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ABSTRACT: CD133, a member of the prominin family, is found in a variety of tissues with at least three variants. The function of CD133 is not well understood, but its expression is subject to changes in the microenvironment cues including bioenergetic stress. Knockout of CD133 does not affect renewal, but mammary gland branching. A point mutation of CD133 (R733C) leads to retinal disorder. CD133 is found in embryonic stem cells, normal tissue stem cells, stem cell niches, and circulating endothelial progenitors as well as cancer stem cells. Maintenance of stemness in cancer may be attributable to asymmetric cell division in association with a set of embryonic expression signatures in CD133+ tumor cells. CD133 could enrich cancer stem cells, which are associated with chemo- and radiation resistance phenotype. High CD133 is associated with poor survival in a variety of solid tumors, including lung, colon, prostate, etc. Monitoring CD133+ cells in peripheral blood, and targeting CD133 in cancer, may further predict and improve the clinical outcomes.
Current Colorectal Cancer Reports 12/2011; 7(4):253-259.
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ABSTRACT: CD133-positive colon cancer stem like cells (CSLCs) are resistant to the conventional cytotoxic drug 5-fluorouracil (5-FU). Wnt signaling pathway plays important roles in colon cancer carcinogenesis and metastasis, and regulates the self-renewal capacity of CSLCs. In the present study, we explored the impact of 5-FU on Wnt signaling pathway of CD133-positive colon CSLCs, and the relation between Wnt signaling pathway and drug resistance of CD133-positive colon CSLCs.
Magnetic activation cell separation was used to collect CD133-positive cells from colon cancer cell line DLD1, which was transfected with luciferase reporter for Wnt signaling activity. The activity of Wnt signaling pathway was compared between CD133-positive and CD133-negative cells. After the treatment with 1 μg/mL of 5-FU, the cell proliferation rates of DLD1 cells, CD133-positive cells, and CD133-negative cells were compared. After the treatment with 1 μg/mL and 10 μg/mL of 5-FU for 48 h, Wnt activity was compared between CD133-positive and CD133-negative cells. The expression of CD133 and cell apoptosis of CD133-positive cells was detected after exposure to 50 ng/mL of dickkopf (DKK)-1, a Wnt pathway inhibitor.
After the treatment with 5-FU, the cell proliferation rate of CD133-positive cells was higher than that of CD133-negative cells and the sensitivity of CD133-positive cells to 5-FU decreased. Wnt activity was higher in CD133-positive cells than in CD133-negative cells [(46.3 ± 0.3)% vs. (33.9 ± 2.7)%, P = 0.009]. After the treatment with 1 μg/mL and 10 μg/mL of 5-FU, Wnt activity of CD133-positive cells was (90.1 ± 10.0)% (P = 0.012) and (52.9 ± 2.5)% (P = 0.047), respectively, whereas that of CD133-negative cells was (35.5 ± 3.3)% (P = 0.434) and (26.5 ± 0.4)% (P = 0.046), respectively. CD133 expression in CD133-positive cells decreased from (87.2 ± 5.3)% to (60.6 ± 3.1)% (P = 0.022) after treatment with DKK-1, whereas the cell apoptosis rate increased from (11.8 ± 0.2)% to (28.3 ± 0.6)% (P = 0.013).
Wnt activity is higher in CD133-positive DLD1 cells than in CD133-negative DLD1 cells. 5-FU can upregulate Wnt activity of CD133-positive colon CSLCs. Blocking Wnt activity may reverse drug sensitivity of CD133-positive cells to 5-FU.
Chinese journal of cancer 09/2010; 29(9):810-5.
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Hee Chul Park,
Nora A Janjan,
Tito R Mendoza, Edward H Lin,
Saroj Vadhan-Raj,
Mandeep Hundal,
Yiqun Zhang,
Marc E Delclos,
Christopher H Crane,
Prajnan Das,
Xin Shelley Wang,
Charles S Cleeland,
Sunil Krishnan
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ABSTRACT: To investigate whether symptom burden before and during preoperative chemoradiation therapy (CRT) for rectal cancer predicts for pathologic tumor response.
Fifty-four patients with T3/T4/N+ rectal cancers were treated on a Phase II trial using preoperative capecitabine and concomitant boost radiotherapy. Symptom burden was prospectively assessed before (baseline) and weekly during CRT by patient self-reported questionnaires, the MD Anderson Symptom Inventory (MDASI), and Brief Fatigue Inventory (BFI). Survival probabilities were estimated using the Kaplan-Meier method. Symptom scores according to tumor downstaging (TDS) were compared using Student's t tests. Logistic regression was used to determine whether symptom burden levels predicted for TDS. Lowess curves were plotted for symptom burden across time.
Among 51 patients evaluated for pathologic response, 26 patients (51%) had TDS. Fatigue, pain, and drowsiness were the most common symptoms. All symptoms increased progressively during treatment. Patients with TDS had lower MDASI fatigue scores at baseline and at completion (Week 5) of CRT (p = 0.03 for both) and lower levels of BFI "usual fatigue" at baseline.
Lower levels of fatigue at baseline and completion of CRT were significant predictors of pathologic tumor response gauged by TDS, suggesting that symptom burden may be a surrogate for tumor burden. The relationship between symptom burden and circulating cytokines merits evaluation to characterize the molecular basis of this phenomenon.
International journal of radiation oncology, biology, physics 03/2009; 75(3):775-81. · 4.59 Impact Factor
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ABSTRACT: Isolation of putative cancer stem cells (CSCs) in various tumors has generated much excitement among researchers who consider these cells the potential "culprits" behind resistance to conventional therapy. Both cancer and cardiovascular disease are believed to be stem cell disorders involving circulating endothelial progenitors (CEPs) and mesenchymal stem cells (MSCs). CD133 and CD44, markers of CSCs in many tumors, also enrich CEPs and MSCs, respectively. We propose an integrated tumorigenesis model that involves all three interdependent stem cell (CSC, CEP, MSC) compartments by revisiting the "seed and soil" model. Developing therapeutics that can effectively target CSCs and spare normal cardiovascular tissue will remain a challenge. Preliminary laboratory and clinical data on monitoring and targeting colon CSCs, using such a modeling system, are discussed.
Gastrointestinal cancer research: GCR 08/2008; 2(4):169-74.
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ABSTRACT: Light microscopy method offers unique abilities for the determination of membrane transport properties of either single or multiple cells. A stream imaging system composed of a microfluidic device, a charge-coupled device camera, and a microscope has been developed to study the osmotic behavior of multiple cells in response toward their extracellular environment. Cells of interest were first mixed with the desired extracellular medium and streamed into a microchannel. The microchannel confines the movement of the cells in a monolayer and allows cells to move along the flow direction only. The cells then pass through a sensing zone where the images of cells were capable of being captured under a microscope. Using mouse dendritic cells (mDCs) as a model system, the membrane transport properties were investigated. The kinetics volume changes of mDCs under various extracellular conditions at room temperature (22°C) were analyzed using a biophysical model to determine water and cryoprotectant transport properties of the cell membrane. This prototype system directly allows us to observe, trace, capture, and store the sample information in terms of number, concentration, dynamic size, or shape for further analyses and documentations. We believe that the system has the potential of being used as a stand-alone equipment, or integrated into a lab-on-a-chip system, or embedded into commercialized instruments.
Cell Preservation Technology 06/2008; 6(2):125-132. · 1.03 Impact Factor
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ABSTRACT: CD133 is a specific surface marker for bone marrow-derived circulating endothelial progenitors, which are vital in postnatal physiologic and pathologic (eg, tumor) angiogenesis. In this study, the authors examined whether increased levels of expression of CD133 messenger RNA (mRNA) in peripheral blood predicted disease recurrence in patients with colon cancer.
Semiquantitative real-time reverse transcriptase-polymerase chain reaction analysis was used to quantify CD133 mRNA levels in peripheral blood mononuclear cells from patients with colon cancer. The assay was developed first and tested at laboratory A (n = 34) and then was validated independently at laboratory B (n = 66). All patients were enrolled between February 2002 and December 2003. A central statistician performed the analysis.
At laboratory A, the median CD133 mRNA level was elevated in patients with recurrent disease (4.2; range, 0.017-106.9) compared with patients without recurrence (0.0017; range, 0.0-9.51; P < .001), leading to a 14.6 odds ratio of recurrence (95% confidence interval [95% CI], 1.7-126; P = .004). At laboratory B, it was confirmed that elevated CD133 mRNA levels at a cutoff point >or=4.79 versus <4.79 were associated with an odds ratio of 22.6 for recurrence (95% CI, 1.7-291.2; P = .02). By comparison, the odds ratio for recurrence was 17.2 (95% CI, 1.8-164; P = .01) for patients with stage III-IV disease versus stage I-II disease according to the Tumor, Lymph Node, Metastasis (TNM) classification. An association also was observed between elevated carcinoma embryonic antigen levels (P = .03; 1-sided) and decreased survival (P = .035; 1-sided) with a CD133 mRNA cutoff level of >or=4.79.
Elevated CD133 mRNA levels at >or=4.79 predicted colon cancer recurrence independent of TNM stage IV disease. Larger prospective studies comparing the current assay with standardized methodology are warranted.
Cancer 08/2007; 110(3):534-42. · 4.77 Impact Factor
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Edward H. Lin MD,
Manal Hassan PhD,
Yanan Li PhD,
Hua Zhao PhD,
Ajay Nooka MD,
Elizabeth Sorenson BS,
PhD Keping Xie MD,
Richard Champlin MD,
PhD Xifeng Wu MD,
Donghui Li PhD, Edward H. Lin,
Manal Hassan,
Yanan Li,
Hua Zhao,
Ajay Nooka,
Elizabeth Sorenson,
Keping Xie,
Richard Champlin,
Xifeng Wu,
Donghui Li
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ABSTRACT: BACKGROUND.CD133 is a specific surface marker for bone marrow-derived circulating endothelial progenitors, which are vital in postnatal physiologic and pathologic (eg, tumor) angiogenesis. In this study, the authors examined whether increased levels of expression of CD133 messenger RNA (mRNA) in peripheral blood predicted disease recurrence in patients with colon cancer.METHODS.Semiquantitative real-time reverse transcriptase-polymerase chain reaction analysis was used to quantify CD133 mRNA levels in peripheral blood mononuclear cells from patients with colon cancer. The assay was developed first and tested at laboratory A (n = 34) and then was validated independently at laboratory B (n = 66). All patients were enrolled between February 2002 and December 2003. A central statistician performed the analysis.RESULTS.At laboratory A, the median CD133 mRNA level was elevated in patients with recurrent disease (4.2; range, 0.017–106.9) compared with patients without recurrence (0.0017; range, 0.0–9.51; P < .001), leading to a 14.6 odds ratio of recurrence (95% confidence interval [95% CI], 1.7–126; P = .004). At laboratory B, it was confirmed that elevated CD133 mRNA levels at a cutoff point ≥4.79 versus <4.79 were associated with an odds ratio of 22.6 for recurrence (95% CI, 1.7–291.2; P = .02). By comparison, the odds ratio for recurrence was 17.2 (95% CI, 1.8–164; P = .01) for patients with stage III–IV disease versus stage I–II disease according to the Tumor, Lymph Node, Metastasis (TNM) classification. An association also was observed between elevated carcinoma embryonic antigen levels (P = .03; 1-sided) and decreased survival (P = .035; 1-sided) with a CD133 mRNA cutoff level of ≥4.79.CONCLUSIONS.Elevated CD133 mRNA levels at ≥4.79 predicted colon cancer recurrence independent of TNM stage IV disease. Larger prospective studies comparing the current assay with standardized methodology are warranted. Cancer 2007. © 2007 American Cancer Society.
Cancer 07/2007; 110(3):534 - 542. · 4.77 Impact Factor
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ABSTRACT: To evaluate the safety and efficacy of conformal radiotherapy (RT) of the dominant liver metastasis as palliative treatment of patients with unresectable colorectal cancer liver metastases.
We retrospectively reviewed the hospital and RT records of 17 patients with unresectable colorectal liver metastases who had been treated with palliative RT to the dominant liver metastasis at our institution.
The median size of the dominant liver metastasis was 10 cm (range, 3-19 cm). Twelve patients (71%) had evidence of extrahepatic disease. A median of 2 (range, 0-4) prior chemotherapy regimens had been administered. Median radiation dose was 42 Gy (range, 7.5-72 Gy). Concurrent chemotherapy included celecoxib in 1 (6%), capecitabine in 6 (35%), and both agents in 9 (53%) patients. Frequencies of acute diarrhea, nausea, vomiting, fatigue, hand-foot syndrome, and neutropenia were 29%, 47%, 6%, 29%, 7%, and 0%, respectively (all grade 2 or lower; no grade 3 toxicities). No late toxicities were noted. With a median follow-up time of 9.2 months, the median actuarial overall survival time from RT was 12.6 months (95% confidence interval [CI]: 3.3-40.9 months). The actuarial in-field local control rate was 62% at 6 months. The median actuarial time to in-field, out-of-field hepatic and distant progression were 6.8, 3.9, and 4.1 month, respectively (95% CIs, 3.9-15.8, 1.8-6.3, and 1.8-11.5 months, respectively).
Conformal RT to the dominant liver metastasis as palliative therapy for unresectable colorectal cancer liver metastases has an acceptable toxicity profile and may improve survival. This approach merits further exploration.
American journal of clinical oncology 01/2007; 29(6):562-7. · 2.21 Impact Factor
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Prajnan Das, Edward H Lin,
Sumita Bhatia,
John M Skibber,
Miguel A Rodriguez-Bigas,
Barry W Feig,
George J Chang,
Paulo M Hoff,
Cathy Eng,
Robert A Wolff,
Marc E Delclos,
Sunil Krishnan,
Nora A Janjan,
Christopher H Crane
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ABSTRACT: To retrospectively compare the acute toxicity, pathologic response, relapse rates, and survival in rectal cancer patients treated with preoperative radiotherapy (RT) and either concurrent capecitabine or concurrent protracted infusion 5-fluorouracil (5-FU).
Between June 2001 and February 2004, 89 patients with nonmetastatic rectal adenocarcinoma were treated with preoperative RT and concurrent capecitabine, followed by mesorectal excision. These patients were individually matched by clinical T and N stage (as determined by endoscopic ultrasound and CT scans) with 89 control patients treated with preoperative RT and concurrent protracted infusion 5-FU between September 1997 and August 2002.
In each group, 5 patients (6%) had Grade 3-4 toxicity during chemoradiotherapy. The pathologic complete response rate was 21% with capecitabine and 12% with protracted infusion 5-FU (p = 0.19). Of the 89 patients in the capecitabine group and 89 in the 5-FU group, 46 (52%) and 55 (62%), respectively, had downstaging of the T stage after chemoradiotherapy (p = 0.20). The estimated 3-year local control (p = 0.15), distant control (p = 0.86), and overall survival (p = 0.12) rate was 94.4%, 86.3%, and 89.8% for patients treated with capecitabine and 98.6%, 86.6%, and 96.4% for patients treated with protracted infusion 5-FU, respectively.
Preoperative concurrent capecitabine and concurrent protracted infusion 5-FU were both well tolerated, with similar, low rates of Grade 3-4 acute toxicity. No significant differences were seen in the pathologic response, local and distant recurrence, or overall survival among patients treated with preoperative RT and concurrent capecitabine compared with those treated with RT and concurrent protracted infusion 5-FU.
International Journal of Radiation OncologyBiologyPhysics 01/2007; 66(5):1378-83. · 4.11 Impact Factor
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Sunil Krishnan,
Nora A Janjan,
John M Skibber,
Miguel A Rodriguez-Bigas,
Robert A Wolff,
Prajnan Das,
Marc E Delclos,
George J Chang,
Paulo M Hoff,
Cathy Eng,
Thomas D Brown,
Christopher H Crane,
Barry W Feig,
Jeffrey Morris,
Saroj Vadhan-Raj,
Stanley R Hamilton, Edward H Lin
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ABSTRACT: The aim of this study was to determine the efficacy of capecitabine (Xeloda), an oral fluoropyrimidine, as a radiosensitizer in the neoadjuvant treatment of locally advanced rectal cancer (LARC).
We conducted a phase II study of capecitabine (825 mg/m2 orally, twice daily continuous) with radiotherapy (52.5 Gy/30 fractions to the primary tumor and perirectal nodes) in 54 patients with LARC (node-negative > or = T3 or any node-positive tumor) staged by endoscopic ultrasound (EUS). The primary endpoint was pathologic response rate; secondary endpoints included toxicity profiles and survival parameters.
Of the 54 patients (median age, 56.7 years; range, 21.3-78.7 years; male:female ratio, 1.7; Eastern Cooperative Oncology Group performance status 0-1: 100%), 51 patients (94%) had T3N0 or T3N1 disease by EUS. Surgery was not performed in 3 patients; 2 of these patients had metastatic disease, and the third patient refused after a complete clinical response. Of the 51 patients evaluable for pathologic response, 9 patients (18%) achieved complete response, and 12 patients (24%) had microscopic residual disease (< 10% viable cells). In addition, 26 patients of all 54 patients (51%) achieved T-downstaging, and 15 patients of 29 patients (52%) achieved N-downstaging. Grade 3/4 toxicities were radiation dermatitis (9%) and diarrhea (2%). Sphincter preservation rate for tumor < or = 5 cm from the anal verge was 67% (18/27).
This regimen of radiotherapy plus capecitabine is well tolerated and is more convenient than protracted venous infusion of 5-FU. The pathologic response rate is comparable to our previous experience using protracted venous infusion 5-FU for LARC.
International Journal of Radiation OncologyBiologyPhysics 11/2006; 66(3):762-71. · 4.11 Impact Factor
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Edward H Lin,
Steven A Curley,
Christopher C Crane,
Barry Feig,
John Skibber,
Marc Delcos,
Saroj-Raj Vadhan,
Jeffrey Morris,
Gregory D Ayers,
Alicia Ross,
Thomas Brown,
Miguel A Rodriguez-Bigas,
Nora Janjan
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ABSTRACT: COX-2 activation may mediate capecitabine induced toxicities, eg, hand-foot syndrome (HFS) and colorectal cancer progression, both of which may be improved by concurrent celecoxib.
From October 2000 to December 2003, 66 patients with metastatic colorectal cancer received concurrent capecitabine at 1000 mg/m/d b.i.d. and celecoxib at 200 mg b.i.d. (XCEL). Twenty-four patients were chemo-naive, 42 patients were second-line; while 34 had XCEL with radiation.
The median duration of XCEL was 7.2 months (range, 1.5-38 months). Ninety percent of Grade 2/3 HFS (17%) occurred after 6 months and incidence of grade 3/4 diarrheas was 8%. The overall response rate was 38% (95% confidence interval [CI], 26-51%), with 11 patients (17%) achieving complete responses and 2 patients (3%) with near complete responses. Six patients (9%) become resectable after sustaining treatment response. The median progression-free survival (PFS) and overall survival (OS) was 8.3 months (95% CI, 7.0-11.0 months) and 22 months (95% CI, 17.8-31.5 months), respectively. Improved median PFS of 14.5 months (P = 0.0001) and OS of 31.5 months (P = 0.005) were noted in patients with normal lactate dehydrogenase (LDH) levels (n = 37) than patients with high levels of LDH (n = 29).
XCEL integrating radiation may improve response rate and survival and reduce toxicities, notably HFS for patients with metastatic colorectal cancer, leading to a randomized phase III study.
American journal of clinical oncology 07/2006; 29(3):232-9. · 2.21 Impact Factor
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Christopher H Crane,
John M Skibber,
Elisa H Birnbaum,
Barry W Feig,
Anurag K Singh,
Marc E Delclos, Edward H Lin,
James W Fleshman,
Howard D Thames,
Ira J Kodner,
Mary Ann Lockett,
Joel Picus,
Thinh Phan,
Anshu Chandra,
Nora A Janjan,
Thomas E Read,
Robert J Myerson
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ABSTRACT: To compare the outcome from preoperative chemoradiation (CXRT) and from radiation therapy (RT) in the treatment of rectal cancer in two large, single-institutional experiences.
Between 1978 and 1995, 403 patients with localized, nonmetastatic, clinically staged T3 or T4 rectal cancer patients were treated with preoperative RT alone at two institutions. Patients at institution 1 (n = 207) were treated with pelvic CXRT exclusively, and patients at institution 2 were treated (except for 8 given CXRT) with pelvic RT alone (n = 196). In addition, a third group (n = 61) was treated with CXRT at institution 2 between 1998 and 2000 after a policy change. Both institutions delivered 45 Gy in five fractions as a standard dose, but institution 2 used 20 Gy in five fractions in selected cases (n = 26). At both institutions, concurrent chemotherapy consisted of a continuous infusion of 5-fluorouracil (5-FU) at a dosage of 1500 mg/m(2)/week. The end points were response, sphincter preservation (SP), relapse-free survival (RFS), pelvic disease control (PC), and overall survival (OS).
Median follow-up was 63 months for all living patients at institution 1 and in the primary group of institution 2. Multivariate analysis of the patients in these groups showed that the use of concurrent chemotherapy improved tumor response (T-stage downstaging, 62% vs. 42%, p = 0.001, and pathologic complete response, 23% vs. 5% p < 0.0001), but did not significantly improve LC, RFS, or OS. Follow-up for the secondary group at institution 2 was insufficient to allow the analysis of these endpoints. In the subset of patients receiving 45 Gy who had rectal tumors < or /=6 cm from the anal verge (institution 1: n = 132; institution 2 primary: n = 79; institution 2 secondary: n = 33), there was a significant improvement in SP with the use of concurrent chemotherapy (39% at institution 1 compared with 13% in the primary group at institution 2, p < 0.0001). A logistic regression analysis of clinical prognostic factors indicated that the use of concurrent chemotherapy independently influenced SP in these low tumors (p = 0.002). This finding was supported by a 36% SP rate in the secondary group at institution 2. Thus SP increased after the addition of chemotherapy at institution 2.
The use of concurrent 5-FU with preoperative radiation therapy for T3 and T4 rectal cancer independently increases tumor response and may contribute to increased SP in patients with low rectal cancer.
International Journal of Radiation OncologyBiologyPhysics 09/2003; 57(1):84-9. · 4.11 Impact Factor
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Christopher H Crane,
John M Skibber,
Barry W Feig,
Jean-Nicolas Vauthey,
Howard D Thames,
Steve A Curley,
Miguel A Rodriguez-Bigas,
Robert A Wolff,
Lee M Ellis,
Marc E Delclos, Edward H Lin,
Nora A Janjan
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ABSTRACT: Although controversial, some believe that preoperative chemoradiation increases the use of sphincter-preserving surgery in low rectal carcinoma patients. This article investigates the relationship between objective tumor response and sphincter preservation in low rectal carcinoma patients.
The authors reviewed the records of 238 patients with T3 or T4 low rectal carcinoma (< or = 6 cm from the anal verge) who underwent preoperative pelvic chemoradiation (45 Gy/25 fractions/5 weeks, n = 182 or 52.5 Gy/30 fractions/5 weeks, n = 56 with continuous infusion 5-fluorouracil at 300 mg/m(2), Monday to Friday) followed by mesorectal (n = 223) or local excision (n = 15). A logistic regression analysis was used to analyze the influence of objective tumor response (defined as complete clinical response) and other prognostic factors on sphincter preservation. Because degrees of partial response could not be objectively defined retrospectively, the influence of partial response on sphincter preservation could not be evaluated.
Overall, 49% of patients (117 of 238) had sphincter-preserving surgery. The clinical complete response rate was 47%. Independent predictors of sphincter preservation included the year of surgery, tumor distance from the anal verge, circumferential tumor involvement, and response to chemoradiation. The sphincter preservation rate increased over the period of the study (from 28% [December 1989 to December 1992] to 44% [January 1993 to December 1996] to 67% [January 1997 to December 2000]). The difference in the rates of sphincter preservation according to response was most striking among patients with tumors 3 cm or less from the anal verge (44% vs. 22%, P = 0.01). The pelvic disease recurrence rate among patients undergoing sphincter-preserving surgery has been less than 10% since January 1993 and was not statistically different between the groups treated from January 1993 to December 1996 and from January 1997 to December 2000.
There has been an increase in the use of sphincter-preserving surgery without an increase in pelvic disease recurrence over the past decade. Although not necessary for sphincter preservation, clinical response to preoperative chemoradiation independently contributed to sphincter-preserving surgery, particularly in patients with low rectal tumors.
Cancer 01/2003; 97(2):517-24. · 4.77 Impact Factor
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ABSTRACT: A multimodality approach is required for the treatment of rectal cancer. All disciplines must understand and exploit the biological
basis of the components of therapy. Adjuvant chemotherapy has allowed significant advances in disease-free and overall survival.
Adjuvant radiation therapy has provided tremendous benefit by improving local control rates and sparing patients the morbidity
of recurrent disease. Tumor regression with preoperative chemoradiation has allowed sphincter-preserving surgical procedures
with excellent functional outcome, even among patients with locally advanced distal rectal tumors. Even higher rates of sphincter
preservation may be possible with further surgical advances and newer chemotherapeutic agents that have improved synergy with
radiation and increased systemic activity.
01/1970: pages 137-164;
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ABSTRACT: More than 70% of all cancer patients develop symptoms from either their primary tumor or metastatic disease. Approximately
half of patients diagnosed with cancer will develop metastatic disease. Controlling symptoms due to cancer or its treatment
is an important obligation in cancer care. When cancer is not curable, it should be treated like a chronic disease with interventions
aimed to prevent or control newly developed symptoms. Treatment needs to be indexed to the site and volume of disease and
the prognosis. The time required for palliative care and the toxicity of palliative care must be minimized. Patients should
not spend a disproportionate percentage of their remaining life receiving palliative treatment. Ineffective therapies that
involve morbidity and cost and provide little or no palliative benefit should not be administered. The burden of palliative
care should not exceed the burden of disease.
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