Role of HE4, CA72.4, and CA125 in monitoring ovarian cancer

The aim of this study was to investigate the role of biomarkers CA125, HE4, and CA72.4 at diagnosis and throughout the follow-up in patients with epithelial ovarian cancer (EOC). Thirty-nine patients with EOC were deemed eligible, and 20 were followed up. CA125, HE4, and CA72.4 serum levels were determined for all patients at initial diagnosis of EOC. Among these patients, the number of cases with an elevated level of each individual marker was CA125 77?%, HE4 85?%, and CA72.4 72?%. A statistically significant difference was observed between the level of HE4 when compared to CA72.4 (p?<?0.02). In the follow-up phase, we observed tumor marker levels fluctuating according to response to chemotherapy. When combining two out of the three biomarkers together, we observed increased values of CA125 and CA72.4 in 55?% of the patients, increased values of CA125 and HE4 in 65?% of the patients, and finally increased HE4 and CA72.4 in 75?% of the patients. A statistically significant difference was observed when combining HE4 and CA72.4, but not CA125 and CA 72.4 (p?<?0.002). In conclusion, our study demonstrates that the association of three biomarkers CA125, HE4, and CA72.4 provides a valuable contribution in the follow-up of EOC patients.     

上皮性卵巢癌血清miR-1294及miR-4443的表达及其与预后的关系

目的:探讨上皮性卵巢癌（epithelial ovarian cancer,EOC）患者血清miR-1294及miR-4443的表达水平及其与患者临床病理特征和预后的关系。方法:选取我院2015年1月至2017年12月收治的106例EOC患者作为EOC组,另选取90例卵巢良性肿瘤患者作为良性组和60例正常健康女性作为对照组,检测血清miR-1294及miR-4443表达水平。以miR-1294及miR-4443的最佳截断值为标准将EOC患者分为高miR-1294组（n=33）、低miR-1294组（n=73）和高miR-4443组（n=36）、低miR-4443组（n=70）。EOC患者预后不良的危险因素应用单因素及多因素COX回归模型进行分析。结果:血清miR-1294表达水平（0.48±0.13 vs 1.16±0.57、1.21±0.62）在EOC组明显低于良性组和对照组（P均<0.001）。血清miR-4443表达水平（0.71±0.18 vs 1.36±0.64、1.45±0.70）在EOC组明显低于良性组和对照组（P均<0.001）。miR-1294和miR-4443高表达组的EOC患者临床分期、分化程度、淋巴结转移及腹膜转移与miR-1294和miR-4443低表达组比较,差异均有统计学意义（P<0.05）。Kaplan-Meier分析显示,EOC患者生存期短与miR-1294及miR-4443低表达有关（P<0.001）。多因素分析显示,EOC患者预后不良的独立危险因素为淋巴结转移［HR（95%CI）=1.885（1.206～4.118）］、腹膜转移［HR（95%CI）=3.106（2.315～6.226）］、miR-1294＜0.73［HR（95%CI）=2.614（1.865～5.512）］及miR-4443＜1.04［HR（95%CI）=1.975（1.508～4.903）］。结论:miR-1294及miR-4443的低表达与EOC患者生存期短有关,是EOC患者预后预测的生物标志物。     

血清miR-552-5p、HE4及CA125在上皮性卵巢癌中的表达及其临床价值北大核心

目的:探讨miR-552-5p、血清人附睾蛋白4(HE4)及糖类抗原125(CA125)在上皮性卵巢癌(EOC)中的表达及其诊断价值。方法:选取127例EOC患者,90例卵巢良性肿瘤者(良性组)和50例正常对照组作为研究对象,采用实时定量PCR法检测miR-552-5p表达水平,化学发光法测定血清HE4及CA125水平。应用受试者工作特征(ROC)曲线分析miR-552-5p、HE4及CA125诊断EOC的价值。Pearson相关分析EOC患者miR-552-5p表达水平与HE4及CA125的相关性。结果:EOC组血清miR-552-5p(4.25±1.70 vs 1.90±0.83,1.61±0.74)、HE4(350.35±60.12 vs 52.93±11.72,46.80±9.25,pmol/L)及CA125(319.50±96.14 vs 27.14±12.15,20.36±8.95,U/m L)水平均明显高于良性组和对照组(P<0.001)。EOC患者血清miR-552-5p、HE4及CA125表达与临床分期、分化程度及淋巴结转移有关(P<0.05)。ROC曲线显示,miR-552-5p、HE4及CA125三项联合诊断EOC的曲线下面积(0.954,95%CI:0.895~0.998)最大,其敏感度为97.8%,特异度为87.6%。相关分析显示,EOC患者血清miR-552-5p表达水平与HE4及CA125均呈正相关(r=0.872,r=0.805,P<0.001)。结论:血清miR-552-5p、HE4及CA125水平在EOC患者中明显升高,三项联合检测对EOC诊断具有较好的价值。     

Chemotherapy for patients with two favourable subsets of unknown primary carcinoma: active, but how effective?

Carcinoma of unknown primary (CUP) is characterized by dismal patient survival. The outcome of patients with two favourable risk CUP subsets was studied. Eighty patients diagnosed with either midline lymph node metastases (n=33) or peritoneal carcinomatosis (n=47) were analysed retrospectively. The majority had poorly differentiated adenocarcinoma or undifferentiated carcinoma, treated with platinum-taxane based chemotherapy from 1996 till 2002. Females with peritoneal carcinomatosis also underwent surgical debulking. Objective tumour regression was present in 44% of patients (nodal group 30% versus peritoneal group 53%, p=0.066). Complete responses were seen more often in peritoneal carcinomatosis patients (nodal group 9%, peritoneal group 36%, p=0.008). At a median follow up of 60 months, median progression-free and overall survival were 5 and 10 months respectively in the nodal group, 7 and 15 months in the peritoneal group. Five-year survival was 7% (nodal group 0% vs. peritoneal group 10%, p=0.05). Complete responders fared better than non-CR patients. Fewer than four metastatic sites, elevated CA 125, and normal CA 19-9 levels were favourable prognostic factors for survival. Modern combination chemotherapy has satisfactory activity, with a minority of CUP patients enjoying long-term responses. Research efforts towards complete remission consolidation and molecular profiling are imperative.     

Diagnostic Model of Serum miR-193a-5p,HE4 and CA125 Improves the Diagnostic Efficacy of Epithelium Ovarian Cancer

Epithelium ovarian cancer (EOC) is currently the prevalent malignant cancer worldwide. However, there is a lack of efficient biomarkers for EOC screening. Accumulating evidence reveals that serum miRNA detectable in various types of cancer. Therefore, we explore the diagnostic value of combined detection of plasma miR-193a-5p, HE4 and CA125 for EOC. Serum samples were collected from 45 patients with primary EOC, 30 patients with benign ovarian tumor patients and 40 healthy controls. The expression of serum miR-193a-5p was detected by real-time quantitative PCR, and serum HE4 and CA125 were detected by chemiluminescent immunoassay. Moreover, a diagnostic model combining miR-193a-5p, HE4 and CA125 or alone in EOC patients was evaluated by ROC curve analysis. The relative expression quantity (RQ) of serum miR-193a-5p in EOC patients, benign ovarian tumor patients and healthy control groups were 0.419 (0.093, 2.215), 3.667 (1.633, 6.691) and 1.130 (1.000, 7.087), respectively. The RQ of serum miR-193a-5p in EOC patients was significantly lower than that in benign ovarian tumor patients and healthy controls (both P?<?0.001), and there was no significant difference between benign ovarian tumor patients and healthy controls (both P?>?0.05). There was no significant correlation between serum miR-193-5p, HE4 and CA125 levels (both P?>?0.05). Additionally a risk model for miR-193a-5p, HE4 and CA125 was correlated with Grading and Lymph node metastasis (P?=?0.016, P?=?0.029). The area under the receiver operating characteristic curve of a risk model for distinguishing EOC patients from healthy individuals was 0.996, which higher than any single biomarker. Combined detection of miR-193-5p, HE4 and CA125 by logistic regression analysis could greatly improved the diagnostic ability of EOC and may prove to be a candidate biomarker, providing new directions for further investigation.     

Clinical application of total parenteral nutrition in patients with peritoneal carcinomatosis

Cancer patients with terminal stage peritoneal carcinomatosis are often unable to eat, rendering total parenteral nutrition (TPN) as the only option to avoid starvation. In this retrospective study, we reviewed the medical records of 46 patients with peritoneal carcinomatosis and compared them to the records of 51 patients who had gastrointestinal malignancy without evidence of peritoneal carcinomatosis. The factors evaluated include demographic data, cause of primary malignancy, ascites formation, anthropometric measurements, laboratory tests, and outcome measurements as well as factors associated with greater than 90‐day survival. In‐hospital mortality was observed in 31 of the 46 patients with peritoneal carcinomatosis, with a median survival time of 40 days (4–148 days) for all 46 patients. The median duration of TPN administration in the peritoneal carcinomatosis group was 24.1 ± 27.4 days (3–68 days). Severe infection related to TPN application was seen in 5/46 (10.7%) patients with peritoneal carcinomatosis and 6/51 (9.8%) patients without peritoneal carcinomatosis. The length of survival varied widely among terminal patients with peritoneal carcinomatosis. The average survival time in peritoneal carcinomatosis patients receiving TPN was short, indicating that the nutrition support of TPN was relatively suboptimal. Ascites was not a prognostic factor for peritoneal carcinomatosis, while body mass index was a predictor for 90‐day survival.     

Intraperitoneal chemohyperthermia with mitomycin C for digestive tract cancer patients with peritoneal carcinomatosis

BACKGROUND: Most patients with peritoneal carcinomatosis of digestive tract origin die within 6 months. Intraperitoneal chemohyperthermia (IPCH) associated with surgery has been reported as a possible new therapeutic approach. METHODS: A prospective Phase II trial was carried out with 83 patients who had digestive tract cancer and peritoneal carcinomatosis to evaluate the tolerance and efficacy of IPCH with mitomycin C (MMC) associated with surgery. Eighty-six IPCH treatments with MMC were given as complementary therapy after surgery (peritoneal perfusate with a 10 mg/L dose of MMC; inflow temperature, 46-49 degrees C; use of a closed circuit; duration, 90 minutes). Primary tumors were mainly gastric (in 42 cases) or colorectal (in 27 cases). RESULTS: Mortality and morbidity occurred in 3 of 83 cases and 8 of 83 cases, respectively. For patients with resectable tumors, the median survival time was 16 months when carcinomatosis was Stage I and II (malignant granulations less than 5 mm in greatest dimension), whereas it was 6 months when carcinomatosis was Stage III and IV (malignant granulations more than 5 mm in greatest dimension). For patients with resectable gastric cancer and Stage I and II carcinomatosis, 1-, 2-, and 3-year actuarial survival rates were 80%, 61%, and 41%, respectively, whereas the rate was 10% at 1 year for patients with bulky disease (Stage III and IV). CONCLUSIONS: IPCH appears to be a promising new approach to treating patients with digestive tract cancers and peritoneal carcinomatosis with small, malignant granulations (Stage I and II).     

上皮性卵巢癌术后复发的相关影响因素分析

目的 分析上皮性卵巢癌(EOC)术后复发的相关影响因素.方法 选择124例EOC患者作为研究对象,入选患者均行手术及化疗治疗,并进行长期随访.根据5年随访结果将患者分为复发组(51例)和未复发组(73例).采用单因素和多因素Logistic回归分析EOC术后复发的相关影响因素.结果 两组年龄、分娩次数、组组织学类型、有...     

人附睾蛋白4和Lewis y抗原在上皮性卵巢癌组织中的表达及其与化疗耐药和预后的关系

目的:探讨人附睾蛋白4（HE4）与Lewis y抗原在上皮性卵巢癌组织中的表达及其与化疗耐药、患者预后的关系。方法:应用免疫组织化学方法检测HE4和Lewis y抗原在92例上皮性卵巢癌组织（36例化疗耐药,56例化疗敏感）中的表达,分析其与临床病理参数、化疗耐药及预后之间的关系。结果:HE4及Lewis y抗原以胞膜着色为主,卵巢癌耐药组中HE4及Lewis y抗原的高表达率明显高于敏感组（75%,83.3% vs 30.4%,30.4%,P＜0.001）,且二者的表达呈正线性相关(r=0.240,P=0.021),其与临床病理参数未见显著性差异,回归分析发现FIGO分期、HE4及Lewis y抗原的高表达是化疗耐药的独立危险因素(HR:10.230,10.496,10.065,所有P＜0.05),单因素生存分析表明年龄、FIGO分期、残余病灶大小、淋巴转移、化疗是否耐药、Lewis y抗原及HE4的表达都是影响总体生存时间（OS）的重要因素（所有P＜0.05）,Cox多因素生存分析显示FIGO分期和Lewis y抗原是影响OS的独立因素（所有P＜0.05）。结论:HE4与Lewis y抗原在卵巢癌组织中的表达呈正相关性,可以预测卵巢癌的化疗耐药,其高表达提示着患者更差的预后。     

Feasibility of peritonectomy associated with intraperitoneal hyperthermic perfusion in patients with Pseudomyxoma peritonei

AIMS AND BACKGROUND: Pseudomyxoma peritonei is a rare disease characterized by a complete redistribution of mucin within the peritoneal cavity. It can be classified into three histologic groups: disseminated peritoneal adenomucinosis, peritoneal mucinous carcinomatosis, and an intermediate group. The aim of the present study was to evaluate the feasibility of cytoreductive surgery requiring peritonectomy procedures associated with intraperitoneal hyperthermic perfusion, a technique that combines hyperthermia and high drug doses administered locally. METHODS: Twenty-seven patients with pseudomyxoma peritonei (19 males and 8 females) were enrolled in a phase II clinical trial. Twenty-two cases underwent cytoreductive surgery plus intraperitoneal hyperthermic perfusion, and 6 received debulking surgery only. One patient was operated on twice for disease recurrence. All patients with peritoneal mucinous carcinomatosis presented serous ascites, whereas all but one patient with disseminated peritoneal adenomucinosis or in the intermediate group presented mucinous ascites. Cytoreductive surgery was performed with peritonectomy procedures. The closed abdomen technique was adopted for intraperitoneal hyperthermic perfusion using a preheated polysaline perfusate containing cisplatin (25 mg/m2/L) plus mitomycin-C (3.3 mg/m2/L) through a heart-lung pump at a mean flow of 600 mL/min for 60 mins from the hyperthermic phase (42.5 degrees C). RESULTS: All but one of the patients with disseminated peritoneal adenomucinosis and 2 of the 3 patients in the intermediate group were optimally cytoreduced. Patients with serous ascites (all patients with peritoneal mucinous carcinomatosis and 1 patient with disseminated peritoneal adenomucinosis) were considered ineligible for treatment because of tumor diffusion. The morbidity rate was 22%. There was one case of treatment-related mortality 30 days after treatment. CONCLUSIONS: The following conclusions can be drawn from this phase II clinical trial: 1) patients with pseudomyxoma peritonei originating from undifferentiated mucinous adenocarcinoma (peritoneal mucinous carcinomatosis), with complete distribution into the peritoneal cavity, are not eligible for the cytoreductive surgery plus intraperitoneal hyperthermic perfusion technique; 2) the presence of serous ascites would seem to exclude patients from the treatment; 3) cytoreductive surgery associated with intraperitoneal hyperthermic perfusion is the most suitable approach for patients with disseminated peritoneal adenomucinosis and in the intermediate group.     

HE4、OPN、MSLN水平对上皮性卵巢癌的诊断价值

目的 探讨血清人附睾分泌蛋白4(HE4)、骨桥蛋白(OPN)及间皮素(MSLN)水平对上皮性卵巢癌(EOC)的诊断价值.方法 选择100例EOC患者(EOC组)、60例卵巢上皮良性肿瘤患者(良性组)和60例健康女性体检者(健康组),检测3组研究对象的血清HE4、OPN及MSLN水平,分析3种指标单独及联合诊断EOC的临床价值.结果 EOC组患者的血清HE4、OPN、MSLN水平均高于良性组和健康组,差异均有统计学意义(P﹤0.05);良性组和健康组的血清HE4、OPN、MSLN水平比较,差异均无统计学意义(P﹥0.05);血清OPN+HE4+MSLN正确诊断EOC患者92例,诊断灵敏度为92.00%,特异度为90.83%,漏诊率为8.00%,误诊率为9.17%,曲线下面积(AUC)为0.916.结论 血清OPN+HE4+MSLN联合检测对EOC具有较高的诊断价值,较单一指标检测提高了灵敏度和特异度.     

Serum HE4 superior to CA125 in predicting poorer surgical outcome of epithelial ovarian cancer

Epithelial ovarian cancer (EOC) remains the deadliest form of gynecological cancers. Optimal tumor debulking, no matter the primary or the interval, is the most important prognostic factor for EOC, so there is an urgent demand for biomarkers to predict surgical outcome. The aim of this study was to investigate whether serum human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) could predict surgical outcome of EOC. The levels of preoperative serum HE4 and CA125 were determined by electrochemiluminescence (ECLIA) in 82 EOC patients, comprising 39 subjected to primary debulking surgery (PDS) and 43 with extensive stage III or IV disease to neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS). Among 39 patients subjected to primary debulking surgery, HE4 was superior to CA125 in predicting surgical outcome (area under curve [AUC] 0.758 vs. 0.633). At a cutoff of 353.22 pmol/L, HE4 reached 77.4 % in sensitivity and 75 % in specificity. The prediction of surgical outcome of interval debulking surgery based on preoperative HE4 and CA125 values was performed in 43 patients who received NACT-IDS. The difference of AUC between HE4 and CA125 (0.793 vs. 0.663) indicating that HE4 was the better biomarker to predict surgical outcome of IDS. A pre-IDS HE4 value of 154.3 pmol/L is the optimal cutoff to identify patients who would not benefit from IDS with a sensitivity of 92.9 % and a specificity of 69 %. The change (>70 %) of HE4 before and after neoadjuvant chemotherapy could predict optimal interval debulking surgery. Serum HE4 was superior to CA125 in predicting surgical outcome of primary debulking surgery and interval debulking surgery. The change (absolute value or percentage) of HE4 in neoadjuvant chemotherapy could predict the outcome of interval debulking surgery.

     

Correlation of preoperative ROMA scores with clinical stage in epithelial ovarian cancer patients

Purpose

The significance of the Risk of Ovarian Malignancy Algorithm (ROMA) in differentiating benign and malignant ovarian lesions has been evidenced. In our clinical work, we found that advanced ovarian cancer were accompanied commonly with high ROMA scores. Thus, this study aimed to clarify the performance of ROMA in different disease stage of epithelial ovarian cancer (EOC) prior to surgery.

Methods

Carbohydrate antigen (CA125) and human epididymis protein 4 (HE4) levels and ROMA scores in 221 patients with FIGO stage I, II or III/IV stage EOC were analyzed. The positive rates of CA125, HE4 and ROMA at each disease stage were calculated. Their cutoff values, sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for distinguishing patients with FIGO stage I/II from those with FIGO stage III/IV were estimated via ROC curves.

Results

Serum CA125 and HE4 levels and ROMA scores rose significantly with advancing stage. ROMA and CA125 were significantly elevated more frequently in comparing with HE4 in EOC patients at with the same stage. Based on ROC curves, the cutoff values for FIGO stage III/IV EOC were 110 IU/mL, 126 pmol/L, 78 and 68% for CA125, HE4, premenopausal and postmenopausal ROMA, respectively. ROMA was the strongest predictor of FIGO stage, with the highest specificity, accuracy, and PPV, which were 84.4, 82.5, and 87.0% for postmenopausal patients, 89.3, 85.6, and 74.3% for premenopausal patients.

Conclusions

Our data suggest high ROMA scores correlated with advanced ovarian cancer prior to surgery. These observations suggest potential utility of ROMA in the comprehensively preoperative evaluation of EOC patients.

     

Usefulness of human epididymis protein 4 in predicting cytoreductive surgical outcomes for advanced ovarian tubal and peritoneal carcinoma

Objective

Human epididymis protein 4 (HE4) is a promising biomarker of epithelial ovarian cancer (EOC). But its role in assessing the primary optimal debulking (OD) of EOC remains unknown. The purpose of this study is to elucidate the ability of preoperative HE4 in predicting the primary cytoreductive outcomes in advanced EOC, tubal or peritoneal carcinoma.

Methods

We reviewed the records of 90 patients with advanced ovarian, tubal or peritoneal carcinoma who underwent primary cytoreduction at the Department of Obstetrics and Gynecology of Peking University People’s Hospital between November 2005 and October 2010. Preoperative serum HE4 and CA125 levels were detected with EIA kit. A receiver operating characteristic (ROC) curve was used to determine the most useful HE4 cut-off value. Logistic regression analysis was performed to identify significant preoperative clinical characteristics to predict optimal primary cytoreduction.

Results

OD was achieved in 47.7% (43/48) of patients. The median preoperative HE4 level for patients with OD vs. suboptimal debulking was 423 and 820 pmol/L, respectively (P<0.001). The areas under the ROC curve for HE4 and CA125 were 0.716 and 0.599, respectively (P=0.080). The most useful HE4 cut-off value was 473 pmol/L. Suboptimal cytoreduction was obtained in 66.7% (38/57) of cases with HE4 ≥473 pmol/L compared with only 27.3% (9/33) of cases with HE4 <473 pmol/L. At this threshold, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for diagnosing suboptimal debulking were 81%, 56%, 67%, and 73%, respectively. Logistic regression analysis showed that the patients with HE4 ≥473 pmol/L were less likely to achieve OD (odds ratio =5.044, P=0.002).

Conclusions

Preoperative serum HE4 may be helpful to predict whether optimal cytoreductive surgery could be obtained or whether extended cytoreduction would be needed by an interdisciplinary team.     

HE4 as a Serum Biomarker for ROMA Prediction and Prognosis of Epithelial Ovarian Cancer

Background and Purpose: Human epididymis protein 4 (HE4) has been suggested to be a novel biomarkerof epithelial ovarian cancer (EOC). The present study aimed to evaluate and compare HE4 with the commonlyused marker, carbohydrate antigen 125 (CA125), in prediction and therapy-monitoring of EOC. Patients andMethods: Serum HE4 concentrations from 123 ovarian cancer patients and 174 controls were measured by Rocheelectrochemiluminescent immunoassay (ECLIA). Risk of ovarian malignancy algorithm (ROMA) values werecalculated and assessed. In addition, the prospects of HE4 detection for therapy-monitoring were evaluated inEOC patients. Results: The ROMA score could classify patients into high- and low-risk groups with malignancy.Indeed, lower serum HE4 was significantly associated with successful surgical therapy. Specifically, 38 patientswith EOC exhibited a greater decline of HE4 compared with CA125. In contrast, elevation of HE4 better predictedrecurrence (of 46, 11 patients developed recurrence, and with it increased HE4 serum concentrations) and apoor prognosis than CA125. Conclusions: This study suggests that serum HE4 levels are closely associated withoutcome of surgical therapy and disease prognosis in Chinese EOC patients.     

The role of serum CA-125 levels in early-stage epithelial ovarian cancer on preoperative CT and MRI

Background

We sought to identify the role of serum CA-125 levels in early-stage epithelial ovarian cancer (EOC) on preoperative CT and MRI.

Methods

Clinical data of 101 patients with early-stage EOC on preoperative CT and MRI were collected between January 2000 and December 2007. Clinical stage I (n = 59) was defined as tumor limited to the ovaries with or without ascites, whereas clinical stage II (n = 42) was defined as tumor within the pelvis with or without ascites. The primary endpoint was to investigate the efficacy of serum CA-125 levels for the prediction of advanced-stage disease, and secondary endpoints were to evaluate the accuracy of preoperative CT and MRI, and to examine the role of serum CA-125 levels as a prognostic factor for survival.

Results

The results of preoperative CT and MRI were concordant with no peritoneal implants outside the pelvis in 50/101 (50%) and no lymph node metastasis in 71/101 (70%) patients. The receiver operating characteristic curves showed that best cut-off values of serum CA-125 levels were 320 U/ml (71% sensitivity, 84% specificity) and 510 U/ml (67% sensitivity, 80% specificity) for the prediction of peritoneal implants outside the pelvis and lymph node metastasis. The serum CA-125 level (≥320 U/ml) was a significant factor for the prediction of advanced-stage disease (adjusted OR, 7.43; 95% CI, 2.39–23.04). However, it was not an independent prognostic factor for survival.

Conclusions

Serum CA-125 levels may be very useful for the prediction of advanced-stage disease in early-stage EOC on preoperative CT and MRI.     

Laboratory and clinical basis for hyperthermia as a component of intracavitary chemotherapy.

Intraoperative chemotherapy with heat has been identified as a treatment option for patients with cancer spread to peritoneal surfaces. This treatment modality is viewed as a supplement to several other treatments for this group of patients including cytoreductive surgery, systemic chemotherapy, early postoperative intraperitoneal chemotherapy, and long-term bidirectional chemotherapy. The pharmacologic basis for using heat to supplement chemotherapy effects are related to the increased penetration of chemotherapy into tumor with hyperthermia, the delayed clearance of chemotherapy from the peritoneal cavity after direct instillation, and an increased cytotoxicity that has been documented with selected chemotherapy agents. Data to support the use of perioperative hyperthermic intraperitoneal chemotherapy with mucinous appendiceal carcinomatosis comes from a large number of single institution phase II studies. Also, peritoneal and pleural mesothelioma are benefited. In colon cancer carcinomatosis, large phase II multi-institutional trials and a single phase III trial documented an increased median survival of these patients from approximately 1 year to over 2 years. Prophylaxis against peritoneal carcinomatosis in gastric cancer has been demonstrated in phase III trials. In ovarian cancer the rationale for this treatment remains large but its current application is limited. Much work needs to be done to identify a proper clinical perspective on hyperthermia used with chemotherapy in patients with peritoneal surface malignancy.     

Laboratory and clinical basis for hyperthermia as a component of intracavitary chemotherapy

Intraoperative chemotherapy with heat has been identified as a treatment option for patients with cancer spread to peritoneal surfaces. This treatment modality is viewed as a supplement to several other treatments for this group of patients including cytoreductive surgery, systemic chemotherapy, early postoperative intraperitoneal chemotherapy, and long-term bidirectional chemotherapy. The pharmacologic basis for using heat to supplement chemotherapy effects are related to the increased penetration of chemotherapy into tumor with hyperthermia, the delayed clearance of chemotherapy from the peritoneal cavity after direct instillation, and an increased cytotoxicity that has been documented with selected chemotherapy agents. Data to support the use of perioperative hyperthermic intraperitoneal chemotherapy with mucinous appendiceal carcinomatosis comes from a large number of single institution phase II studies. Also, peritoneal and pleural mesothelioma are benefited. In colon cancer carcinomatosis, large phase II multi-institutional trials and a single phase III trial documented an increased median survival of these patients from approximately 1 year to over 2 years. Prophylaxis against peritoneal carcinomatosis in gastric cancer has been demonstrated in phase III trials. In ovarian cancer the rationale for this treatment remains large but its current application is limited. Much work needs to be done to identify a proper clinical perspective on hyperthermia used with chemotherapy in patients with peritoneal surface malignancy.     

Carboplatin plus paclitaxel in unknown primary carcinoma: a phase II Hellenic Cooperative Oncology Group Study.

PURPOSE: To evaluate the efficacy of the carboplatin/paclitaxel combination in patients with carcinoma of unknown primary site (CUP). PATIENTS AND METHODS: Seventy-seven consecutive CUP patients (45 women and 32 men; median age, 60 years) were treated with carboplatin at target area under the curve 6 mg/mL/min followed by paclitaxel 200 mg/m(2) as a 3-hour infusion and granulocyte colony-stimulating factor from days 5 to 12. Treatment courses were repeated every 3 weeks to a maximum of eight cycles. Forty-seven patients had adenocarcinomas, 27 had undifferentiated carcinomas, and three had squamous cell carcinomas. Thirty-three patients presented with liver, bone, or multiple organ metastases, 23 with predominantly nodal/pleural disease, and 19 (16 women) with peritoneal carcinomatosis. RESULTS: The overall response rate by intent-to-treat analysis was 38.7% (95% confidence interval, 27.5% to 49.9%). There were no differences in response between adenocarcinomas and undifferentiated carcinomas, but efficacy varied among clinical subsets. The response rates and median survival times in the three clinically defined subsets were 47.8% and 13 months, respectively, for patients with predominantly nodal/pleural disease, 68.4% and 15 months, respectively, in women with peritoneal carcinomatosis, and 15.1% and 10 months, respectively, in patients with visceral or disseminated metastases. Chemotherapy was well-tolerated. CONCLUSION: Carboplatin plus paclitaxel combination chemotherapy is effective in patients with predominantly nodal/pleural metastases of unknown primary carcinoma and in women with peritoneal carcinomatosis. However, in patients with liver, bone, or multiple organ involvement, the combination offers limited benefit. The investigation of novel treatment approaches is highly warranted for this group of patients.     

Role of Galectin-3 Combined with Multi- Detector Contrast Enhanced Computed Tomography in Predicting Disease Recurrence in Patients with Ovarian Cancer

Galectin-3 (Gal-3) is an endogenous β-galactoside-binding lectin, playing an important role in the pathogenesis of multiple malignancies. Aim of the study was to evaluate in a group of patients treated for ovarian cancer (EOC), the role of Gal-3 combined with multi-detector contrast-enhanced computed tomography (MDCT), as predictor of recurrence disease. Seventeen follow-up patients with recurrent ovarian cancer and 13 follow-up patients with stable ovarian disease, who performed MDCT at one-year follow-up after cytoreductive treatment, were enrolled. Serum Gal-3 concentrations were determined by using ELISA method. Twenty healthy controls were included in the analysis. Two radiologist blinded to patients status, reviewed MDCT exams, recording the following signs of disease recurrence: local tumor spread, enlarged lymph-nodes, carcinomatosis implants and metastases. We calculated the respective threshold values of Gal- 3 identified by ROC curve analysis for each imaging findings related to disease recurrence : lymphoadenopathies 92.45 ng/ml (AUC: 0.81, Se=91% Spe=73%), carcinomatosis 85.95 ng/ml (AUC:0.93 Se= 93.7%, Spe=92.8%), local tumor spread 99.05 (AUC:0.90, Se=100%, Spe=73% ) and metastasis 99.05ng/ml (AUC :0,78, Se=100% , Spe=70%). A significant correlation between high Gal-3 serum levels and presence of local tumor spread (n=11/17, p:0.001), carcinomatosis (n=16/17, p:0.00), lymphoadenopathies (n=15/17, p:0.00) and metastasis (n=11/17, p:0.003) related with recurrence disease was observed. Patients with recurrence of ovarian cancer presents higher Gal-3 values compared to women with stable diseases. Gal-3 combined to CECT should be used to improve the monitoring of EOC patients.