Nadeem Q. Mirza

Simplified Staging for Hepatocellular Carcinoma

PURPOSE The current American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC) fails to stratify patients adequately with respect to prognosis. PATIENTS AND METHODS The ability of the currently proposed tumor (T) categories to effectively stratify the survival of 557 patients who underwent complete resection for HCC at four centers was examined. Independent predictors of survival were combined into a new staging system. RESULTS Using the current AJCC T classification, patients with T1 and T2 tumors had similar 5-year survivals (P =.6). In addition, the survival of patients with multiple bilobar tumors (T4) matched that of T3 patients (P =.5). Independent predictors of death were major vascular invasion (P <.001), microvascular invasion (P =.001), severe fibrosis/cirrhosis of the host liver (P =.001), multiple tumors (P =.007), and tumor size greater than 5 cm (P =.01). Based on our results, a simplified stratification is proposed: (a) patients with a single tumor and no microvascular invasion, (b) patients with a single tumor and microvascular invasion or multiple tumors, none more than 5 cm, and (c) patients with either multiple tumors, any more than 5 cm, or tumor with major vascular invasion (P <.001). Severe fibrosis/cirrhosis had a negative impact on survival within all categories. The survival of patients with lymph node involvement matched that of patients with major vascular invasion (P =.3). CONCLUSION The current AJCC staging system for HCC is unnecessarily complex. We propose a simplified model of stratification that is based on vascular invasion, tumor number, and tumor size and incorporates the effect of fibrosis on survival.

Allogeneic peripheral-blood progenitor-cell transplantation for poor-risk patients with metastatic breast cancer.

PURPOSE To evaluate the feasibility of allogeneic peripheral-blood progenitor-cell (PBPC) transplantation and to assess graft-versus-tumor effects in patients with metastatic breast cancer. PATIENTS AND METHODS Ten patients with metastatic breast cancer that involved the liver or bone marrow were treated with high-dose chemotherapy and allogeneic PBPC transplantation. The median age was 42 years (range, 29 to 55). The median number of metastatic sites was three (range, one to five). The conditioning regimen was cyclophosphamide (6,000 mg/m2), carmustine (BCNU; 450 mg/m2), and thiotepa (720 mg/m2) (CBT regimen). Patients received graft-versus-host disease (GVHD) prophylaxis using cyclosporine- or tacrolimus-based regimens. RESULTS All patients had engraftment and hematologic recovery. Three patients developed grade > or = 2 acute GVHD and four patients had chronic GVHD. After transplantation, one patient was in complete remission (CR), five achieved a partial remission (PR), and four had stable disease (SD). In two patients, metastatic liver lesions regressed in association with skin GVHD after withdrawal of immunosuppressive therapies. The median follow-up time was 408 days (range, 53 to 605). The median progression-free survival duration was 238 days (range, 53 to 510). CONCLUSION We conclude that allogeneic PBPC transplantation is a feasible procedure for patients with poor-risk metastatic breast cancer. The regression of tumor associated with GVHD provides suggestive clinical evidence that graft-versus-tumor effects may occur against breast cancer. Compared with autologous transplantation, allogeneic PBPC transplantation is associated with the additional risks of GVHD and related infections. Allogeneic transplantation should only be performed in the context of clinical trials and its ultimate role requires demonstration of improved progression-free survival.

Breast cancer on the world wide web: cross sectional survey of quality of information and popularity of websites.

Abstract Objectives: To determine the characteristics of popular breast cancer related websites and whether more popular sites are of higher quality. Design: The search engine Google was used to generate a list of websites about breast cancer. Google ranks search results by measures of link popularity—the number of links to a site from other sites. The top 200 sites returned in response to the query “breast cancer” were divided into “more popular” and “less popular” subgroups by three different measures of link popularity: Google rank and number of links reported independently by Google and by AltaVista (another search engine). Main outcome measures: Type and quality of content. Results: More popular sites according to Google rank were more likely than less popular ones to contain information on ongoing clinical trials (27% v 12%, P=0.01), results of trials (12% v 3%, P=0.02), and opportunities for psychosocial adjustment (48% v 23%, P<0.01). These characteristics were also associated with higher number of links as reported by Google and AltaVista. More popular sites by number of linking sites were also more likely to provide updates on other breast cancer research, information on legislation and advocacy, and a message board service. Measures of quality such as display of authorship, attribution or references, currency of information, and disclosure did not differ between groups. Conclusions: Popularity of websites is associated with type rather than quality of content. Sites that include content correlated with popularity may best meet the publics desire for information about breast cancer. What is already known on this topic Patients are using the world wide web to search for health information Breast cancer is one of the most popular search topics Characteristics of popular websites may reflect the information needs of patients What this study adds Type rather than quality of content correlates with popularity of websites Measures of quality correlate with accuracy of medical information

Clinicopathologic factors predicting involvement of nonsentinel axillary nodes in women with breast cancer

Background: It is unclear which breast cancer patients with positive sentinel lymph nodes (SLNs) require a completion axillary lymph node dissection. Our aim was to determine factors that predict involvement of nonsentinel axillary nodes (NSLNs) in patients with positive SLNs.Methods: We reviewed the records of all patients with invasive breast cancer who underwent SLN biopsy at our institution between 1993 and August 2001. Multivariate analysis was used to identify clinicopathologic features in SLN-positive patients that predict involvement of NSLNs.Results: A total of 131 patients had a positive SLN and underwent completion axillary lymph node dissection. Multivariate analysis revealed that primary tumor >2 cm (P = .009), SLN metastasis >2 mm (P = .024), and lymphovascular invasion (P = .028) were independent predictors of positive NSLNs. The number of SLNs harvested was a significant negative predictor (P = .04). In our model, based on the presence of these factors, the positive predictive value was 100% for a score of 4.Conclusions: The likelihood of positive NSLNs correlates with primary tumor size, size of the largest SLN metastasis, and presence of lymphovascular invasion. A scoring system incorporating these factors may help determine which patients would benefit from additional axillary surgery.

Adenovirus infections in adult recipients of blood and marrow transplants

Adenoviruses are increasingly recognized pathogens that affect blood and marrow transplant (BMT) recipients. Experiences with 2889 adult BMT recipients were reviewed to study the incidence, clinical spectrum, risk factors for dissemination, response to therapy, and outcome of adenovirus infections. Eight-five patients (3%) were diagnosed by means of culture (n=85) or culture and histopathological examination (n=6). Nine patients had asymptomatic viruria, and 76 had symptomatic infections, which included upper respiratory tract infection (n=20), enteritis (n=18), hemorrhagic cystitis (n=10), pneumonia (n=15), and disseminated disease (n=13). The overall mortality rate was 26%. A higher mortality rate was observed among patients with pneumonia (73%) and disseminated disease (61%). Risk factors for dissemination included receipt of an allogeneic transplant, presence of graft-versus-host disease (GVHD), and receipt of concurrent immunosuppressive therapy. Intravenous ribavirin was not associated with an appreciable benefit among 12 patients who received this treatment. In conclusion, adenovirus infections are an important cause of morbidity and mortality in adult BMT recipients, particularly allogeneic transplant recipients with GVHD who are receiving immunosuppressive therapy. The need for an effective, nontoxic antiviral therapy is apparent.

Prognostic Factors in Node-Negative Breast Cancer: A Review of Studies With Sample Size More Than 200 and Follow-Up More Than 5 Years

ObjectiveTo review the published literature on prognostic factors in patients with node-negative breast cancer, focusing principally on recent studies with large sample sizes and extended follow-up periods. Summary Background DataAlthough numerous studies have examined prognostic factors in patients with breast cancer, relatively few have dealt specifically with node-negative disease, and interpretation has been limited by small sample size and limited follow-up times. MethodsA review of the Medline database from 1996 to 2000 was undertaken, with additional papers published before 1996 identified through review articles. For inclusion in the analysis, papers needed to meet the following core criteria: 200 or more node-negative patients with invasive breast carcinoma; median follow-up time at least 5 years; method of testing and cut-off points specified; overall survival and/or disease-free survival specified; and relative risk or statistical probability values given for comparisons. ResultsThree or more papers that met the core criteria were retrieved for each of 11 potential prognostic factors. Of these, tumor size, tumor grade, cathepsin-D, Ki-67, S-phase fraction, mitotic index, and vascular invasion showed a significant association with survival outcomes; HER2/ neu and DNA ploidy showed no significant association; and estrogen receptor status and p53 showed mixed results. Lack of standardization in measurement techniques for many of the markers, including cathepsin-D, Ki-67, HER2/ neu, and p53, limited their current clinical usefulness. ConclusionsIn large studies with extended follow-up periods, tumor size, tumor grade, cathepsin-D, Ki-67, S-phase fraction, mitotic index, and vascular invasion showed a significant association with survival outcome measures in patients with early-stage node-negative breast cancer. Because of technical difficulties and variations in the measurement of many of these factors, tumor size and tumor grade remain the only markers that currently have broad clinical usefulness for this patient group.

Long-term complications associated with breast-conservation surgery and radiotherapy.

Background Breast-conservation surgery plus radiotherapy has become the standard of care for early-stage breast cancer; we evaluated its long-term complications.

Long-term survival after an aggressive surgical approach in patients with breast cancer hepatic metastases.

AbstractBackground: Metastatic breast cancer is generally believed to be associated with a poor prognosis. Therapeutic advances over the past two decades, however, have resulted in improved outcomes for selected patients with limited metastatic disease. Methods: Between March 1991 and October 2002, 31 patients had hepatic resection for breast cancer metastases limited to the liver. Clinical and pathologic data were collected prospectively from breast and hepatobiliary databases. Results: Median age of patients was 46 years (range, 31 to 70). Liver metastases were solitary in 20 patients and multiple in 11 patients. Median size of the largest liver metastasis was 2.9 cm (range, 1 to 8). Major liver resections (three or more segments resected) were performed in 14 patients, whereas minor resections (fewer than three segments resected) with or without radiofrequency ablation (RFA) were performed in 17 patients. No postoperative mortality occurred. Of the 31 patients, 27 (87%) received either preoperative or postoperative systemic therapy as treatment for metastatic disease. The median survival was 63 months; a single patient died within 12 months of hepatic resection. The overall 2- and 5-year survival rates were 86% and 61%, respectively, whereas the 2- and 5-year disease-free survival rates were 39% and 31%, respectively. No treatment- or patient-specific variables were found to correlate with survival rates. Conclusions: In selected patients with liver metastases from breast cancer, an aggressive surgical approach is associated with favorable long-term survival. Hepatic resection should be considered a component of multimodality treatment of breast cancer in these patients.

Clinicopathologic characteristics and prognostic factors in 420 metastatic breast cancer patients with central nervous system metastasis.

Breast cancer is the second most common cause of central nervous system (CNS) metastases. Several risk factors for CNS metastases have been reported. The objective of the current study was to describe clinicopathologic characteristics and prognostic factors in breast cancer patients with CNS metastases.

Predictors of locoregional recurrence among patients with early-stage breast cancer treated with breast-conserving therapy

BackgroundOur aim was to identify predictors of locoregional recurrence (LRR) in patients with early-stage breast cancer treated with breast-conserving therapy (BCT) and long-term follow-up.MethodsFrom 1970 to 1994, 1153 patients with stage I to II breast cancer underwent BCT and radiotherapy at our institution. Patients with prior breast cancer or other primary malignancies were excluded. Clinical and pathologic characteristics evaluated were age, race, tumor size, stage, pathologic tumor margins, axillary nodal involvement, estrogen and progesterone receptor status, Blacks nuclear grade, type of surgery, and use of adjuvant therapy.ResultsOf 1083 patients, 54% presented with stage I disease and 46% with stage II disease. Median age was 50 years, and median follow-up was 9 years. Axillary nodes were positive in 31% of the patients who underwent axillary dissection. LRR developed in 6%, LRR followed by systemic recurrence in 5%, and systemic recurrence alone in 13%, 76% had no evidence of recurrence at last follow-up. Age, tumor size, positive lymph nodes, and not receiving chemotherapy or hormonal therapy were independent predictors of LRR. Disease-specific survival among patients with LRR was similar to that among patients with no recurrence.ConclusionsMultidisciplinary treatment strategies should be used to accomplish durable locoregional control after BCT.