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Loss of Bcl-2 expression in Barrett's dysplasia and adenocarcinoma is associated with tumor progression and worse survival but not with response to neoadjuvant chemoradiation.

Esophageal adenocarcinoma arising on a background of Barrett's esophagus is increasing in incidence. A molecular understanding of both the progression of Barrett's esophagus and the factors determining the response of adenocarcinoma to neoadjuvant therapy is required, and this study focused on the role of proteins regulated by the bcl-2 family of genes, which are important regulators of programmed cell death (apoptosis). In total, 48 patients (36 men, 12 women) with Barrett's adenocarcinoma were studied. All patients received preoperative chemoradiotherapy followed by surgery. Bcl-2, bax and bcl-x protein expression were detected by standard avidin-biotin peroxidase method. Bcl-2, bax and bcl-x expression were detected in 84%, 80%, and 76%, respectively, of normal squamous mucosa. An increasing degree of dysplasia in Barrett's mucosa both before and after chemoradiotherapy was significantly associated with a reduction of bcl-2 expression (P = 0.03 and 0.009, respectively). Bcl-2 expression was significantly associated with tumor differentiation (P = 0.03) and a trend towards earlier T stage (P = 0.08), but not with nodal status. Pre-therapeutic bcl-2, bax and bcl-x protein expression (27%, 75%, and 87.5%, respectively) were not associated with tumor response or resistance to therapy. Bcl-2-positive patients had a significantly improved survival compared with bcl-2-negative tumors. A significant reduction of bcl-2 expression is associated with the progression of Barrett's mucosa to adenocarcinoma. Bcl-2 expression was associated with improved survival. Preoperative chemoradiotherapy induces expression of bax and bcl-x protein. The pretreatment expression of bcl-2 and related proteins did not predict response or resistance to neoadjuvant chemoradiotherapy, suggesting that regulators of apoptosis alone do not determine the response of Barrett's adenocarcinoma to neoadjuvant therapy.

Adenocarcinoma↗

Role of systematic ultrasound-guided staging biopsies in predicting extraprostatic extension and seminal vesicle invasion in men with prostate cancer.

PURPOSE: To assess the presence of extraprostatic extension and seminal vesicle invasion in men with prostate cancer, we performed systematic staging biopsies targeting neurovascular bundles, seminal vesicles, and other extraprostatic tissues before the men underwent radical prostatectomy. We retrospectively evaluated the clinical efficacy of these systematic staging biopsies compared with digital rectal examination (DRE) and transrectal sonography (TRUS). METHODS: Two hundred forty-four candidates for prostatectomy who had a diagnostic biopsy Gleason score of 8 or higher and/or indications of extraprostatic extension (eg, seminal vesicle invasion) by DRE or TRUS underwent staging biopsies using an 18-gauge Tru-Cut needle under real-time TRUS guidance between June 1997 and March 2000. We determined the number of staging biopsy cores to be taken based on the Gleason score of the diagnostic biopsy as well as abnormal DRE and/or TRUS findings. The chi-square test was used to evaluate the statistical significance of differences. RESULTS: There were no complications of staging biopsy. In 75 (31%) of the 244 patients, results of the staging biopsies were positive. The clinical stage was upgraded by staging biopsy in 18 (24%) of these 75 patients. After the staging biopsies, 90 patients underwent radical prostatectomy. Among these 90 patients, staging biopsy specimens were positive for cancer in 20 (47%) of the 43 patients who received neoadjuvant therapy and in 1 (2%) of the 47 patients who did not receive neoadjuvant therapy. There were no false-positive staging biopsies in either group. Among the 90 patients who underwent radical prostatectomy, the false-negative rate for the prediction of organ-confined disease was 43% (30/69) for staging biopsies compared with 29% (10/34) for TRUS. The diagnostic accuracy of staging biopsies (67%; 60/90) was higher than that of DRE (52%; 47/90; p < 0.05) but lower than that of TRUS (79%; 71/90; p = 0.066). CONCLUSIONS: Staging biopsies can reliably sample extraprostatic tissue, including the seminal vesicles and neurovascular bundles. Positive staging biopsy results can aid in the selection of treatment options and in the prediction of outcome for individual patients by providing definitive histologic confirmation of locally advanced disease. Conventional predictive variables for staging can be applied when the results of staging biopsies are negative.

Aged↗

Possible use of transrectal power Doppler imaging as an indicator of microvascular density of prostate cancer.

OBJECTIVES: To reveal the possible use of transrectal power Doppler imaging (PDI) of the prostate in the assessment of the microvascular density (MVD) of cancer lesions. METHODS: In 22 patients with clinically organ-confined prostate cancer, PDI was performed before radical prostatectomy and the degree of vascularity of the cancer lesions as evaluated by PDI was compared with the MVD determined on the surgical specimens. The vascularity by PDI of each cancer lesion was graded on a scale of DS0 to DS2, according to the degree of Doppler signal accumulation. MVD was obtained using factor VIII immunohistochemistry. RESULTS: The vascularity of the PDI of 46 cancer lesions categorized 23 (50%), 10 (22%), and 13 (28%) cancer lesions as DS0, DS1, and DS2, respectively. Significant differences were found in the MVD between DS0 (46.6 +/- 26.8) and DS2 (89.0 +/- 18.1, P <0.005) lesions and between DS1 (50.9 +/- 25.4) and DS2 (P <0.001) lesions. The MVD of 30 cancer lesions in 13 patients without neoadjuvant therapy was significantly higher than that of the 16 lesions in 9 patients with therapy (70.2 +/- 28.2 versus 39.5 +/- 23.9, P <0.001). In the 13 patients without neoadjuvant therapy, the MVD of the DS2 lesions (89.1 +/- 18.9) was significantly higher than that of the DS0 lesions (59.3 +/- 32.5, P <0.01) and DS1 lesions (55.9 +/- 20.9, P <0.005). CONCLUSIONS: The semiquantitative assessment of Doppler flow signals using PDI appears to be of clinical value as an indicator of MVD.

Aged↗

Assessment of clinical impact of endoscopic ultrasound on esophageal cancer.

BACKGROUND AND AIM: Endoscopic ultrasound (EUS) with fine needle aspiration (FNA) is the most accurate imaging modality for locoregional staging of esophageal cancer. It remains unclear whether this technology impacts on the outcome of patients with this malignancy. The aim of the present study was to assess the impact of EUS FNA by comparing the clinical outcomes of patients with esophageal cancer before and after the introduction of this staging modality in our institution. METHODS: Outcomes of patients with de novo non-metastatic esophageal cancer seen in 1998 without EUS FNA evaluation (non-EUS control group) were compared to patients evaluated in 2000 with EUS FNA (EUS group). RESULTS: Outcomes of 60 (non-EUS control group) and 107 (EUS group) patients with non-metastatic esophageal cancer were compared. Preoperative neoadjuvant therapy was administered to 35 patients in the EUS group, all of whom had advanced disease. Cox proportional hazards demonstrated EUS FNA to be associated with reduced recurrence risk (hazard ratio [HR]: 0.63; 95% confidence interval [CI]: 0.43-0.87), P = 0.004, and reduced mortality (HR: 0.66; 95% CI: 0.47-0.90), P = 0.008. CONCLUSIONS: The EUS staging of esophageal cancer leads to appropriate use of preoperative neoadjuvant therapy in patients with advanced disease. Use of EUS is associated with a recurrence-free survival advantage and overall survival advantage in patients, thus supporting its routine use in esophageal cancer staging.

Biopsy, Needle↗

Preoperative combined modality therapy with paclitaxel, carboplatin, prolonged infusion 5-fluorouracil, and radiation therapy in localized esophageal cancer: preliminary results of a Minnie Pearl Cancer Research Network phase II trial.

PURPOSE: To evaluate the feasibility, toxicity, and therapeutic efficacy of 1-hour paclitaxel, carboplatin, continuous low-dose infusional 5-fluorouracil, and concurrent radiation therapy administered preoperatively in patients with localized esophageal cancer. PATIENT AND METHODS: Forty-nine patients with localized esophageal cancer, of either squamous cell carcinoma or adenocarcinoma histology, were enrolled into this phase II trial. All patients were candidates for surgical resection and received the following neoadjuvant therapy: paclitaxel, 200 mg/m2, 1 hour IV on days 1 and 22; carboplatin, AUC 6.0, IV on days 1 and 22; 5-fluorouracil, 225 mg/m2/day, continuous IV infusion on days 1 to 42; and radiation therapy, 45 Gy, administered by 1.8-Gy daily fractions beginning on day 1 of chemotherapy. Upon completion of this neoadjuvant regimen, patients were reevaluated, and all responding patients were resected within 6 weeks of completing neoadjuvant treatment. RESULTS: Administration of this combined modality regimen was associated with moderate toxicity and was tolerated by most patients. Leukopenia (65%) and esophagitis (31%) were the most common toxicities. Most patients did not require nutritional support. There were no treatment-related deaths during neoadjuvant therapy; however, three patients (9%) experienced postoperative death. Preliminary assessment of treatment efficacy is encouraging, with 17 of 37 evaluable patients (46%) achieving pathologic complete remission and an additional 11 patients (30%) having only microscopic residual disease. CONCLUSIONS: This novel, combined-modality neoadjuvant approach for the treatment of localized esophageal carcinoma is feasible and can be administered with toxicity that compares favorably to previously reported neoadjuvant regimens containing high-dose cisplatin. Preliminary assessment of efficacy is also encouraging, with 46% of patients having pathologic complete response. Further follow-up and larger numbers of patients are required to assess efficacy more definitively.

Adenocarcinoma↗

Does cell type influence post-esophagectomy survival in patients with esophageal cancer?

The change in the prevalence of esophageal cancer by cell type from predominantly squamous cell carcinoma to adenocarcinoma has been well documented in the USA, UK, and Western Europe. The objective of this study was to determine if this shift in cell type resulted in a change in survival in patients treated by esophagectomy without neoadjuvant therapy. Our study group included 106 consecutive esophageal cancer patients who underwent esophagectomy without neoadjuvant therapy. Cell type was adenocarcinoma in 76, and squamous cell in 30 patients. For stage 1 tumors there was a trend towards survival advantage for patients with adenocarcinoma, but this did not reach significance. For stage 2-4 tumors and overall, there was no statistical difference in survival as a function of cell type. Therefore, the observed shift in cell type to a higher prevalence of adenocarcinoma does not alter expected post-surgical outcome.

Adenocarcinoma↗

High-grade and hormone-treated prostate cancer express high levels of thymidylate synthase.

OBJECTIVE: To evaluate the expression of thymidylate synthase and dihydropyrimidine dehydrogenase in prostate tissue. MATERIALS AND METHODS: Tissue from 79 patients with localized prostate cancer was used. Thymidylate synthase and dihydropyrimidine dehydrogenase expression were determined semiquantitatively by immunohistochemistry. RESULTS: Thymidylate synthase and dihydropyrimidine dehydrogenase immunostaining grades of benign tissue were significantly higher than those of cancer tissue (both P < 0.01). Cancer tissue with a primary Gleason grade of > or = 4 expressed a higher thymidylate synthase staining grade than those with a primary Gleason grade of <4 (P < 0.01). Cancer tissue spots from patients treated with neoadjuvant therapy revealed significantly higher thymidylate synthase and dihydropyrimidine dehydrogenase grades than those with no neoadjuvant therapy (P < 0.01). CONCLUSION: High thymidylate synthase expression in localized prostate cancer might reflect an aggressive status. High expression in high-grade prostate cancers and prostate cancers after hormonal therapy suggest that thymidylate synthase could be a new therapeutic target for advanced prostate cancer.

Aged↗

The effects of neoadjuvant anastrozole (Arimidex) on tumor volume in postmenopausal women with breast cancer: a randomized, double-blind, single-center study.

Anastrozole, an orally active, nonsteroidal aromatase inhibitor, was evaluated in a randomized, double-blind, single-center study to determine its efficacy as neoadjuvant therapy in postmenopausal women with newly diagnosed, estrogen receptor-rich, locally advanced or large (>3 cm), operable breast cancers. Twenty-four eligible patients were recruited into the study and received either 1 mg (n = 12) or 10 mg (n = 12) of anastrozole daily over a 3-month period. Tumor volumes were estimated clinically, by using caliper measurements and ultrasound (at baseline and after 1, 2, and 3 months' treatment) and by mammography (at baseline and after 3 months). Tumor volume was also measured in surgical specimens. Twenty-one patients were classified as T2, two patients as T3, and one patient as T4B at baseline. Three patients had clinical evidence of lymph node involvement. When considering the difference between the volume as measured by each assessment and the actual pathological volume, the interquartile range and the difference between the maximum and minimum values were smaller for ultrasound when compared with those measured with calipers and mammography. Therefore, of the three clinical assessments of tumor volume used in this study, the data suggest that ultrasound may be the most accurate. The median reductions in tumor volumes as measured by ultrasound for those patients with a measurable 12-week assessment were 80.5 and 69.6% for anastrozole (1 and 10 mg, respectively) after 12 weeks of treatment and 75.5% when both doses were grouped together. Moreover, of these patients, 11 of 12 given 1 mg and 7 of 11 given 10 mg of anastrozole were found on ultrasound to have a >50% reduction in tumor volume after 12 weeks of treatment. Of the 17 patients who would have required a mastectomy at initiation of treatment, 15 were suitable for breast conservation after anastrozole treatment. These results suggest that anastrozole is highly effective as neoadjuvant therapy in postmenopausal women with estrogen receptor-rich, large, operable breast cancer. Future studies comparing anastrozole with tamoxifen as a neoadjuvant treatment should be considered.

Aged↗

CA 19-9 is an index of response to neoadjunctive chemoradiation therapy in pancreatic cancer.

PURPOSE: This study examines the changes of serum levels of CA 19-9 in patients with pancreatic cancer following neoadjuvant irradiation and chemotherapy to define the potential role of this tumor marker in preoperative management of these patients. MATERIALS AND METHODS: Serum CA 19-9 levels were measured in 42 patients before receiving external beam irradiation with concurrent 5-fluorouracil in preparation for laparotomy and Whipple procedure or intraoperative irradiation (IORT). The CA 19-9 levels were determined again after irradiation, and changes were correlated with findings of restaging computed tomography (CT) scan and laparotomy. RESULTS: Following preoperative irradiation, 10 patients (24%) experienced an increase in CA 19-9 levels whereas 29 patients (69%) showed a decrease in CA 19-9. There was no change in the CA 19-9 levels of 3 patients (7%) after treatment. Of the 10 patients with increased CA 19-9 levels after irradiation, 9 (90%) had developed distant metastases or local tumor progression as determined by restaging CT scan or at laparotomy. In contrast, only 6 of 29 patients (21%) with declining CA 19-9 levels after irradiation demonstrated metastases or local tumor progression on restaging CT scan or at laparotomy. The correlation of CA 19-9 increase or decrease with disease progression or control, respectively, was statistically significant (P = 0.009). CONCLUSIONS: Serum CA 19-9 levels may rise or fall during neoadjuvant therapy. A rising CA 19-9 reliably indicates cancer progression while a falling CA 19-9 connotes disease control in the majority of patients. In developing strategies for application of neoadjuvant therapy for pancreatic cancer, monitoring of CA 19-9 appears most useful for the identification of patients who manifest progressive tumor growth and metastasis in spite of this treatment.

Adult↗

Long-term results after neoadjuvant radiochemotherapy for locally advanced resectable extraperitoneal rectal cancer.

PURPOSE: This study was designed to evaluate long-term outcome in locally advanced resectable extraperitoneal rectal cancer treated by preoperative radiochemotherapy. METHODS: Eighty-three consecutive patients who developed locally advanced resectable extraperitoneal rectal cancer underwent preoperative concomitant radiochemotherapy followed by surgery, including total mesorectal excision. RESULTS: Median follow-up was 108 (range, 10-169) months. The living patients underwent complete follow-up of, at least, nine years. Fourteen patients developed local recurrence. The time to detection was longer than two years in eight cases and longer than five years in four. Twenty-one patients developed metastases, 19 within the first five years from surgery. At the univariate analysis, clinical stage at presentation, lymph node involvement at clinical restaging after neoadjuvant therapy, and pT and pN stage were found positively correlated to the incidence of metastases. At the multivariate analysis, the only factors which confirmed a positive correlation were pT stage and pN stage. The actuarial overall survival at five, seven, and ten years was 75.5, 67.8, and 60.4 percent, respectively. The same figures for cancer-related survival were 77.9, 70, and 65.8 percent. At the univariate analysis, factors directly correlated with worse survival were: TNM stage at clinical restaging after neoadjuvant therapy (in particular lymph node involvement) pTNM, pT, and pN. At the multivariate analysis the only factors that confirmed a correlation with worse survival were pTNM, pT, and pN. CONCLUSIONS: Long- term follow-up allows to individuate 28 percent of all local relapses after the first five years from surgery. Postoperative stage is highly predictive of prognosis.

Adult↗

Successful treatment of intracranial nongerminomatous malignant germ cell tumors by administering neoadjuvant chemotherapy and radiotherapy before excision of residual tumors.

OBJECT: The goal of this study was to confirm the effectiveness of our novel treatment strategy, neoadjuvant therapy (NAT) consisting of combined chemo- and radiotherapy, which are performed before complete excision of residual tumor in patients with intracranial nongerminomatous malignant germ cell tumors (NGMGCTs). METHODS: The authors treated 11 consecutive patients with NGMGCTs by applying NAT consisting of combined platinum-based chemotherapy and radiotherapy, followed by complete excision of residual tumors. The pretreatment diagnosis, based on tumor markers with or without biopsy, was yolk sac tumor in five patients, embryonal carcinoma in one patient, immature teratoma in one patient, and mixed germ cell tumor containing malignant tumor components in four patients. Among the 11 patients, NAT achieved a complete response in two and a partial response in six patients; two patients manifested no change and one suffered disease progression. Residual tumors that occurred post-NAT were surgically removed in nine patients. Of the 11 patients, 10 are currently alive without recurrence of their disease, 30 to 177 months (mean 96 months) after diagnosis. In one patient a leptomeningeal tumor recurred and he died of the disease 21 months after diagnosis. CONCLUSIONS: Neoadjuvant therapy, consisting of combined chemo- and radiotherapy, followed by complete excision of residual tumors is highly effective in patients with intracranial NGMGCTs.

Adolescent↗

Detrimental immunologic effects of preoperative chemoradiotherapy in advanced rectal cancer.

PURPOSE: Preoperative chemoradiotherapy for advanced rectal cancer has been an important therapeutic tool to improve the long-term results of curative resection. It is not known whether preoperative chemoradiotherapy for advanced rectal cancer influences the perioperative course of immune parameters. METHODS: Thirty patients with rectal cancer underwent surgery with (study group, n = 15) or without (control group, n = 15) preoperative chemoradiotherapy (2 cycles of 5-fluorouracil, 45 Gy). Blood samples were taken before neoadjuvant therapy, preoperatively, and on Days 1, 2, and 5 after surgery. Cell numbers of lymphocyte subpopulations, granulocytes, monocytes, and natural killer cells were determined by flow cytometry; tumor necrosis factor-alpha and interleukin-6 serum levels were measured with enzyme-linked immunosorbent assay. RESULTS: Significant differences between study and control patients (P < 0.05) were detected regarding circulating interleukin-6 and tumor necrosis factor-alpha levels, with depression of the proinflammatory response to surgery in study patients. Similarly, granulocytosis and monocytosis after surgery were significantly lower in patients after neoadjuvant therapy. Furthermore, cell counts of total T lymphocytes, T helper cells, B lymphocytes, and natural killer cells were significantly reduced after preoperative chemoradiotherapy. This depression of cell-mediated immunity in study patients was even more pronounced after surgery. CONCLUSIONS: Preoperative chemoradiotherapy for advanced rectal cancer results in a significant preoperative and postoperative immune dysfunction as indicated by depression of lymphocyte subpopulations, monocytes, granulocytes, and proinflammatory cytokine release. These findings are of importance because increased perioperative morbidity and mortality rates have been observed after preoperative chemoradiotherapy.

Aged↗

Role of positron emission tomography in the (re-)staging of oesophageal cancer.

BACKGROUND: Various studies have demonstrated that 18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET), measuring altered tissue glucose metabolism, is a promising non-invasive method for detecting both distant nodal and haematogenous metastases in patients with oesophageal carcinoma (OC) and might thus prevent futile esophagectomy. Moreover, FDG-PET is a promising tool in assessing response to non-surgical treatment, and might therefore be used for an early decision on whether treatment should be stopped or continued. MATERIAL AND METHODS: Review of the recent literature regarding the diagnostic performance of FDG-PET in the preoperative staging of patients with OC and regarding diagnostic accuracy of FDG-PET in assessing response to neoadjuvant therapy in patients with OC compared to conventional techniques (especially computed tomography (CT) and endoscopic ultrasonography (EUS)). RESULTS: A search of the literature resulted in the inclusion of 16 studies on the diagnostic value of FDG-PET. Sensitivity and specificity for the detection of locoregional metastases were moderate. Sensitivity and specificity were reasonable for distant metastases. The diagnostic accuracy of FDG-PET in assessing response to treatment was similar to the accuracy of EUS, but significantly higher than that of CT. CONCLUSIONS: The staging value of FDG-PET in OC patients is limited in the detection of locoregional metastases; however; its value is higher in the detection of distant lymphatic and haematogenous metastases. Moreover, FDG-PET is a valuable tool for the non-invasive assessment of histopathologic tumour response after neoadjuvant therapy..

Adenocarcinoma↗

The accuracy of endoscopic ultrasonography with fine-needle aspiration, integrated positron emission tomography with computed tomography, and computed tomography in restaging patients with esophageal cancer after neoadjuvant chemoradiotherapy.

BACKGROUND: Patients with esophageal cancer who receive neoadjuvant chemoradiotherapy are restaged with computed tomography (CT), endoscopic ultrasound with fine needle aspiration (EUS-FNA), and integrated positron emission computed tomography (FDG-PET/CT), and the results affect treatment. METHODS: This is a prospective trial on a consecutive series of patients who had initial chest, abdomen, and pelvis CT scan; EUS-FNA; and fluoro-2-deoxy- d -glucose (FDG)-integrated PET/CT; neoadjuvant chemoradiotherapy; repeat staging tests; pathologic staging; and, if appropriate, resection with lymphadenectomy. The primary objective was to assess the accuracy of these 3 tests in restaging patients after neoadjuvant therapy. RESULTS: There were 48 patients (41 men), and 41 underwent Ivor Lewis esophagogastrectomy with lymphadenectomy. The accuracy of each test for distinguishing pathologic T4 from T1 to T3 disease is 76%, 80%, and 80% for CT scan, EUS-FNA and FDG-PET/CT, respectively. The accuracy for nodal disease was 78%, 78%, and 93% for CT scan, EUS-FNA and FDG-PET/CT, respectively ( P = .04). FDG-PET/CT correctly identified M1b disease in 4 patients, falsely suggested it in 4 patients, and missed it in 2 patients, whereas for CT, it was 3, 3, and 3 patients. Fifteen (31%) patients were complete responders, and FDG-PET/CT accurately predicted complete response in 89% compared with 67% for EUS-FNA ( P = .045) and 71% for CT ( P = .05). CONCLUSIONS: FDG-PET/CT is more accurate than EUS-FNA and CT scan for predicting nodal status and complete responders after neoadjuvant therapy in patients with esophageal cancer. FDG-PET/CT and CT alone provide targets for biopsy, but results are often falsely positive.

Adenocarcinoma↗

Underestimation of nodules while staging hepatocellular carcinoma prior to neoadjuvant treatment on waiting list for transplantation.

Neoadjuvant therapy of hepatocellular carcinoma (HCC) has increasing importance for patients awaiting liver transplantation, as waiting time increases. The therapeutic options (ethanol injection, radiofrequency ablation, chemoembolization) are only effective locally. Therefore, occult carcinomas can overcome the efficacy of these therapies. To evaluate the impact of occult nodules, we analyzed the staging results and histology from 21 HCC patients. The average pretransplant waiting time was 5.2 +/- 3.2 months. The staging before transplantation was reliable concerning the maximum diameter of the HCC. The number of HCC nodules increased from 30 at the time of clinical staging to 59 in histology, hence from 1.4 +/- 1.5 to 2.8 +/- 1.9 per patient. Patients with pT1/2 HCCs experienced an even larger increase (from 1.3 to 3.2 nodules) than patients suffering of pT3/4 HCCs (2.6 to 3.4 nodules). All occult HCCs were less than 2 cm in diameter and showed no prognostically negative histological features such as vascular invasion. The 3-year survival of the patients with small HCCs was 86% compared to 34% for those with advanced cancer. The survival of patients with small HCCs was similar to the survival of patients receiving a transplant for a nonmalignant indication. Only after neoadjuvant therapy with radiofrequency ablation or ethanol injection but not with chemoembolization, was significant necrosis of HCC observed. Considering the current average waiting time, repetitive staging and treatment of new nodules seems justified to achieve a low dropout rate during the waiting time.

Carcinoma, Hepatocellular↗

Progressing prostate carcinoma.

In the Karnell Cancer Center Grand Rounds, we present a patient who underwent radical prostatectomy with bilateral pelvic lymphadenectomy, but had positive margins and subsequently developed local recurrence and then systemic disease. Pathologic and radiologic aspects of his disease are discussed. Therapeutic options at different stages of the disease are examined from the point of view of the urologist, radiation oncologist, and medical oncologist. The surgical portion of the discussion focuses on the selection of initial therapy. Both the selection of surgical candidates and choice of pre- or post-operative therapy in patients can be aided by prognostic tools looking at several variables, including prostate-specific antigen (PSA) level, Gleason score of the tumor, seminal vesicle invasion, extracapsular invasion, and lymph node involvement. Low-risk patients can be treated with monotherapy, such as radical prostatectomy, external beam radiation therapy, prostate brachytherapy, or cryosurgical ablation of the prostate. Higher risk patients may require adjuvant and possibly neoadjuvant therapy in addition. The radiation portion of the discussion focuses on the use of radiation therapy as salvage for relapsing disease. Of particular importance is the point that treating high-risk patients whose PSA levels have started to rise but are less than 1 ng/ml results in a long-term PSA control rate as high as 75%, but that limiting the use of salvage radiation therapy to patients with high PSA levels or biopsy confirmation of local recurrence in the face of a negative bone scan results in biochemical long-term control of less than 40%. In the medical oncology part of the discussion, the major focus is on the use of chemotherapy to treat patients whose disease has become resistant to hormonal therapy. Mitoxantrone plus a corticosteroid has been found to offer significant palliation for such patients. Combination therapy with estramustine plus taxanes, other microtubule inhibitors, or other agents such as topoisomerase II inhibitors, has been found to cause shrinkage of measurable soft tissue disease and diminution of serum PSA levels. The development of effective hormonal and chemotherapeutic drugs for treatment of metastatic disease has led to new interest in adjuvant and neoadjuvant therapy of high-risk patients.

Adenocarcinoma↗

Phase II trial combining docetaxel and doxorubicin as neoadjuvant chemotherapy in patients with operable breast cancer.

BACKGROUND: This study was conducted to assess the antitumour activity of docetaxel in combination with doxorubicin for neoadjuvant therapy of patients with breast cancer. PATIENTS AND METHODS: Forty-eight women were treated with intravenous doxorubicin 50 mg/m(2) over 15 min followed by a 1-h infusion of docetaxel 75 mg/m(2) every 3 weeks for six cycles. Dexamethasone or prednisolone premedication was allowed. Granulocyte colony-stimulating factor was not allowed as primary prophylaxis. The primary end point was the pathologically documented complete response rate (pathological response). RESULTS: The mean relative dose intensity calculated for four or more cycles was 0.99 for doxorubicin and 0.99 for docetaxel. Overall, the pathological response rate was 13%. There were 11 complete and 29 partial clinical responses for an overall response rate of 85% [95% confidence interval (CI) 75% to 95%] in the evaluable population (n = 47). Disease-free and overall survival rates were 85% (95% CI 71% to 94%) and 96% (95% CI 85% to 99%), respectively, after a median follow-up of 36.6 months. Grade 3/4 neutropenia was observed in 65% of patients and 17% reported grade 4 febrile neutropenia. CONCLUSIONS: Docetaxel and doxorubicin is an effective and well-tolerated combination in the neoadjuvant therapy of breast cancer. Future controlled trials are warranted to investigate the best schedules and to correlate response with biological factors.

Adult↗

Esophagogastrectomy for carcinoma of the esophagus and cardia: a comparison of findings and results after standard resection in three consecutive eight-year intervals with improved staging criteria.

OBJECTIVE: A review of findings and results after standard resection for carcinoma of the esophagus and cardia without neoadjuvant therapy was done to provide a basis for comparison with current reports of radical resection and neoadjuvant therapy. METHODS: A 24-year experience on one surgical service with 454 operations for carcinoma of the esophagus and cardia was reviewed. A comparison of findings and results in three consecutive 8-year intervals was analyzed, and new staging criteria were developed and compared with those currently favored by the American Joint Committee on Cancer. RESULTS: From January 1, 1970, to January 1, 1994, 454 patients with carcinoma of the esophagus or cardia underwent operation, of whom 408 (90%) had esophagogastrectomy with a 30-day mortality rate of 2.5% and an additional hospital mortality rate of 1.2%. Of the 121 complications (30.7%), 71 (18%) were major and 50 (12.7%) were minor. Cardiovascular complications predominated. The overall 5-year survival was 24.7%, with a 33.7% survival after complete resections in the most recent interval under study. Palliation of dysphagia was achieved in nearly 80% of patients who survived the operation. During the three intervals under review, resectability, mortality, and complication rates remained constant. The percentages of left thoracotomies and transhiatal resections increased, and there was a decrease in thoracoabdominal incisions. The percentages of patients with Barrett's esophagus and stage 0 and I tumors increased. The percentage of complete resections (R0) increased, whereas that for resections with residual microscopic tumor (R1) decreased, and there was no change in the percentage of patients with residual gross tumor after resection (R2). Modified WNM staging criteria are proposed that provide better prognostic stratification of the disease than those currently favored by The American Joint Committee on Cancer. CONCLUSIONS: Standard esophagogastrectomy is applicable in 90% of patients with operable carcinoma of the esophagus or cardia, with consistently low mortality and morbidity rates and satisfactory palliation of dysphagia. The 5-year survival (24.7% overall) remains suboptimal, but the current figure for complete resections (33.7%) is encouraging. There is a need for revision of the current American Joint Committee on Cancer staging criteria.

Adenocarcinoma↗