 15 years, overall survival and disease-free survival rates were significantly higher in the group who had a pathological complete response than in the group who had less than a pathological complete response (P=0.047 and P=0.024, respectively). In the absence of pathological complete response and furthermore when there is a notable remaining pathological disease, axillary dissection is still important to determine a major prognostic factor and subsequently, a second non cross resistant adjuvant regimen or high dose chemotherapy could lead to a survival benefit.

The Scarff-Bloom-Richardson (SBR) grade, an important prognostic factor in breast cancer, was also associated with cell proliferation, a consistent indicator of response to chemotherapy. The determination of an association between SBR grade and responsiveness would be clinically useful. We explored the influence of SBR grade on response to neoadjuvant chemotherapy in patients with invasive ductal breast carcinoma. The present study centered on 431 patients registered onto one of four prospective phase II trials. SBR grading was performed according to the Elston method on needle core biopsies prospectively collected prior to treatment from 290 patients and on residual tumour at surgery from 171 patients. The post-operative grades were then compared with those obtained at diagnosis. Univariate and multivariate analysis were used to evaluate the significance of SBR grade on response to neoadjuvant chemotherapy. Both statistical analysis revealed that SBR grade III tumours responded better to neoadjuvant treatment than SBR grade I (p<10(-6)). None of the other patient and tumour characteristics tested correlated with response. Moreover, tumour responsiveness was significantly related to changes of the SBR grade (p=7 x 10(-3)). As a conclusion, we showed that SBR grade is a strong predictive factor of response to induction chemotherapy in breast cancer, independently of the type of regimen used. The association between evolution of the histological grade following chemotherapy and response to treatment may prove valuable for clinicians as they make their decision regarding patient therapy.

Purpose: In order to improve the breast conservation rate for noninflammatory operable breast cancer stage II and IIIa, neoadjuvant chemotherapy containing vinorelbine, 25 mg/m(2), epirubicin, 35 mg/m(2), and methotrexate, 20 mg/m(2), VEM, was administered days 1 and 8 every 28 days for six cycles., Methods: From October, 1991 to April, 1996, 89 patients (median age 52 years, range 31-72; 68 stage II and 19 stage IIIa) received 519 cycles (median six) of VEM chemotherapy., Results: Hematotoxicity was mild (World Health Organization grade 3-4 neutropenia in 28% of cycles for 22 patients, and anemia or thrombocytopenia >grade 2) when it occurred, and there were no toxic deaths. The clinical objective response was 90% (28% complete response and 62% partial response). All patients underwent surgery: 77 (87%) had conservative and 12 (13%) had modified radical mastectomy, and 12 (14%) reached pathological complete response. At December, 2000, with a median follow-up of 86 months (39-100), 13 patients had relapsed, and five had died of metastatic disease. Median disease-free survival was 100 months (8.4 years) and median survival had not yet been reached.

Objectives: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the radiotherapy of carcinoma of the endometrium., Methods: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French Cancer Centres., Results: The main recommendations for the radiotherapy of carcinoma of the endometrium are: 1) For grade 1 and 2 stage IA tumours, follow-up alone is standard as additional treatment. For grade 1 and 2 stage IB tumours, vaginal brachytherapy or follow-up alone are options. For grade 3, stage IB tumours and stage IC disease, there are two treatment options: external pelvic radiotherapy with a brachytherapy boost or vaginal brachytherapy. 2) Treatment for stage II disease can be preoperative when stage II disease has been suggested by a positive endometrial curettage. Postoperative vaginal brachytherapy is given for stage IIA tumours if the penetration of the myometrium is less than 50% or if the tumour is grade 1 or 2. In the case of deep penetration, or higher grade disease, or for stage IIB external radiotherapy with brachytherapy boosting must be undertaken routinely. 3) After surgery, for stage IIIA disease, either external pelvic radiotherapy or abdomino-pelvic radiotherapy is indicated, along with medical treatment in certain patients. For stage IIIB tumours, postoperative external radiotherapy with brachytherapy (if possible) should be undertaken. For stage IIIC tumours, standard treatment is external (pelvic or pelvic and para-aortic) radiotherapy followed or not by a brachytherapy boost. In case of extrauterine sites involved abdomino-pelvic irradiation is recommended. 4) Standard treatment for inoperable stage I and II disease is external radiotherapy and brachytherapy. For patients with inoperable stage III or IV disease, treatment is often symptomatic, combining external radiotherapy and medical treatment.

Context: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery., Objectives: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the surgical management of carcinoma of the endometrium., Methods: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French Cancer Centres., Results: The main recommendations for the surgical management of carcinoma of the endometrium are: 1) where-ever possible, surgery is the primary treatment of both localised and advanced disease; 2) surgery is performed according to the stage of the cancer and the status of the patient; 3) surgery for stages I and II disease entails total abdominal hysterectomy and bilateral salpingo-oophorectomy. A modified radical hysterectomy is undertaken in cases of macroscopic cervical involvement. An omenectomy is recommended for serous papillary types. Pelvic lymphadenectomy for the purposes of precise staging is undertaken if the patient is of good performance status and without bad pronostic factors. Para-aortic lymphadenectomy can be undertaken to determine involvement of para-aortic nodes; 4) surgery for stages III and IV: radical surgery must be undertaken if at all possible with additional treatment as indicated. In the case of advanced disease, debulking surgery is indicated.

Objectives: To evaluate the place of ovarian transposition by laparoscopy in an effort to preserve ovarian function without compromising oncological safety among young women requiring intravaginal brachytherapy before surgery for cervical cancer., Material and Methods: The series was represented by 20 cases, all FIGO stage I squamous cell malignant diseases of the cervix. Mean age: 32 years (range 23-40). Oophoropexy (7 instances) or lateral high ovarian transposition (13 instances) was performed by laparoscopy, just before brachytherapy using cesium 137., Results: Continued hormonal function was achieved in 58% of the available cases, 50% (3/6) after oophoropexy, 68% (8/11) after ovarian transposition. Mean follow-up was 8.5 years (range 5-13). The mean radiation dose absorbed by the displaced ovary was 2.6 Gy (range 1. 2-5.9)., Conclusion: Ovarian transposition through laparoscopy before brachytherapy should be advised for selected stage I squamous type malignant tumor size 2 cm without lymphatic/vascular channel invasion by neoplastic emboli and without lymph node involvement. This procedure has been abandoned in our institution, instead of this, primary surgical treatment is accomplished (laparoscopically-assisted vaginal) radical hysterectomy is associated with orthotopic ovarian conservation.

The objective of this phase II multicenter study was to assess the efficacy and tolerance of triptorelin (a sustained-release LHRH agonist) in advanced or recurrent endometrial cancer. A total of 101 monthly intramuscular injections were administered to 24 eligible patients (median number/patient = 3; range 1-12). Mainly due to progression, only 16 patients received 3 or more injections. Among the 23 evaluable patients, 1 complete and 1 partial response (response rate of 8.7%) and 5 disease stabilizations were observed, often of long duration, but never in an irradiated area or after progestogens treatment failure. Median survival for eligible patients was 7.2 months (range: 1-36 months). Only grade 1 toxicities possibly related to the treatment were observed in 4 patients. In conclusion, triptorelin was safe, well tolerated, and easily manageable, and the very low toxicity did not impair the quality of life in these patients with a very poor prognosis. Although the response rate was disappointing, several patients showed early evidence of efficacy which may be of long duration. Response rates range between 0 and 45% in different published studies. Additional studies with stricter inclusion criteria and a larger sample size are necessary to better evaluate the role of LHRH agonists in endometrial adenocarcinomas., (Copyright 1999 Academic Press.)

This study focused on the correlation between tumor response and patient outcome in 329 breast cancers treated with primary chemotherapy. There were 141 stage IIIB tumors, including 109 inflammatory carcinomas. Other malignancies (34 IIIA, 99 IIB, 55 IIA) were operable but considered to be too large (> 3 cm) for conservative surgery and received primary chemotherapy to avoid mastectomy. All received the AVCF regimen, comprising 4-week cycles of doxorubicin (30 mg/m2) day 1, vincristine (1 mg/m2) day 1, 5-fluorouracil (5-FU; 400 mg/m2) days 2 through 5, cyclophosphamide (300 mg/m2) days 2 through 5. In 189 cases, methotrexate (15 mg/m2) was added at day 2 and day 3. Patients received 6 cycles, then underwent locoregional treatment (surgery, radiotherapy, or both) according to tumor regression. The response rate was assessed by clinical, mammographic, and echographic examinations: a 50% rate of objective responses were noted, of which 15% were complete responses (tumor shrinkage allowed breast conservation in 68% of patients who had stages II or IIIA). For the whole population studied, median follow-up was 111 months (range, 60- 196). One hundred fifty-seven patients had disease relapse (48 local, 14 contralateral, 95 distant). Kaplan-Meier estimates showed an increased 10-year overall survival for patients in complete response, as compared with noncomplete response: 70% versus 50% (p < 0.03). Complete response to neoadjuvant chemotherapy seems a good prognostic factor.

Between 1975 and 1986, 326 patients with stage II breast cancer were treated with an adjuvant combination of doxorubicin, vincristine, cyclophosphamide, and 5-fluorouracil (AVCF) following regional therapy (232 modified radical mastectomy, 94 lumpectomies, 304 irradiations). The AVCF regimen consisted of 4-week cycles of doxorubicin (30 mg/m2 day 1, modified radical mastectomy), vincristine (1 mg/m2 day 2), 5-fluorouracil 400 (mg/m2), and cyclophosphamide (300 mg/m2) days 3-6. Two hundred twenty-four patients (pts) had six cycles and 102 pts 12 cycles; 90 pts also received 30 mg daily tamoxifen for 1 year after chemotherapy. As of March 1994, the median follow-up was 130 months (range 86-221). One hundred eighteen pts developed recurrences (7 local, 19 controlateral, 92 metastatic) and 104 died. Estimated disease-free survival (DFS) was 5 years, 76 +/- 5%; 10 years, 64 +/- 5%; 15 years, 54 +/- 9%. Overall survival (OS) was 5 years, 85 +/- 4%; 10 years, 70 +/- 5%; 15 years, 58 +/- 10%. Survival was affected by the number of involved lymph nodes (258 pts were N+), menopausal status (OS at 15 years: 53% for MP+ and 65% for MP-) and Scarff-Bloom-Richardson grading, but not by hormonal receptors, number of courses, or associated hormonotherapy. Minimal cardiac toxicity was induced by doxorubicin either during or subsequent to treatment completion.

In order to avoid modified radical mastectomy, a neoadjuvant approach was adopted in our institute for operable bulky breast cancers. From January, 1982, to December, 1995, 288 patients received primary chemotherapy with 3 different regimens (all doses mg/m2): (1) AVCF/AVCFM, 167 patients (adriamycin 30, vincristine 1 d1, cyclophosphamide 300, fluorouracil 400 d2-d5 and methotrexate 20 d2 and d4, every 28 days); (2) NEM, 78 patients (vinorelbine 25, epirubicin 35, methotrexate 20 d1 and d8, every 28 days); and (3) TNCF, 43 patients (THP-adria 20, d1-d3, vinorelbine 25 d1 and d4, cyclophosphamide 300, fluorouracil 400 d1-d4, every 21 days). Evaluation of the response comprised 3 methods: clinical (C), echographic (E), mammographic (M). The overall objective response rate (C: 63/90/93; E: 49/61/85; M: 53/65/83%) is higher with regimens (2) and (3). The complete response rate was increased 2-fold with TNCF but the hematologic toxicity was very superior with this combination. Patients were all operated for (2) and (3), only several for (1), and the breast conservation rate (68/83/79%) was quite similar in the 3 regimens. The pathological complete response rate reached 23% with TNCF. However the impact on patient survival has to be confirmed.

Between 1978 and 1987, 109 patients without metastatic disease were treated by induction chemotherapy for inflammatory breast cancer (IBC) or "neglected" locally advanced breast cancer (LABC): 62 patients had a clinical history of rapidly growing tumours (doubling time < or = 4 months) and inflammatory signs; conversely, the 47 neglected patients had local inflammation with a longer history of LABC. 103 patients were fully evaluable. All patients received the same induction chemotherapy with doxorubicin, vincristine, cyclophosphamide and 5-fluorouracil. After six cycles, locoregional treatment was by radiotherapy if a complete or nearly complete response had been obtained, and total mastectomy, with pre or postoperative radiotherapy, in other cases. The chemotherapy after local treatment comprised of six cycles for LABC and 12 cycles for IBC (six without doxorubicin). With a median follow-up of 120 months, the median overall survival (OS) time was 70 months as against 45 months for disease-free survival (DFS). No difference was observed for OS and DFS between LABC and IBC. The regional recurrence rate was 24% (15% for radiotherapy alone). 20 factors of potential prognostic significance were evaluated by univariate and multivariate analysis. For DFS and OS, univariate analysis suggested a worse prognostic significance for "peau d'orange" appearance of the skin, clinical evidence of node involvement and poor response to chemotherapy after three cycles, on mammographic criteria. The cumulative dose of doxorubicin after three cycles seemed to have a significant effect on OS (P < 0.03) but was too closely correlated with age to draw definite conclusions. In the multivariate analysis, "peau d'orange", menopausal status and clinical node involvement predicted DFS. "Peau d'orange" and clinical node involvement also predicted OS. Our results indicate that IBC and LABC do not behave differently when treated with our procedure.

126 patients with non-inflammatory operable breast cancer, who otherwise would have undergone modified radical mastectomy (MRM), were treated by induction chemotherapy. Before treatment, every patient had a local and general assessment, and pathological or cytological evidence of malignancy. Patients received, every 3 weeks, the same treatment with doxorubicin, vincristine, cyclophosphamide, 5-fluorouracil (AVCF); methotrexate was added in 80 cases (AVCFM). Tumour shrinkage greater than 50% was documented in 105 (83%) of the 126 women. A higher objective response rate was obtained in aneuploid or high S phase tumours, especially in the patients treated with methotrexate. After chemotherapy, 41 patients were then treated by radiotherapy alone after complete or sub-complete response; 64 had a residual tumour that could be treated by conservative surgery and radiotherapy. Only 19 had MRM and radiotherapy. Histopathological complete remission was documented in 1 case; isolated residual tumour cells were found in 5 patients. Thus primary chemotherapy enhanced the possibility of breast conservation in up to 83% of the cases in a series in which most would have been otherwise subjected to a MRM because of tumour size.

Ovarian preservation is recommended for young patients with early invasive cancer of the uterine cervix. We describe the laparoscopic technique of ovariopexy we performed among seven patients before brachytherapy and Wertheim surgery and we report our functional results: menopause was avoided in four instances but three failures were observed. The laparoscopic procedure could be improved with coagulation and section of the utero-ovarian ligament, mobilization of the infundibulopelvic ligament; finally the ovary could be transposed in the paracolic gutter. According to the authors, this protocol must be applied only to patients with stage IA or IB squamous cervical cancer, aged less than 35 years.

Results obtained by the authors and a review of the literature have made them able to point out recent developments in cases of epithelial cancer of the ovary diagnosed in an advanced stage of the disease. This is the most frequent finding when the diagnosis is made and it is most important in assessing the future prognosis to know how far on the disease has progressed. Cancer of the ovary has long been thought of as a peritoneal disease, but all the same 40% of metastases occur further away and the majority of these are in the pleura or the lung and more rarely in the brain; and all these have been observed. The degree of differentiation is another important element for prognosis. Deciding how differentiated tissue is, is relatively subjective. A scoring protocol is suggested to make the assessment more systematic. The grading can be varied according to the response to treatment. A great majority of authorities believe that reduction of the size of the tumour surgically should be the first procedure but how useful this is has never been proved because there has never been any controlled study. It is possible in most cases to reduce the size of the tumour greatly but often this may need removal of some of the intestines with acceptable morbidity. Chemotherapy with Cisplatin, Cyclophosphamide and in the hands of certain authors, Doxorubicine, has been shown to be helpful in 80% of cases and seems to be the most appropriate treatment.

The dosage of radiations delivered during gynaecological brachytherapy is usually calculated for the bladder and the rectum. A new technical approach is described in order to known the dose of radiation received by the terminal portion of the ureter. During placement of the Fletcher suit one of the ureters is catheterized by a special stent which appears on the X-rays control used for dosimetry. Data of 16 pre-operative brachytherapies for carcinoma of the cervix were studied. In half of the cases, the dose debit was higher on the ureter than on the bladder and the rectum. In 7 cases, the dose delivered was also higher on the ureter rather than on the bladder and the rectum. And in 3 cases this dose was higher than 50 grays. It is concluded that the ureter is frequently the most irradiated organ in the pelvis during brachytherapy for carcinoma of the cervix. This may be a physiopathologic explanation for some ureterovaginal fistulas occurring after radical hysterectomy.

The authors report the case of a 49-years-old man with an undifferentiated malignant gonadal stromal tumor of the right testis. Malignancy is confirmed by metastasis in the retroperitoneal lymph nodes. After 6 courses of chemotherapy with Cis-platinum, a retroperitoneal lymphadenectomy was performed and the section of the nodes showed a muscular differentiation of the tumor. This drug regimen did nod induce a complete response and an early recurrence occurs after lymphadenectomy which included the right ureter. The renal function was preserved by the way of a double J indwelling ureteral stent. A total remission was obtained with chemotherapy using Cis-platinum and 5-Fluorouracil, associated with a rapid fraction irradiation for six courses. Total response was assessed by scanner and by a laparotomy for bowel radiation sclerosis.

Based on the synergistic action of 5-fluorouracil (5-FUra), cis-dichlorodiamminoplatinum(II) (cis-DDP) and gamma-rays, which was suggested in experiments on murine tumours, a sequential treatment combining irradiation and chemotherapy for human solid tumours known to be resistant to conventional treatments has been developed. A pilot study was carried out on 30 patients with recurring head and neck cancers previously treated by radiotherapy and surgery. The good tolerance and the initial results justified applying this protocol to previously untreated cases. The second study involved 40 patients with stage III and IV tumours. After 3 cycles of combined radio- and chemotherapy followed by a conventional radiotherapy, 78% were good responders (51% in complete remission). Oropharynx and oral cavity, without base of tongue, have a 51% actuarial survival at 3 years when they achieved an early complete remission.