Effect of cholecystokinin on human cholangiocarcinoma xenografted into nude mice.

Gastrointestinal polypeptide hormones regulate growth of various normal gastrointestinal tissues as well as certain visceral cancers. Since cholecystokinin (CCK) promotes growth of normal biliary tract, we sought to determine whether CCK affects the growth and metabolism of human cholangiocarcinoma line SLU 132. Twenty-six nude mice with s.c. xenografts of this cancer received either CCK octapeptide (50 micrograms/kg/dose) or 0.9% NaCl solution (saline) twice a day i.p. for 14 days. Tumor volume was calculated from Vernier caliper measurements. At sacrifice on Day 15, tumors were excised, weighed, and examined histologically. DNA, RNA, and protein were measured in the xenografted carcinomas. Because this cholangiocarcinoma produces carcinoembryonic antigen (CEA), we obtained serum at sacrifice for CEA radioimmunoassay and also tumor tissue for CEA immunolabeling with murine anti-CEA monoclonal antibody. Serum CEA levels were 90% higher in the CCK-treated group. Tumor tissue in the CCK-treated group also contained more CEA than did the controls. Mean tumor volume increased significantly in the saline group during the 14-day treatment period, whereas mean tumor volume did not increase significantly in the CCK group. Exogenous high-dose CCK thus appears to increase production and release of CEA from SLU-132; it also appears to retard growth of this tumor line in the nude mouse.

Overexpression of sigma receptors in nonneural human tumors.

Previous data indicated that opioid receptors occur in both neural and nonneural human tumors. However, it has recently been shown that some of the putative opioid binding may be attributable to sigma sites. In this study the occurrence of sigma and opioid receptors in nonneural human tumors was assessed. The neoplasms included renal and colon carcinomas and a sarcoma. [3H]1,3-di-o-tolylguanidine was used to assay sigma receptors by homologous competition binding assays, which when analyzed provided dissociation constant and receptor density values. Opioid binding was measured with [3H]-(-)-ethylketocyclazocine, a ligand which interacts with mu, delta, and kappa subtypes. Fresh surgical specimens were obtained from 9 human neoplasms, selected for their large size, and compared with nonmalignant tissues. All 9 tumors contained sigma sites, and dissociation constant values were within the range of 27-83 nM. Occasionally, two-site fit the data better than one-site binding, suggesting the presence of multiple sigma sites. Opioid binding was not detected. Intratumoral variability was evaluated by sampling several locations on the periphery of the mass and one in the center. Each of the samples was bisected, with a portion reserved for histological examination to correlate morphological features with receptor data. Changes in sigma binding were not associated with the extent of fibrosis, viability, or necrosis. Receptor density values displayed moderate intra- and intertumoral variation (coefficients of variation, 8-39 and 27-49%, respectively). More important, sigma binding in tumors was found to be greater than or equal to 2-fold higher than that of control nonmalignant tissue.

A sign on CT that predicts a hazardous ureteral anomaly.

INTRODUCTION: An aberrant course of the distal ureter can pose a risk of ureteral injury during surgery for inguinal hernia repair and other groin operations. In a recent case series of inguinoscrotal hernation of the ureter, we found that each affected ureter was markedly anterior to the psoas muscle at its mid-point on abdominal CT. We hypothesized that this abnormality in the abdominal course of the ureter would predict the potentially hazardous aberrant course of the distal ureter. PRESENTATION OF CASES: We reviewed all evaluable CT urograms performed at St. Louis University Hospital from June 2012 to July 2013 and measured the ureteral course at several anatomically fixed points. DISCUSSION: 93% (50/54) of ureters deviated by less than 1cm from the psoas muscle in their mid-course (at the level of the L4 vertebra). Reasons for anterior deviation of the ureter in this study included morbid obesity with prominent retroperitoneal fat, congenital renal abnormality, and post-traumatic renal/retroperitoneal hematoma. We determined that the optimal level on abdominal CT to detect the displaced ureter was the mid-body of the L4 vertebra. CONCLUSION: Anterior deviation of the ureter in its mid-course appears to predict inguinoscrotal herniation of the ureter. This finding is a sensitive predictor and should raise concern for this anomaly in the appropriate clinical setting. It is not entirely specific as morbid obesity and congenital anomalies may result in a similar imaging appearance. We believe that this association has not been reported previously. Awareness of this anomaly can have significant operative implications.

Geographic variation in the conduct of patient surveillance after lung cancer surgery.

PURPOSE: Considerable variation among surgeons exists in the current practice of patient surveillance after lung cancer treatment. We evaluated whether geographic factors are responsible for this observed variation. METHODS: Profiles of hypothetical patients suitable for postoperative surveillance and a detailed questionnaire based on the profiles were mailed to the 3,700 members of the Society of Thoracic Surgery (STS). The influence of the geographic location of the respondents on practice patterns was assessed among eight large metropolitan statistical areas (MSAs) with sufficient numbers of respondents, among nine broad geographic areas (United States census regions), and by the population size of the MSA from which the respondents reported. RESULTS: There were 2,009 responses (54% return rate); 768 of those respondents both operate on and provide long-term follow-up care for lung cancer patients. There were sizeable effects of tumor-node-metastasis (TNM) stage and year postsurgery on practice patterns. Respondents from the Los Angeles/Long Beach MSA consistently had the highest frequency of follow-up test usage and those from the Tampa/St Petersburg MSA usually had the lowest. This held true for most testing modalities and was consistent across TNM stages I to III and years 1 to 5 postsurgery. Follow-up strategy was generally most intensive in the largest MSAs (population size, 2.5 to 10 million). The STS respondents from the Pacific US census region generally used the most intensive follow-up strategies and those from the East North Central and Mountain regions often used the least intensive. The differences disclosed in all three analyses were small. CONCLUSION: There is marked variation among STS members in surveillance strategy, and the determinants of testing intensity are complex and interrelated. TNM stage and year postsurgery clearly affect follow-up practice; this analysis provides the first evidence that geographic setting has rather little effect on the surveillance strategies of clinicians.

Geographic variation in patient surveillance after colon cancer surgery.

PURPOSE: Considerable variation among surgeons exists in the current practice of patient surveillance after colon cancer treatment. We evaluated whether geographic factors are responsible for this observed variation. METHODS: Profiles of hypothetical patients and a detailed questionnaire based on the profiles were mailed to 2,733 members of two national surgical societies. The influence of the geographic location of the respondents on practice patterns were assessed in two ways. Repeated-measures analysis of variance was used to compare the practice patterns among 19 large metropolitan statistical areas (MSAs) and chi 2 analysis was used to determine whether these patterns differed by MSA population size. RESULTS: Seven of nine commonly used surveillance modalities were ordered significantly more frequently with increasing tumor-node-metastasis (TNM) stage and significantly less frequently with year postsurgery among the 995 respondents with assessable responses, but MSA population size and geographic location of physicians generally had no effect on documented practice variability. The remaining two modalities (bone scan and computed tomography [CT]) were used so infrequently as to preclude meaningful analysis. CONCLUSION: Surveillance after potentially curative colon cancer surgery for otherwise healthy patients is not significantly affected by the geographic location of the surgeon who performs the surveillance testing and only modestly affected by the population size of the MSA in which he/she practices. These data should help in the design of prospective trials of this topic.

Young maternal age and parity. Influences on pregnancy outcome.

The influence of very young maternal age and parity on pregnancy outcome was examined in a cohort of nearly 900 adolescents and mature women from Camden, New Jersey. Young primigravid primiparas (aged 12 to 15 years) were compared with mature primigravid primiparas (18 to 29 years). Young multiparas (19 years or younger, with a first pregnancy at the age of 12 to 15 years) were compared with mature, multiparas (19 to 29 years old, with a first pregnancy at 18 years or older). After controlling for confounding factors, young primiparas were found to have a modest increase in preterm delivery, which was not statistically significant. However, low gynecologic age contributed disproportionately to the risk of preterm delivery in this group, with risk decreasing with each year from menarche (Cox's proportional hazard, 0.80; 95% confidence interval [CI], 0.68 to 0.94). Among multiparas, there were several statistical interactions associated with increased risk of small-for-gestational-age infants, including interactions between young age and low pre-pregnancy body mass (adjusted odds ratio [AOR], 5.74; 95% CI, 2.18 to 15.08), young age and a prior low-birth-weight infant (AOR, 10.58; 95% CI, 3.89 to 28.77), and young age and a prior preterm delivery (AOR, 5.52; 95% CI, 2.04 to 14.98). Thus, while chronologic age per se may not be a good predictor of pregnancy outcome, adolescents remain a high-risk group because of factors that are more common among them (e.g., biologic immaturity, inadequate prenatal care, poverty, minority status, low prepregnancy weight) and because factors associated with an early adolescent pregnancy, such as low gynecologic age, may continue to influence the outcome of subsequent pregnancies.

PIP: The authors explored the influence of young maternal age and parity upon pregnancy outcome in a cohort of almost 887 adolescents and mature women from Camden, New Jersey. Primigravid primiparas aged 12-15 years were compared with mature primigravid primiparas aged 18-29 years. Multiparas aged 19 years and younger were compared with multiparas aged 19-29. The young multiparas had their first pregnancy at age 12-15 years, while the older multiparas had their first pregnancy at age 18 years or older. After controlling for confounding factors, the younger primiparas were found to have a modest, statistically insignificant increase in preterm delivery. Low gynecologic age, however, contributed disproportionately to the risk of preterm delivery in the group, with risk decreasing with each year from menarche. Statistical interactions associated with increased risk among multiparas of small-for-gestational-age infants included interactions between young age and low pre-pregnancy body mass, young age and a prior low-birth-weight infant, and young age and a prior preterm delivery. Although chronologic age may not be a good predictor of pregnancy outcome, adolescents remain a high-risk group due to factors which are more common among them such as biologic immaturity, inadequate prenatal care, poverty, minority status, and low prepregnancy weight, and because factors associated with an early adolescent pregnancy, such as low gynecologic age, may continue to influence the outcome of subsequent pregnancies.

Mechanical deformation induces proliferation of human colorectal carcinoma cells.

The cell biology of intravascular tumor cells is clinically important but the many important variables of this environment have proved difficult to model. We studied the effects of repetitive mechanical deformation, a phenomenon affecting all intravascular cells, on human colon cancer cell line HCT 116 in vitro. Cell proliferation, assessed by [3H]-thymidine incorporation and cell count, increased by about 30% at two days in cells subjected to deformation at 30 cycles/min as compared to controls; levels of the nuclear proliferation antigen detected by monoclonal antibody MIB-1 were also increased. Deformation increased transforming growth factor beta1 (TGF-beta1) and plasminogen activator inhibitor-1 gene expression sevenfold at two days, but mannose-6-phosphate did not affect cell proliferation, indicating that endogenous TGF-beta is not involved in the proliferative response. HCT 116 cells lack TGF-beta type II receptors, but stable transfection of TGF-beta type II receptor cDNA did not alter the cellular response to mechanical deformation, as assessed by cell proliferation, morphology, or gene expression. Mechanical deformation affects several important aspects of HCT 116 cell biology, suggesting that the intravascular environment may regulate tumor cell biology in general. Endogenous TGF-beta and TGF-beta receptor-mediated signaling are not responsible for the deformation-induced proliferative response in HCT 116.

Adrenalectomy for isolated adrenal metastases from non-adrenal cancer.

Adrenalectomy for metastatic cancer is rarely performed. The survival benefit for patients undergoing resection of isolated adrenal metastases is not clear. The goal of this study was to compile a series of such cases from national and international sources and examine patient survival. The patient series was derived from published series and case reports, plus eight new cases from an international registry of patients. We found 77 patients. We examined the effect of primary tumor site, metastasis size, and disease-free interval on postoperative survival duration, including only cases where complete resection with negative margins was achieved. We compared these patients with a large series from Memorial Sloan-Kettering Cancer Center (N=37). The median survival time after adrenalectomy was 23 months, with an operative mortality rate of 3.9%. There was a significant difference in survival duration depending on primary tumor site. A longer disease-free interval from time of primary cancer therapy to adrenal metastasis was associated with a longer postoperative survival after adrenalectomy. Metastasis size did not affect survival. Survival times for USA and non-USA patients were similar. Survival duration of the 77 analytical patients was similar to that of the 37 non-analytical patients from Memorial Sloan-Kettering Cancer Center. Selected patients, particularly those with long disease-free intervals and favorable tumor biology, should be offered resection for isolated adrenal metastases.

Quality of life measurements do not support palliative pancreatic cancer treatments.

Although resection for pancreatic cancer is occasionally curative, its major value lies in restoring patients to a more normal life. The objective of this study was to evaluate the functional quality of life (QoL) of patients undergoing various treatments for pancreatic cancer using a nationwide, multi-institutional, non-referral patient population. From 822 pancreatic cancer patients treated from 1989 to 1995, and listed in the Department of Defense (DoD) hospital central computerized tumor registry, we selected 781 with evaluable survival information. Local tumor registrars had contacted patients at least yearly and prospectively compiled a QoL index using a self-reported Karnofsky performance status (KPS); values were obtained for patients alive in March of 1995 and/or 1996. Survival duration and KPS scores were then compared by stage and treatment using analysis of variance (F-test). Resection significantly increased KPS and mean survival time with stage I-II cancers and improved mean survival time, but not KPS, in patients with node positive (stage III) disease. The projected five-year survival rate after resection in stages I-II was 24% but zero for stage III. Patients receiving combined chemo- and radiation therapies, whether given as adjuvant or primary treatment, had significantly longer mean survival duration. However, KPS scores were not higher in treated patients. These data indicate that patients live longer and better lives after resection of localized pancreatic cancers, but QoL measurements do not support resection for pancreatic cancer involving lymph nodes. Unresected patients selected for combined chemo- and radiation therapy live longer, but not better, lives.

Effect of initial tumor stage on patient follow-up after potentially curative surgery for cutaneous melanoma.

The optimal follow-up strategy after completion of therapy for melanoma is not known. We evaluated the effect of TNM stage on the self-reported surveillance strategies employed by practicing plastic surgeons caring for otherwise healthy patients subjected to potentially curative treatment for cutaneous melanoma. Hypothetical patient profiles and a detailed questionnaire based on these profiles were mailed to a random sample (N=3,032) of the 4,320 members of the American Society of Plastic and Reconstructive Surgeons. The effect of TNM stage on the surveillance strategies chosen was analyzed by repeated-measures ANOVA. There were 1,142 responses to the 3,032 surveys; 395 were evaluable. Plastic surgeons often do not provide postoperative follow-up themselves; this was the most frequent reason for non-evaluability. Surveillance of patients after resection of melanoma relies most heavily on office visits, chest X-ray, CBC, and liver function tests. All other surveillance modalities are used infrequently. Most respondents modify their surveillance practices slightly according to the patient's initial TNM stage. Most commonly used modalities are employed significantly more frequently with increasing TNM stage. This effect persists through ten years of follow-up, but the differences across stages are tiny. We conclude that most plastic surgeons performing surveillance after potentially curative surgery in otherwise healthy patients with melanoma use similar follow-up strategies for patients of all TNM stages. These data permit the rational design of a controlled clinical trial of high-intensity vs. low-intensity follow-up.

How tumor stage affects american urologists' surveillance strategies after prostate cancer surgery.

The factors which influence decision-making among urologists are not well understood. We evaluated how tumor stage in patients subjected to potentially curative surgery for carcinoma of the prostate affects the self-reported follow-up strategies employed by practicing United States urologists. Standardized patient profiles and a detailed questionnaire based on these profiles were mailed to 4,467 randomly selected members of the American Urological Association (AUA), comprising 3,205 US and 1,262 non-US urologists. The effect of TNM stage on the surveillance strategies chosen by respondents was analyzed by repeated-measures ANOVA. There were 1, 050 respondents who provided evaluable data of whom 760 were from the US. The three most commonly used surveillance modalities by urologists were office visit, serum PSA level, and urinalysis. Nine of the 11 most commonly requested modalities were ordered significantly (p<0.001) more frequently with increasing TNM stage. This effect persisted through 10 years of follow-up, but the differences across stage were tiny. Fifty-five percent of US respondents do not modify their strategies at all according to the patient's TNM stage. Most American AUA members performing surveillance after potentially curative radical prostatectomy for otherwise healthy patients use the same follow-up strategies irrespective of TNM stage. These data permit the rational design of a randomized clinical trial of two alternate follow-up plans. The two trial arms would employ office visits, blood tests, and urinalyses at different frequencies based on current actual practice patterns; there would be no imaging tests in either arm.

A phase II evaluation of pentoxifylline combined with radiation in the treatment of brain metastases.

Pentoxifylline (PTX) has pharmacological properties that suggest potential utility as a radiation sensitizer, and preclinical animal studies have been promising. In a non-randomized phase II trial, we used PTX plus standard-dose external-beam whole-brain radiation treatment (WBRT) in patients with brain metastases. Seventeen patients were entered; 14 received both WBRT and PTX and were considered evaluable. Nine of the 14 completed treatment. Analyzing data on all 14 evaluable patients according to intent to treat, median survival time was 33 days, comparable to published data from historical controls. PTX toxicity was not a common cause of patient dropout, supporting higher PTX doses in future trials.

How surgeon age affects post-treatment surveillance strategies for melanoma patients.

The intensity of post-treatment melanoma patient follow-up varies widely among physicians. We investigated whether physician age accounts for the observed variation in surveillance intensity among plastic surgeons. A custom-designed questionnaire was mailed to USA and non-USA surgeons, all of whom were members of the American Society of Plastic and Reconstructive Surgeons. Subjects were asked how they use 14 specific follow-up modalities during years 1-5 and 10 following primary treatment for patients with cutaneous melanoma. Repeated-measures analysis of variance was used to compare practice patterns by TNM stage, year post-surgery, and age. Of the 3,032 questionnaires mailed, 1,142 (38%) were returned. Of those returned, 395 (35%) were evaluable. Non-evaluability was usually due to lack of melanoma patient follow-up in surgeons' practices. Follow-up strategies for most of the 14 modalities were highly correlated across TNM stages and years post-surgery, as expected. The pattern of testing varied significantly by surgeon age for 3 modalities (complete blood count, liver function tests, and chest X-ray), but the variation was quite small. We concluded that the post-treatment surveillance practice patterns of ASPRS members caring for patients with cutaneous melanoma vary only marginally with physician age. Continuing medical education could account for this observation.

Tension pneumothorax complicating small-caliber chest tube insertion.

We report two patients who developed tension pneumothorax as a result of improper attachment of a Heimlich valve to a chest tube.

How tumor stage affects surgeons' surveillance strategies after lung cancer surgery.

The factors that influence decision making among surgeons are not well understood. We evaluated how tumor stage in patients subjected to potentially curative surgery for lung cancer affects the self-reported follow-up strategies employed by practicing surgeons. Hypothetical patient profiles and a detailed questionnaire based on these profiles were mailed to the 3,700 members of the Society of Thoracic Surgeons. The effect of TNM stage on the surveillance strategies chosen by the respondents was analyzed. All of the ten most commonly employed surveillance modalities were ordered significantly more frequently with increasing TNM stage, although the differences are small. Only 23% of respondents modified their strategies according to the patient's TNM stage. This effect persisted through 5 years of follow-up. We conclude that most surgeons performing surveillance after potentially curative surgery for otherwise healthy patients with lung cancer use the same follow-up strategy irrespective of TNM stage. These data should help in the design of prospective trials of this topic.

Lung cancer patient follow-up: motivation of thoracic surgeons.

STUDY OBJECTIVES: To analyze variation in beliefs that potentially motivate thoracic surgeons in the design of posttreatment surveillance strategies for lung cancer patients and to examine the relationship between motivation and follow-up intensity. DESIGN: International survey. SETTING: Ambulatory care. PARTICIPANTS: All 3,700 members of the Society of Thoracic Surgeons were surveyed to measure their follow-up practices during the 5-year period after treatment, physician beliefs, and variation in these beliefs. The relationship between beliefs, as potentially motivating factors, and follow-up intensity was also analyzed. MEASUREMENTS AND RESULTS: Age, General Thoracic Surgery Club membership, percentage of practice that was noncardiac, South Central United States practice location, and overseas practice location were most frequently related to beliefs that potentially motivate physicians in the design of surveillance strategies. When viewed independently of follow-up practice patterns, thoracic surgeons appear to be motivated by the desire to please patients, avoid malpractice suits, and improve patient quality of life. When viewed in relation to self-reported follow-up, none of these motivating factors were consistently associated with follow-up intensity. Belief in curative treatment of recurrence and enhanced likelihood of immediate palliative treatment leading to improved survival were the factors most frequently associated with variation in follow-up. Although the ability of the logistic and stepwise regression models to predict test use and follow-up intensity was less than optimal for TNM stage I patients, predictive ability was substantially improved for TNM stage II and III patients by including earlier-stage practice patterns as an independent variable. CONCLUSIONS: Physician characteristics and beliefs predicted a less than expected amount of the variation in self-reported follow-up intensity by TNM stage when modelled without knowledge of follow-up practice for any other TNM stage. Discrepancies between self-reported and actual follow-up may be partially responsible, although lack of surveillance guidelines is more likely. The inclusion of barriers to follow-up may improve future models.

Preoperative chemotherapy and radiotherapy for esophageal carcinoma.

From October 1986 to January 1991, 47 patients with esophageal cancer (29 squamous, 18 adenocarcinoma) were treated with simultaneous radiotherapy (3000 or 3600 cGy) and chemotherapy (infusional 5-fluorouracil, cisplatin) delivered during a 5-week period. This treatment was well tolerated; 44 patients (94%) completed a full course of therapy, 40 (85%) had relief from dysphagia, and 21 (45%) noted either weight gain or no net weight loss. One patient (2%) died of complications (tracheoesophageal fistula, perforated ulcer) during chemotherapy and radiotherapy. The remaining 46 patients were referred for operation. Six refused because of excellent relief of their dysphagia, and one was denied operation. Thirty-nine patients went to operation, and 34 (83%) had lesions that were resectable. Eight of the 39 surgically treated patients (21%) had no evidence of residual tumor identified in the resected specimens. One of these complete responders died 7 weeks postoperatively after multiple complications (3% operative mortality rate). Three of the remaining seven have also died since the operation, one of recurrent cancer and two with no known recurrent disease. Actuarial survival in this present series was significantly better than that of our 1980 to 1985 historical control patients (p less than 0.005). There was no difference between patients with squamous carcinoma and those with adenocarcinoma with regard to the prevalence of complete response or long-term survival. Survival of the seven patients who did not undergo operation was comparable with that of the 34 patients in whom esophagectomy was performed. This study suggests that combined preoperative chemotherapy plus radiotherapy for esophageal cancer is well tolerated, provides excellent palliation of symptoms, allows for a high rate of resectability, is equally effective for squamous carcinoma and adenocarcinoma, and provides encouraging early results with regard to long-term survival. The data also call into question the role of esophagectomy, particularly in patients who have a complete response to preoperative therapy.

Cost of patient follow-up after potentially curative lung cancer treatment.

The two objectives of this study were to determine the range of recommended follow-up strategies for patients with lung cancer treated with curative intent and to estimate the cost of such follow-up. Ten articles delineating eight specific follow-up strategies were identified from a Medline search of the literature for 1980 through 1995. An economic analysis was done of the costs associated with the identified strategies. Charge data obtained from the Part B Medicare Annual Data file and the Hospital Outpatient Bill file were used as a proxy for cost. Follow-up intensity varied widely across strategies for 5 years of posttreatment follow-up. Medicare-allowed charges for 5-year follow-up ranged from a low of $946 to a high of $5645. When Medicare-allowed charges were converted to a proxy for actual charges by a conversion ratio of 1.62, the range was $1533 to $9145, a fivefold difference in charges. There was no indication that more intensive, higher-cost strategies increased survival or quality of life. The published literature, including textbooks, holds few answers in this area.

A technique for transrectal drainage of pelvic abscess.

Pelvic collections of pus may be drained transrectally in some cases. When this is done, satisfactory fixation of drains within the cavity is often difficult and frequently uncomfortable for the patient. Creation of a rectal counterincision permits a loop-shaped drain to be used. This provides good drainage, enhances patient comfort, and can be removed easily.