Quality of life and cost effectiveness analysis of therapy for locally recurrent rectal cancer.

PURPOSE: This study was performed to determine the quality of life and cost-effectiveness of therapeutic options for patients with locally recurrent rectal carcinoma, determined from the perspectives of patients and health care providers. METHODS: We reviewed the records of patients (N = 68) with locally recurrent rectal carcinoma evaluated from 1992 through 1995. We constructed a decision-analytic model incorporating outcomes, survival, and costs. Utilities were elicited from convenience samples of health care providers and patients using the standard gamble technique. RESULTS: The median survival for patients undergoing surgical resection (n = 40) was 42 months, compared with 16.8 months for patients undergoing diagnostic or palliative surgery (n = 16) and 18.3 months for patients treated nonoperatively (n = 12; P < 0.005). The mean cost of treatment per patient was $19,283 for the nonoperative group, $45,647 for the diagnostic or palliative surgery group, and $70,878 for the surgical resection group. The diagnostic or palliative surgical strategy was dominated by the nonoperative strategy because the former had greater costs with fewer health benefits. The incremental cost-utility ratio of surgical resection compared with nonoperative management using health care provider utilities was $109,777 per quality-adjusted life year gained; it was reduced to $56,698 using per quality-adjusted life year using mean patient utilities. CONCLUSIONS: Patients with recurrent rectal carcinoma view surgery and morbidity to be less severe than health care providers. Diagnostic or palliative surgery is expensive and affects quality-adjusted survival adversely compared with nonoperative therapy. Surgical resection may be a cost-effective use of resources, particularly when cost-effectiveness is calculated using patient preferences.

Port site recurrences after laparoscopy for malignant disease.

Reports of recurrent malignant disease developing at laparoscopic port sites has created considerable controversy among surgeons. Many have implicated the technique of laparoscopy as a cause of metastases and this has led to condemnation of laparoscopy in malignant disease by many surgeons. A review of the case reports, as well as animal studies, reveals the problem to be considerably more complex. Based on experimental models, reported cases, and our experience at the University of Texas M. D. Anderson Cancer Center, we have arrived at some substantive conclusions regarding this phenomenon. Port site recurrences (PSRs) after laparoscopy for malignant disease can occur as the only site of recurrence, but this is an extremely rare event, and the incidence does not appear to be significantly different from the development of wound recurrences after open laparotomy for malignancy. It is likely that port site recurrences reflect the underlying biology of the malignant disease, rather than an effect of the technique of laparoscopy.

Re-resection with brachytherapy for locally recurrent soft tissue sarcoma arising in a previously radiated field.

PURPOSE: The use of further radiotherapy among patients with soft tissue sarcoma that recurs in a previously irradiated area is controversial. Presented is a review of our 7-year experience with brachytherapy for recurrent soft tissue sarcoma. METHODS: A retrospective review was performed of 26 patients who underwent perioperative brachytherapy between 1990 and 1997 for recurrent soft tissue sarcoma. In all cases, the sarcoma recurred within a previously irradiated field. After-loading brachytherapy catheters were placed at the time of surgical extirpation of the sarcoma within a single-plane implant by use of 1-cm intercatheter spacing. Insertion of the radioactive 192Ir wire was delayed until the fifth to seventh postoperative day to allow initial wound healing. The prescribed dose rate for the 192Ir wire ranged between 50 and 80 cGy an hour, and the dose was specified at 0.5 cm from the plane of the implant. The anatomic locations treated included lower extremity (N = 10), upper extremity (N = 7), trunk (N = 7), and head and neck (N = 2). RESULTS: Total tumor extirpation, confirmed by negative frozen section margins, was accomplished in all cases. The mean dose of external-beam irradiation received before brachytherapy was 55.6 Gy +/- 1.8 Gy (range, 30.0 to 70.3 Gy). The mean dose of radiation prescribed at the implant procedure was 47.2 Gy +/- 1.6 Gy (range, 11.0 to 50.0 Gy). A tissue transfer flap was placed over the bed of resection in 13 cases. Complications occurred in five patients including, three with wound breakdown, one with osteonecrosis, and with neuralgia. Operative intervention was required in four of the five patients with complications; each of the patients requiring operative intervention for wound-related complications had undergone primary wound closure without tissue transfer. Recurrence of disease occurred in 13 patients: nine local and four distant metastases. The median follow-up was 16 months (range, 2 to 73 months). The 5-year local recurrence-free, distant recurrence-free, disease-free, and overall survival rates after brachytherapy were 52%, 75%, 33%, and 52%, respectively. CONCLUSION: Re-irradiation of recurrent soft tissue sarcoma by brachytherapy in conjunction with resection can be performed with acceptable complication rates. Local control can be achieved for the majority of patients who would otherwise require more radical surgical procedures.

Hormone replacement therapy and breast cancer.

The use of hormone replacement therapy by postmenopausal women with a history of breast cancer is a subject of considerable controversy. There are no scientific studies that have appropriately examined the issue, and current practice is often based on inferences from indirect evidence, anecdotal experience, and personal bias. Our understanding of the effects of exogenous, as well as endogenous, hormones on normal and neoplastic breast tissue provides some insights but is not an appropriate basis for clinical practice. The effects of exogenous hormone replacement on the overall health of postmenopausal women, including psychosocial issues, cardiovascular risks, and the morbidity of osteoporosis, must be understood before patients can be counseled appropriately. Treatment of patients must be individualized. The rapidly expanding area of nonhormonal therapies for the treatment of postmenopausal health risks and the treatment of symptomatic complaints in postmenopausal women has already led to a reevaluation of the use of exogenous hormones among all women. A prospective randomized trial that examines the effects of hormone replacement on women with a history of breast cancer is currently underway and will provide valuable data to address these issues. The aim of this review is to outline the scientific basis for the association between estrogen and breast cancer and to provide a framework in which individualized recommendations concerning the use of hormone replacement therapy can be made for patients with breast cancer.

Patterns of recurrence in extremity liposarcoma: implications for staging and follow-up.

BACKGROUND: Liposarcoma is one of the most common histologic types of soft tissue sarcoma and presents a wide spectrum of clinical behavior. The authors examined the correlation among histologic subtypes, outcomes, and patterns of recurrence among patients with extremity liposarcomas. METHODS. A retrospective review of all patients with intermediate and high grade extremity liposarcoma referred to the University of Texas M. D. Anderson Cancer Center from January 1, 1980, to December 31, 1992, was performed. Data on clinical presentation, treatment, patterns of treatment failure, and outcome were evaluated. RESULTS: During the 13-year study period, 122 patients with intermediate or high grade extremity liposarcoma were identified: 102 patients (84%) with myxoid subtype, 18 patients (15%) with pleomorphic subtype, and 2 patients (2%) with mixed histology. There were no differences between the myxoid and pleomorphic subtype groups in tumor size (T1 vs. T2), depth in relation to the muscular fascia, or anatomic site. The median follow-up was 70 months. The 5-year overall survival rate for all intermediate and high grade extremity liposarcoma patients presenting with primary disease (n=85) was 74%; the 5-year local recurrence free survival, distant recurrence free survival, and disease free survival rates were 93%, 78%, and 73%, respectively. Among the 102 patients with myxoid tumors, 33 had distant recurrences; 31 of these were to extrapulmonary soft tissue sites (e.g., the retroperitoneum, chest wall, pleura, pericardium, pelvic sidewall, and soft tissue of the back), and 2 were to the lung only. Among the 18 patients with pleomorphic tumors, 10 had distant recurrences; 3 occurred at extrapulmonary sites, and 7 occurred in the lung only (P < 0.05 for myxoid vs. pleomorphic subtypes). CONCLUSIONS: Myxoid liposarcomas often metastasized to extrapulmonary sites and did so significantly more frequently than pleomorphic tumors. Imaging of the abdomen, retroperitoneum, and extrapleural chest should be performed for accurate staging and posttreatment follow-up of patients with myxoid liposarcoma. Patients presenting with "primary" myxoid liposarcoma of the trunk should be carefully evaluated for an occult primary tumor in an extremity.

Growth hormone, alone and in combination with insulin, increases whole body and skeletal muscle protein kinetics in cancer patients after surgery.

OBJECTIVE: To investigate the impact of growth hormone, alone and in combination with insulin, on the protein kinetics of patients with upper gastrointestinal (GI) tract cancer who have undergone surgery and are receiving total parenteral nutrition (TPN). SUMMARY BACKGROUND DATA: Patients with malignancies of the upper GI tract are at increased risk for malnutrition and perioperative death and complications. Standard nutritional support has not significantly altered outcome. Growth hormone (GH) and insulin have been shown to have some benefit in patients with cancer; however, their action in patients undergoing resection has not previously been studied. METHODS: Thirty patients undergoing surgery for upper GI tract malignancies were prospectively randomized into one of three nutritional support groups after surgery: 10 patients received standard TPN, 10 received TPN plus daily injections of GH, and 10 received daily GH, systemic insulin, and TPN. The patients underwent a protein kinetic radiotracer study on the fifth day after surgery to determine whole body and skeletal muscle protein kinetics. RESULTS: Patients who received standard TPN only were in a state of negative skeletal muscle protein net balance. Those who received GH and insulin had improved skeletal muscle protein net balance compared with the TPN only group. Whole body protein net balance was improved in the GH and the GH and insulin groups compared with the TPN only group. GH and insulin combined did not improve whole body net balance more than GH alone. GH administration significantly increased serum IGF-1 and GH levels. Insulin infusion significantly increased serum insulin levels and the insulin/glucagon ratio. CONCLUSION: Growth hormone and GH plus insulin regimens improve protein kinetic parameters in patients with upper GI tract cancer who are receiving TPN after undergoing surgery.

Laparoscopy in 533 patients with abdominal malignancy.

BACKGROUND: Laparoscopy in patients with intra-abdominal malignancy remains controversial. This study evaluates the incidence of tumor recurrence at the port site after laparoscopy in patients with intra-abdominal malignancy. METHODS: The medical records of all patients with nongynecologic malignancies who underwent laparoscopic procedures between May 1, 1990, and June 30, 1996, at the University of Texas M.D. Anderson Cancer Center were reviewed. Data on extent of tumor, histologic findings, primary location, procedures performed, and complications were recorded. RESULTS: During this time, 533 patients with known intra-abdominal malignancies underwent laparoscopy. Mean follow-up time was 13.2 +/- 0.5 months (range 1 to 71 months; median 10.6 months). Four recurrences at the port site were identified (0.8%). Three of these patients had advanced intra-abdominal disease at the time of laparoscopy; 1 patient without advanced disease at the time of laparoscopy had a recurrence at the port site as the only site of recurrent disease (0.19%). The incidence of port site recurrences among patients with advanced intra-abdominal disease at the time of laparoscopy (3/71) was significantly greater than the risk of development of a recurrence at the port site among patients without advanced intra-abdominal disease at the time of laparoscopy (1/462; P < .0003, by chi-square analysis). CONCLUSION: Recurrence at the port site is very rare. When implantation at the port site does occur, it is most commonly associated with advanced intra-abdominal disease.

The management of gallbladder cancer: before, during, and after laparoscopic cholecystectomy.

Carcinoma of the gallbladder is a rare disease, but when encountered in the patient undergoing laparoscopic cholecystectomy, it can pose a number of dilemmas. Familiarity with the risk factors for malignant gallbladder disease can help identify patients in whom more extensive preoperative evaluation is warranted. When carcinoma is identified preoperatively, cholecystectomy should be performed as an open procedure. If malignancy is encountered unexpectedly during laparoscopic cholecystectomy, the procedure should be converted to an open resection to allow for appropriate evaluation of the stage of disease and appropriate surgical management. Most commonly, malignancy is identified postoperatively, only after pathological examination of the resected gallbladder. Except in rare circumstances, open reoperation is necessary to achieve an adequate curative resection. The current concerns about port site recurrence and carcinomatosis after laparoscopic resection of a gallbladder carcinoma are unwarranted based on current published data. The role of prophylactic excision or irradiation of port sites is uncertain based on current understanding of the biological behavior of the disease.

Effect of enteral and parenteral nutrition on amino acid levels in cancer patients.

BACKGROUND: The syndrome of cancer cachexia can have a significant impact on response to therapy as well as on survival in cancer patients. Therapies directed at metabolic perturbations in cachectic patients are dependent on nutritional repletion and maintenance of adequate amino acid substrate levels. This study compares the ability of oral feeding, enteral nutrition, and total parenteral nutrition to alter plasma amino acid levels in cancer patients. METHODS: Patients with esophageal cancer were stratified by weight loss. Patients with < 20% weight loss were randomized to continue an ad libitum oral diet (group I) or to receive total parenteral nutrition (group II) for 2 weeks; patients with > 20% weight loss were randomized to receive either enteral nutrition (group III) or total parenteral nutrition (group IV) for 2 weeks. Plasma amino acid levels were measured before the study and again after 2 weeks of nutrition support. RESULTS: Before therapy, there was no difference between the groups in total or essential amino acid levels; however, patients in all groups had significantly lower total amino acid levels compared with those of normal controls. After 2 weeks of treatment, patients in group I and III showed no difference in individual, essential, or total amino acid levels. However, patients in groups II and IV showed significant increases in a number of individual amino acids as well as in essential and total amino acid levels after 2 weeks of TPN. CONCLUSIONS: Patients with esophageal cancer demonstrated significant alterations in amino acid profiles compared with those of normal controls. Total parenteral nutrition was superior to ad libitum oral feeding and jejunostomy feeding in repleting plasma amino acid levels.

Effect of systemic insulin on protein kinetics in postoperative cancer patients.

BACKGROUND: Cancer cachexia is a significant cause of postoperative morbidity and mortality in patients with tumors of the upper gastrointestinal tract. Standard parenteral nutrition (TPN) has failed to alter this. The anabolic effect of insulin has been well documented, and its positive effect on protein economy in cancer patients has been recently demonstrated. This study examines the effect of high-dose insulin and parenteral nutrition on protein kinetics in postoperative cancer patients. METHODS: Eleven patients underwent surgery for pancreatic, esophageal, or gastric carcinoma. Postoperatively, patients received standard TPN for 4 days (1 g/kg/day amino acids, 1,000 kcal/day dextrose, 100 g/day lipid), and hyperinsulinemic parenteral nutrition for 4 days (same as standard TPN plus 1.44 U/kg/day regular human insulin) in a crossover design. All patients received both treatments, and the order of treatment was determined randomly. Euglycemia was maintained during insulin infusion via a variable 30% dextrose infusion. Patients underwent protein metabolic studies after each treatment period and rates of whole body and skeletal muscle protein synthesis, breakdown, and net balance were determined by radioisotopic tracer methods using 14C-leucine and 3H-phenylalanine. RESULTS: Compared with standard TPN (STD), hyperinsulinemic TPN (INS) resulted in a significant increase in skeletal muscle protein synthesis (INS: 52.04 +/- 10.22 versus STD: 26.06 +/- 6.71 nmol phe/100 g/min, p < 0.05) and net balance of protein (INS: 7.75 +/- 4.61 versus STD: -15.10 +/- 6.44 nmol phe/100 g/min, p < 0.01), but no difference in skeletal muscle protein breakdown (INS: 44.29 +/- 11.54 versus STD: 41.17 +/- 5.89 nmol phe/100 g/min). Whole-body net balance of protein also significantly increased with insulin-based TPN, compared with standard TPN (INS: 0.04 +/- 0.05 versus STD: -0.08 +/- 0.07 mumol leu/kg/min, p < 0.05), but no difference in whole-body protein synthesis (INS: 2.52 +/- 0.15 versus STD: 2.49 +/- 0.15 mumol leu/kg/min) or whole-body protein breakdown (INS: 2.48 +/- 0.16 versus STD: 2.58 +/- 0.19 mumol leu/kg/min) was observed. Patients received significantly more calories during the hyperinsulinemic TPN period than during the standard TPN period. There was no difference in total, essential, or branched-chain amino acids, and no difference in serum free fatty acids, triglycerides, or cholesterol was observed between the two treatment periods. CONCLUSION: High-dose insulin in conjunction with hypercaloric parenteral nutrition causes improved skeletal muscle protein synthesis, skeletal muscle protein net balance, and whole-body protein net balance compared with standard TPN in postoperative cancer patients.

Protein and amino acid metabolism in cancer cachexia: investigative techniques and therapeutic interventions.

Cancer cachexia is a complex syndrome characterized primarily by diminished nutrient intake and progressive tissue depletion that is manifest clinically as anorexia and host weight loss. The gradual loss of host protein stores is central to this process. This review outlines the techniques that have been used to evaluate human amino acid metabolism, their application in patients with cancer cachexia, and possible therapeutic interventions designed to overcome alterations in host protein and amino acid metabolism associated with malignant cachexia. The techniques of nitrogen balance and 3-methylhistidine excretion provide indirect estimates of overall nitrogen metabolism and skeletal muscle myofibrillar protein breakdown. Measurement of circulating amino acid concentrations, particularly when combined with assessment of arterial-venous differences and regional amino acid balance allows for investigation of interorgan amino acid metabolism. One of the most significant advances in in vivo amino acid metabolic research has been the development of labeled amino acid tracer studies to evaluate whole body and regional amino acid kinetics. The use of stable and unstable amino acid isotopes in these techniques is reviewed in detail. Virtually all of these techniques have now been employed in the evaluation of human cancer cachexia. The results of studies evaluating amino acid concentrations, regional amino acid balance, and 3-methylhistidine excretion are summarized. The use of regional and whole body kinetic studies in cancer cachexia are reviewed extensively. Most investigators have observed increased rates of whole body protein turnover, synthesis, and catabolism in both weight-stable and weight-losing cancer patients. Some studies have suggested a relationship between the extent of disease and the degree of aberration in amino acid kinetic parameters. Investigators have attempted to reverse some of these alterations by provision of substrate (nutritional support) or administration of specific pharmacologic or anabolic agents such as hydrazine sulfate, insulin, growth hormone, and beta-2 agonists. The role of total parenteral nutrition (TPN) in cancer and its effects on protein and amino acid kinetics and tumor growth are addressed. The possible benefits of specific amino acid nutritional formulations with increased branched chain amino acids, arginine, and glutamine are reviewed. Although many of these approaches appear promising, significant impact on clinically definable parameters remains to be demonstrated. A better understanding of the underlying protein catabolic mechanisms of cancer cachexia will likely lead to more effective therapies to reverse the protein calorie malnutrition associated with cancer cachexia.

Growth hormone and insulin reverse net whole body and skeletal muscle protein catabolism in cancer patients.

The authors examined the effect of recombinant-human growth hormone (r-hGH) and insulin (INS) administration on protein kinetics in cancer patients. Twenty-eight cancer patients either received r-hGH for 3 days (GH group, n = 12, weight loss = 6 +/- 2%) or were not treated (control [CTL] group, n = 16, weight loss = 11 +/- 2%) before metabolic study. Recombinant-human growth hormone dose was 0.1 mg/kg/day (n = 6) or 0.2 mg/kg/day (n = 6). Patients then underwent measurement of baseline protein kinetics (GH/B, CTL/B) followed by a 2-hour euglycemic insulin infusion (1 mU/kg/minute) and repeat kinetic measurements (GH/INS,CTL/INS). Whole-body protein net balance (mumol leucine/kg/minute) was higher (p less than 0.05) in GH/INS (0.20 +/- 0.06) than in CTL/INS (0.06 +/- 0.03) or GH/B (-0.19 +/- 0.03). Skeletal muscle protein net balance (nmol phenylalanine/100 g/minute) in GH/INS (25 +/- 6) and CTL/INS (19 +/- 5) was higher than CTL/B (-18 +/- 3). Recombinant-human growth hormone and insulin reduce whole-body and skeletal muscle protein loss in cancer patients. Simultaneous use of these agents during nutritional therapy may benefit the cancer patient.

Growth hormone and insulin combine to improve whole-body and skeletal muscle protein kinetics.

BACKGROUND: A cooperative effect of exogenous insulin and recombinant human growth hormone (r-hGH) with respect to whole-body and skeletal muscle protein metabolism has not been demonstrated previously. This study examined the effect of r-hGH and insulin administration during euglycemic clamping and concurrent amino acid supplementation. METHODS: Twenty-three normal volunteers in the postabsorptive state were either treated with r-hGH for 3 consecutive days before a metabolic study (GH group; n = 10) or not treated (CTRL group; n = 13). The r-hGH dose was 0.2 mg/kg/day (n = 5) or 0.1 mg/kg/day (n = 5). All subjects then received an infusion of 14C-labeled leucine and tritiated phenylalanine, followed by measurement of baseline protein kinetics (GH and CTRL). Subsequently a euglycemic insulin infusion (1 mU/kg/min) with concurrent amino acid infusion was administered, and protein kinetic measurements were repeated at steady state. RESULTS: GH and insulin separately produced an increase in whole-body and skeletal muscle protein net balance. GH plus insulin was associated with a higher net balance of protein than was insulin alone. CONCLUSIONS: r-hGH and insulin in the presence of amino acids and glucose combine to improve whole-body and skeletal muscle protein kinetics.