Osteoplastic bone metastasis in esophageal squamous cell cancer: report of a case.

This report presents a case of esophageal squamous cell cancer with osteoplastic bone metastasis. A 58-year-old male patient underwent multimodality treatment for esophageal cancer. Sclerotic changes resembling bone metastasis from prostate cancer were detected in the 4th thoracic and the 5th lumber vertebral body soon after the adjuvant chemoradiotherapy. Systemic examinations revealed no primary cancer as a cause of osteoplastic bone metastasis and no esophageal cancer recurrence. A needle biopsy revealed metastases of esophageal squamous cell cancer with osteoplastic changes. Multiple sclerotic changes were detected in the systemic bones at that time, and new carcinomatous bilateral pleural effusion developed. The drastic systemic progression of the cancer caused the rapid deterioration of the patient's general condition.

[Usefulness of induction chemotherapy followed by chemo-radiotherapy for patients with advanced cervical esophageal cancer].

To obtain a good prognosis and preserve laryngeal function is one of the most important issues for patients with advanced cervical esophageal cancer. It is reported that induction chemotherapy (ICT) followed by concurrent chemoradiotherapy (CRT) is useful. We treated 8 consecutive patients with advanced cervical esophageal cancer by ICT and following CRT between 2003 and 2006. The regimen of ICT was FAP therapy (fluorouracil 1,000 mg/day and cisplatin 20mg/day on days 1-5, and doxorubicin 50mg/day on day 1) every 4 weeks. After 2-4 courses of FAP therapy, low-dose FP-CRT (fluorouracil 200mg/24 hours/day and cisplatin 5mg/day with radiation of 60-66 Gy, 2 Gy/day) were given. Effect of ICT was PR in 5 cases, SD in 1 case, and PD in 2 cases. Furthermore, the effect of ICT+CRT was CR in 5 cases and PD in 3 cases. The one-year survival rate was 62. 5%. Grade 3 hematological toxicity related to ICT was observed in 1 patient (12.5%). Grade 3 anorexia and esophagitis related to CRT were observed in 3 patients (37.5%) and 2 patients (25.0%), respectively. Radiation pneumonitis as a late toxicity occurred in 1 patient (12.5%). The therapeutic effect of ICT and CRT was suggested to be useful for patients with advanced cervical esophageal cancer because it was performed safely with no serious adverse effect and the outcome of ICT predicted the effect of the subsequent CRT.

A pilot trial of docetaxel and nedaplatin in cisplatin-pretreated relapsed or refractory esophageal squamous cell cancer.

BACKGROUND/AIMS: This study documents the clinical efficacy and toxicity of docetaxel and nedaplatin in cisplatin-pretreated relapsed or refractory esophageal squamous cell cancer. METHODOLOGY: From February 2002 to February 2007, 20 patients with metastatic or locally recurrent or residual disease previously treated with cisplatin-based chemotherapy or chemoradiotherapy were included. The median age was 66.0 (range 52-74) years, and 17 patients had undergone a previous esophagectomy. A total of 36 cycles with docetaxel 60 mg/m2 plus nedaplatin 80 mg/m2 were administered. RESULTS: The response rate was 25% including one complete response, and the rate of disease stabilization (% of complete response, partial response and stable disease) was 80%. The median progression-free survival was 14 weeks and the median overall survival was 26 weeks. Severe neutropenia occurred in 12 patients (grade 3/4 = 4/8) and 5 out of 20 patients showed severe febrile neutropenia (grade 3/4 = 4/1), whereas no severe non-hematological toxicity was observed. CONCLUSIONS: In conclusion, the combination chemotherapy of docetaxel and nedaplatin did not show drastic clinical efficacy. However, it was considered to be a feasible regimen as tumor dormancy therapy in CDDP-pretreated esophageal cancer, and to have a potent possibility to become a useful second-line chemotherapy for relapsed or refractory esophageal cancer. The control and prevention of severe neutropenia and febrile neutropenia is also very important in use of this regimen.

[Successful management of the recurrent esophageal cancer following esophagectomy at a different time with combined local treatment of chemoradiotherapy and hepatic arterial infusion chemotherapy].

A 63-year-old man who underwent radical resection for esophageal cancer (cStage III)was diagnosed with metastasis of the paraaortic lymph node 5 months after the surgery. He was treated with concomitant chemoradiotherapy (CRT)with low-dose FP(5-FU, CDDP)and 60 Gy of irradiation. The effect of CRT was a complete response. Seven months later, there was a metastasis to the liver(S4). He received systemic chemotherapy(5-FU, ADR, CDDP: FAP), but it was not effective, so hepatic arterial infusion chemotherapy(FAP)was performed. Hepatic artery infusion therapy( 5-FU 1,000 mg/3.5 h x ADR 10 mg/1 h x CDDP 10 mg/1 h)was given for 1 day at an interval of 2 weeks for 18 months. Since ADR reached the maximum dose, hepatic artery infusion of 5-FU(1,000 mg/3.5 h)and CDDP(10 mg/ 1 h)was continued for 14 months at an interval of 4 weeks. The recurrent lesion disappeared completely 9 months after beginning hepatic artery infusion therapy. The patient is alive 69 months after surgery without any evidence of recurrence. Most cases with recurrent esophageal cancer have multiple metastases, and the treatment is mainly systemic therapy. However, in a patient with recurrent tumors at different times, it is possible to achieve a complete response and long-time survival by local treatment with fewer side effects as in this case. Combined local treatments could be the second treatment option after failed systemic chemotherapy for recurrent tumors in patients with esophageal cancer. Further investigations are necessary.

[Esophageal carcinoma - from the viewpoint of surgery].

Therapeutic performance of the esophageal cancer has improved rapidly. Now in the decision of therapeutic strategy not only life prognosis but also treatments-related morbidity and late term quality of life should be considered. The most important factor of the improvement of esophageal cancer treatment is a progress in early detection of esophageal cancers and active use of treatment methods such as endoscopic mucosal resection. In addition,the role of radiotherapy and chemotherapy has improved as an arm of multidisciplinary therapy,and the establishment of chemoradiotherapy as one of the standard therapy for esophageal cancer is also very important. This shows that surgical and non-surgical approach has been getting more interactive and the relationship to one another should always be considered. Surgical therapy is very effective in patients with localized esophageal tumor and the patient's satisfaction is high. However, many problems are remained, and the improvement of diagnosis for metastasis and lessening surgical invasiveness and early/late complications are expected. Moreover,the chemoradiotherapy as an esophagus preserving method will establish more important standpoint and the salvage surgery will be applied more actively. On the other hand, a new strategy such as chemoradiotherapy immediate after esophagectomy for the patients with possible residual tumor for improving therapeutic results may be considered under the status of reliable surgical procedures.

[Thymic carcinoid accompanied by elevation of serum gastrin-releasing peptide precursor; report of a case].

A 74-year-old male was admitted with an abnormal mediastinal shadow. Computed tomography (CT) and magnetic resonance imaging (MRI) of the thorax showed an anterior mediastinal mass without invasion to the ascending aorta and pulmonary artery. In addition, serum gastrin-releasing peptide precursor (Pro GRP) was increased (60.6 pg/ml, normal range <46 pg/ml). Video-assisted thoracoscopic biopsy demonstrated that the mass was thymic carcinoid. Therefore, median sternotomy was performed to facilitate thymectomy, including the tumor with partial resection of the left upper lobe and pericardium. The patient received mediastinal irradiation postoperatively. The postoperative serum level of Pro GRP decreased to the normal limit 6 months later. Although a biological relationship between Pro GRP and thymic carcinoid was not proven, it might be useful marker for detecting tumor recurrence.

Enhancement of the caspase-independent apoptotic sensitivity of pancreatic cancer cells by DHMEQ, an NF-kappaB inhibitor.

The effects of the nuclear factor (NF)-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), combined with tumor necrosis factor (TNF)-alpha were evaluated in PK-8 pancreatic cancer cells. NF-kappaB was activated by TNF-alpha; however, the administration of DHMEQ abrogated its transcriptional activity. The addition of DHMEQ to TNF-alpha markedly induced apoptosis in PK-8 cells with down-regulation of anti-apoptotic c-FLIP and survivin. Combined treatment significantly suppressed cell viability in vitro, and the anti-tumor effect of DHMEQ was also significant in vivo. We investigated the apoptosis signaling pathway involved in these cell killing effects. Truncated Bid was produced by activated caspase-8, and the subsequent depolarization of the mitochondrial membrane potential (Delta Psi m) peaked at 6 h. Then, the activity of caspase-3 was up-regulated 8-fold. Z-VAD-fmk (a pan-caspase inhibitor) perfectly inhibited the up-regulation of caspase-3 but failed to reverse the cell viability. The above findings indicated that the growth inhibitory effect of combined treatment largely depended on mitochondria-associated caspase-independent apoptosis. The intracellular behavior of apoptosis-inducing factor (AIF) following depolarization of Delta Psi m suggested that AIF executed such a caspase-independent apoptosis. Interestingly, caspase-dependent apoptosis appeared within 6 h, whereas the caspase-independent apoptosis lagged. Thus, the addition of DHMEQ to TNF-alpha was capable of inducing caspase-independent apoptosis in pancreatic cancer cells. Once caspase-independent apoptosis was induced, the apoptosis demonstrated powerful cytotoxicity. Therefore, DHMEQ in combination with TNF-alpha may be a promising treatment for pancreatic cancer.

Changes in the microvascular structure of mucosal squamous cell carcinoma of the esophagus and their significance in tumor progression.

BACKGROUND: To identify the clinical T stage by endoscopy is a major diagnostic goal for superficial esophageal squamous cell carcinoma (ESCC). The completion of a microvascular morphological study of mucosal lesions is necessary to optimize therapy. MATERIALS AND METHODS: Images of 197 intra-papillary capillary loops (IPCLs) captured by magnified endoscopy from 15 esophagectomy specimens were studied for their morphological features and IPCL dimensions. RESULTS: The microvascular morphology was classified into four basic major patterns: 1. spiral loop, 2. wide loop (WL), 3. globular (G) and 4. reticular pattern. The microvascular features and dimensions differed according to the depth of tumor invasion. Especially the mean bundle outline (IPCL diameter) showed significant changes as 20.02, 22.32, and 27.08 µm, respectively, for M1, M2 and M3, respectively (M1:M2 P < 0.05, M2:M3 P < 0.01). CONCLUSIONS: During tumor stage progression, a high-volume blood demand and cancer cell overgrowth to occupy the laminar propria mucosa (LPM) cause obvious elongation, thickening, branching, irregularity and deformity of the IPCL, which were characteristics of M3 lesions. The results of the present study support and can be applied with the current Japanese classification for improving the diagnostic accuracy, especially to differentiate between M2 and M3 lesions based on the endoscopic findings.

Metachronous Carcinomas of the Biliary Tract in a Patient Treated Three Times with Curative Surgery.

We here report on a case of metachronous multicentric carcinomas of the biliary tract treated 3 times with curative surgery over 23 years. A 28-year-old woman underwent cholecystectomy because of papillary carcinoma of the gallbladder. After 17 years, 3 carcinomas developed in the biliary tract: intrahepatic cholangiocarcinoma of the left liver, common bile duct carcinoma, and remnant cystic duct carcinoma. They were successfully removed via left hepatectomy combined with pylorus-preserving pancreatoduodenectomy. Furthermore, another intrahepatic cholangiocarcinoma developed 6 years after the second surgery, which was removed again via partial resection of the posterior segment of the liver. Histological findings of carcinomas represented various grades of cell differentiation. No predisposition toward carcinogenesis was found, since neither pancreaticobiliary maljunction nor primary sclerosing cholangitis was present, and the overexpression of cyclooxygenase-2 was negative in all resected specimens. Close monitoring for recurrence is warranted for early detection of metachronous carcinoma that might be effectively treated with repeated resection.

Early breast cancer.

Breast cancer remains a common disease throughout the world. Here we review new knowledge about early breast cancer obtained during the past 5 years. The prognosis of early breast cancer is generally favorable. Especially, ductal carcinoma in situ has been regarded as a non-life-threatening disease. Therefore, early diagnosis and early onset of the treatment has been important. Early age at menarche, late age at first birth, and late age at menopause are related to breast cancer risk. Examination by mammography and ultrasonography is still the most effective means of detection for premenopausal and postmenopausal women, respectively. Additionally, there have been important advances in MRI, sentinel lymph node biopsy, breast-conserving surgery, partial breast irradiation, neoadjuvant systemic therapy, and adjuvant systemic therapy. Another approach to keeping the disease under control is the elucidation of breast cancer's molecular biological features. Assessment of potential molecular targets can lead to early diagnosis and molecular targeted treatment.