Predicting recurrence and metastasis of primary esophageal cancer with or without lymph node metastasis

We studied 42 patients, consisting of 11 stage I/II patients who were node-negative (LN-) and 31 stage II/III patients who were node-positive (LN+). In the LN- patients, detection of occult neoplastic cells (ONCs) in lymph nodes had a sensitivity of 0.0% (0/5), a false-positive (FP) rate of 33.3% (2/6), a specificity of 66.7% (4/6), a false-negative (FN) rate of 100% (5/5), a positive predictive value (PPV) of 0.0% (0/2), and a negative predictive value (NPV) of 44.4% (4/9). In the LN+ patients, the sensitivity of ONCs was 25.0% (5/20), FP rate was 36.4% (4/11), specificity was 63.6% (7/11), FN rate was 75.0% (15/20), PPV was 55.6% (5/9), and NPV was 31.8% (7/22). In LN- patients, positivity for at least 2 of the 3 high-risk criteria had a sensitivity of 20.0% (1/5), FP rate of 16.7% (1/6), specificity of 83.3% (5/6), FN rate of 80.0% (4/5), PPV of 50.0% (1/2), and NPV of 55.6% (5/9). In LN+ patients, these criteria had a sensitivity of 75.0% (15/20), FP rate of 9.1% (1/11), specificity of 90.9% (10/11), FN rate of 25.0% (5/20), PPV of 93.8% (15/16), and NPV of 66.7% (10/15). These results suggest that the high-risk criteria may be useful for predicting recurrence or metastasis in stage II/III lymph node-positive patients with esophageal cancer.     

Radiation therapy with or without chemotherapy for cervical cancer with periaortic lymph node metastasis

The purpose of this article is to evaluate the efficacy of chemoradiation therapy (CRT) and radiation therapy (RT) alone for cervical cancer with periaortic nodal metastasis (PANM). Twenty-one patients with cervical cancer with PANM were identified. Eleven patients received concomitant CRT with cisplatin-based chemotherapy and 10 received RT alone. The median age was 44 years. Ten, 5, and 6 patients had International Federation of Gynecology and Obstetrics stages IB, IIB, and IIIB disease. The RT doses to point A and the periaortic region were 80 to 85 Gy (low dose rate equivalent) and 45 Gy. The median follow-up was 26 months (range 3 to 141 months). The 1- and 3-year disease-specific survival were 81.8% and 81.8%, and 70% and 30%, respectively, for the CRT and RT groups, (P = 0.11). The 1- and 3-year pelvic and periaortic control rates (PPC) were 100% and 100% (CRT), and 56.3% and 42.2% (RT) (P = 0.03). The 1- and 3-year free-from-distant metastasis (DM) rates were 81.8% and 81.8% (CRT), and 78.7% and 49.2% (RT) (P = 0.54). All patients who developed DM died of their disease. CRT is a feasible treatment option to improve the PPC for these patients. Because of the high rate of distant metastasis despite PPC, more effective systemic therapy should be explored.     

Antitumor effects of an antiangiogenic polysaccharide from an Arthrobacter species with or without a steroid

A sulfated polysaccharide-peptidoglycan complex, DS-4152, isolated from the culture supernatant of an Arthrobacter species inhibited angiogenesis and tumor growth and enhanced the antiangiogenic activity of 11 steroid hormones by 2 to 100 times. In the presence of cortisone acetate or tetrahydro S, DS-4152 suppressed chick chorioallantoic membrane angiogenesis and murine tumor M5076 cell-induced s.c. angiogenesis. The antitumor effects of DS-4152 administered in combination with a steroid whose dose level did not affect tumor growth were examined. DS-4152 significantly inhibited the growth of s.c.-implanted B16 melanoma in combination with cortisone acetate. DS-4152 plus tetrahydro S inhibited the growth of s.c. solid tumors and prolonged the survival time of mice bearing highly metastasizing M5076. The body weight increase was not affected by any administration. On the other hand, the survival of mice with ascitic M5076 tumors was not affected by the combination of DS-4152 plus tetrahydro S. The antiangiogenic activity of DS-4152 was more potent than that of heparin. Furthermore, DS-4152 is an angiogenesis inhibitor by itself, without steroid hormones. Successive s.c. treatment with heparin caused hemorrhagic death, but with DS-4152, suppressed tumor growth without reducing body weight.     

Clinical implications of mRNA expression of KAI1 in ovarian cancer with or without metastasis

Background. KAI1 is a potential metastasis suppressor gene for prostate cancer. Decreased expression of KAI1 mRNA has been shown to be associated with the formation of metastasis and the progression of prostate, lung, breast, pancreatic, and bladder cancer. It has also been reported, however, that KAI1 expression is unchanged in metastatic and nonmetastatic esophageal and gastric cancer. We performed the present study to investigate the function of KAI1 in the progression and/or metastasis of ovarian cancer. Methods. We investigated the mRNA expression levels of the KAI1 gene, using quantitative polymerase chain reaction (PCR), in 29 ovarian tumors (1 adenoma, 2 low- malignant potential tumors, 9 adenocarcinomas without metastasis, and 17 adenocarcinomas with metastasis), seven ovarian cancer cell lines, and two normal ovaries. Using a thermal cycler, we found that the KAI1 gene was amplified in parallel with an internal control gene, β-Actin. The relative expression ratio (KAI1/β-Actin) as measured by densitometry was used to evaluate gene expression. Immunohistochemical localization of the KAI1 protein in ovarian cancer tissues was confirmed by the avidin-biotin peroxidase complex (ABC) method. Results. The mRNA expression levels of KAI1 were consistent in normal ovary, ovarian tumor samples, and ovarian cancer cell lines. No statistically significant difference in the KAI1 mRNA expression level was found in ovarian cancer samples with or without metastasis. Immunohistochemistry revealed that the KAI1 protein was expressed in the cell membranes of ovarian cancer cells. Conclusions. Our results suggest that reductions in KAI1 mRNA expression are not involved in either the progression or metastasis of ovarian carcinomas. Received: April 22, 1999 / Accepted: July 26, 1999     

Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for small bowel neuroendocrine tumors with peritoneal metastasis

BackgroundUp to 20% of patients with small-bowel neuroendocrine tumors (SB-NETs) may present with peritoneal carcinomatosis (PM). Surgical cytoreduction (CRS) has been proposed as an adequate management as it confers a survival benefit in selected patients. The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to CRS in this context may be an option but data on its added benefits is lacking.MethodsA search was performed in the prospective multicenter international collaborative database of the Peritoneal Surface Oncology Group International (PSOGI) and BIG-RENAPE working groups, and patients who underwent a surgical treatment (CRS or CRS with HIPEC) for a SB-NET with PM were identified and compared.ResultsBetween 2002 and 2016, a total of 67 patients were identified as having a CRS for SB-NET, with 36 receiving HIPEC during surgery. Median postoperative follow-up was 34 months. The peritoneal cancer index (PCI) and the completeness of cytoreduction score (CCR-score) were higher in the CRS-HIPEC group. More grade III-IV complications occurred in this group as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0. Despite a tendency toward a better progression/recurrence-free survival in patients receiving HIPEC, no significant differences were noted between the CRS and CRS-HIPEC groups in terms of postoperative recurrence.ConclusionsHIPEC does not seem to provide additional benefits in terms of postoperative evolution and survival in patients with SB-NET undergoing CRS. It is associated with higher morbidity. It may possibly lead to an improved recurrence-free survival, but further reports are required to confirm this assumption.     

Predicting recurrence and metastasis of Dukes' A primary colorectal cancer with or without proper muscle invasion

This study compared the prediction of recurrence based on detection of occult neoplastic cells (ONCs) in lymph nodes or using 3 criteria to identify high-risk patients among 72 patients who had Dukes' A colorectal cancer with or without proper muscle invasion. Predicting recurrence based on the detection of ONCs had a sensitivity of 40.0% (2/5) and a false-negative rate of 60.0% (3/5), while there was a specificity of 97.0% (65/67) and false-positive rate of 3.0% (2/67), resulting in an accuracy of 68.5%, PPV of 50.0% (2/4), and NPV of 95.6% (65/68). Predicting recurrence based on the presence of at least 2 of the 3 high-risk criteria showed a sensitivity of 60.0% (3/5) and a false-negative rate of 40.0% (2/5), while it had a specificity of 74.6% (50/67) and a false-positive rate of 25.4% (17/67), resulting in an accuracy of 67.3%, PPV of 15.0% (3/20), and NPV of 96.2% (50/52). These results suggest that a prediction based on ONCs was similar to use of the high-risk criteria, with both methods having a high specificity for recurrence/metastasis of Dukes' A colorectal cancer.     

Effect of incadronate on proliferation of mesenchymal tumor cells with or without activated Ras mutation

The present investigation examined the effect of bisphosphonates on six mesenchymal tumor cell lines and the mechanisms of inhibition of tumor cell proliferation. HT-1080, a fibrosarcoma cell line that exhibits increased Ras activity due to a mutation of the Ras gene, demonstrated significantly reduced tumor cell proliferation upon treatment with incadronate. The other cell lines, however, which lack mutation of the Ras gene, showed no influence upon treatment with incadronate. Autoradiography demonstrated no difference in the uptake of 3H-labelled incadronate between susceptible and unaffected cells. The anti-proliferation of HT-1080 was reversed by the addition of geranylgeranyl pyrophosphate. Etidronate exhibited no influence on all tested cell lines. On the basis of these data, we hypothesized that incadronate inhibits the mevalonate pathway and blocks oncogenic Ras signaling. In an effort to confirm this hypothesis, the influence of incadronate on an oncogenic Ras transfected BALB/3T3 cell line (Bhas 42) and a parental BALB/3T3 cell line were compared. The parental BALB/3T3 cells showed slight inhibition upon treatment with incadronate, however, the proliferation of Bhas 42 cells was significantly reduced. These results suggest that incadronate suppresses oncogenic Ras-activated mesenchymal tumors through the inhibition of Ras signaling pathways.     

Comparison of matrix metalloproteinase expression between primary tumors with or without liver metastasis in pancreatic and colorectal carcinomas

BACKGROUND AND OBJECTIVES: Matrix metalloproteinases (MMPs) are known to play an important role in carcinoma cell invasion and hematogenous metastasis by mediating the degradation of the extracellular matrix. METHODS: We investigated the relationship between MMP-2 and -9 enzymatic activities and liver metastases in human pancreatic and colon carcinomas, using xenograft tumors in nude mice. RESULTS: We found that type IV collagenase activity in pancreatic and colon carcinomas with liver metastases was significantly higher than in pancreatic and colon carcinomas without liver metastases. Gelatin zymography showed the presence of gelatinolytic activity bands at M(r) 92,000 and 72,000, indicating MMP-9 and MMP-2, respectively. MMP-2 and -9 expression levels in pancreatic and colon carcinomas with liver metastases were higher than in pancreatic and colon carcinomas without liver metastases. TIMP-2 levels in pancreatic and colon carcinomas with liver metastases were also higher than in those without liver metastases. CONCLUSIONS: MMP-2 and MMP-9 expression in primary tumors is associated with liver metastases in pancreatic and colon carcinomas. In addition, the balance of activity between MMP-2, MMP-9, and TIMP-2 may be relevant to carcinoma invasion and metastasis, including liver metastases in pancreatic and colon carcinoma.     

Delayed Effect of Radiation Therapy with or without Chemotherapy on Ovarian Function in Women with Hodgkin's Disease

In this retrospective investigation of 51 female patients with Hodgkin's disease, the age of the patient at the time of primary treatment and the extent of radiation therapy were the two most important factors determining post-therapy ovarian function. Favourable indicators of ovarian preservation included young age, especially premenarchal, at the time of primary therapy, and irradiation confined to above the pelvic brim, whereas, age over 40 and irradiation below the pelvic brim predicted high probability of ovarian failure. Overall, 55 per cent of female patients under the age of 50 treated with chemotherapy alone or with radiation therapy above the pelvic brim retained normal ovarian function. The stage of disease at presentation and the post-therapy status of disease had no apparent effect on subsequent menstrual function.     

Aurora-A异常表达在食管鳞癌淋巴结转移中的作用

目的 探讨Aurora-A在T3期食管鳞癌中的表达及其与预后的关系.方法 建立食管鳞癌患者的组织芯片,采用免疫组织化学方法检测食管鳞癌组织及其对应的癌旁正常组织中AuroraA的表达情况,分析Aurora-A的表达水平与淋巴结转移及生存率的相关性.结果 Aurora-A在食管鳞癌组织中的阳性表达率为74.1%(140/189),在癌旁正常组织中的阳性表达率为18.5%(35/189),差异有统计学意义(x2=105.162,P＜0.05).淋巴结阳性组的Aurora-A强阳性表达率为43.0%(46/107),淋巴结阴性组为7.4%(7/95),差异有统计学意义(x2=36.132,P＜0.05).Aurora-A强阳性表达者的生存率明显低于Aurora-A阴性者(P=0.0042).结论 Aurora-A的表达水平与T3期食管鳞癌的淋巴结转移和预后有关,可能对食管鳞癌患者的淋巴结转移和预后有一定的预测作用.     

Imaging in resectable colorectal liver metastasis patients with or without preoperative chemotherapy: results of the PROMETEO-01 study

Background:

The aim of the PROMETEO-01 Study was to define the diagnostic accuracy of imaging techniques in colorectal cancer liver metastasis (CRCLM) patients.

Methods:

Patients referred to Bologna S. Orsola-Malpighi Hospital performed a computed-tomography scan (CT), magnetic resonance (MR), 18F-FDG-PET/CTscan (PET/CT) and liver contrast-enhanced-ultrasound (CEUS); CEUS was also performed intraoperatively (i-CEUS). Every pathological lesion was compared with imaging data.

Results:

From December 2007 to August 2010, 84 patients were enrolled. A total of 51 (60.71%) resected patients were eligible for analysis. In the lesion-by-lesion analysis 175 resected lesions were evaluated: 67(38.3%) belonged to upfront resected patients (group-A) and 108 (61.7%) to chemotherapy-pretreated patients (group-B). In all patients the sensitivity of MR proved better than CT (91% vs 82% P=0.002), CEUS (91 vs 81% P=0.008) and PET/CT (91% vs 60% P=0.000), whereas PET/CT showed the lowest sensitivity. In group-A the sensitivity of i-CEUS, MR, CT, CEUS and PET/CT was 98%, 94%, 91%, 84% and 78%, respectively. In group-B the i-CEUS proved equivalent in sensitivity to MR (95% and 90%, respectively, P=0.227) and both were significantly more sensitive than other procedures. The CT sensitivity in group-B was lower than in group-A (77% vs 91%, P=0.024).

Conclusions:

A thoraco-abdominal CT provides an adequate baseline evaluation and guides judgment as to the resectability of CRCLM patients. In the subset of candidates for induction chemotherapy to increase the chance of liver resection, the most rational approach is to add MR for the staging and restaging of CRCLM.     

是否合并桥本甲状腺炎的甲状腺乳头状癌患者的临床病理特征及与淋巴结转移相关性的分析

目的:探讨甲状腺乳头状癌合并桥本甲状腺炎患者临床病理特征以及合并桥本甲状腺炎对淋巴结转移的影响。方法:回顾性分析我院2014年10月至2019年10月术后病理证实为甲状腺乳头状癌3 411例患者临床资料,其中合并桥本患者498例,未合并桥本患者2 913例,经过倾向性评分匹配方法对两组患者进行匹配,得到组间协变量均衡样本,比较两组患者临床病例特征并分析患者淋巴结转移的危险因素。结果:经过倾向性评分匹配后,甲状腺乳头状癌患者是否合并桥本甲状腺炎仅与病灶大小和BRAF V600E基因突变显著相关（P＜0.05）,而与病灶数目、侵犯包膜、淋巴结转移、中央区淋巴结转移、颈侧区淋巴结转移以及淋巴结转移数目无关（P＞0.05）。Logistic回归分析显示年龄≥55岁PTC患者淋巴结转移的发生风险是年龄<55岁患者的0.957倍（OR=0.957,P＜0.001）。肿瘤病灶＞1 cm患者淋巴结转移的发生风险是病灶≤1 cm患者的2.697倍（OR=2.697,P＜0.001）。肿瘤病灶多灶的患者淋巴结转移的发生风险是单灶患者的2.186倍（OR=2.186,P＜0.001）。结论:合并桥本甲状腺炎与更小的肿瘤病灶和更高的BRAF V600E基因突变率显著相关,而与淋巴结转移无关。患者年龄≥55岁是甲状腺乳头状癌患者淋巴结转移的独立保护因素,而病灶>1 cm和病灶多灶是淋巴结转移的独立危险因素。     

Effect of tamoxifen on steroid hormone receptors and creatine kinase activity in human endometrial carcinoma

Estrogen receptor (ER), progesterone receptor (PR) and creatine kinase (CK) were measured in cancerous tissue from 29 post-menopausal patients with endometrial carcinoma under basal conditions and after a short course of tamoxifen treatment. ER and PR were detected in nearly all tumors. CK was detected in all of the tumors examined. After tamoxifen, PR and CK increased simultaneously in 26% of cases, while they were either enhanced, decreased or unmodified in the remainder. No correlation could be found between increase of PR and tumor differentiation. CK, however, was enhanced only in the more differentiated cancers. These results indicate that only a percentage of endometrial cancers are responsive to tamoxifen. It is hypothesized that patients bearing these tumors are those likely to benefit from endocrine therapy.     

Electrogene therapy using endostatin, with or without suicide gene therapy, suppresses murine mammary tumor growth and metastasis

Syngeneic inoculated metastatic mammary cancers received direct intratumoral injection of a plasmid vector containing either endostatin (pEndo) with or without a suicide gene (pHSVtk), pHSVtk alone or control vector once a week for 8 weeks. We applied electrogene transfer to the tumors after each injection and administered ganciclovir (GCV) to pHSVtk-transfected mice using an osmotic minipump. Anticancer efficacy was monitored using a variety of parameters, namely tumor volume, intratumoral microvessel density and DNA synthesis, number of mice with metastasis, and number of sites of metastasis per mouse. Tumor volume was significantly lower in all therapeutic groups, with the most effective growth suppression in the pEndo+pHSVtk/GCV group. Lymph node metastasis was significantly less frequent in all therapeutic groups, whereas the multiplicity of lung metastases was significantly lower only in the pEndo and pEndo+pHSVtk/GCV groups. All therapeutic groups showed significantly lower intratumor microvessel density and DNA synthesis. The pEndo and pEndo+pHSVtk/GCV groups also showed a significant reduction in the numbers of dilated lymphatic vessels containing intralumenal tumor cells. Our data suggest that endostatin electrogene therapy alone or in combination with pHSVtk/GCV suicide gene therapy is more beneficial than suicide gene therapy alone. The observed antimetastatic activity of endostatin may be of high clinical significance in the treatment of metastatic breast cancer.