External compression dressing versus standard dressing after axillary lymphadenectomy.

BACKGROUND: Closed-catheter drainage after axillary lymph node dissection (ALND) for breast cancer may constitute a significant inconvenience to the recovering patient, and may also serve as portals of entry for bacteria. Any intervention that could reduce the volume and duration of postoperative drainage would be beneficial. The purpose of this study was to determine whether an external compression dressing after ALND would decrease postoperative drainage, afford earlier drain removal, and reduce subsequent seroma formation. PATIENTS AND METHODS: One hundred thirty-five women undergoing definitive surgical treatment for breast cancer were randomized to receive a compression dressing (n = 66) or standard dressing (n = 69). They were also stratified for modified radical mastectomy (MRM; n = 74) or breast conservation therapy (BCT; n = 61). All patients had ALND. The compression dressing consisted of a circumferential chest wrap of two 6-inch Ace bandages, held in place by circumferential Elastoplast bandage, and it was applied by the same nurse. This dressing remained intact until postoperative day 4. Patients in the standard dressing group (control) were fitted with a front-fastening Surgibra only. Drains were removed when the total daily amount was <50 cc. Postoperative drainage volume, total days with drain, and frequency of seroma formation were recorded for each patient. RESULTS: After 4 days, wound drainage in both groups was nearly identical (compression = 490 cc, standard = 517 cc; P = 0.48). Total days with drain were also similar (compression = 6.4 days, standard = 6.1 days; P = 0.69). The compression dressing did not reduce seroma formation. In fact, there was a statistically significant increase in the number of seroma aspirations per patient in the compression group (compression = 2.9, standard = 1.8; P <0.01). The increase in seroma aspirations was more significant in MRM patients (compression = 3.1, standard = 1.7; P <0.01) than in BCT patients (compression = 2.6, standard = 1.8; P = 0.20). CONCLUSIONS: External compression dressing fails to decrease postoperative drainage and may increase the incidence of seroma formation after drain removal. Thus, routine use of a compression dressing to reduce postoperative drainage after ALND for breast cancer is not warranted.

Insulin-like growth factor-II participates in the biphasic effect of a gonadotropin-releasing hormone agonist on ovarian cancer cell growth.

OBJECTIVE: To examine the involvement of insulin-like growth factors (IGFs) in growth regulation of an ovarian cancer cell line and to investigate whether the GnRH agonist tryptorelin might influence a potential autocrine or paracrine loop involving IGFs. DESIGN: In vitro, prospective, randomized controlled study. SETTING: In vitro experiments at the Section of Gynecologic Oncology, Surgery Branch, National Cancer Institute. PATIENT(S): None. Human ovarian adenocarcinoma cell line IGROV-1. INTERVENTION(S): The proliferative effect of tryptorelin on IGROV-1 cells was analyzed by using the MTT (93-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide) colorimetric assay. The ribonuclease protection assay was used to investigate whether an autocrine pathway involving IGF-I or IGF-II might participate in the growth of these cells. The expression of GnRH receptor was assessed by the 125I-GnRH binding assay. MAIN OUTCOME MEASURE(S): Changes in cell growth and expression of IGF-I and IGF-II messenger RNA (mRNA). RESULT(S): Tryptorelin exhibited a bimodal, dose- and time-dependent effect on IGROV-1 cells when compared with untreated control cells: Cellular proliferation was enhanced during the first 24 hours of exposure, but longer incubations resulted in growth inhibition. The mitogenic effect of tryptorelin was inhibited when cells were co-incubated with either IGF binding protein-5 (IGFBP-5) or anti-IGF-II antibody, which can both bind to IGF-II and neutralize it. Insulin-like growth factor-I mRNA was not detected in IGROV-1 cells. However, IGF-II transcripts were detected after incubation with tryptorelin for 12 hours, but thereafter, no mRNA was observed, even after prolonged exposure. Binding analysis revealed a specific, high-affinity GnRH binding site. CONCLUSION(S): These data suggest that tryptorelin exerts a bimodal growth effect on ovarian cancer cells by a mechanism involving the autocrine production of IGF-II. The effect of tryptorelin on IGF-II gene transcription in these ovarian cancer cells appears to mirror the desensitizing effects of prolonged GnRH exposure on pituitary gonadotropin production.

Implementing national standards for cancer pain management: program model and evaluation.

The purpose of this quasi-experimental (pre and posttest) study was to test a model pain management program (PMP) to implement the American Pain Society (APS) quality assurance standards for the management of acute and chronic cancer pain using a continuous quality improvement (CQI) approach to improve professionals' knowledge and skills, patient satisfaction, and to identify areas needing improvement. The sample consisted of 1210 nurse responses and 698 interviews of patients with pain during hospitalization at a major urban cancer center. The PMP provided a structure (standards), educational opportunities, and training in CQI methods. Outcome measures included a patient evaluation questionnaire and concerns checklist; nurse knowledge, attitude and barriers questionnaire; and focus groups to identify areas needing improvement. Significant improvements were found in patients' satisfaction, nurses' knowledge and attitude scores, and reductions in nurses' perceptions of barriers. Focus groups revealed the need for improved communication among disciplines about pain and better assessment of patients unable to self-report. The program met its goal of implementing the APS standards, educating nurses, and identifying "system" problems, and improving overall patient satisfaction.

CT bone window photography in patients with cancer.

PURPOSE: To assess the utility of routinely photographing computed tomographic (CT) bone windows in patients with cancer. MATERIALS AND METHODS: The impression section of body CT reports were reviewed in 4,683 patients with cancer (2,240 female and 2,443 male patients, aged 2 months to 97 years [mean, 55 years]). RESULTS: The presence of definite or possible bone metastasis was mentioned in 523 (11.2%) patients. No prior radiologic examination was available in 165 patients. In the 358 patients who had undergone previous radiologic examinations, findings were positive in 271 and normal or indeterminate in 87. In 252 (5.4%) patients, CT with bone windows may have been needed for diagnosis of bone metastasis: 110 had extensive nonosseous metastases, 77 had no osseous metastasis, 19 had bone findings that were not followed up radiologically, and 46 had bone lesions that were new findings. These new lesions were visible on scans photographed at soft-tissue windows in 45 (97.8%) patients. CONCLUSION: Routine photography of CT bone windows is not necessary in patients with cancer.

Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup.

BACKGROUND: The current practice of removing adenomatous polyps of the colon and rectum is based on the belief that this will prevent colorectal cancer. To address the hypothesis that colonoscopic polypectomy reduces the incidence of colorectal cancer, we analyzed the results of the National Polyp Study with reference to other published results. METHODS: The study cohort consisted of 1418 patients who had a complete colonoscopy during which one or more adenomas of the colon or rectum were removed. The patients subsequently underwent periodic colonoscopy during an average follow-up of 5.9 years, and the incidence of colorectal cancer was ascertained. The incidence rate of colorectal cancer was compared with that in three reference groups, including two cohorts in which colonic polyps were not removed and one general-population registry, after adjustment for sex, age, and polyp size. RESULTS: Ninety-seven percent of the patients were followed clinically for a total of 8401 person-years, and 80 percent returned for one or more of their scheduled colonoscopies. Five asymptomatic early-stage colorectal cancers (malignant polyps) were detected by colonoscopy (three at three years, one at six years, and one at seven years). No symptomatic cancers were detected. The numbers of colorectal cancers expected on the basis of the rates in the three reference groups were 48.3, 43.4, and 20.7, for reductions in the incidence of colorectal cancer of 90, 88, and 76 percent, respectively (P < 0.001). CONCLUSIONS: Colonoscopic polypectomy resulted in a lower-than-expected incidence of colorectal cancer. These results support the view that colorectal adenomas progress to adenocarcinomas, as well as the current practice of searching for and removing adenomatous polyps to prevent colorectal cancer.

VMA13 encodes a 54-kDa vacuolar H(+)-ATPase subunit required for activity but not assembly of the enzyme complex in Saccharomyces cerevisiae.

Previous purifications and characterizations of the Saccharomyces cerevisiae vacuolar proton-translocating ATPase (V-ATPase) have indicated that this enzyme is a multisubunit complex composed of at least eight subunits of 100-, 69-, 60-, 42-, 36-, 32-, 27-, and 17-kDa (Kane, P. M., Yamashiro, C. T., and Stevens, T. H. (1989) J. Biol. Chem. 264, 19236-19244). We report the cloning and characterization of an additional V-ATPase subunit, the 54-kDa subunit, which is encoded by the VMA13 gene. VMA13 was isolated by complementation of the growth phenotypes associated with the vma13 mutation, which was originally described as cls11 (Ohya, Y., Umemoto, N., Tanida, I., Ohta, A., Iida, H., and Anraku, Y. (1991) J. Biol. Chem. 266, 13971-13977). The nucleotide sequence of the VMA13 gene predicted a hydrophilic polypeptide with a calculated molecular mass of 54,415 daltons. The VMA13 54-kDa gene product resides on the vacuolar membrane and co-purified with the active V-ATPase complex. Characterization of a null vma13 mutant (delta vma13) revealed that the Vma13 polypeptide is essential for V-ATPase activity. However, the Vma13 polypeptide is not required for targeting of the other V-ATPase subunits (100-, 69-, 60-, 42-, 27-, or 17-kDa subunits) to the vacuolar membrane as shown by the association of these subunits with vacuolar membranes isolated from delta vma13 cells. The nature of the V-ATPase "complex" in delta vma13 mutant is, nevertheless, fundamentally different from the wild-type enzyme. This is evidenced by the fact that the inactive V-ATPase complex from delta vma13 cells is less stable than the wild-type enzyme. Taken together, these results indicate that VMA13 encodes the 54-kDa subunit of the V-ATPase and that this subunit is essential for activity, but not assembly, of the enzyme complex.

The Saccharomyces cerevisiae VMA6 gene encodes the 36-kDa subunit of the vacuolar H(+)-ATPase membrane sector.

The yeast vacuolar membrane proton-translocating ATPase (V-ATPase) is a multisubunit complex comprised of peripheral catalytic, and integral membrane domains. At least eight proteins cofractionate with purified preparations of the enzyme including 100-, 69-, 60-, 42-, 36-, 32-, 27-, and 17-kDa polypeptides (Kane, P.M., Yamashiro, C.T., and Stevens, T.H. (1989a) J. Biol. Chem. 264, 19236-19244). We took a reverse genetic approach to clone the structural gene for the 36-kDa subunit of the V-ATPase, VMA6, vma6 null mutants displayed growth characteristics typical of other vma mutants including sensitivity to media buffered at neutral pH or media containing 100 mM Ca2+. Vacuolar acidification was defective in vma6 cells and isolated vacuolar membrane preparations contained no detectable V-ATPase activity. The VMA6 gene encodes a hydrophilic polypeptide of 345 amino acids (predicted molecular mass 39.8-kDa). We present evidence that the VMA6 gene product (Vma6p) is a non-integral membrane component of the membrane pore domain and is required for V-ATPase complex assembly. Vma6p was removed from wild type vacuolar membranes by strong chaotropic agents such as alkaline Na2CO3 or 5M urea, which did not remove integral membrane polypeptides. In yeast cells lacking the integral membrane portion of the V-ATPase complex, Vma6p was unable to stably associate with vacuolar membranes. Conversely, in mutants specifically lacking Vma6p, components of the V-ATPase integral membrane domain were destabilized, and peripheral subunits failed to assemble onto vacuolar membranes. These results are discussed in the context of a developing model for V-ATPase assembly in yeast.

Randomized comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps. The National Polyp Study Workgroup.

BACKGROUND: The identification and removal of adenomatous polyps and post-polypectomy surveillance are considered to be important for the control of colorectal cancer. In current practice, the intervals between colonoscopies after polypectomy are variable, often a year long, and not based on data from randomized clinical trials. We sought to determine whether follow-up colonoscopy at three years would detect important colonic lesions as well as follow-up colonoscopy at both one and three years. METHODS: Patients were eligible if they had one or more adenomas, no previous polypectomy, and a complete colonoscopy and all their polyps had been removed. They were randomly assigned to have follow-up colonoscopy at one and three years or at three years only. The two study end points were the detection of any adenoma, and the detection of adenomas with advanced pathological features (defined as those > 1 cm in diameter and those with high-grade dysplasia or invasive cancer). RESULTS: Of 2632 eligible patients, 1418 were randomly assigned to the two follow-up groups, 699 to the two-examination group and 719 to the one-examination group. The percentage of patients with adenomas in the group examined at one and three years was 41.7 percent, as compared with 32.0 percent in the group examined at three years (P = 0.006). The percentage of patients with adenomas with advanced pathological features was the same in both groups (3.3 percent). CONCLUSIONS: Colonoscopy performed three years after colonoscopic removal of adenomatous polyps detects important colonic lesions as effectively as follow-up colonoscopy after both one and three years. An interval of at least three years is recommended before follow-up colonoscopy after both one and three years. An interval of at least three years is recommended before follow-up examination after colonoscopic removal of newly diagnosed adenomatous polyps. Adoption of this recommendation nationally should reduce the cost of post-polypectomy surveillance and screening.

VMA12 is essential for assembly of the vacuolar H(+)-ATPase subunits onto the vacuolar membrane in Saccharomyces cerevisiae.

vma12 mutants of the yeast Saccharomyces cerevisiae, which were originally identified as calcium-sensitive (cls) mutants that were also respiratory deficient (Pet-), have a defect in vacuolar membrane H(+)-ATPase activity (Ohya, Y., Umemoto, N., Tanida, I., Ohta, A., Iida, H., and Anraku, Y. (1991) J. Biol. Chem. 266, 13971-13977). The VMA12 gene was cloned by complementation of the growth defects of vma12 mutants. The nucleotide sequence of the gene predicts a polypeptide of 215 amino acids (25.2 kDa) with two putative membrane-spanning domains. A null vma12 mutant, constructed by chromosomal deletion of the gene, is viable but has completely lost the vacuolar membrane H(+)-ATPase activity and exhibits the same growth defects as observed for the original vma12 mutants. Synthesis and targeting of the subunits of the H(+)-ATPase in the delta vma12 mutant cells were examined by Western blotting analyses of whole cell and vacuolar membrane protein extracts. None of the peripheral membrane subunits that we analyzed (the 69-, 60-, 42-, and 27-kDa subunits) was detected in the vacuolar membrane fractions, although the cellular levels of these polypeptides appeared to be normal. The 100- and 17-kDa integral membrane subunits of the enzyme were absent or present at a substantially reduced level in mutant vacuolar membrane fractions. Anti-Vma12p antibodies recognized a vacuolar protein with the expected molecular mass of 25 kDa. However, the Vma12 protein was not detected in the vacuolar membrane ATPase complex that had been solubilized with a zwitterionic detergent, ZW3-14, and purified by glycerol gradient centrifugation (Kane, P. M., Yamashiro, C. T., and Stevens, T. H. (1989) J. Biol. Chem. 264, 19236-19244). These results indicate that the VMA12 gene product is not a component of the active vacuolar ATPase complex and instead suggest that this protein is required during the process of assembly and/or targeting of the enzyme complex to the vacuolar membrane.

Isolation of vacuolar membrane H(+)-ATPase-deficient yeast mutants; the VMA5 and VMA4 genes are essential for assembly and activity of the vacuolar H(+)-ATPase.

The vacuolar membrane H(+)-ATPase of the yeast Saccharomyces cerevisiae is a multisubunit enzyme complex composed of an integral membrane V0 sector, and a peripherally associated V1 sector. Deletion of one of several structural genes for vacuolar H(+)-ATPase subunits was previously demonstrated to prevent proper assembly of the remaining V1 subunits onto the vacuolar membrane (Kane, P.M., Kuehn, M.C., Howald-Stevenson, I., and Stevens, T.H. (1992) J. Biol. Chem. 267, 447-454). A genetic screen was designed to identify new genes whose products were essential for the synthesis, assembly, and/or function of the yeast vacuolar H(+)-ATPase. Mutants were identified based on phenotypes associated with vacuolar membrane H(+)-ATPase loss of function (vma), including an inability to grow on media buffered at neutral pH. Representatives in five complementation groups were identified, including four novel mutant vma5, vma21, vma22, and vma23, all of which were defective in vacuolar ATPase enzyme activity. We report here the characterization of two genes, VMA4 and VMA5, that encode peripheral subunits of the vacuolar H(+)-ATPase. We determined that VMA5 encodes the 42-kDa subunit of the vacuolar H(+)-ATPase. The VMA4 gene, originally described by Foury (Foury, F. (1990) J. Biol. Chem. 265, 18554-18560), was determined to encode the 27-kDa subunit of the purified yeast vacuolar H(+)-ATPase. Characterization of the vma5 and vma4 mutants revealed that the 42- and 27-kDa subunits are essential for the assembly of the peripheral membrane portion of the H(+)-ATPase onto the vacuolar membrane.