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Pancreatic acinar cell carcinoma (ACC) is a comparatively rare tumor and account for ~1% of all cases of pancreatic cancer. Clinical presentation is usually related to either local spread or metastasis. The clinical features, especially those related to the prognosis and treatment outcomes, have not yet been fully clarified. There are no established treatments for unresectable pancreatic ACC. We administered gemcitabine monotherapy to four patients with ACC; however, the results were not satisfactory. Disease control without obvious tumor shrinkage was observed in one patient. Another patient showed severe renal damage caused by gemcitabine. On the other hand, fluoropyrimidine-based chemotherapy may have some activity against this tumor, because one of the three patients who received S-1 as second-line chemotherapy showed a partial response. Prospective clinical trials are necessary to confirm the effectiveness of fluoropyrimidine for the treatment of pancreatic ACC.
The purpose of this study is to evaluate the improved method of arterial infusion therapy of SMANCS (SX) with lipiodol under the angiotensin-induced hypertensive state for various difficult-to-treat solid tumors. Most patients were unresectable with no other therapeutic options, recurrence after resection, or patients do not respond to common treatments. The new method utilizes angiotensin II (AT) to induce hypertension (e.g. ~15–30 mmHg above norm) for 15–20 min. This method was successfully applied to metastatic liver cancer, cholangiocarcinoma, massive renal cell carcinoma, pancreatic and other abdominal solid cancers. This AT-induced hypertension resulted in remarkably enhanced tumor delivery accompanied by improved therapeutic response, and a shorter time to achieve 50% regression of tumor size with least toxicity. We demonstrated clinically herein improved therapy for various advanced solid tumors with SX by elevating the tumor blood flow selectively. This is the first clinical proof that modulations of vascular pathophysiology can uniquely accomplish enhanced tumor selective delivery of polymeric drugs and thus yielded better clinical outcome.
‘Cost saving’ was suggested in our recent economic evaluation of chemoprevention of breast cancer targeting women at high risk in Japan. However, this budget impact analysis reveals that the introduction of chemoprevention appears to be not budget saving for ~20 years, whereas the level of budget impact seems affordable.
To identify any gender differences in the outcomes of concurrent platinum-based chemotherapy and thoracic radiotherapy for unresectable stage III non-small cell lung cancer (NSCLC).
A comparative retrospective review of the clinical characteristics and treatment outcomes between female and male NSCLC patients receiving chemoradiotherapy.
Of a total of 204 patients, 44 (22%) were females and 160 (78%) were males. There was no difference in age, body weight loss, performance status or disease stage between the sexes, whereas never-smokers and adenocarcinoma were more common in female patients (55% vs. 3%, P < 0.001, and 73% vs. 55%, P = 0.034, respectively). Full cycles of chemotherapy and radiotherapy at a total dose of 60 Gy were administered to ~70% and >80% of the patients, respectively, of both sexes. Grade 3–4 neutropenia was observed in 64% of the female patients and 63% of the male patients. Severe esophagitis was encountered in <10% of the patients, irrespective of the sex. The response rate was higher in the female than in the male patients (93% vs. 79%, P = 0.028), but the median progression-free survival did not differ between the sexes. The median survival time in the female and male patients was 22.3 and 24.3 months, respectively (P = 0.64).
This study failed to show any gender differences in the survival or toxicity among patients treated by concurrent chemoradiotherapy. These results contrast with the better survival in female patients undergoing surgery for localized disease or chemotherapy for metastatic disease.
A lot of hematologists are often faced with the difficulty of diagnosing bone marrow micrometastasis of carcinoma cells. We employed a new flow cytometric immunophenotyping by a combination of CD45 with three neuroendocrine markers: CD56, microtubule-associated protein-2 and synaptophysin, and successfully detected micrometastatic tumor cells in the bone marrow of a 61-year-old male patient with small cell lung cancer (SCLC), whose marrow smears never showed a distinct morphology of metastasis. It was noteworthy that these SCLC cells accompanied the aberrant expression of CD45, leukocyte common antigen known as a specific marker for hematolymphoid neoplasms, which was not detected in the tumor of primary lesion. We describe this rare case to arouse an attention that tumors of non-hematolymphoid origin can exhibit exceptional CD45-positvity in metastatic sites.
Herein, we report a rare case in which bisphosphonate zoledronic acid (ZA) effectively treated not only multiple bone metastases but also lung, pleural and liver metastases from renal cell carcinoma (RCC). Recently, ZA is used to treat skeletal-related events (SREs) such as bone pain caused by bone metastasis from many kinds of cancer. The patient in the present report had multiple bone metastases from RCC. Remarkable improvement of the bone metastasis was observed following treatment with ZA at a dosage of 4 mg administered once every 4 weeks. Moreover, lung, pleural and liver metastases also diminished markedly in size in response to the treatment. The metastases have shown no progression for 20 months since starting the ZA treatment. We believe that the present report is the first of its kind announcing that ZA monotherapy has been effective for lung, pleural and liver metastases from RCC.
We conducted a Phase II trial to investigate the efficacy of combined therapy with meloxicam, a cyclooxygenase-2 inhibitor and natural interferon (IFN)- in renal cell carcinoma patients with distant metastasis.
The subjects of this study were patients with untreated renal cell carcinoma who were diagnosed from the results of imaging or pathological studies and who had measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST). Patients could be enrolled in the study irrespective of whether nephrectomy had been performed. Treatment involved the subcutaneous injection of natural IFN- at 3 x 106 or 5 x 106 U three times weekly plus oral administration of meloxicam at 10 mg once daily.
A total of 43 patients were enrolled in the present study, included 11 patients without nephrectomy, 23 patients with a high C-reactive protein (CRP) level and 23 patients with extrapulmonary metastasis. Four patients of complete response and 12 patients of partial response were confirmed, given an overall response rate of 37.2% (95% confidence interval, 23.0–53.3%). Stable disease for 6 months or longer was also obtained in 14 patients. The median time to progression was 14 months. Adverse events (AEs) observed were mainly flu-like symptoms due to cytokine. Although the Grade 3 or 4 AEs were fatigue, hepatic dysfunction, arthritis and gastric ulcer, all but one (gastric ulcer) were immediately improved by discontinuation of this combined therapy.
The combination of meloxicam and natural IFN- is considered to be an active regimen with tolerable toxicities as a first-line treatment of metastatic renal cell carcinoma.
A multicenter trial was conducted to evaluate the efficacy and safety of paclitaxel every 2 weeks in patients with advanced or recurrent gastric cancer who had previously received fluoropyrimidine-based chemotherapy.
The subjects were patients with gastric cancer who had disease progression or recurrence while receiving fluoropyrimidine-based chemotherapy. All patients had adequate major organ functions with an Eastern Cooperative Oncology Group performance status (PS) of 0–2. Paclitaxel 140 mg/m2 was administered intravenously on days 1 and 15 of a 4-week cycle. The primary endpoint was the response rate. Secondary endpoints were progression-free survival (PFS), overall survival and safety.
Response was assessable in 40 of 41 enrolled patients. Their median age was 63 (range: 48–77) years, and PS was 0 in 22 patients, 1 in 13 and 2 in 5. Previous treatment included S-1 (1 M tegafur–0.4 M gimestat–1 M otastat potassium) monotherapy in 32 patients and S-1-based combination therapy in 5. The median number of administered courses of paclitaxel was 3.5 (1–14). The response rate was 17.5% (95% confidence interval: 7.3–32.8%, partial response: 7, stable disease: 21, progressive disease: 10 and not evaluable: 2). The disease control rate was 70.0%, the median PFS was 111 days and the median overall survival was 254 days. Major adverse events of Grade 3 or 4 were neutropenia (27.5%), anemia (12.5%), diarrhea (2.5%) and sensory neuropathy (2.5%).
Biweekly paclitaxel seemed to be one of the useful chemotherapies after failure of fluoropyrimidine-based treatment in patients with advanced or recurrent gastric cancer.
Reconstruction for osteosarcoma around the knee after wide resection faces the challenge of great bone defect and future limb length discrepancy in the skeletally immature patients. Modern prosthetic reconstruction may provide good results, but the longevity may be of concern and may not be affordable in certain communities. Allograft knee arthrodesis still has its role in light of bone stock preservation and cost-effectiveness.
We developed the innovative trident fixation technique utilizing three Steinmann pins to minimize limb length inequality without jeopardizing knee fusion stability. Twelve patients were enrolled. The mean age was 11.5 (10–13) years. Two had high-grade osteosarcoma in proximal tibia and others in distal femur.
Two patients died of oncological disease. The median follow-up of the disease-free 10 patients was 47 (41–60) months. All allograft-host bone junctions healed uneventfully without major complications except one allograft fracture. The average limb length discrepancy was 1.45 (1.0–2.1) cm at latest follow-up.
This straightforward technique was successful in knee arthrodesis with minimized limb length inequality. Accordingly, in light of bone stock preservation and longevity for the young children, it may be a surgical alternative for malignant bone tumors around the knee.
Detection of prostate cancer needs a biopsy of the prostate. Suspecting cancer from an increase in prostate-specific antigen (PSA) has a high negative rate at an initial prostate biopsy. Cases with negative initial biopsy may be the candidates of subsequent biopsy. For lowering unnecessary repeat biopsy, the use of predictive factors before a repeat biopsy is applied for indication.
Seventy-seven cases with negative initial prostate biopsy received a repeat biopsy and factors for the detection of cancer were examined.
PSA doubling time distinguished a part of cancer cases. Its sensitivity of 30, 50 and 70 months was 36.6%, 30.4% and 10%, respectively. Cancer case did not show PSA doubling time of >100 months in general. Values of PSA transition zone density, %Free/total PSA and PSA velocity were similar between cancer and no cancer cases.
PSA doubling time was one of the predictive factors for the detection of prostate cancer and was valuable for avoiding unnecessary repeat biopsy in some cases.
This Phase II study was conducted to evaluate efficacy and safety of gemcitabine monotherapy in anthracycline and taxane pre-treated Japanese metastatic breast cancer patients.
At Step 1, twelve patients were divided into two groups of six patients each and the dose-limiting toxicity was evaluated at gemcitabine 1000 and 1250 mg/m2 to determine the dose for Step 2. At Step 2, an additional 56 patients were assessed for efficacy and safety of gemcitabine monotherapy. Patients were treated with gemcitabine on days 1 and 8 of a 21-day cycle and explored incidence of adverse events graded by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, overall response rate (RR), time to progression disease and overall survival time.
Gemcitabine 1250 mg/m2 was determined as the dose for Step 2. Adverse events reported in this study were similar in type, frequency and toxicity grades as seen in other tumor types. Of the 62 patients at 1250 mg/m2, 1 complete response (1.6%), 4 partial response (6.5%) and 20 stable disease (32.3%) were achieved, yielding an RR of 8.1% (95% CI: 2.7%, 17.8%). Median time to progression was 92.0 days (range: 29–651 days). The median survival time was 17.8 months (95% CI: 14.9 months to incalculable).
Gemcitabine at 1250 mg/m2 on days 1 and 8 of a 21-day cycle was tolerable and can be a salvage treatment option for Japanese metastatic breast cancer patients previously treated with anthracyclines and taxanes.
We evaluated health-related quality of life (HRQOL) in patients with localized prostate cancer who underwent intensity-modulated radiation therapy (IMRT) or three-field conformal radiotherapy (3DCRT).
A total of 97 patients underwent 3DCRT and 36 underwent IMRT for localized prostate cancer between 2002 and 2004. We measured the general and disease-specific HRQOL with the Medical Outcomes Study 36-Item Health Survey and University of California, Los Angeles Prostate Cancer Index, respectively.
There were no significant differences in the pre-operative characteristics of the two groups. The patients in the 3DCRT group were more likely to receive hormonal therapy compared with the IMRT group before and after radiation therapy (P < 0.001 and P = 0.011, respectively). With regard to general HRQOL domains, both the 3DCRT and IMRT group scores showed no significant difference between baseline and any of the observation periods. At 60 months after treatment, the 3DCRT group had significantly worse bowel function and bother scores than baseline (both P < 0.001). On the other hand, there were no significant differences between the baseline and any of the post-treatment time periods in the IMRT group. In the 3DCRT group, sexual function remained substantially lower than the baseline level (P = 0.023). The IMRT group tended to show a decrease in sexual function, which was not statistically significant (P = 0.11).
IMRT can provide the possibility to deliver a high irradiation dose to the prostate with satisfactory functional outcomes for long-term periods.
Desmoplastic reaction of the stroma is a part and parcel of several malignancies. It may be seen within or at a site distant from the main tumour. Irrespective of the site of fibrosis in tumours, it portends a poor prognosis as it is generally associated with invasion and metastasis. In this report, we present a unique case of a 78-year-old male patient with clear cell renal carcinoma (CCRC) who presented with a lump in the right loin. On magnetic resonance imaging scan, the mass was arising from the middle part of the right kidney. The nephrectomy was done and specimen on examination revealed a variegated tumour with another whitish solid mass in the surrounding perirenal fat. The kidney tumour showed features of CCRC, whereas whitish mass was entirely composed of proliferating spindle cells. Therefore, the mass mimicked a second tumour not only on gross but even on microscopy. The special stains (Elastic-van Gieson, Masson-Trichrome, Periodic acid schiff's, alcian blue and mucicarmine), immunostaining (cytokeratin, vimentin, epithelial membrane antigen, smooth muscle actin, S-100, HMB-45, CD34 and CD117) patterns and ultrastructural features all, however, favoured it to be an extensive peritumoural fibrotic reaction rather than a neoplasm. The observation provokes important questions like whether the reaction in the index case is an example of tumour-induced fibrosis or is an unassociated phenomenon and, in the case of former, what are factors that govern the extent and site of fibrosis, i.e. intratumoural, peritumoural or away from the tumour. The finding may also help in further research and understanding of the role of stroma in cancer progression and developing stromal antigen-targeted therapies in CCRC.
Bone morphogenetic protein-2 (BMP-2) is normally expressed in the embryo promoting the development of several organs. Aberrant expression of BMP-2 occurs in various tumors. However, a correlation between BMP-2 expression in human gliomas and patients' prognosis has not been reported. To address this question, this study was to investigate the BMP-2 expression pattern in human gliomas and to evaluate its prognostic relevance.
We analyzed the expression of the BMP-2 antigen in a series of 98 gliomas of various grade and histology by immunohistochemistry on paraffin-embedded sections. Then, the correlation of BMP-2 expression pattern with clinical–pathological features of patients and its prognostic relevance were determined.
Immunohistochemical analysis with anti-BMP-2 antibody revealed dense and spotty staining in the tumor cells and its expression levels became significantly higher as the gliomas' grade advanced (P < 0.001). The median survival of patients with intensively positive BMP-2 expression was significantly shorter than that with negative expression (318 vs. 1197 days, P < 0.0001). The Kaplan–Meier survival curves showed that the BMP-2 expression was not only a significant predictor of survival in high-grade gliomas (grade IV, P = 0.02), but also in lower-grade gliomas (grades II and III, P < 0.001).
These results indicate that BMP-2 is a highly sensitive marker for gliomas prognosis and suggest that the expression level of BMP-2 may be a potent tool for the clinical prognosis of gliomas patients.
The study objective was to evaluate the efficacy and toxicity of chemoradiotherapy with 5-fluorouracil (5-FU) plus cisplatin in patients with Stage I esophageal squamous cell carcinoma (ESCC). The primary endpoint was proportion of complete response (%CR).
Patients with Stage I (T1N0M0) ESCC, aged 20–75 years, without indication of endoscopic mucosal resection were eligible. Treatment consisted of cisplatin 70 mg/m2 (day 1) and 5-FU 700 mg/m2/day (days 1–4) combined with 30 Gy radiotherapy (2 Gy/day, 5 days/week, days 1–21). The cycle was repeated twice with 1-week split. Salvage surgery was recommended for residual tumor or local recurrence.
From December 1997 to June 2000, 72 patients were enrolled. No ineligible patient or major protocol violation was observed. There were 63 CRs for %CR of 87.5% [95% confidence interval (CI): 77.6–94.1]. Six patients with residual tumor successfully underwent esophagectomy. There was no Grade 4 toxicity. Four-year survival proportion was 80.5% (95% CI: 71.3–89.7), and 4-year major relapse-free survival proportion was 68% (95% CI: 57.3–78.8) (mucosal recurrence removed by endoscopy was not counted as an event).
High CR proportion and survival proportion with mild toxicity suggest that this regimen could be considered as a candidate of new standard treatment to be compared with surgery in patients with Stage I ESCC.
Standard treatment for clinical stage I esophageal cancer with submucosal invasion (T1b) has been surgical resection. We conducted a Phase II trial to evaluate the efficacy and the safety of combined treatment of endoscopic mucosal resection (EMR) and chemoradiotherapy for clinical stage I (T1b) esophageal cancer. Patients diagnosed as having clinical stage I (T1b) esophageal cancer which is considered to be resectable by EMR are eligible. When pathological examination of the EMR specimen confirms T1b tumor with negative or positive resection margin, the patient undergoes chemoradiotherapy. The study continues until 82 patients with T1b tumor with negative resection margin are enrolled from 20 institutions. The primary endpoint is 3-year overall survival (OS) in pT1b cases with negative resection margin. The secondary endpoints are 3-year OS and progression-free survival in all eligible cases, OS in pT1a-MM cases with margin-negative, complications of EMR and adverse events of chemoradiotherapy. The data from this trial will be expected to provide a non-surgical treatment option to the patients with clinical stage I (T1b) esophageal cancer.
Idiopathic plasmacytic lymphadenopathy (IPL) with polyclonal hypergammaglobulinemia has been proposed as a new disease entity resembling the plasma cell type of multicentric Castleman's disease. Here, we report a case of IPL accompanied by renal failure and skin involvement. A 35-year-old man was admitted for advanced renal failure, anemia, systemic lymphadenopathy and skin rashes. Laboratory examinations indicated polyclonal hypergammaglobulinemia and elevated serum interleukin-6 (IL-6). Biopsy of a cervical lymph node revealed follicular hyperplasia with normal germinal centers, sheets of polyclonal proliferating plasma cells and the absence of marked proliferation of blood vessels in the interfollicular area. Lesions of the kidney and skin also had pathological characteristics of IPL. Following a diagnosis of IPL, corticosteroid therapy successfully improved the anemia and hypergammaglobulinemia, and serum IL-6 levels decreased to a normal range. This case may give suggestions about diagnosing and preventing the progression of complications from this disease entity.