The surgeon's role in cancer prevention. The model in colorectal carcinoma.

Cancer Prevention is an emerging field, capturing the old traditional concept of anticipating the development of a major disease and preventing its full impact by early detection, treatment, or aborting the tumorigenic process by a "molecular vaccine" and alleviating the full impact of the disease. Surgeons are important clinician scientists who can carry this discipline forward and develop its full potential in the clinics and in the community. Advances in molecular biology, genetics, and other technologies have permitted seminal understanding of the carcinogenic pathways and identification of targets and intermediate end points in neoplasia. In this review, we will see that we have the means of preventing significant numbers of colorectal carcinomas (CRC).

Clinicopathologic significance of synchronous and metachronous adenomas in colorectal cancer.

PURPOSE: Colorectal cancers (CRCs) evolve from a multiple-step tumorigenesis and, morphologically, are characterized by adenoma. Colorectal cancers with adenomas have distinct clinical features, including reports of improved survival. It is hypothesized that this survival advantage is related to biologic differences in CRC with adenomas rather than earlier diagnosis or earlier stage of disease presentation. PATIENTS AND METHODS: A retrospective chart review of 569 patients treated from 1983 through 2002 was conducted. Data on age, sex, and survival; CRC stage, location, and recurrence; adenoma number, size, histology, and location; and colonoscopy history were analyzed. RESULTS: The mean patient age was 62 years (range, 17-90 years), and 54% of patients were men. The majority of CRCs were left-sided (67%). The American Joint Committee on Cancer stage distribution was 0/I (12%), II (21%), III (34%), and IV (33%). Colorectal cancer with synchronous adenoma was seen in 33% of cases; overall, CRC with adenoma comprised 42% of cases. The event-free survival and overall survival favored CRC with adenoma. After adjusting for age, disease stage, sex, and total number of colonoscopic examinations, the relative risk for an event was 1.51 (P < 0.003) for patients without adenomas versus those with adenomas. CONCLUSION: Colorectal cancer with adenoma represents a distinct population of patients with CRC. The apparent association seems to confer a survival advantage that is not based on age, sex, or disease stage. The survival benefit, although slightly less dramatic, remained significant even when controlled for the number of colonoscopies.

Intraoperative radiation therapy for patients with recurrent rectal and sigmoid colon cancer in previously irradiated fields.

A retrospective study evaluated 15 patients with pelvic recurrence of colorectal cancer in a previously irradiated region who received intraoperative radiation therapy (IORT) as part of salvage therapy. Total prior external beam radiation therapy (EBRT) doses ranged from 45 to 79.2 Gy. Tumor resection was accomplished in 14 patients, with an exenteration performed in seven. IORT dose was 15-20 Gy. Three patients received additional EBRT as a post-operative course of 25.2 Gy in 14 fractions. Actuarial 3-year local control rate was 25%. The 3-year overall survival rate was 29%. Patients with fixed and/or bulky pelvic tumors had a local control rate of 19% at 12 months and median overall survival of 9 months. Patients with less extensive clinical presentations of anastomotic non-fixed transmural recurrence, isolated pelvic node metastasis and rectal recurrence following local excision had a local control rate of 42% at 36 months and median survival of 43 months. We conclude that clinical presentation of recurrent disease is an important prognostic factor. The value of IORT may be limited to patients with less extensive clinical presentations.

Decision making in palliative surgery.

BACKGROUND: Palliative surgery for advanced cancer patients involves complex decision making. Surgeons with a cancer-focused practice were surveyed to determine the extent to which palliative surgery was currently practiced, to identify ethical dilemmas and barriers they faced in performing palliative surgery, and to evaluate their treatment choices in four different clinical scenarios. STUDY DESIGN: A 110-item survey was devised after extensive review of the palliative care and palliative surgery literature to evaluate current practices and attitudes regarding palliative surgery. Case vignettes were devised to evaluate dinical factors influencing surgeons' selection of treatment for symptomatic patients with advanced malignancy. RESULTS: Survey response rate was 24% (419 of 1,740). Respondents reported 74% of their surgery caseload as cancer related, and 21% of these as palliative. On a scale of 1 (uncommon problem) to 7 (common problem), surgeons reported that the most common ethical dilemmas in palliative surgery were providing patients with honest information without destroying hope (5.6 +/- 1.4) (mean +/- standard deviation), and preserving patient choice (5.0 +/- 1.7). Bound on error of the average frequency estimate for ethical dilemmas, based on response rate, was 0.08. On a scale of 1 (not a barrier) to 7 (a severe barrier), surgeons rated the most severe barriers to optimum use of palliative surgery as limitations of managed care (4.1 +/- 2.0) and referral to surgery by other specialists (3.9 +/- 1.8). Bound on error of the estimate for average severity of barriers, based on response rate, was 0.09. They rated the least severe barriers to palliative surgery as surgeon avoidance of dying patients (3.0 +/- 1.8) and surgery department reluctance to perform palliative surgery (2.6 +/- 1.6). Analysis of surgeons' treatment selection in case vignettes indicated that patient age, aggressiveness of tumor biology, local extent of disease, and severity of patient symptoms were all variables of influence for treatment selection in patients with advanced malignancies. CONCLUSIONS: Palliative surgery involves numerous ethical dilemmas, the most prominent being providing honest information to patients without destroying hope, and complex treatment decision making. We have identified variables of major influence to surgeons in the palliative treatment selection for patients with advanced, solid malignancies. Validation of these variables as meaningful will require future studies focusing on patient outcomes.

The role of pelvic exenteration in the management of recurrent rectal cancer.

BACKGROUND: Use of extirpative surgery in the setting of recurrent rectal cancer is controversial given the poor overall outcome of such patients and the morbidity associated with exenteration. METHODS: A retrospective review of patients treated for recurrent rectal cancer from 1990 to 2002 was performed. RESULTS: Twenty-two patients underwent pelvic exenteration. Seventeen underwent potentially curative resection, 5 were for palliation only. There was 1 operative death. Fifteen suffered at least 1 complication; 9 suffered multiple complications. Ten patients required readmission to the hospital. The overall disease-free interval was 11 months. Potentially curative and palliative resections resulted in median survivals of 20.4 and 8.4 months, respectively (P = 0.049). CONCLUSIONS: While patients may derive oncologic and palliative benefits from exenteration, the price in terms of operative morbidity remains high. Newer measures of operative morbidity are necessary to better appraise the value of this radical approach to recurrent rectal cancer.

Long-term survival after radical operations for cancer treatment-induced sarcomas: how two survivors invite reflection on oncologic treatment concepts.

Extent and radicality of surgical oncologic treatment has changed in the past 30 years. Two patients with node-positive breast cancer are presented, who underwent (total or radical) mastectomy with lymphadenectomy and postoperative radiation 24 and 40 years ago. A radiation-associated sarcoma of the parascapular soft tissue developed in one patient 9 years after treatment; the other one sought treatment for a lymphedema-associated Stewart-Treves lymphangiosarcoma 16 years after initial therapy. Both patients underwent a forequarter amputation for their treatment-associated high-grade sarcoma. Both are currently alive and cancer-free 15 and 24 years after amputation. These reports remind us that radical locoregional treatment can cure some solid cancers in the absence of systemic therapy; that such extensive treatment may induce significant disability or secondary malignancies long-term; that even advanced treatment-associated sarcomas can be cured with aggressive resection; that today's multimodality therapy approaches and appropriate patient selection have rendered such extensive locoregional treatment for many tumors obsolete or unnecessary; and that if no effective alternative treatment exists and organ or limb preservation is not feasible, an aggressive resection approach for high-grade cancer should not be discounted unless systemic failure is certain or imminent.

Impact of intraoperative radiation on postoperative and disease-specific outcome after pancreatoduodenectomy for adenocarcinoma: a propensity score analysis.

For periampullary cancer,intraoperative radiation therapy (IORT) administered to the site with the highest locoregional recurrence risk carries the rationale to improve tumor control. An IORT effect on survival remains unclear. IORT impact on postoperative outcomes after pancreatectomy for adenocarcinoma was analyzed, with a specific attempt to correct for the nonrandom IORT treatment assignment, and to account for treatment group imbalances in the interpretation of outcome differences. A propensity-score-adjusted analysis, based on variable selection by logistic regression, was used to rebalance treatments. Between 1989 and 1999, 61 patients underwent partial or total pancreatectomy for a primary periampullary adenocarcinoma at the City of Hope National Medical Center. Diagnoses included pancreatic (n = 36), duodenal (n = 11), ampullary (n = 10), and bile duct cancer (n = 4). Thirty patients received IORT to the resection area, with a median dose of 15 Gy (range: 10-20), followed by postoperative external beam radiation (n = 24). Mortality was 0%, the complication rate 61%. Of 33 patients with a documented recurrence, 6 had an isolated locoregional recurrence only (1 IORT versus 5 no IORT, = 0.05); the systemic recurrence pattern differed as well (IORT 94%, no IORT 67%; = 0.04). IORT had no significant impact on hospital stay (overall median: 17 days), disease-free survival (16 months), and overall survival (23 months) when adjusted for those most relevant variables reflecting IORT treatment group assignment propensity. After adjustment for relevant propensity factors, IORT was not linked to a significantly increased risk for complications, hospital stay, or survival hazard. The recurrence pattern may be affected in some patients, but systemic recurrences predominate. We continue to explore IORT in combination with systemic chemotherapy.

Colorectal Chemoprevention Pilot Study (SWOG-9041), randomized and placebo controlled: the importance of multiple luminal lesions.

BACKGROUND: Colorectal cancer is common worldwide and chemoprevention has the potential of reducing the number of individuals who may suffer and perish from this disease. METHODS: A randomized placebo controlled pilot study in colorectal cancer patients was performed using calcium carbonate as the test agent in a multi-institutional oncology study group. RESULTS: Two hundred twenty volunteers were randomized in the study. The primary goals of compliance, accrual, and toxicity monitoring are presented. Presence of multiple adenomas at study entry and subsequent development of metachronous adenomas were recorded and found to be associated with synchronous adenomas. The secondary endpoint of recurrent adenomas indicated lower rates of new adenoma in the volunteers randomized to the calcium group. CONCLUSION: This pilot study indicates the feasibility of enrolling survivors of colorectal cancer as study volunteers in a colorectal neoplasm chemoprevention clinical trial and oral calcium continues to be a potentially effective drug in reducing colorectal adenomas.

Current surgical options in the control of cancer pain.

PURPOSE: Pain syndromes resulting from recurrent or metastatic cancer require careful evaluation to determine the cause of the pain and the appropriate and judicious use of antitumor treatment. The choice of therapy must integrate the type of pain, its function, the overall disease burden of the patient, and psychological aspects of the cancer. As a general rule, opioid analgesics are the mainstay of treatment in patients with cancer-related pain. When pharmacologic pain control is insufficient or is associated with intolerable side effects, the surgical management of pain can be considered. OVERVIEW: In this article, we review the options, indications, and side effects of the interventional and surgical methods available for the treatment of cancer-related pain. CLINICAL IMPLICATIONS: Planning surgical treatment for cancer-related pain after a patient's lack of response to therapy with opioid analgesics requires an understanding of sensory innervation as well as a realistic expectation of survival, anesthetic risk, or possibility of incomplete pain relief. As such, surgical interventions must be tailored to the individual patient. Clinicians should keep in mind the surgical alternatives for the effective control of pain when it becomes apparent that medical therapy is ineffective.

Quality of life in patients with colorectal metastasis and intrahepatic chemotherapy.

BACKGROUND: Liver metastasis from colorectal cancer remains an oncological challenge. Hepatic chemotherapy has been used; however, rigorous quality of life (QOL) measurements are lacking. The aim of this study was to describe unique QOL issues to formulate a specific tool for this population. METHODS: A purposive sample was identified of patients treated with intrahepatic chemotherapy. Consenting patients completed a demographic tool and the City of Hope QOL Scale/Cancer Patient survey. An in-depth interview on QOL concerns was conducted, taped, and transcribed verbatim. The data from the interviews were coded to identify recurrent themes. RESULTS: Sixteen patients participated. Physical well-being was maintained. Significantly lower subscale scores were noted for psychological, social, and spiritual domains compared with nonpatient norms (City of Hope volunteers; n = 169). Patients found intrahepatic chemotherapy convenient but were unable to pursue vigorous activity, and their sleep habits changed. Psychologically, patients felt reassured to receive specific therapy to their liver. CONCLUSIONS: Pilot evaluation of QOL in this population revealed changes in physical, psychological, social, and spiritual dimensions. Both disease- and treatment-specific concerns were identified, and the results provide evidence for items to include in a QOL questionnaire specific to this population.

Concerns of family caregivers of patients with cancer facing palliative surgery for advanced malignancies.

PURPOSE/OBJECTIVES: To describe the concerns of family caregivers of patients undergoing palliative surgeries for advanced malignancies. DESIGN: Descriptive study with repeated measures. SETTING: A National Cancer Institute-designated Comprehensive Cancer Center in the western United States. SAMPLE: Family caregivers (N = 45) of patients with cancer. METHODS: Family caregivers were assessed prior to planned palliative surgery and at two weeks and six weeks postsurgery. Quantitative assessment of caregiver quality of life (QOL) occurred at each interval. A subset of nine caregivers also participated in a structured interview presurgery and at two weeks postsurgery. MAIN RESEARCH VARIABLES: Caregiver concerns, QOL, decision making. FINDINGS: Family caregivers have important QOL concerns and needs for support before and after surgery for advanced disease. Psychological issues were most pronounced, and common concerns included uncertainty, fears regarding the future, and loss. Family caregivers have concerns about surgical risks and care after surgery and voiced recognition of the declining status of patients. CONCLUSIONS: Surgery is an important component of palliative care and profoundly impacts family caregivers of patients with cancer. The needs of family caregivers are multiple and complex, requiring ongoing assessment to provide interventions that help them cope and ultimately improve their QOL. This important topic requires further research and clinical attention. IMPLICATIONS FOR NURSING: Findings suggest that family caregivers experience their own trajectory during the course of their loved ones' cancer, with surgery being a part of the course. This includes their profound emotions that may swing like a pendulum from one minute to the next. Nurses need to assess family caregivers in addition to patients to provide support and resources that will help increase caregivers' QOL.

Online exclusive: patient and surgeon decision making regarding surgery for advanced cancer.

PURPOSE/OBJECTIVES: To describe a program of research related to outcomes of palliative surgery and focus on one phase of this research involving decision making by patients and surgeons considering surgery for advanced disease. DESIGN: Descriptive. SAMPLE: 10 patients undergoing surgery and 3 oncology surgeons. METHODS: Qualitative interviews were conducted with patients and their surgeons pre- and postoperatively. Transcripts were content analyzed to identify major themes in patient and surgeon interviews based on study questions. MAIN RESEARCH VARIABLES: Decision making, palliative surgery, quality of life. FINDINGS: The study findings highlight the issues of greatest concern to patients and surgeons considering palliative surgery. This phase was an important component of the overall program of palliative surgery research. CONCLUSIONS: Comprehensive care for patients with advanced cancer seeks to achieve a balance of providing aggressive care, ensuring optimum symptom management, and maintaining a focus on comfort. Further study of palliative surgery as an aspect of interdisciplinary care is warranted. IMPLICATIONS FOR NURSING: Patients undergoing surgery for advanced disease require expert nursing care to address quality-of-life concerns. Further research is needed in this area.

The surgical treatment of cancer: a comparison of resource utilization following procedures performed with a curative and palliative intent.

BACKGROUND: Costs associated with the provision of medical care continue to escalate. Therefore, providers must evaluate the cost-effectiveness and benefit to individual healthcare practices. The authors evaluated the immediate and short-term resource utilization needs of patients undergoing surgical intervention with curative or palliative intent. METHODS: Three hundred two patients undergoing surgery with therapeutic intent were observed from the time of admission for intervention until the time of death or until 6 months from the time of the surgical procedure. Surgeons preoperatively identified each case as either curative or palliative in intent. Demographic information, as well as the nature of all interactions with the cancer center, was recorded. RESULTS: Surgeons identified 58 (19%) procedures as palliative and 244 (81%) as curative in intent. Demographic characteristics between the two groups were similar, although recurrent or metastatic disease was more often present in palliative rather than curative patients (P = 0.0078) and palliative intent patients were more likely to have received previous therapy. During the 6-month period, 4690 encounters occurred with the cancer center. The mean number of encounters per patient in each group was similar, although curative intent patients were more likely to have visits with therapeutic intent including chemotherapy administration (P = 0.01), radiation (P = 0.003), or repeat surgical procedures (P = 0.006). In contrast, palliative patients were more likely to be admitted for management of symptoms (P = 0.0001) and had fewer hospital-free days than did curative patients (P = 0.0069). CONCLUSIONS: The average number of encounters for patients undergoing treatment of disease was not significantly different, suggesting that patients undergoing surgery with palliative intent do not require a greater amount of resources than curative intent patients. The nature of the interactions, however, was different, suggesting that resource needs are different and may need to be anticipated in the assessment of how better quality outcomes can be achieved in the palliative surgery setting.

A prospective evaluation of palliative outcomes for surgery of advanced malignancies.

BACKGROUND: We prospectively evaluated the effectiveness of major surgery in treating symptoms of advanced malignancies. METHODS: Fifty-nine patients were evaluated for major symptoms of intent to treat and were followed up until death or last clinical evaluation. Surgeons identified planned operations before surgery as either curative or palliative and estimated patient survival time. An independent observer assessed symptom relief. A palliative surgery outcome score was determined for each symptomatic patient. RESULTS: Surgeons identified 22 operations (37%) as palliative intent and 37 (63%) as curative intent. The median overall survival time was 14.9 months and did not differ between curative and palliative operations. Surgical morbidity was high but did not differ between palliative (41%) and curative (44%) operations. Thirty-three patients (56%) were symptomatic before surgery, and major symptom resolution was achieved after surgery in 26 (79%) of 33. Good to excellent palliation, defined as a palliative surgery outcome score >70, was achieved in 64% of symptomatic patients. CONCLUSIONS: Most symptomatic patients with advanced malignancies undergoing major operations attained good to excellent symptom relief. Outcome measurements other than survival are feasible and can better define the role of surgery in multimodality palliative care. A new outcome measure to evaluate major palliative operations is proposed.

Adenoma recurrences after resection of colorectal carcinoma: results from the Southwest Oncology Group 9041 calcium chemoprevention pilot study.

BACKGROUND: Colorectal adenomas are the usual precursors to carcinoma in sporadic and hereditary colorectal cancers (CRC). METHODS: A total of 220 CRC patients (stages 0, I, and II) were randomized prospectively in a double-blind pilot study of calcium chemoprevention by using recurrent colorectal adenomas as a surrogate end point. This trial is still in progress, and we report the preliminary findings on adenoma recurrence rates. RESULTS: Synchronous adenomas were present in 60% of patients, and cancer confined in a polyp was present in 23% of patients. The overall cumulative adenoma recurrence rate was 31% (19% in the first year, 29% for 2 years, and 35% for 3 years). The recurrence rates were greater for patients with synchronous adenomas: 38% at 3 years (P =.01). Lower stage was associated with higher adenoma recurrence rates (P =.04). Factors including age, sex, site of primary cancer, and whether the cancer was confined to a polyp were not significantly associated with differences in adenoma recurrence rates. CONCLUSIONS: The substantial adenoma recurrence rate in patients resected of CRC justifies colonoscopic surveillance on a periodic basis. Patients with higher rates of adenoma recurrences, such as CRC with synchronous adenomas, are ideal subjects for chemoprevention trials.