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Cervical cancer has been and still is a major global health problem and a major treatment challenge for which surgical interventions have played a key role throughout the past century. In early stages (I/A2-II/B), where high-risk factors are not present, the efficacy of surgical and radiotherapy treatment has been considered equivalent with different (treatment modality specific) complications and quality of life consequences. Negative prognostic factors in early stages of the disease (pelvic lymph-node positivity) and in more advanced stages (parametrial and/or surgical margins' tumor involvement) forecast the deterioration of outlooks for good life expectancy. In these high-risk cases, when radio- or chemoradiotherapy is contraindicated, we investigated the potential role of a more radical surgical approach than the traditional radical hysterectomy. Twenty-five years ago, a hyperradical surgical procedure for the treatment of high-risk cervical cancer patients was introduced in Budapest. The procedure was named as laterally extended parametrectomy (LEP) in Budapest Hungary. The surgical intention was the complete removal of the fibro-fatty tissue content of the pelvis, which contains the lymphatic vessels, lymph nodes, and tumor-affected pelvic side wall structures. We initiated observational studies on the primary treatment in parametrium and/or lymph-node tumor-positive early-stage cases and on second-line surgical therapy of pelvic side wall recurrent tumors following radiotherapy. Promising results of our observational studies propose that prospective randomized trials are worth to be initiated to clarify the potential of this treatment modality in this poor prognosis cohort of patients.
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A new type of terahertz source containing only two optical elements - a volume phase holographic grating, and a semiconductor nonlinear slab - is proposed. The setup does not require any microstructuring, has only one diffraction order, and can be scaled to large pump sizes without any principal limitations. Furthermore, it can be easily adapted to different pump wavelengths and THz phase-matching frequencies. The Fresnel loss at the boundary of the materials can be significant at conventional pump polarizations (s-pol), but a single-layer anti-reflection (AR) coating can reduce it. Pumping such a setup with polarization in the dispersion plane (p-pol, TM mode) can reduce the effective nonlinear polarization and consequently the terahertz generation efficiency. However, in the absence of AR coating, this reduction is overcompensated by the reduced Fresnel loss.
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In recent years several microstructured lithium niobate THz pulse source were suggested for high-energy applications. Two types of those, the reflective and the transmissive nonlinear slab are adopted here for semiconductors. These new sources are scalable both in THz energy and size. Furthermore, they can outperform the already demonstrated contact grating source in diffraction and THz generation efficiency. Compared to the lithium niobate sources, they are more feasible, thanks to the easier manufacturing and the longer pump wavelength. They can produce intense, nearly single-cycle THz pulses at higher frequencies. With 20 mJ pumping at 1.8 µm wavelength, 45 µJ THz energy, and 17 MV/cm focused peak electric field can be expected at 3 THz phase matching frequency from the transmissive nonlinear echelon slab setup consisting of a 4 mm thick structured plan-parallel gallium phosphide crystal.
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A new type of THz source, working in reflection geometry, is proposed, where the pulse-front-tilt is introduced by a periodically micro-structured metal profile. For optical coupling, high refractive index nanocomposite fluid is used between the nonlinear optical material and the structured metal surface. Numerical simulations predict â¼87 and â¼85% optimized diffraction efficiencies for lithium niobate and lithium tantalate at 1030 and 800 nm pump wavelengths. The largest diffraction efficiencies can be achieved for a larger refractive index of the nanocomposite fluid than the index of the nonlinear material, for both cases. THz generation efficiencies of â¼3 and â¼1% are predicted for lithium niobate and lithium tantalate, respectively.
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A tilted-pulse-front pumped terahertz pulse source is proposed for the generation of extremely high field single-cycle terahertz pulses. The very simple and compact source consists of a single crystal slab having a blazed reflection grating grooved in its back surface. Its further important advantages are the energy scalability and the symmetric THz beam profile. Generation of â¼50 MV/cm focused field with 10.8 mJ terahertz pulse energy is predicted for a 7 cm diameter LiNbO 3 crystal, if the pump pulse is of 870 mJ energy, 1030 nm central wavelength and 1 ps pulse duration. Such sources can decisively promote the realization of THz driven electron and proton accelerators and open the way for a new generation concept of terahertz pulses having extreme high field.
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Recently a hybrid-type terahertz (THz) pulse source was proposed for high energy terahertz pulse generation. It is the combination of the conventional tilted-pulse-front setup and a nonlinear crystal with a transmission stair-step echelon of period in the hundred-micrometer range etched into the front face. The tilt angle introduced by the conventional tilted-pulse-front setup (pre-tilt) was chosen to be equal to the tilt-angle needed inside the nonlinear crystal (62° for lithium niobate (LN)) in order to fulfill velocity-matching. In this case, plane-parallel nonlinear optical crystals can be used. The possibility of using a plane-parallel nonlinear optical crystal for producing good-quality, symmetric THz beams was considered the most important advantage of this setup. In the present paper, a thorough numerical investigation of a modified version of that setup is presented. In the new version, the tilted pulse-front is created by a transmission grating without any imaging optics, and a wedged nonlinear optical crystal with a small wedge angle is supposed. According to a 1D numerical code, significantly higher THz generation efficiency can be achieved with a transmission stair-step echelon-faced nonlinear crystal having a 5 - 15-degree wedge angle than with a plane-parallel one or with the conventional tilted-pulse-front setup. Because of the spatially-dependent group-delay dispersion introduced by the transmission grating, a small wedge in the nonlinear crystal improves the spatial homogeneity of the THz-generation process, resulting in higher efficiencies and better beam profiles. At 100 K temperature, and by using 800 nm pump pulses with 20 mJ pulse energy, 100 fs pulse length and 8 mm beam spot radius, approximately 4.5% conversion efficiency and close to 1 mJ terahertz pulse energy can be reached with the newly-proposed setup.
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A new type of tilted-pulse-front pumped terahertz (THz) source has been demonstrated, which is based on a LiNbO3plane-parallel slab with an echelon structure on its input surface. Single-cycle pulses of 1 µJ energy and 0.30 THz central frequency have been generated with 5×10-4 efficiency from such a source. One order-of-magnitude increase in efficiency is expected by pumping a cryogenically cooled echelon of increased size and thickness with a Ti:sapphire laser. The use of a plane-parallel nonlinear optical crystal slab enables straightforward scaling to high THz pulse energies and the production of a symmetric THz beam with a uniform pulse shape for good focusability and high field strength.
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A hybrid-type terahertz pulse source is proposed for high energy terahertz pulse generation. It is the combination of the conventional tilted-pulse-front setup and a transmission stair-step echelon-faced nonlinear crystal with a period falling in the hundred-micrometer range. The most important advantage of the setup is the possibility of using plane parallel nonlinear optical crystal for producing good-quality, symmetric terahertz beam. Another advantage of the proposed setup is the significant reduction of imaging errors, which is important in the case of wide pump beams that are used in high energy experiments. A one dimensional model was developed for determining the terahertz generation efficiency, and it was used for quantitative comparison between the proposed new hybrid setup and previously introduced terahertz sources. With lithium niobate nonlinear material, calculations predict an approximately ten-fold increase in the efficiency of the presently described hybrid terahertz pulse source with respect to that of the earlier proposed setup, which utilizes a reflective stair-step echelon and a prism shaped nonlinear optical crystal. By using pump pulses of 50 mJ pulse energy, 500 fs pulse length and 8 mm beam spot radius, approximately 1% conversion efficiency and 0.5 mJ terahertz pulse energy can be reached with the newly proposed setup.
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Several optical methods including ultraviolet absorption, infrared absorption of the hydroxyl ions, Raman spectroscopy, and the Z-scan method have been used to determine the damage resistance threshold in 0-0.72 mol. % Zr-containing, flux-grown, nearly stoichiometric LiNbO3 single crystals. All spectroscopical methods used indicate that samples containing at least ≈0.085 mol. % Zr in the crystal are above the threshold while Z-scan data locate the photorefractive damage threshold between 0.085 and 0.314 mol. % Zr.
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OBJECTIVE: Invasive cervical cancer is one of the most common cancers, with 500,000 new cases diagnosed annually. Fertility preservation has become an important component of the overall quality of life of many cancer survivors. Expert opinion has suggested that fertility-sparing surgery should be limited to those patients diagnosed with cervical cancer less than 2 cm in diameter. Our objective was to report our abdominal radical trachelectomy (ART) experience in the opposite group of patients-those with a cervical cancer more than 2 cm in diameter. METHODS: Between 1999 and 2006, a total of 45 patients with cervical carcinoma at International Federation of Gynecology and Obstetrics stage IB1-IB2 measuring more than 2 cm in diameter underwent fertility-sparing ART and pelvic lymphadenectomy at the 3 institutions where the authors are based (Budapest, Hungary; London, United Kingdom; New York, United States). They were followed up for more than 5 years. RESULTS: For 69% of patients (n = 31), completed ART was considered to have been curative, and no adjuvant treatment was advised. Of those patients, 93.5% (n = 29) were alive at the time of follow-up. Thirty-one percent of patients (n = 14) underwent immediate completion of radical hysterectomy. Three of 8 patients who wished to fall pregnant delivered healthy neonates. CONCLUSIONS: The 5-year survival rate (93.5%) for this case series is equal (or better) to rates reported in the literature for patient treated with radical hysterectomy. Our survival data seem to support the hypothesis that ART is a safe treatment option for patients with invasive cervical cancer lesions of more than 2 cm.
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Adenocarcinoma/cirugía , Carcinoma de Células Escamosas/cirugía , Cuello del Útero/cirugía , Histerectomía , Recurrencia Local de Neoplasia/cirugía , Neoplasias del Cuello Uterino/cirugía , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Cuello del Útero/patología , Femenino , Fertilidad , Estudios de Seguimiento , Humanos , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Complicaciones Posoperatorias , Embarazo , Pronóstico , Estudios Prospectivos , Calidad de Vida , Tasa de Supervivencia , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patologíaRESUMEN
INTRODUCTION: Recurrence originating from the pelvic lymph node containing fibro-fatty tissue has consistently been identified as the most frequent pattern of treatment failure in early-stage cervical cancer. A surgical technique for the complete removal of the connective tissue content of the pelvis was introduced at St. Stephen Hospital in 1993 to improve oncological outcome by reducing the risk of recurrence from the pelvis. Efficacy and toxicity of the procedure were studied in 563 patients with stage IB cervical cancer with a completed 5-year follow-up. METHODS: Final pathology in 492 (87.4%) of 563 consecutive completed radical hysterectomies suggested that all tissue, which could contain tumor dissemination, was removed from the pelvis; thus, no adjuvant treatment was applied. Adjuvant chemoradiotherapy was advised in 71 cases (12.6%), where pathologic finding alluded tumor spread beyond the study criteria. FINDING: At completed 5-year follow-up, the overall survival of 492 patients who had surgery without adjuvant therapy was 94.0%. Pathologic stage, lymphovascular space involvement, pelvic lymph node metastases, histology classification, and grade had no significant influence on prognosis. The only factor that influenced the overall survival was International Federation of Gynecology and Obstetrics stage (IB1 or IB2). Five-year overall survival of 71 patients to whom adjuvant therapy was recommended was 56.3%. Five-year overall survival of the whole cohort (n = 563) was 88.8%. The complication rate did not seem to be different from the published data on traditional radical surgery in cervical cancer. CONCLUSIONS: Our results (in accordance with other recent publications) suggest that complete excision of the connective tissue content of the pelvis provides equal or better survival chances without any adjuvant treatment for almost 90% of operable patients with stage IB cervical cancer than less radical surgery with or without adjuvant treatment. We suggest this strategy to be mentioned as one alternative in future treatment protocols.
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Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Histerectomía/métodos , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugía , Adulto , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/mortalidad , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Histerectomía/efectos adversos , Histerectomía/estadística & datos numéricos , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Análisis de Supervivencia , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/mortalidad , Adulto JovenRESUMEN
Optical rectification of ultrashort laser pulses in LiNbO3 by tilted-pulse-front excitation is a powerful way to generate near single-cycle terahertz (THz) pulses. Calculations were carried out to optimize the output THz peak electric field strength. The results predict peak electric field strengths on the MV/cm level in the 0.3-1.5 THz frequency range by using optimal pump pulse duration of about 500 fs, optimal crystal length, and cryogenic temperatures for reducing THz absorption in LiNbO3. The THz electric field strength can be increased further to tens of MV/cm by focusing. Using optimal conditions together with the contact grating technique THz pulses with 100 MV/cm focused electric field strength and energies on the tens-of-mJ scale are feasible.
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Óptica y Fotónica/métodos , Espectroscopía de Terahertz/métodos , Absorción , Cristalización , Electricidad , Radiación Electromagnética , Análisis de Fourier , Rayos Láser , Ensayo de Materiales , Modelos Teóricos , TemperaturaRESUMEN
INTRODUCTION: In 2003, we published our preliminary experience with the use of an operative technique (laterally extended parametrectomy, the LEP procedure) without adjuvant therapy, in the treatment of 29 stage IB, cervical cancer patients with pelvic lymph node metastases. In our present paper, by an extended recruiting period, with a completed 5 year follow up, we studied the outcome of LEP operations, used with the same indications. METHODS: In 70 out of 106 LEP-Wertheim operated patients, no adjuvant treatment was used. In 36 patients, where histology suggested tumor spread beyond the threshold of our surgery, adjuvant chemo-radiotherapy was advised. 5 year follow up was completed (without any patient lost for follow up) for the whole cohort of patients. RESULTS: In 70 patients treated by LEP procedure alone, the overall 5-year survival was 91.4%. For those 36 patients, who were excluded due to disease spread above study criteria, 5 year survival was 44%. Complications in 10% of the cases necessitated a second operation. Apart from transient hyper continence and one case of permanent incontinence, no severe quality of life consequence of the operation was observed. CONCLUSIONS: Our results suggest that in two-thirds of pelvic lymph node positive, stage IB cervical cancer cases surgery alone could provide equal or better survival (without the toxicity of chemo-radiotherapy), than any kind of multimodality treatment alternatives. LEP procedure should be considered a treatment option for stage IB cervical cancer patients with pelvic lymph node metastases.
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Escisión del Ganglio Linfático/métodos , Neoplasias del Cuello Uterino/cirugía , Adulto , Femenino , Estudios de Seguimiento , Humanos , Escisión del Ganglio Linfático/efectos adversos , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patologíaAsunto(s)
Cuello del Útero/cirugía , Histerectomía/métodos , Complicaciones Neoplásicas del Embarazo/cirugía , Neoplasias del Cuello Uterino/cirugía , Femenino , Humanos , Escisión del Ganglio Linfático , Embarazo , Complicaciones Neoplásicas del Embarazo/patología , Neoplasias del Cuello Uterino/patologíaRESUMEN
Despite the reports of a number of leading institutions concerning the use of primary exenteration, there are differences in regard to definition, indications, and interpretation of results of this treatment approach to cervical cancer. In this paper we present our own experience with 41 cervical cancer patients treated with primary exenteration at St. Stephen Hospital Budapest. We explore some important unsettled aspects (definition, indications, and quality of life consequences) of this treatment modality in view of our own experience and the literature. Between January 1993 and June 2006, 2540 invasive cervical cancer patients were seen at the gynecologic oncology service of the St. Stephens Hospital Budapest. Two hundred twelve (8%) of these patients were surgically explored with the plan of an exenterative surgery. Exenteration was the primary treatment in 41 (25%) of 166 completed exenterations; these 41 cases included 2 cases of supralevator total exenteration, 9 cases of supralevator anterior exenteration, and 30 cases of partial supralevator anterior exenteration. In the 2 total exenteration patients, anal function was restored with a low rectal anastomosis, with a temporary defunctioning colostomy in 1 patient. Urethral function was restored in 9 out of 11 supralevator exenteration cases with the Budapest pouch bladder replacement technique. In the remaining 2 cases, a Bricker conduit was used for urinary diversion. There was no operation-related mortality in this cohort of patients. An external fecal or urinary stoma was avoided in 38 (93%) out of the 41 primary exenteration patients; in 1 patient a temporary defunctioning colostomy was used; and in 2 patients a permanent ileal conduit was created. In 9 patients (22%), complications (ileus and peritonitis, occlusion of the femoral artery, stricture of the implanted ureter, and postoperative ureterovaginal fistula) necessitated surgical intervention. A quality of life study revealed the need for prolonged self-catheterization, partial (mainly night time) incontinence, and lymphedema in 7 patients. We consider and suggest that an en bloc resection of part(s) of the urinary bladder and/or the rectum with the uterine cervix should be considered an exenteration (partial exenteration). A 50% survival rate of a select group of stage IVA cervical cancer patients treated with primary exenteration can be considered significant, but cannot be considered superior to that of chemoradiation therapy. The same applies when considering treatment-related mortality and complications that require operative interventions. Low rectal anastomosis and orthotopic bladder replacement with a relative low risk of fistula formation in non-irradiated patients constitute a strong quality of life argument in favor of primary exenteration in a select group of stage IVA cervical cancer patients.
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Exenteración Pélvica/métodos , Neoplasias del Cuello Uterino/cirugía , Estudios de Cohortes , Femenino , Humanos , Exenteración Pélvica/efectos adversos , Calidad de Vida , Resultado del TratamientoRESUMEN
BACKGROUND: For 10,000-40,000 women each year, cervical cancer complicates pregnancy. Current therapy usually terminates the pregnancy and results in the loss of future fertility. Abdominal radical trachelectomy is a fertility-preserving alternative to radical hysterectomy for young women with cervical cancer. CASES: We report five pregnancies complicated by cervical cancer treated by abdominal radical trachelectomy with preservation of the concurrent pregnancy and the birth of two healthy term infants. CONCLUSION: Pregnancy complicated by concurrent cervical cancer can be managed with abdominal radical trachelectomy during pregnancy while preserving future fertility.
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Procedimientos Quirúrgicos Ginecológicos/métodos , Complicaciones Neoplásicas del Embarazo/cirugía , Neoplasias del Cuello Uterino/cirugía , Abdomen/cirugía , Aborto Espontáneo/epidemiología , Adulto , Cerclaje Cervical , Femenino , Fertilidad , Humanos , Imagen por Resonancia Magnética , Estadificación de Neoplasias , Embarazo , Resultado del Embarazo , Resultado del Tratamiento , Neoplasias del Cuello Uterino/patologíaRESUMEN
Abdominal radical trachelectomy is a fertility-preserving alternative to radical hysterectomy or chemoradiation for young women with stage IA2 to IB cervical cancers. Thirty-three patients were offered this procedure. The mean age was 30.5 years (range 23-37). Three procedures were abandoned because of positive pelvic nodes (two patients) and involvement of the margin between the amputated cervix and uterine fundus (one patient). Of the remaining 30 patients, 10 had stage IA2 tumours, 15 had stage IB1 and 5 had stage IB2. During follow up of a median of 47 months (mean 32 months, range 14-75 months), no recurrences have been detected. A normal menstrual pattern resumed within eight weeks of surgery in all but two patients. Five patients attempted to conceive. Three women have fallen pregnant, resulting in one first trimester miscarriage and two caesarean section deliveries at term. Our experience suggests that abdominal radical trachelectomy provides a method of treating women with stage IA2 to IB cervical cancers with conservation of fertility without apparently compromising recurrence or survival rates. It appears to provide equivalent oncological safety to a standard Wertheim hysterectomy using a technique familiar to all practising gynaecologic oncologists.
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Cuello del Útero/cirugía , Infertilidad Femenina/prevención & control , Complicaciones Posoperatorias/prevención & control , Complicaciones Neoplásicas del Embarazo/cirugía , Neoplasias del Cuello Uterino/cirugía , Vagina/cirugía , Adulto , Femenino , Humanos , Tiempo de Internación , Metástasis Linfática , Invasividad Neoplásica/patología , Pelvis , Embarazo , Complicaciones Neoplásicas del Embarazo/patología , Neoplasias del Cuello Uterino/patologíaRESUMEN
A new surgical method was introduced for the treatment of Ib lymph node positive and IIb cervical cancer patients. The lateral resection plane corresponds to the true pelvic side wall, the plane represented by the internal obturator muscle, the linea arcuata, and the piriformis muscle with the convergent branches of the sacral plexus. The LEP procedure overcomes the limitations of the standard class III-IV radical hysterectomy, which leaves in situ the gluteal superior, inferior and pudendal nodes, thus improving local control and survival.