Symptom prevalence, characteristics and distress in a cancer population.

Despite the importance of symptom control in the cancer population, few studies have systematically assessed the prevalence and characteristics of symptoms or the interactions between various symptom characteristics and other factors related to quality of life (QOL). As part of a validation study of a new symptom assessment instrument, inpatients and outpatients with prostate, colon, breast or ovarian cancer were evaluated using the Memorial Symptom Assessment Scale and other measures of psychological condition, performance status, symptom distress and overall quality of life. The mean age of the 243 evaluable patients was 55.5 years (range 23-86 years); over 60% were women and almost two-thirds had metastatic disease. The Karnofsky Performance Status (KPS) score was < or = 80 in 49.8% and 123 were inpatients at the time of assessment. Across tumour types, 40-80% experienced lack of energy, pain, feeling drowsy, dry mouth, insomnia, or symptoms indicative of psychological distress. Although symptom characteristics were variable, the proportion of patients who described a symptom as relatively intense or frequent always exceeded the proportion who reported it as highly distressing. The mean (+/- SD range) number of symptoms per patient was 11.5 +/- 6.0 (0-25); inpatients had more symptoms than outpatients (13.5 +/- 5.4 vs. 9.7 +/- 6.0, p < 0.002) and those with KPS < or = 80 had more symptoms than those with KPS > 80 (14.8 +/- 5.5 vs. 9.2 +/- 4.9, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Opioid responsiveness of cancer pain syndromes caused by neuropathic or nociceptive mechanisms: a combined analysis of controlled, single-dose studies.

We performed a combined analysis of the results from four controlled single-dose relative-potency studies to assess the impact of inferred pain mechanism on the response to an opioid drug. A total of 168 patients received 474 administrations of either morphine or heroin, and we assessed the analgesic response during a 6-hour period with visual analog scales. We summarized this as a total pain relief (TOTPAR) score. Two experienced pain clinicians reviewed information about pain characteristics and designated each case according to the inferred pain mechanism (neuropathic, nociceptive, or mixed) and the degree of confidence in the inferred mechanism (definite versus probable/possible). They grouped the cases as follows: nociceptive pain only (n = 205), neuropathic pain only (n = 49), and mixed (n = 220). We compared pain relief achieved by patients with different mechanisms, with TOTPAR adjusted for significant covariates (duration of prior opioid administration, doses of opioid administered in the previous 48 hours, pain intensity at the start of the study, BUN:creatinine ratio, and dose of administered opioid). The adjusted mean TOTPAR score of the group with any neuropathic pain was significantly lower than that of the group with nociceptive pain only (26.1 versus 20.4, p = 0.02). The score of the group with definite nociceptive pain alone (adjusted mean TOTPAR = 28.0) was significantly higher than scores of the groups with possible/probable nociceptive pain (TOTPAR = 19.9), mixed mechanisms (TOTPAR = 20.2), definite neuropathic pain alone (TOTPAR = 20.6), and possible/probable neuropathic pain alone (TOTPAR = 22.9).(ABSTRACT TRUNCATED AT 250 WORDS)

The Memorial Symptom Assessment Scale: an instrument for the evaluation of symptom prevalence, characteristics and distress.

The Memorial Symptom Assessment Scale (MSAS) is a new patient-rated instrument that was developed to provide multidimensional information about a diverse group of common symptoms. This study evaluated the reliability and validity of the MSAS in the cancer population. Randomly selected inpatients and outpatients (n = 246) with prostate, colon, breast or ovarian cancer were assessed using the MSAS and a battery of measures that independently evaluate phenomena related to quality of life. Symptom prevalence in the 218 evaluable patients ranged from 73.9% for lack of energy to 10.6% for difficulty swallowing. Based on a content analysis, three symptoms were deleted and two were added; the revised scale evaluates 32 physical and psychological symptoms. A factor analysis of variance yielded two factors that distinguished three major symptom groups and several subgroups. The major groups comprised psychological symptoms (PSYCH), high prevalence physical symptoms (PHYS H), and low prevalence physical symptoms (PHYS L). Internal consistency was high in the PHYS H and PSYCH groups (Cronback alpha coefficients of 0.88 and 0.83, respectively), and moderate in the PHYS L group (alpha = 0.58). Although the severity, frequency and distress dimensions were highly intercorrelated, canonical correlations and other analyses demonstrated that multidimensional assessment (frequency and distress) augments information about the impact of symptoms. High correlations with clinical status and quality of life measures support the validity of the MSAS and indicate the utility of several subscale scores, including PSYCH, PHYS, and a brief Global Distress Index. The MSAS is a reliable and valid instrument for the assessment of symptom prevalence, characteristics and distress. It provides a method for comprehensive symptom assessment that may be useful when information about symptoms is desirable, such as clinical trials that incorporate quality of life measures or studies of symptom epidemiology.

Nativity, complications, and pathology are determinants of surgical results for gastric cancer.

BACKGROUND: About half the patients involved in the current study were born outside of the United States. Epidemiologic and histologic features and survival estimates were compared with persons born in the United States. Results of gastrectomy with lymph node dissection were studied. METHODS: Records of 187 patients with adenocarcinoma of the stomach were reviewed. Seventy-six with a curative gastrectomy were staged retrospectively. Univariate and multivariate analyses were done. RESULTS: Seventy-six percent of histologically reviewed curative resections had the intestinal subtype with the same frequency in U.S.-born and foreign-born patients. Fewer patients with proximal third lesions were foreign born. Thirty-six percent had complications. The overall 5-year Kaplan-Meier survival estimate was 46%: 77% for patients with negative nodes and 33% for patients with positive nodes. N1 survival estimate was 44%; N2, 25%; N3(M1), 0%. All six patients with early gastric cancer are alive 50-147 months after surgery. Other stage I patients had estimated survival of 65%; Stage II, 52%; Stage III, 40%; and Stage IV, 0%. Multivariate analysis revealed four significant prognostic variables: nativity, histologic subgroup, presence of complications, and number of positive nodes. CONCLUSIONS: Proximal gastric cancer was more common in U.S.-born persons. Gastric cancer may be more malignant in U.S.-born persons than in foreign-born persons because their survival was significantly poorer. Complications, a significant adverse factor, were more common in U.S. series. Pancreatectomy with gastrectomy is rarely indicated, because microscopic involvement is rare and complications frequent. The prognostic advantage of a regional lymphadenectomy remains unclear.

Long-term functional results of coloanal anastomosis for rectal cancer.

In a survey of patients treated with coloanal anastomosis for rectal cancer, 81 of 90 eligible patients responded to a questionnaire evaluating current anorectal function. Time from operation to assessment ranged from 1.3 to 12.3 years (median: 4.3 years). The median stool frequency was two per day; 22% of patients reported four or more stools per day. In the patients surveyed, fecal continence was complete in 51%, incontinence to gas only in 21%, minor leak in 23%, and significant leak in 5%. Complete evacuation of the neorectum was problematic in 32%. Overall function was excellent in 28%, good in 28%, fair in 32%, and poor in 12%. The impact of treatment variables on functional outcome was assessed by univariate and multivariate analyses. No surgical technique correlated with improved or impaired outcome. Time since surgery (reduced stool frequency) and use of postoperative adjuvant radiotherapy (increased stool frequency, increased difficulty with evacuation) did appear to influence functional outcome. We conclude that the functional results of coloanal anastomosis are good but not optimal. Continued investigation of the effects of surgical technique and adjuvant therapy is warranted.

Infectious morbidity associated with long-term use of venous access devices in patients with cancer.

OBJECTIVE: To evaluate infectious morbidity associated with long-term use of venous access devices. DESIGN: Prospective, observational study. SETTING: Comprehensive cancer center at a university hospital. PARTICIPANTS: 1431 consecutive patients with cancer requiring 1630 venous access devices for long-term use inserted between 1 June 1987 and 31 May 1989. MEASUREMENTS: Quantitative microbiologic tests to identify device-related bacteremia and fungemia, catheter tunnel infection, pocket infection in implantable port devices, and site infections; number of days the device remained in situ and time until infectious morbidity; vessel or device thrombosis and device breakage. RESULTS: At least one device-related infection occurred with 341 of 788 (43% [95% CI, 39% to 47%]) catheters compared with 57 of 680 (8% [CI, 6% to 10%]) completely implanted ports (P < or = 0.001). Device-related bacteremia or fungemia is the predominant infection occurring with catheters, whereas ports have a more equal distribution of pocket, site, and device-related bacteremia. The predominant organisms isolated in catheter-related bacteremia were gram-negative bacilli (55%) compared with gram-positive cocci (65.5%) in port-related bacteremia. The number of infections per 1000 device days was 2.77 (95% CI, 2.48 to 3.06) for catheters compared with 0.21 (CI, 0.16 to 0.27) for ports (P < or = 0.001). Based on a parametric model of time to first infection, devices lasted longer in patients with solid tumors than in those with hematopoietic tumors. Ports lasted longer than catheters across all patient groups. CONCLUSIONS: The incidence of infections per device-day was 12 times greater with catheters than with ports. Patients with solid tumors were the least likely to have device-related infectious morbidity compared with those with hematologic cancers. The reasons for the difference in infectious complications is uncertain but may be attributable to type of disease, intensity of therapy, frequency with which devices are accessed, or duration of neutropenia.

Long-term results of transhiatal esophagectomy for esophageal carcinoma. A multivariate analysis of prognostic factors.

BACKGROUND: Perioperative mortality and survival after esophagectomy have improved over the past 10 years. Although stage is the most powerful predictor of long-term survival, it remains unclear whether other factors influence prognosis. METHODS: Between 1981-1991, 100 patients with esophageal carcinoma were uniformly treated by transhiatal esophagectomy without adjuvant therapy. Results and prognostic factors of long-term survival were analyzed by univariate and multivariate analyses (log-rank test and Cox regression model). RESULTS: Forty-eight patients had severe associated medical conditions, and 26 patients were older than 69 years of age. Mortality was 3%, and morbidity was 68%. With a median follow-up of 52 months, median survival was 18 months. The overall 5-year survival was 23%, but it was 63% for early stages (pT1 + pT2). In the multivariate analysis, the risk of dying was increased by 4.9 (risk ratio) for patients with carcinomas invading beyond the muscularis propria (pT3 + pT4), compared to lower stages (pT1 + pT2) (P < 0.0001). To a lesser extent, longterm survival was also adversely affected by transfusions (packed erythrocytes) after controlling for stage (risk ratio 1.7; P = 0.047). Age (> 69 years), preoperative weight loss, tumor location, histology (adenocarcinoma versus squamous cell carcinoma), fresh frozen plasma, and splenectomy did not influence survival. CONCLUSION: In this study, transhiatal esophagectomy provided palliation for esophageal cancer with a low-perioperative mortality. Prolonged survival or cure was obtained for the majority of patients operated on in the early stages. Blood transfusions had a slight adverse effect on long-term survival.

A prospective analysis of vascular access device-related infections in children.

To identify significant predictors of device-related infections, we performed a prospective, nonrandomized analysis of our experience with vascular access devices over a 2-year period in a pediatric oncology population. Variables analyzed included: (1) age at placement, (2) sex, (3) underlying disease, (4) type of device used (catheter v port), and (5) total white blood cell count at placement. Quantitative microbiologic criteria were used for diagnosis of bacteremia while clinical and microbiologic criteria were used in diagnosis of tunnel/port/site infections. During the study period a total of 351 devices, comprising 78,159 days in situ, were placed and data for univariate and multivariate analysis were available on 271 (77%). The mean age at placement was 7.2 +/- 4.7 years for catheters and 9.5 +/- 4.8 years for implantable devices (P less than or equal to .01). Significant predictors of device-related infections in univariate analysis were type of device (P less than or equal to .0001) and age (P less than or equal to .002). External catheters and age less than or equal to 7 years were associated with increased risk of infection. Underlying disease had a marginal effect on the infection rate (P = .08). In multivariate analysis, device type (P less than or equal to .0001) and age (P less than or equal to .002) continued to affect infections, whereas underlying disease demonstrated only a borderline effect (P = .14). We conclude that device type and age significantly affect the rate of device-related infections. These data support increased use of implantable devices in pediatric oncology patients.

The metabolite morphine-6-glucuronide contributes to the analgesia produced by morphine infusion in patients with pain and normal renal function.

Morphine-6-glucuronide is a metabolite of morphine that binds to the opioid receptor and is analgesic in animals and humans. Although accumulation of morphine-6-glucuronide in patients with renal insufficiency has been implicated in morphine toxicity, the contribution of the metabolite to morphine analgesia in patients with normal renal function has not been established. To evaluate this contribution, we repeatedly sampled blood and assessed effects during and after a loading infusion with morphine (mean duration, 168 minutes) in 14 patients with chronic pain, all of whom had normal serum creatinine levels. Plasma concentrations of morphine and morphine-6-glucuronide were assayed by use of high performance liquid chromatography with electrochemical detection. Patients were divided into three groups on the basis of the molar concentration ratio of morphine-6-glucuronide:morphine from the start of the infusion until 240 minutes later: Group 1 (n = 5) had a mean ratio greater than or equal to 0.7:1; group 2 (n = 4) had a mean ratio less than 0.7:1 but greater than or equal to 0.4:1; and group 3 (n = 5) had a mean ratio less than 0.4:1. Time-effect plots revealed that average and peak relief were greater in group 1 than group 2 and greater in group 2 than group 3. For all patients, mean morphine-6-glucuronide:morphine ratio throughout the study was significantly correlated with mean pain relief (r = 0.611, p less than 0.02). These data suggest that morphine-6-glucuronide contributes to morphine analgesia in patients with normal renal function. The role of the metabolite should be considered when morphine is used clinically.

The indications for elective treatment of the neck in cancer of the major salivary glands.

To define the indications for elective neck treatment, the cases of 474 previously untreated patients were reviewed who had locally confined major salivary gland cancers treated between 1939 and 1982. Clinically positive nodes were present in 14% (67 of 474). Overall, clinically occult, pathologically positive nodes occurred in 12% (47 of 407). By univariate analysis, several factors appeared to predict the risk of occult metastases; however, multivariate analysis revealed that only size and grade were significant risk factors. Tumors 4 cm or more in size had a 20% (32 of 164) risk of occult metastases compared with a 4% (nine of 220) risk for smaller tumors (P less than 0.00001). High-grade tumors (regardless of histologic type) had a 49% (29 of 59) risk of occult metastases compared with a 7% (15 of 221) risk for intermediate-grade or low-grade tumors (P less than 0.00001). In view of the low frequency of occult metastases in the entire group, routine elective treatment of the neck is not recommended. High-grade tumors and larger tumors have a high rate of occult neck metastases, and treatment should be considered in this group.

Expression of Her2/neu oncogene product p185 in correlation to clinicopathological and prognostic factors of gastric carcinoma.

The expression of the Her2/neu gene product p185 was retrospectively analyzed in 58 patients with gastric carcinoma. The results were correlated to various clinicopathological and prognostic factors. Positive membrane staining for p185 could be detected in 38% of the patients (22/58). Membrane staining was significantly greater in well and moderately differentiated tumors of the intestinal type when compared with poorly differentiated lesions and carcinomas of the diffuse type (P less than 0.01). Positive membrane staining did not correlate with site and tumor stage, but T1 lesions had less membrane staining than more advanced primary tumors. Overall survival showed no difference between p185-positive and negative cases. Multivariate analysis defined a subgroup of curatively resected patients with stage III and IV disease that had a statistically significant poorer survival when p185 was overexpressed (P = 0.005). Overexpression of the Her2/neu product p185 appears to be associated with intestinal-type gastric carcinoma and may help in identifying a subset of patients at increased risk for shorter survival.