Immediate versus delayed chemotherapy in patients with asymptomatic incurable metastatic cancer

Aim: To examine the evidence of benefit in initiating immediate chemotherapy in patients with newly diagnosed asymptomatic metastatic incurable cancer, compared with delaying chemotherapy until symptomatic progression. Methods: Through an extensive review of published reports, we examined the biological, clinical, psychological and ethical background of the issue and reported on the available clinical trial evidence in a variety of tumor types. Results: Only a limited number of clinical trials have directly examined the role of immediate versus delayed chemotherapy in patients with incurable asymptomatic metastatic cancer. Small studies in mesothelioma, colorectal cancer, breast cancer, myeloma, and low‐grade lymphoma suggest no survival benefit for the immediate initiation of chemotherapy. However, there was no evidence in other tumor types. Conclusion: The appropriate timing of chemotherapy initiation in an asymptomatic patient with metastatic cancer remains a substantial question in oncology. Many factors are likely to impact on the decision. However, little if any evidence demonstrates a clear advantage in the immediate initiation of chemotherapy in this setting.     

Complete response, as determined by prostate-specific antigen level, to chlormadinone acetate withdrawal persisting longer than 2 years in patients with advanced prostate cancer: Two case reports

Antiandrogen withdrawal syndrome (AWS) is a well-established phenomenon in prostate cancer. However, responses to AWS are usually of limited duration, and a complete response (CR) is extremely rare. We present two patients who exhibited a chemical CR for more than 2 years after the discontinuation of steroidal antiandrogen chlormadinone acetate use. Whether patients who respond to antiandrogen withdrawal include a group of patients with a better prognosis remains uncertain. However, considering that the usual survival period of patients with hormone-resistant prostate cancer is approximately 12 months, both of the patients reported here, who are present in excellent physical condition, exhibiting an improved quality of life, and attending their hospital as outpatients, obviously acquired a prolonged survival because of AWS.     

Is endoscopic one‐piece mucosal resection essential for early gastric cancer?

Background: Endoscopic mucosal resection (EMR) is widely accepted as a minimally invasive treatment for early gastric cancer (EGC) in Japan. However, the criteria for EMR must be strictly adhered to otherwise patients will miss the chance for additional therapy. We assess the important factor in expanding the indication of EMR. Methods: We investigated 1101 EGCs that had been resected by EMR at the National Cancer Center Hospital (NCCH), Tokyo, Japan, according to the indication recommended by Japanese Gastric Cancer Association (JGCA) and the expanded indication proposed by NCCH. Curability and local recurrence of the EMRs were assessed related to the applied indication and the number of resected specimens. Results: The recurrence rate of non‐evaluable resection was higher than that of evaluable resection (P < 0.0001). Eighty‐three lesions among 772 lesions in the JGCA group were non‐evaluable. Thirty‐seven leisons among 329 lesions in the NCCH group were non‐evaluable. There was no difference in the rate of non‐evaluable resection between JGCA and NCCH groups (P = 0.8329). However, the rate of curative resection was lower in the NCCH group than in the JGCA group (P = 0.0009). In piecemeal resection, there was no difference in the rate of non‐evaluable resection between JGCA and NCCH groups (P = 0.0527). In one‐piece resection, the rate of non‐evaluable resection was lower in the NCCH group than the JGCA group (P = 0.0137). Conclusion: Based on our series of cases, we propose one‐piece resection as a gold standard for EMR because it enables accurate histological evaluation, even in the EMR, according to the expanded indication.     

Progression-free interval in ovarian cancer and predictive value of an ex vivo chemoresponse assay

The study objective was to determine the effectiveness of a phenotypic chemoresponse assay in predicting response to chemotherapy measured by progression-free interval (PFI) in a retrospective series of ovarian cancer patients whose tumor specimens had been tested with the ChemoFx assay. A statistically significant correlation between assay prediction of response and PFI was observed in 256 cases with an exact or partial match between drug(s) assayed and received. In 135 cases with an exact match, the hazard ratio for progression of the resistant group was 2.9 (confidence interval [CI]: 1.4-6.3; P < 0.01) compared to the sensitive group and 1.7 (CI: 1.2-2.5) for the intermediate compared to the sensitive group. The median PFI for patients treated with drugs assayed as resistant was 9 months, 14 months for those with drugs assayed as intermediately sensitive, and PFI had not been achieved for those with drugs assayed as sensitive. These data indicate that the ChemoFx assay is predictive of PFI in ovarian cancer. As the majority of ovarian cancers display different degrees of response to different chemotherapy agents ex vivo, the incorporation of assay information into treatment selection has the potential to improve clinical outcomes in ovarian cancer patients.     

Arsenic trioxide–loaded, microemulsion-enhanced cytotoxicity on MDAH 2774 ovarian carcinoma cell line

The antiproliferative effect of As(2)O(3)-loaded microemulsion (As(2)O(3)-M) on human MDAH 2774 ovarian cancer cells was compared with a regular solution of the As(2)O(3). We used MDAH 2774 as model cell lines for ovarian cancer. The (2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide) (XTT) and trypane blue dye exclusion tests were used to evaluate cytotoxicity. Apoptotic effect of solutions was evaluated using cell death detection kit. Standard microemulsion formulation used in this experiment contains 5 x 10(-6) M As(2)O(3). It was clearly demonstrated that As(2)O(3)-M had a significant cytotoxic effect on MDAH 2774 cell line, and the cytotoxic effect of As(2)O(3)-M was significantly higher than that of regular As(2)O(3) solutions. Even approximately 6000 times diluted microemulsion formulation loaded with 5 x 10(-6) M As(2)O(3) showed a cytotoxic effect. As a result, this diluted concentration (approximately 8 x 10(-10) M) was found to be approximately 6000 times more effective than regular As(2)O(3) solutions (5 x 10(-6) M). Moreover, this diluted concentration resulted in 1.5-fold enhancement of apoptosis. According to the in vitro cytotoxicity studies, we concluded that by incorporating As(2)O(3) into the microemulsion (As(2)O(3)-M), which is a new drug carrier system, it is possible to increase antiproliferative effect of regular As(2)O(3) on MDAH 2774 cells. Translating these results to in vivo conditions would open new windows in the treatment of ovarian cancer.     

A CASE OF EARLY GASTRIC CANCER ACCOMPANIED BY DIEULAFOY ULCER IN A YOUNG WOMAN

A case of early gastric carcinoma accompanied by Dieulafoy ulcer is presented. The patient, a 26‐year‐old female, visited our emergency room with chief complaints of massive hematemesis and tarry stool. The initial endoscopic examination revealed a superficial depressed lesion with a faded color accompanied by a tiny ulcer with converging folds at the anterior wall of the middle gastric body. Although no active bleeding vessel was found at that time, the patient was admitted to our hospital for further check‐ups and treatment. On the 6th hospital day, she developed massive hematemesis resulting in shock. Urgent endoscopy, this time, disclosed an exposed bleeding vessel at the small ulcer floor previously mentioned, and endoscopic hemostasis was achieved. Since, however, a biopsy at initial examination from the surrounding depressed area proved carcinoma, a partial distal gastrectomy was subsequently carried out. Histological examination of the resected specimen confirmed the diagnosis of carcinoma limited to the mucosa and submucosa along with findings consistent with Dieulafoy ulcer. This is a rare case of combination of early cancer and Dieulafoy ulcer particularly in such a young patient. A review of the literature is also presented.     

Epidemiology of nonmelanoma skin cancer (NMSC) in Europe: accurate and comparable data are needed for effective public health monitoring and interventions

Summary Nonmelanoma skin cancer (NMSC) is the most common malignancy occurring in white populations. It is currently becoming an important challenge in terms of public health management as the increasing incidence rates will probably have a tremendous impact on healthcare costs. Possible factors driving this rise in NMSC numbers are increases in both acute and prolonged UV exposure together with increasing numbers of older people in the population. A better understanding of NMSC epidemiology in Europe is essential if an evidence-based European-wide public health policy is to be developed. It is obvious this can only be achieved by recording and analysing comparative epidemiological data. Finally, by improving the skin examination training for physicians, developing guidelines and exchanging best practices, a high level of healthcare could be provided for NMSC.     

Genetic abnormalities and CNS tumors: report of two cases of ependymoma associated with Klinefelter’s Syndrome (KS)

Objects Genetic syndromes associated with ependymoma are uncommon, with the exception of NF2. We describe two cases of ependymoma presenting with Klinefelter’s Syndrome (KS) as co-morbid condition. Materials and methods The first patient was diagnosed for KS during pregnancy; he also presented a thyroid agenesis and a deficit of methyltetrahydrofolate reductase (MTHFR); at 30 months of age he was operated on for a grade II ependymoma of IV ventricle; after a multiple-stage surgery, he underwent oral chemotherapy and stereotactic radiotherapy, but after 15 months he presented a local recurrence and died. The second patient was diagnosed for KS at the age of 16 months; at 10 years of age, due to back pain, he underwent an MRI, which showed a cauda equine tumor. He underwent surgery and radiotherapy. Histology was of mixopapillary ependymoma. Conclusion In a review of literature, various neoplasms have been described in association with KS. To our knowledge, these are the first two cases reported of ependymoma associated to KS. A retrospective study of 44 monoinstitutional ependymoma cases demonstrated association with genetic syndromes in 22%.     

子宫颈癌226例临床病理分析

目的：探讨宫颈癌的临床、病理特点、诊治方法及预后因素。方法：收集1996年1月至2001年1月226例宫颈癌患者进行回顾性分析。结果：平均患病年龄为48．18岁。130例患者为阴道流血，70例为阴道流液，25例下腹疼痛，l例精神减退、贫血、浮肿。病理分期：Ⅰ期病例数为169例(75％)；Ⅱ期病例数为3l例(13．72％)；Ⅲ期病例数为23例(10．18％)；Ⅳ期病例数为3例(1．1％)。比较2l例宫颈鳞癌与宫颈腺癌的转移，显示后者的腹主动脉旁淋巴结转移、肾上腺转移、子宫转移、胸水形成明显高于前者。结论：重视宫颈癌发病相关因素及临床症状，争取早期诊断，严格手术病理分期，选择适当治疗方案。