Clinical significance of weight loss in cancer patients: rationale for the use of anabolic agents in the treatment of cancer-related cachexia.
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Biomedical subjects
Publications and source records attributed to F D Ottery.
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Timely and appropriate nutritional interventions for patients with cancer and/or human immunodeficiency virus (HIV) infection require adoption of routine nutritional screening and comprehensive evaluations into clinical practice. Traditionally, the clinical skills necessary for comprehensive nutritional evaluation have not been a part of medical education. Likewise, the importance of nutritional screening and assessment has not been fully appreciated. In the context of current health care, these skills are increasingly important in maintaining or improving patient care and improving clinical and economic outcomes. It is imperative that nutritional screening be routinely implemented in all clinical settings (eg, office practices, clinics, preadmission units, homecare) to offset the impact of decreased rates of hospital admission. Hospitals have traditionally been the setting for dietetic screening and intervention and nutritional support services. Therapy for patients with cancer or HIV infection is increasingly being managed primarily or entirely in an outpatient setting. When nutritional risk or deficit is identified on screening, it is important to carry out sequential reassessment after intervention. This article reviews the principles of nutritional screening and comprehensive assessment. It includes a detailed overview of an instrument that can be used for either nutritional screening or assessment in patients with either malignancy or HIV infection.
Anorexia is a symptom seen in the majority of patients with cancer or the acquired immunodeficiency syndrome (AIDS) who experience involuntary weight loss. It is frequently not seen as a symptom requiring management in the same proactive manner as pain, nausea, or constipation. Progressive inanition or wasting is a fundamental component of the complex phenomenon known as the anorexia/cachexia syndrome (ACS) of malignancy or AIDS. Weight loss can be seen in the full spectrum of patient care settings: as a presenting complaint, defining condition, treatment-related toxicity, or as a hallmark of impending death. Primary pharmacologic management of ACS includes use of orexigenic agents (appetite stimulants), anticatabolic agents (antimetabolic and anticytokine), and anabolic agents (primarily hormonal). In addition to these specific categories of pharmacologic intervention, broad aspects of symptom management need to be addressed and are complementary. The available literature evaluating pharmacologic management of ACS in both malignancy and AIDS is reviewed.
Weight loss and nutritional deterioration are associated with adverse outcomes in terms of cancer prognosis (response rate and survival) as well as increased complications, prolonged hospitalizations, increased risk of unplanned hospitalization, increased disability, and increased overall cost of care. The nutritional oncology service at Fox Chase Cancer Center defined a proactive, standardized assessment and interventional approach from 1987-1994. In 186 consecutive patients referred to the nutrition clinic and managed solely by oral intervention and aggressive symptom management, the team demonstrated a 50%-80% success rate in getting patients to maintain or gain weight during therapy, with a similar success in maintaining or improving visceral protein status as determined by serum transferrin and/or albumin. Evaluation of the home parenteral nutrition program (n = 65, from 1987-1993) demonstrated similar success when appropriate triaging was carried out, with 58% of patients able to be tapered off parenteral nutrition (PN) entirely or with transition to enteral tube feeding. The assessment of success for a nutritional intervention (e.g., a disease-specific nutritional supplement) requires the standardization of definitions, assessment tools, criteria for nutritional intervention, and appropriate end points for the assessment of outcomes. The Patient-Generated Subjective Global Assessment of nutritional status is used in conjunction with the nutritional risk of planned cancer therapy to define a standardized interventional approach in oncology patients, which can be used in clinical practice, cooperative oncology group protocols, and clinical trials of nutritional intervention regimens.
Nutritional care of cancer patients should always be considered supportive, whether the oncologic aim is cure or palliation. The goals of nutritional care are to support nutritional status, body composition, functional status, and quality of life. Proactive nutritional assessment and early intervention are the cornerstones of success. Failure to address nutrition is associated with longer hospital stays, increased risk of complication and death, and higher health care costs. Supportive nutritional intervention mandates standardized, cost-efficient assessment and aggressive symptom management. The latter includes nutrition-impact symptoms along the entire gastrointestinal tract, sensory changes, psychologic distress, pain, and anorexia. Components of pharmacologic and behavioral intervention are discussed in the context of supportive nutrition of the patient with cancer.
BACKGROUND: The authors performed reexcision lumpectomy on patients with breast cancer with tumor at or close to the resection margin or if the margin status was unknown. Frozen section analysis (FSA) of reexcision lumpectomy margins was performed to allow additional excision of margins or mastectomy, saving the patient another operation or an additional radiation boost. METHODS: The authors reviewed the accuracy of FSA of margins in 107 patients undergoing reexcision lumpectomy between 1987 and 1992. There were 359 frozen sections performed on 156 specimens. Sensitivity and specificity of FSA for each frozen section margin, specimen, and patient were evaluated, as was gross inspection of tumor involvement at the resection margins. The accuracy of each pathologist's use of FSA also was evaluated. RESULTS: FSA sensitivity per frozen section margin, specimen, and patient was 0.90, 0.89, and 0.85, respectively. The specificity of gross inspection was 0.97, 0.96, and 0.96 (sensitivity, 0.44), which was significantly less accurate than that of FSA (P = 0.0015) or permanent section (P = 0.019). There was no significant discordance between FSA and permanent section. Of 19 pathologists doing FSA, 6 evaluated 10 or more specimens. The error rate ranged from 4% to 10% among pathologists with 10 or more readings, whereas 12 of 13 pathologists with fewer readings had no errors. The final pathologist had a 100% error rate, significantly worse (range, P = 0.0085-0.02) than any experienced pathologist. Thirty-four (32%) patients underwent additional excision (24 patients) or mastectomy (10 patients) based on the results of FSA, which saved the patients from undergoing another operation. No one required an additional operation or a mastectomy because of a false FSA result. CONCLUSION: FSA is safe and accurate in evaluating reexcision lumpectomy margins. Gross inspection is not reliable in margin evaluation. FSA saved an additional operation 32% of the time. Obtaining clear margins during one procedure eliminates the necessity of an additional radiation boost and probably will improve cosmesis.
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OBJECTIVE: The aims of this study were to quantify the amount of the residual carcinoma in re-excision lumpectomy specimens and retrospectively analyze the relationship between clinical parameters and the characteristics of the primary excision to these quantities of the residual tumor. SUMMARY BACKGROUND DATA: Because complete gross surgical excision of the primary tumor is important in minimizing local recurrence in women undergoing breast conservation therapy, re-excision of the initial biopsy site is commonly practiced when the initial primary tumor excision shows inadequate or undeterminable margins. Several studies have reported a significant proportion of re-excision specimens to contain residual tumor (32% to 63%), but to the authors' knowledge, none have quantified the amount of residual tumor. METHODS: The authors reviewed 192 re-excisions retrospectively to quantify the amount of residual carcinoma and correlate the quantities with the characteristics of the primary tumor resection. RESULTS: No tumor was found in 105 (54.7%) specimens, 46 (23.9%) had minimal microscopic disease, 23 (12.0%) had extensive microscopic disease, and 18 (9.4%) had gross residual cancer. Characteristics significantly associated with the quantity of residual disease included clinical tumor stage (T stage), pathologic T stage, and the margin status of the primary excision. The majority (62.1%) of re-excision specimens containing residual carcinoma had an invasive component. CONCLUSIONS: It was concluded that re-excision lumpectomy yields an important number of patients with residual carcinoma and that characteristics of both the primary tumor and primary excision significantly predict the quantity of residual cancer in the specimen. In addition, these results support the policy of performing re-excision for patients with inadequate or undeterminable margins for the primary excision.
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Long-term therapy of oncology patients has been facilitated by permanent indwelling central venous catheters, but catheter-related infections remain a serious complication of their use. Using a retrospective matched cohort design, we compared the risk of catheter-related infection in 47 adult solid tumor patients with right atrial Hickman catheters and 94 patients with totally implanted port catheters. Patients were matched for primary solid tumor, presence of metastases, age, gender, and date of catheter insertion. Seven of 47 patients with Hickman catheters developed catheter-related infection (1.8 infections/1,000 catheter days at risk) compared with 10 of 94 patients with implanted port catheters (0.4/1000 catheter days, P less than 0.0002). Hickman catheters were used more often for terminally ill patients than were port catheters which was a potential source of bias, but results were unchanged after stratifying patients on lifespan. Our study suggests that there are fewer infections in port than in Hickman catheters in adult patients with solid tumors, but prospective randomized studies are needed.
The incidence of delayed breast abscess as a complication following the treatment of breast cancer has not been reported. A retrospective review of 112 patients (pts) undergoing lumpectomy and radiation therapy (RT) in our institution revealed a six per cent incidence of delayed breast abscess (range 1.5-8 months, median 5 months). Prophylactic antibiotics (P = 1.0), postoperative chemotherapy (P = 1.0), primary vs. re-excisional lumpectomy (P = 1.0), and different surgeons (P = 0.514) were not associated with increased risk of delayed abscess. All abscesses occurred in the first 32 pts of this series. The size of the lumpectomy cavity correlated with the incidence of infection (P = 0.0440). Since six of seven abscess cultures grew staphylococci (coagulase negative three pts, coagulase positive three pts), and four of these pts experienced prior biopsy site infection, skin necrosis or repeated seroma aspirations, a skin source for contamination was suggested. Treatment of the abscesses with antibiotics and immediate drainage produced acceptable but inferior cosmesis. We conclude that a small but significant subset of patients treated with lumpectomy and RT will develop delayed wound infections and that expeditious treatment affords satisfactory cosmesis.
Transrectal resection of rectal cancers with the use of the urologic resectoscope is a safe, controlled technique that allows good visualization with defined limits of excision. Twenty-three patients have undergone 50 transrectal resections, with a median survival of 10.8 months. Only 1 of 22 patients required subsequent colostomy before death. Patients, followed as long as 29 months, have had good local control of tumor and excellent palliation of symptoms.
Recent repopularization of intrahepatic infusion chemotherapy has been made possible by the development of the implantable Infusaid pump. Surgical placement of a catheter into the gastroduodenal artery with division of collaterals to the stomach, duodenum, and pancreas has reduced the incidence of gastroduodenal ulceration and pancreatitis. The risk of chemical cholecystitis similarly demands prevention. Anatomically, the cystic artery is a branch of the right hepatic artery in over 95 percent of patients. As a result, even a normal gallbladder is subjected to high-dose chemotherapy with the risk of development of drug-induced cholecystitis. In our first six patients undergoing pump implantation who had normal appearing gallbladders at the time of surgery, two developed symptomatic cholecystitis, necessitating cholecystectomy after receiving intrahepatic chemotherapy. As a result, we recommend elective cholecystectomy at the time of arterial catheterization for intrahepatic chemotherapy.
Five centimeters is often taught to be the minimal safe margin of resection distal to a colonic or rectal tumor. The actual time at which this margin is measured can greatly alter the recorded length. We studied the length of the distal margin in ten patients who underwent colonic resection. Depending upon the time that it was measured, a margin of 5.0 centimeters, unstretched in situ, was noted to shrink to as little as 1.9 centimeters. Studies which have advocated a shorter margin distal to carcinoma of the colon and rectum, which do not define the time at which the margin was measured, could give a surgeon inappropriate confidence in an inadequate tumor margin.
Enhancement of tumor growth by operation is a concern often expressed by surgeons and patients anticipating cancer surgery. Two series of experiments were performed in which Fischer 344 rats and a carcinogen-induced transplantable rat colon cancer were used to test whether anesthesia and operation facilitate tumor implantation and growth. In the first experiments two groups of rats were given intraperitoneal tumor cells. One group underwent sham laparotomy; the second did not undergo surgery. In the second set of experiments rats were injected subcutaneously with tumor cells and then divided into four groups. The first group did not undergo laparotomy. The second underwent laparotomy on day 1, the third on day 15, and the fourth on days 15 and 29 after tumor implantation. Animals were followed for the incidence and growth rate of tumors that developed. The initial experiments demonstrated that 89% of the operated versus 49% of the nonoperated animals developed a tumor (p less than 0.001). The second experiment demonstrated that: animals undergoing multiple operations have a higher incidence of subcutaneous tumor nodules than nonoperated animals (p less than 0.05); animals undergoing multiple operations have a higher incidence of subcutaneous tumor nodules than animals undergoing a single operation (p less than 0.05); animals undergoing multiple operations had larger size tumor masses than the nonoperated animals (p less than 0.05) and than animals undergoing only one operation (p less than 0.04). This study supports the hypothesis that multiple operations and anesthesia may enhance tumor implantation and growth of metastases. This should be considered when designing therapy for patients with cancer.
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Neoadjuvant therapy for locally advanced breast cancer improves disease control, but the complications of treatment are not well established. The aim of this study was to assess the operative morbidity in 20 consecutive patients with locally advanced, noninflammatory breast cancer treated with preoperative chemotherapy and radiation. Patients received preoperative cyclophosphamide, methotrexate, 5-fluorouracil, prednisone, and tamoxifen (CMFPT) to maximum response followed by concurrent chemotherapy and radiation to the involved breast and regional lymph nodes. Following modified radical mastectomy, chemotherapy was continued for a total of 10 cycles. Disease progressed in 3 of 20 patients (15%). Seventeen patients underwent mastectomy, 4 (24%) of whom demonstrated a pathologic complete response to chemoradiotherapy. Seven patients (41%) developed wound infections, 2 (12%) necrosis, 5 (29%) delayed healing, 2 (12%) upper extremity lymphedema, and 8 (47%) seromas. Postoperative chemotherapy was delayed in 4 (24%) patients. There was no mortality, and hospitalization was for less than 1 week. Only one patient required readmission. Although this treatment regimen is aggressive with attendant morbidity, complications are easily managed and generally do not delay therapy. Treatment modification to further reduce complications may be indicated.