Características y tratamiento de los pacientes nonagenarios con enfermedad vascular ingresados en los servicios de medicina interna. Registro NONAVASC-2 / Characteristics and treatment of nonagenarian patients with vascular disease admitted to internal medicine services. NONAVASC-2 registry

Introducción La enfermedad vascular es la causa más frecuente de morbimortalidad, y su prevalencia incrementa con la edad. Los pacientes muy añosos no se encuentran incluidos en los estudios sobre enfermedad vascular, desconociéndose sus características y tratamientos. Objetivo Conocer las características clínicas de los pacientes nonagenarios hospitalizados en servicios de medicina interna con diagnóstico de EV establecida y la adecuación de su manejo farmacológico. Material y métodos El Registro NONAVASC-2 es un estudio observacional, prospectivo y multicéntrico. Se incluyeron pacientes hospitalizados por cualquier causa. La recogida de datos se realizó a través de una base anonimizada online con parámetros sociodemográficos, clínicos, analíticos, terapéuticos y evolutivos. Resultados Se incluyeron 1.049 pacientes con una edad media de 93,14 años (57,8% mujeres). La prevalencia de los factores de riesgo fue muy elevada: hipertensión (84,9%), dislipemia (50,9%) y diabetes mellitus (29,4%). El 33,4% presentaba dependencia grave/total. El 82,9% recibía tratamiento antitrombótico (53,7% antiagregantes, 25,4% anticoagulación y 3,8% doble terapia). Solo el 38,2% recibía estatinas. El porcentaje de dependencia (39,2 vs. 24,1%; p=0,00) y deterioro cognitivo grave (30,8 vs. 13,8%; p=0,00) era significativamente mayor entre los pacientes que no las recibían. El 19% falleció durante el ingreso. Conclusión Los pacientes nonagenarios con EV presentan una elevada comorbilidad, dependencia y mortalidad. A pesar de estar en prevención secundaria, el 17% de ellos no recibía antitrombóticos y solo el 38% estatinas. Esta infraprescripción está condicionada por la situación funcional, entre otros factores, por lo que es necesario realizar más estudios para conocer el impacto sobre su pronóstico (AU)

Introduction Vascular disease is the most frequent cause of morbidity and mortality and its prevalence increases with age. Old patients are not included in studies on vascular disease, their characteristics and treatments being unknown. Objective Know the clinical characteristics of nonagenarian patients hospitalized in Internal Medicine services with a diagnosis of established VD and the adequacy of their pharmacological management. Material and methods The NONAVASC-2 registry is an observational, prospective, multicentre study. Hospitalized patients for any cause were included. Data collection was carried out through an anonymous online database with sociodemographic, clinical, analytical, therapeutic and evolutionary parameters. Results One thousand forty-nine patients with a mean age of 93.14 years (57.8% women) were included. The prevalence of risk factors and VD was high: hypertension (84.9%), dyslipidemia (50.9%) and diabetes mellitus (29.4%). 33.4% presented severe-total dependency. 82.9% received antithrombotic treatment (53.7% antiplatelets, 25.4% anticoagulation and 3.8% double therapy). Only 38.2% received statins. The percentage of severe dependence (39.2% vs 24.1%; p=0.00) and severe cognitive impairment (30.8% vs 13.8%; p=0.00) was significantly higher among patients who did not receive them. 19% died during admission. Conclusions Nonagenarian patients with VD present high comorbidity, dependence and mortality. Despite being in secondary prevention, 17% did not receive antithrombotics and only 38% received statins. The underprescription is conditioned, among other factors, by the functional status. More studies are necessary to determine the impact of this issue on their prognosis (AU)

Characteristics and treatment of nonagenarian patients with vascular disease admitted to internal medicine services. NONAVASC-2 registry.

INTRODUCTION: Vascular disease (VD) is the most frequent cause of morbidity and mortality and its prevalence increases with age. Old patients are not included in studies on VD, their characteristics and treatments being unknown. OBJECTIVE: Know the clinical characteristics of nonagenarian patients hospitalized in Internal Medicine services with a diagnosis of established VD and the adequacy of their pharmacological management. MATERIAL AND METHODS: The NONAVASC-2 registry is an observational, prospective, multicentre study. Hospitalized patients for any cause were included. Data collection was carried out through an anonymous online database with sociodemographic, clinical, analytical, therapeutic and evolutionary parameters. RESULTS: One thousand forty-nine patients with a mean age of 93.14 years (57.8% women) were included. The prevalence of risk factors and VD was high: hypertension (84.9%), dyslipidemia (50.9%) and diabetes mellitus (29.4%). 33.4% presented severe-total dependency. 82.9% received antithrombotic treatment (53.7% antiplatelets, 25.4% anticoagulation and 3.8% double therapy). Only 38.2% received statins. The percentage of severe dependence (39.2% vs 24.1%; p = 0.00) and severe cognitive impairment (30.8% vs 13.8%; p = 0.00) was significantly higher among patients who did not receive them. 19% died during admission. CONCLUSIONS: Nonagenarian patients with VD present high comorbidity, dependence and mortality. Despite being in secondary prevention, 17% did not receive antithrombotics and only 38% received statins. The underprescription is conditioned, among other factors, by the functional status. More studies are necessary to determine the impact of this issue on their prognosis.

Has serum CA 125 assay at the time of relapse a prognostic relevance for patients with recurrent ovarian carcinoma after primary cytoreduction and platinum- and paclitaxel-based chemotherapy?

PURPOSE OF INVESTIGATION: To correlate serum CA125 at relapse with survival in ovarian cancer patients who achieved a complete response after primary cytoreduction and paclitaxel- and platinum-based chemotherapy. MATERIALS AND METHODS: The study was conducted in 104 patients. RESULTS: The 25%, 50%, and 75% quantiles of CA125 levels at relapse were 46, 118, and 190 U/ml. By log-rank test, survival after recurrence was related to consolidation treatment (p = 0.046), platinum-free interval (PFI) (p < 0.000005), number of recurrence sites (p = 0.03), treatment at recurrence (p = 0.002), and serum CA125 taking 118 U/ml as cut-off (p = 0.013). On multivariate analysis, consolidation treatment (p = 0.007), PFI (p = 0.0001), treatment at recurrence (p = 0.01), and serum CA125 taking 118 U/ml as cut-off (p = 0.04) were independent prognostic variables for survival. CONCLUSIONS: Serum CA125 at relapse was an independent prognostic variable. Patients with serum CA125 > 118 U/m had 1.943 higher risk of death than those with lower antigen value.

Adjuvant treatment and analysis of failures in patients with high-risk FIGO Stage Ib-II endometrial cancer: an Italian multicenter retrospective study (CTF study).

OBJECTIVES: The purpose of this retrospective study was to assess the clinical outcome of patients with high-risk, early-stage endometrioid endometrial cancer (stage Ib or II with myometrial invasion >50%, grade 2-3). METHODS: We assessed 192 patients who underwent hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy, had histologically negative pelvic nodes, and had negative CT findings for aortic node involvement. RESULTS: Tumor relapsed in 36 patients after a median time of 21.2 months. The recurrence was vaginal in 7 (19.4%), distant in 16 (44.4%), aortic in 8 (22.2%), and involved multiple sites in 5 (13.9%). There was a trend to a lower vaginal recurrence rate in the 143 patients who received adjuvant radiotherapy (+chemotherapy) compared with the 46 who did not (2.1% versus 8.7%). Distant or aortic recurrences were lower in the 37 patients who received adjuvant chemotherapy (+radiotherapy) than in the 152 who did not (2.7% versus 18.4%, p=0.02). Of the 29 patients who received sequential adjuvant chemotherapy and radiotherapy, none developed local recurrence and only one had distant recurrence. There was a trend for a better 5-year progression-free survival and overall survival for the patients who received chemotherapy (+radiotherapy) compared with those who did not (86.0% versus 71.3%, and 92.3% versus 75.6%, respectively). CONCLUSIONS: Our data appear to suggest that adjuvant chemotherapy reduces the risk of distant or aortic recurrences and that sequential adjuvant chemotherapy and radiotherapy achieve an excellent local and distant control of disease in these clinical settings.

Is there a role for postoperative treatment in patients with stage Ib2-IIb cervical cancer treated with neo-adjuvant chemotherapy and radical surgery? An Italian multicenter retrospective study.

PURPOSE: Neoadjuvant chemotherapy [NACT] followed by radical hysterectomy is an alternative therapeutic option to concurrent chemotherapy-radiotherapy for locally advanced cervical cancer. However there are very few data about the effectiveness of any post-operative treatment in this clinical setting. The purpose of this study was to correlate the patterns of recurrence and the clinical outcomes of cervical cancer patients who received NACT, with postoperative adjuvant treatment. PATIENTS AND METHODS: This retrospective multicenter study included 333 patients with FIGO stage Ib2-IIb cervical cancer who underwent platinum-based NACT followed by radical surgery. Pathological responses were retrospectively assessed as complete; optimal partial; and suboptimal response. Overall optimal response rate was the sum of complete and optimal partial response rates. RESULTS: On the whole series, recurrence-free survival was significantly longer in patients who achieved an overall optimal response than in those who did not (p<0.0001), and in patients who received adjuvant chemotherapy compared to those who did not (p=0.0001). On multivariate analysis, consolidation therapy (p=0.0012) was the only independent prognostic variable for recurrence-free survival; whereas FIGO stage (p=0.0169) and consolidation therapy (p=0.0016) were independent prognostic variables for overall survival. CONCLUSION: Optimal responders after chemo-surgical treatment for FIGO stage Ib2-IIb cervical cancer do not need any further treatment. Additional cycles of chemotherapy could be of benefit for patients with suboptimal response and intra-cervical residual disease. Both adjuvant chemotherapy and adjuvant radiation treatments do not seem to improve the clinical outcome of patients with extra-cervical residual disease compared to no further treatment.

Pathological response on surgical samples is an independent prognostic variable for patients with Stage Ib2-IIb cervical cancer treated with neoadjuvant chemotherapy and radical hysterectomy: an Italian multicenter retrospective study (CTF Study).

OBJECTIVES: The purpose of this retrospective multicenter study was to correlate patterns of recurrences and clinical outcome of cervical cancer patients who underwent neoadjuvant chemotherapy [NACT] to surgery. METHODS: This study was conducted on 333 patients with FIGO stage Ib2-IIb cervical cancer who underwent NACT to surgery with pelvic lymphadenectomy. The median follow-up was 66.5 months (range, 8-212 months). Overall optimal response rate was the sum of complete and optimal partial response rates. RESULTS: An overall optimal response was obtained in 64 patients (19.2%). As for the 220 sub-optimal responders (66.1%), 127 patients had negative nodes and negative parametria and/or surgical margins, 75 patients had positive nodes with positive or negative parametria and/or surgical margins, and 18 patients had positive parametria and/or surgical margins with negative nodes. At the time of the present analysis, 79 (23.7%) of the 333 patients had a recurrence after a median time of 14.9 months (range, 4.5-123 months). Recurrent disease was pelvic in 50 (63.3%), extra-pelvic in 22 (27.9%), and both in 7 (8.8%). On multivariate analysis, pathological response to NACT was an independent prognostic variable for recurrence-free and overall survival. Patients who did not achieve an overall optimal response had a 2.757-fold higher risk of recurrence and a 5.413-fold higher risk of death than those who obtained an overall optimal response. CONCLUSIONS: Results appear to suggest that the chemo-surgical approach is an effective therapeutic option for patients with stage Ib2-IIb cervical cancer and that pathological response to NACT is the strongest prognostic factor for the outcome.

Epigenetic regulation of PRAME in acute myeloid leukemia is different compared to CD34+ cells from healthy donors: effect of 5-AZA treatment.

PRAME is a tumor associated antigen (TAA) of particular interest since it is widely expressed by lymphoid and myeloid malignancies. Several studies have associated high PRAME RNA levels with good prognosis in acute myeloid leukemia (AML). PRAME expression is regulated at the epigenetic level. For this reason inhibitors of DNA methylation, such as 5-azacytidine, can modulate the expression of this TAAs. In the current study we analyzed the effect of 5-azaC on the expression of PRAME in blasts versus CD34+ cells from healthy donors in an attempt to increase its expression, thus inducing a potential target for therapeutic strategies.

Ovarian metastases in early-stage cervical cancer (IA2-IIA): a multicenter retrospective study of 1965 patients (a Cooperative Task Force study).

This is a retrospective study of patients treated for early-stage cervical cancer to identify pathologic risk factors associated with ovarian metastases and, therefore, to establish when ovarian preservation can be performed without increasing the risk of relapse in order to improve the quality of life in premenopausal patients. Between 1982 and 2004, 1965 patients with FIGO stage IA2-IB-IIA cervical squamous cell carcinoma and nonsquamous histology types were surgically treated; 1695 (86%) patients underwent primary radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic node dissection, the remaining 270 patients (14%) had their ovaries preserved. The clinical records were reviewed for all patients and clinical features at presentation, the histopathology and follow-up data were recorded. Overall, ovarian metastases were diagnosed in 16 of 1695 patients, for an incidence rate of 0.9%. Univariate analysis shows age (45 years: P = 0.0079), FIGO stage (IB1-IIA 4 cm: P = 0.0133), histology (squamous vs nonsquamous, P = 0.0014), noninvolved peripheral stromal thickness (<3 vs >3 mm: P = 0.0001), lymphvascular space involvement (present vs absent, P = 0.0007), lymph node status (positive vs negative, P = 0.00009) to be statistically associated with the presence of ovarian metastases. Multivariate analysis shows only age (P = 0.0119), FIGO stage (P = 0.011), histology (P = 0.001), and unaffected peripheral stromal thickness (<3 mm: P = 0.037) to be independent risk factors for ovarian metastases. Based on the present data and on the data available in the literature, ovarian preservation could be safely performed in young patients with early-stage squamous cell carcinoma (histology as the most significant risk factor), with macroscopically normal ovaries, and with preserved peripheral unaffected cervical stroma.

Surveillance procedures for patients treated for epithelial ovarian cancer: a review of the literature.

Epithelial ovarian cancer is the leading cause of death from gynecological cancer in the Western countries. Approximately 20%-30% of patients with early-stage disease and 50%-75% of those with advanced disease who obtain a complete response following first-line chemotherapy will ultimately develop recurrent disease, which more frequently involves the pelvis and abdomen. Few formal guidelines exist regarding the surveillance of these patients, and there is no agreement in the literature about the type and timing of examinations to perform. Moreover, the objective of follow-up is unclear as recurrent epithelial ovarian cancer continues to be a therapeutic dilemma and quite all the relapsed patients will eventually die of their disease. The follow-up of asymptomatic patients generally include complete clinical history, serum cancer antigen (CA)125 assay, physical examination, and often ultrasound examination, whereas additional radiologic imaging techniques are usually performed when symptoms or signs appear. (18)Fluoro-2-deoxy-glucose ((18)FDG)-positron emission tomography (PET) has a sensitivity of 90% and a specificity of 85% approximately for the detection of recurrent disease, and this examination appears to be particularly useful for the diagnosis of recurrence when CA125 levels are rising and conventional imaging is inconclusive or negative. Recently, technologic advances have led to novel combined (18)FDG-PET/computed tomography (CT) devices, which perform contemporaneous acquisition of both (18)FDG-PET and CT images. The role of (18)FDG-PET/CT for the detection of recurrent ovarian cancer is very promising, and this technique may be especially useful for the selection of patients with late recurrent disease who may benefit from secondary cytoreductive surgery.

The clinical outcome of patients with stage Ia1 and Ia2 squamous cell carcinoma of the uterine cervix: a Cooperation Task Force (CTF) study.

PURPOSE OF INVESTIGATION: The objective of this retrospective multicenter study was to assess the clinical outcome of patients with microinvasive squamous cell carcinoma of the uterine cervix. METHODS: The hospital records of 166 patients with microinvasive squamous cell carcinoma of the uterine cervix were reviewed. All cases were retrospectively staged according the 1994 International Federation of Gynecology and Obstetrics (FIGO) nomenclature. One hundred and forty-three cases were in Stage Ia1 and 23 in Stage Ia2 disease. Surgery consisted of conization alone in 30 (18.1%) patients, total hysterectomy in 82 (49.4%), and radical hysterectomy in 54 (32.5%). All patients in whom conization was the definite treatment had Stage Ia1 disease and had cone margins negative for intraepithelial or invasive lesions. RESULTS: None of the 67 patients submitted to pelvic lymphadenectomy had histologically proven metastatic lymph nodes. Of the 166 patients, eight (4.8%) had an intraepithelial recurrence and four (2.4%) had an invasive recurrence. With regard to FIGO substage, disease recurred in nine (6.3%) out of 143 patients with Stage Ia1 and three (13.0%) out of 23 with Stage Ia2 cervical cancer. With regard to type of surgery, disease recurred in three (10.0%) out of the patients treated with conization alone, four (4.9%) out those who underwent total hysterectomy, and five (9.3%) out of those who underwent radical hysterectomy. It is worth noting that none of the 30 patients treated with conization alone had recurrent invasive cancer after a median follow-up of 45 months. However three (10%) of these patients developed a cervical intraepithelial neoplasia (CIN) III after 16, 33, and 94 months, respectively, from conization. CONCLUSIONS: Conization can represent the definite treatment for patients with Stage Ia1 squamous cell cervical cancer, if cone margins and apex are disease-free. For patients with Stage Ia2 cervical cancer extrafascial hysterectomy with pelvic lymphadenectomy might be an adequate standard therapy, although the need for lymph node dissection is questionable.

Is pretreatment hemoglobin level a predictor of complete response to salvage chemotherapy for recurrent platinum-pretreated ovarian carcinoma?

PURPOSE OF INVESTIGATION: The aim of this retrospective study was to correlate some patient characteristics at relapse, including also baseline hemoglobin levels, with complete response rate and survival following second-line chemotherapy for recurrent platinum-pretreated ovarian carcinoma. METHODS: The investigation was conducted on 63 patients who received salvage chemotherapy with different agents for clinically detectable recurrent ovarian carcinoma following initial surgery and first-line platinum-based chemotherapy. Some patient characteristics at relapse (patient age, serum CA 125 level, baseline hemoglobin level, number of recurrence sites, ascites, platinum-free interval, and treatment-free interval) were related to complete response rate to salvage chemotherapy and survival after recurrence. Median baseline hemoglobin level was 11.6 g/dl (range, 7.5-15.0 g/dl). RESULTS: Second-line chemotherapy obtained a complete response in 17 (27.0%) patients and a partial response in 11 (17.5%), whereas stable disease and progressive disease were detected in 19 (30.1%) and 16 (25.4%) patients, respectively. By univariate analysis, complete response rate was related to baseline hemoglobin level (p = 0.0019), platinum-free interval (p = 0.0012) and treatment-free interval (p = 0.0048). Multiple logistic regression showed that platinum-free interval (p = 0.0107) and baseline hemoglobin level (0.0312) were independent predictors of complete response. Patients with baseline hemoglobin levels >11.6 g/dl had a 5.338 higher chance of obtaining a complete response when compared to those with lower hemoglobin values. The platinum-free interval was the only independent prognostic variable for survival after recurrence (p = 0.0141), whereas baseline hemoglobin level was not related to survival at univariate nor at multivariate analysis. CONCLUSIONS: Baseline hemoglobin level is an independent predictor of complete response to salvage chemotherapy in patients with recurrent platinum-pretreated ovarian carcinoma. Attention must be paid to anemia correction in these patients, with the aim of improving both the chance of response to salvage treatment and the quality of life.

First-line chemotherapy with epidoxorubicin, paclitaxel, and carboplatin for the treatment of advanced epithelial ovarian cancer patients.

OBJECTIVE: A combination of carboplatin (CBDCA) and paclitaxel (TAX) is the standard treatment in advanced ovarian cancer (AOC) patients. Epidoxorubicin (EDX) is an active treatment in AOC and exhibits nonoverlapping toxicities with CBDCA and TAX; moreover, when added to platinum-based chemotherapy, it improves long-term survival. We have therefore conducted a phase II study to evaluate the tolerability and antitumor activity of an EDX/TAX/CBDCA (ETC) triplet in AOC patients. METHODS: Patients with histologically confirmed suboptimal stage III-IV ovarian cancer who had not previously received cytotoxic drugs were treated with TAX (175 mg/m(2) in a 3-h iv infusion), CBDCA (AUC 6, Calvert formula), and EDX (75 mg/m(2) iv bolus) all given on day 1 every 28 days for a maximum of six courses on an outpatient basis. EDX dosage was chosen after a pilot phase I study. RESULTS: Fifty-five patients were registered, of whom 5 were determined ineligible bacause of age. Forty-two of the 50 are evaluable for response; 27 (64%) achieved a clinical complete response (CR) and 9 (21%) a partial response (PR) for a response rate of 86% (95% CI 71-94%). Thirty-three patients underwent a secondary debulking procedure after a median of 6 courses (range 2-6). Pathological CR and PR were observed in 9 (27.3%) and 21 (63.6%), respectively; among patients with persistent disease a successful cytoreduction (<1 cm) was obtained in 53.8% of patients. At a median follow up of 35.6 months (range 0-55.5) median progression-free survival is 19.5 months and median overall survival is 36 months. The most common adverse effects were G3-4 leukopenia and thrombocytopenia which occurred in 59 and 37% of patients, respectively. CONCLUSIONS: The ETC combination given according to the outlined doses and schedule is highly active in AOC patients with poor prognostic factors and deserves further study.

Molecular mechanisms of apoptosis and chemosensitivity to platinum and paclitaxel in ovarian cancer: biological data and clinical implications.

Apoptosis is a genetically regulated biological process that plays a major role in chemotherapy-induced tumor cell killing. It may be triggered by two major intracellular signaling cascades, the mitochondrial pathway and the death receptor pathway, both leading to caspase activation and cleavage of specific cellular substrates. The p53 gene is involved in the regulation of apoptosis. Caspase activation following wild-type p53 induction is associated with the release of the apoptogenic factors cytochrome c and Smac/DIABLO from the mitochondria, that is in turn controlled by the pro-apoptotic and anti-apoptotic Bcl-2 family proteins. In ovarian cancer p53 status is a strong predictor of response to platinum-based chemotherapy. Patients whose tumors have p53 mutations experience a lower chance of achieving a complete response following platinum-based regimens when compared to patients without p53 mutations. Conversely, experimental and clinical data seem to show that paclitaxel enhances apoptosis through a p53-independent pathway, that probably involves the Bax gene. Whereas patients with wild-type p53 tumors have a good chance to respond to platinum, patients with mutant p53 tumors may have a clinical benefit from the addition of paclitaxel to platinum-based chemotherapy. Therefore determining p53 status can be useful in predicting therapeutic response to specific drugs. Moreover the understanding of cellular mechanisms regulating apoptosis might offer a strong rationale for the combination of chemotherapy with other biological treatments.

The prognostic relevance of histological type in uterine sarcomas: a Cooperation Task Force (CTF) multivariate analysis of 249 cases.

PURPOSE OF INVESTIGATION: The objective of this retrospective multicenter study was to assess the prognostic relevance of histologic type in uterine sarcomas. METHODS: The hospital reports of 249 patients with uterine sarcomas were reviewed. Surgery was the initial therapy for all patients. Histologic type was leiomyosarcoma in 95 cases, low-grade endometrial stromal sarcoma (ESS) in 19, high-grade ESS in 34, and carcinosarcoma in 101. Postoperative treatment was given without well-defined protocols. Median follow-up of survivors was 97 months. RESULTS: In the whole series 2-year, 5-year, and 10-year survival rates were 53.5%, 41.6%, and 35.8%, respectively, and median survival was 31 months. At univariate analysis survival was significantly related to stage (p = 0.0001), mitotic count (p = 0.0001), and histologic type (low-grade ESS vs leiomyosarcoma vs carcinosarcoma vs high-grade ESS, median: not reached vs 27 months vs 21 months vs 16.5 months, p = 0.0011), but not to postoperative therapy and patient age. The Cox model revealed that tumor stage, mitotic count and histologic type were independent prognostic variables for survival. In detail, the risk of death was significantly lower for low-grade ESS (risk ratio [RR] = 0.257; 95% confidence interval [CI] = 0.071-0.931) and carcinosarcoma (RR = 0.509; 955 CI = 0.324-0.799) when compared to leiomyosarcoma. Conversely, no significant difference in survival was found between leiomyosarcoma and high-grade ESS. CONCLUSIONS: Histologic type is an independent prognostic variable for survival in uterine sarcomas. Low-grade ESS has the best clinical outcome, whereas leiomyosarcoma has the poorest one. It is noteworthy that, when adjusting for stage and mitotic count, leiomyosarcoma has a significantly worse prognosis than carcinosarcoma.

Malnutrition and cachexia in ovarian cancer patients: pathophysiology and management.

In ovarian cancer patients the poor nutritional status and cachexia are caused by the metabolic effects of the enlarging tumor masses and bowel obstruction. These patients may have a high resting energy expenditure due to increase in Cori cycle activity, glucose and triglyceride-fatty acid cycling and gluconeogenesis. Biochemical mediators of cachexia include cytokines, such as tumor necrosis factor and interleukin-6, and tumor-produced catabolic factors, such as lipid-mobilizing factor, proteolysis-inducing factor, and anemia-inducing factor. Mechanisms involved in the pathogenesis of obstruction may include extrinsic occlusion of the bowel due to pelvic, mesenteric omental masses, or intestinal motility disorders due to infilor tration of the mesentery or bowel muscle and nerves. The relief of malnutrition and cachexia may be attempted through nutritional support, pharmacological approach (megestrol acetate, cyclooxygenase inhibitors) and palliative treatment of bowel obstruction. Very few agents have been demonstrated to have true anticachectic activity, so future research should be addressed to the identification of drugs able to block the activity of tumor-produced catabolic factors. The decision regarding optimum management of bowel obstruction should be individualized. Krebs' and Goplerud's score (based on age, nutritional status, tumor status, ascites, previous chemotherapy and irradiation) seems to offer reliable eligibility criteria for those patients who can benefit from surgery.

The clinical relevance of serum CYFRA 21-1 assay in patients with ovarian cancer.

CYFRA 21-1 assay, which detects serum fragments of cytokeratin 19, has been widely assessed as a serum marker of several malignancies. Preoperative serum CYFRA 21-1 levels were retrospectively measured in 60 patients with ovarian cancer and in 59 control patients with benign ovarian disease. CYFRA 21-1 levels were also serially measured in 90 serum samples drawn from patients with advanced (FIGO stage III-IV) ovarian cancer followed after surgery and chemotherapy. Preoperative serum CYFRA 21-1 levels were higher in patients with ovarian cancer compared with controls (median, range = 2.6, 0.1-51.4 ng/ml versus 0.4, 0.0-3.6 ng/ml, P < 0.0001), and among the former, antigen values were higher in the 39 patients with advanced-stage than in the 21 patients with early (FIGO stage I-II) disease (P < 0.0001). In advanced ovarian cancer patients, the 25%, 50%, and 75% quantiles of preoperative CYFRA 21-1 levels were 1.9, 4.8 and 14.4 ng/ml, respectively. Preoperative CYFRA 21-1 levels were lower in the 11 patients who achieved a pathologic complete response at second-look compared with those who had clinically or surgically detectable persistent disease after first-line chemotherapy (median, range 1.9, 0.6-9.2 ng/ml versus 10.2, 0.1-51.4 ng/ml, P = 0.007). The pathologic complete response rate was significantly greater in patients with low preoperative CYFRA 21-1 levels compared with those with elevated CYFRA 21-1 levels at any cut-off limit for the antigen (1.9, 4.8 and 14.4 ng/ml). However, Cox regression analysis failed to detect a significant association between preoperative CYFRA 21-1 assay and survival. As for the follow-up of advanced ovarian cancer patients, CYFRA 21-1 levels were higher in the 42 samples drawn from patients with clinically detectable disease compared with the 48 specimens collected from patients with no clinical evidence of disease (median, range = 1.15, 0.3-40.7 ng/ml versus 0.4, 0.1-9.1 ng/ml, P < 0.0001). In conclusion, preoperative serum CYFRA 21-1 assay appears to be predictive of response to chemotherapy, but not prognostic of survival, for patients with advanced ovarian cancer. Moreover, the serial measurement of CYFRA 21-1 levels might have a potential clinical relevance for the assessment of disease status in patients followed after surgery and chemotherapy.

Analysis of treatment failures and survival of patients with fallopian tube carcinoma: a cooperation task force (CTF) study.

OBJECTIVE: The objective of this retrospective multicenter study was to assess the pattern of failures and survival of patients with primary carcinoma of the fallopian tube. METHODS: The hospital records of 88 patients with primary carcinoma of the fallopian tube were reviewed. Surgery was the initial therapy for all patients. Tumor stage was I in 21 (23.9%), II in 21 (23.9%), III in 43 (48.8%), and IV in 3 (3.4%) patients. Postoperative treatment was given without well-defined protocols. The median follow-up of survivors was 55 months (range, 7-182). RESULTS: Of the 21 patients with stage I disease, 10 had no postoperative treatment and 11 had platinum-based chemotherapy. Five (23.8%) patients recurred after a median of 29 months (range, 8-93) from initial surgery. Of the 21 patients with stage II disease, 2 had no postoperative treatment, 2 underwent external pelvic irradiation, 16 received platinum-based chemotherapy, and 1 patient had oral melphalan. Eight (38.1%) patients recurred after a median of 25.5 months (range, 7-57). Of the 46 patients with stage III-IV disease, 1 patient refused chemotherapy and died after 19 months and 45 patients received platinum-based chemotherapy. A clinical complete response was obtained in 29 (64.4%) patients and a partial response in 8 (17.8%). A second-look laparotomy was performed in 14 of the 29 clinically complete responders: 12 patients were found to be in pathological complete response and 2 had persistent disease. Six (50.0%) of the former recurred after a median of 22 months (range, 13-101) from initial surgery. The two patients with persistent disease developed tumor progression after 15 and 11 months, respectively. Fifteen clinically complete responders did not undergo second-look, and 7 (46.7%) of them had a recurrence after a median of 18 months (range, 9-41). For the whole series, 5-year survival was 57%. By log-rank test, survival was related to FIGO stage (III-IV vs I-II, P = 0.0001), tumor grade (G3 vs G1 + G2, P = 0.0038), and patient age (>58.5 years vs <58.5 years, P = 0.0069), but not to histological type. The Cox model showed that FIGO stage (P = 0.0018) and patient age (P = 0.0290) were independent prognostic variables for survival. Among the patients with stage III-IV disease, 5-year survival was 55% for the patients who had residual tumor <1 cm compared with 21% for those who had larger residuum (P = 0.0169). CONCLUSIONS: Primary carcinoma of the fallopian tube shares several biological and clinical features with ovarian carcinoma. However, when compared with the latter, fallopian tube carcinoma more often tends to recur in retroperitoneal nodes and distant sites. Stage, patient age, and, among patients with advanced disease, residual tumor after initial surgery represent important prognostic variables for survival.

Neoadjuvant chemotherapy and concurrent chemoradiation in the treatment of advanced cervical cancer.

The role of chemotherapy in the management of advanced cervical cancer has been long debated. Whereas some phase II trials have shown promising results with neoadjuvant chemotherapy followed by irradiation, most phase III trials failed to demonstrate any benefit with this sequential treatment in terms of loco-regional control and survival, mainly because chemotherapy could cause accelerated tumor clonogen resistant cell repopulation The data on cisplatin-based neoadjuvant chemotherapy before surgery appear to be more promising. This treatment modality can increase the operability rate and reduce the incidence of positive nodes and other pathological risk factors. However, very few randomized trials comparing cisplatin-based neoadjuvant chemotherapy followed by radical hysterectomy versus conventional irradiation treatment are currently available, whilst data about long-term survival of chemo-surgical-treated patients are scanty. Recently five prospective randomized trials compared concurrent cisplatin-based chemotherapy and irradiation versus hydroxyurea plus irradiation or irradiation alone. All showed a significant improvement in the outcome of patients treated with concurrent cisplatin-based chemoradiation. Based on these data, the National Cancer Institute released a Clinical Announcement stating that concurrent cisplatin-based chemoradiation should be the new standard of therapy for high-risk early stage and locally advanced cervical cancer. The introduction of taxanes in both neoadjuvant chemotherapy followed by radical hysterectomy and concurrent chemoradiation could further improve the results of these two treatment modalities. A multicenter randomized trial comparing chemo-surgical treatment with concurrent chemoradiation is warranted to better define the optimum therapeutic strategy for patients with advanced cervical cancer.