Evaluation of the SCA instrument for measuring patient satisfaction with cancer care administered via paper or via the Internet.

BACKGROUND: Patients' perspectives provide valuable information on quality of care. This study evaluates the feasibility and validity of Internet administration of Service Satisfaction Scale for Cancer Care (SCA) to assess patient satisfaction with outcome, practitioner manner/skill, information, and waiting/access. PATIENTS AND METHODS: Primary data collected from November 2007 to April 2008. Patients receiving cancer care within 1 year were recruited from oncology, surgery, and radiation clinics at a tertiary care hospital. An Internet-based version of the 16-item SCA was developed. Participants were randomised to Internet SCA followed by paper SCA 2 weeks later or vice versa. Seven-point Likert scale responses were converted to a 0-100 scale (minimum-maximum satisfaction). Response distribution, Cronbach's alpha, and test-retest correlations were calculated. RESULTS: Among 122 consenting participants, 78 responded to initial SCA. Mean satisfaction scores for paper/Internet were 91/90 (outcome), 95/94 (practitioner manner/skill), 89/90 (information), and 86/86 (waiting/access). Response rate and item missingness were similar for Internet and paper. Except for practitioner manner/skill, test-retest correlations were robust r = 0.77 (outcome), 0.74 (information), and 0.75 (waiting/access) (all P < 0.001). CONCLUSIONS: Internet SCA administration is a feasible and a valid measurement of cancer care satisfaction for a wide range of cancer diagnoses, treatment modalities, and clinic settings.

Diagnostic accuracy of 99mTc-sestamibi breast imaging: multicenter trial results.

UNLABELLED: Although mammography is well established as a first-line tool for breast cancer screening and detection, efforts to develop complementary procedures continue. Observation of 99mTc-sestamibi tumor uptake provided the impetus for its evaluation as an adjunctive technique. This trial's objectives were to determine in a multicenter trial the diagnostic accuracy of 99mTc-sestamibi in women with suspected breast cancer and to investigate factors influencing diagnostic accuracy. METHODS: Our multicenter trial enrolled 673 women (387 with nonpalpable abnormalities; 286 with palpable abnormalities) scheduled for excisional biopsy or mastectomy. Blinded and unblinded interpretations of scintigraphic images were compared with core laboratory established histopathologic diagnoses to define the diagnostic accuracy of 99mTc-sestamibi breast imaging. RESULTS: Blinded readers' diagnostic accuracy was 78%-81%. Inter-reader agreement was excellent, ranging from 95% to 100% (kappa = 0.82-0.99). Overall institutional sensitivity and specificity for 99mTc-sestamibi breast imaging were 75.4% and 82.7%, respectively. In this population with a 40.1% disease prevalence, the positive predictive value was 74.5% and the negative predictive value was 83.4%. The negative predictive value was 94% in patients with a 40% or lower mammographic likelihood of breast cancer. Sensitivity was higher for palpable abnormalities; specificity was higher for nonpalpable abnormalities. Sensitivity was decreased for tumors <1 cm in largest dimension but appeared not to be affected by patient's age. CONCLUSION: As an adjunct to current procedures, 99mTc-sestamibi breast imaging may contribute to patient management decisions in selected populations, including women with dense breasts, mammographically indeterminate lesions >1 cm, and palpable abnormalities.

Skin-sparing mastectomy and immediate reconstruction: oncologic risks and aesthetic results in patients with early-stage breast cancer.

Skin-sparing mastectomy has been advocated as an oncologically safe approach for the management of patients with early-stage breast cancer that minimizes deformity and improves cosmesis through preservation of the skin envelope of the breast. Because chest wall skin is the most frequent site of local failure after mastectomy, concerns have been raised that inadequate skin excision could result in an increased risk of local recurrence. Precise borders of the skin resection have not been well established, and long-term local recurrence rates after skin-sparing mastectomy are not known. The purpose of this study was to evaluate the oncologic safety and aesthetic results for skin-sparing mastectomy and immediate breast reconstruction with a latissimus dorsi myocutaneous flap and saline breast prosthesis. Fifty-one patients with early-stage breast cancer (26 with ductal carcinoma in situ and 25 with invasive carcinoma) undergoing primary mastectomy and immediate reconstruction with a latissimus flap were studied from 1991 through 1994. For 32 consecutive patients, skin-sparing mastectomy was defined as a 5-mm margin of skin designed around the border of the nipple-areolar complex. After the mastectomy, biopsies were obtained from the remaining native skin flap edges. Patients were followed for 44.8 months. Histologic examination of 114 native skin flap biopsy specimens failed to demonstrate breast ducts in the dermis of any of the 32 consecutive patients studied. One of 26 patients with ductal carcinoma in situ had metastases to the skin of the lateral chest wall and back. Four other patients, one with stage I disease and three with stage II-B disease, had recurrent breast carcinoma. The stage I patient had a local recurrence in the subcutaneous tissues near the mastectomy specimen. Two patients suffered axillary relapse, and one had distant metastases to the spine. The findings of this study support the technique of skin-sparing mastectomy as an oncologically safe one, based on an absence of breast ductal epithelium at the margins of the native skin flaps and a local recurrence rate of 2 percent after 45 months of follow-up. Although these results need to be confirmed with greater numbers of patients and longer follow-up, skin-sparing mastectomy and immediate breast reconstruction may be considered an excellent alternative treatment to breast conservation for patients with ductal carcinoma in situ and early-stage invasive breast cancer.

High resolution CT mammography of surgical biopsy specimens.

PURPOSE: Our goal was to assess the performance of high resolution CT on breast biopsy specimens before considering the reevaluation of refined CT techniques in patients with breast abnormalities. METHOD: High resolution CT was done in 44 surgical biopsy specimens following conventional X-ray specimen mammography. The specimens comprised 38 palpable and nonpalpable soft tissue abnormalities with mean size of 19 mm and 6 specimens with clustered microcalcifications only. There were 21 carcinomas, 10 fibroadenomas, and 13 other benign conditions. Evaluation of CT and conventional images was done separately, and a feature-grading list was used to compare the two modalities. RESULTS: In fatty specimens, grading of morphologic features of masses and the confidence to detect a soft tissue abnormality were equal with both techniques. CT significantly improved the confidence to detect a mass in 17 specimens with dense tissue: On a scale of 0-10, the mean score for detection was 3.8 with radiography and 5.8 with CT (p<0.008). For clustered microcalcifications, X-ray was superior to CT. The mean CT attenuation of 18 malignant masses (82 HU) was significantly lower than the mean attenuation of 10 fibroadenomas (131 HU; p = 0.003). CT scans of the American College of Radiology test phantom met the requirements for X-ray accreditation. CONCLUSION: For soft tissue abnormalities, CT specimen mammography performed equally as or better than specimen radiography. These in vitro results suggest potential advantages for increased sensitivity and specificity with CT and justify further investigations.

Axillary lymph nodes and breast cancer: a review.

BACKGROUND: The value of surgical staging and treatment of the axillary lymph nodes with either surgery or radiotherapy in the initial management of patients with Stage I or II invasive breast cancer is controversial. METHODS: A review of retrospective and prospective clinical studies was performed to assess the risks of axillary lymph node involvement and the effectiveness and morbidity of various treatment options. RESULTS: The risk of axillary lymph node involvement is substantial for most patients, even those with small tumors. The morbidity resulting from a careful Level I/II axillary dissection or moderate-dose axillary radiotherapy is limited. Such treatment is highly effective in preventing axillary recurrence. The symptoms resulting from axillary failure can be controlled in many, but not all, patients. The available data suggest, but do not prove, that the initial use of effective axillary treatment may result in a small improvement in long term outcome in some patient subgroups. CONCLUSIONS: Most patients should be treated with either axillary surgery or irradiation. Highly selected subgroups of patients may have such low risks of involvement that specific axillary treatment is of little value. However, such subgroups have not yet been well defined. Treatment approaches that do not involve specific axillary treatment should be considered investigational at present, and the patients should be informed as to their potential risks. Prospective clinical studies of these issues should be pursued.

Conservative surgery without radiotherapy in the treatment of patients with early-stage invasive breast cancer. A review.

OBJECTIVE: The authors determined whether some patients with clinical stage I or II invasive breast cancer can be adequately treated by conservative surgery without radiotherapy. SUMMARY BACKGROUND DATA: Currently, there are many patients who are being treated in this manner in both academic and community hospitals. This approach is not as effective as either mastectomy or conservative surgery followed by radiotherapy in preventing local recurrence. However, there may be subsets of patients who might be adequately treated by surgery alone with acceptably low recurrence rates. METHODS: The authors reviewed retrospective studies of conservative surgery alone and of randomized trials comparing the results of treatment with and without postoperative radiotherapy. RESULTS: The local recurrence rate is unacceptably high when random patients are treated with conservative surgery without radiotherapy. More favorable results may be possible when relatively wide excisions are performed on selected postmenopausal patients with small lesions without an extensive intraductal component, lymphatic or blood-vessel invasion, and histologically negative axillary nodes. The role of tamoxifen in reducing the risk of breast recurrence is uncertain. Despite salvage therapy, some individuals may develop disseminated disease as a result of local recurrence. CONCLUSIONS: The authors believe that conducting carefully designed prospective studies of conservative surgery alone is reasonable for patients who are adequately informed of the potential risks of omitting radiation therapy. However, currently, patients should not be treated with conservative surgery alone (without radiotherapy) without such stringent guidelines.

Diminished agonist-stimulated inositol trisphosphate generation blocks stimulus-secretion coupling in mouse pancreatic acini during diet-induced experimental pancreatitis.

Young female mice fed a choline-deficient, ethionine-supplemented (CDE) diet rapidly develop acute hemorrhagic pancreatitis. We have observed that pancreatic acini prepared from these mice are unable to secrete amylase in response to addition of the cholinergic agonist carbachol, although they retain the ability to secrete amylase in response to the Ca2+ ionophore A23187. The CDE diet does not alter the binding characteristics (Kd or the maximal number of binding sites) for muscarinic cholinergic receptors as tested using the antagonist [3H]N-methylscopolamine nor the competition for this binding by carbachol. Addition of carbachol to acini prepared from mice fed the CDE diet does not result in as marked an increase in cytosolic free Ca2+ levels as that noted in control samples (evaluated using quin2 fluorescence). These observations indicate that the CDE diet interferes with stimulus-secretion coupling in mouse pancreatic acini at a step subsequent to hormone-receptor binding and prior to Ca2+ release. This conclusion is confirmed by our finding that the hormone-stimulated generation of [3H]inositol phosphates (inositol trisphosphate, inositol bisphosphate, and inositol monophosphate) from acini labeled with [3H]myoinositol is markedly reduced in acini prepared from mice fed the CDE diet. This reduction is not due to a decrease in phosphatidylinositol-4,5-bisphosphate. This communication represents the first report of a system in which a blockade of inositol phosphate generation can be related to a physiologic defect and pathologic lesion.

Failure of extracellular digestive enzymes to alter in vitro secretion by rat pancreas.

The basal rate of amylase secretion from rat pancreatic lobules was found to diminish with time. This decline, which is not due to depletion of amylase stores or loss of tissue integrity, has been attributed to the build-up of amylase in the extracellular space [Ho and Rothman, Am. J. Physiol. 245 (Cell Physiol. 14): C21-C27, 1983]. This accumulation of amylase would result in a decrease in the intracellular-extracellular amylase gradient, which, according to the so-called equilibrium hypothesis, is responsible for net amylase secretion under basal conditions. Using rat pancreatic lobules and acini, we have tested the validity of this hypothesis by adding to the incubation medium at the onset of incubation either collected secretory products or purified amylase. Based on the equilibrium hypothesis, one would have predicted that these additions would also reduce the concentration gradient favoring net secretion and would result in an apparent reduction in the initial rate of basal in vitro digestive enzyme secretion. The results obtained from these studies, however, were not in accord with those predictions, since these additions did not diminish the initial rate of basal amylase secretion. Our observations therefore indicate that the decrease in the rate of basal amylase secretion from rat pancreas with time is not due to the loss of a concentration gradient favoring efflux. These results argue against the validity of the equilibrium hypothesis.

In vivo rat pancreatic acinar cell function during supramaximal stimulation with caerulein.

Infusion of a supramaximal dose of caerulein results in acute interstitial pancreatitis in rats. We report studies of in vivo pancreatic acinar cell function during the initial 3.5 h of supramaximal stimulation with caerulein (5 micrograms X kg-1 X h-1). Amino acid [( 3H]phenylalanine) uptake was not altered, and there was no change in the rate or extent of protein synthesis or in intracellular transport of in vivo pulse-labeled proteins from microsome to zymogen granule-enriched fractions. However, the discharge of labeled protein was markedly inhibited. Radioautographic studies indicated that the pulse-labeled proteins retained in the gland were not located extracellularly but had accumulated within acinar cells, with a preferential distribution at the cell apex (presumably in zymogen granules) and in large vacuoles that form within the cell during hyperstimulation. Supramaximal stimulation with caerulein also caused increasing amounts of amylase and labeled proteins to be recovered in the postmicrosomal fraction. These findings suggest that supramaximal stimulation causes digestive enzymes to become localized in organelles that are fragile and subject to disruption during tissue homogenization. These organelles may be the vacuoles noted in morphological studies and believed to represent immature condensing vacuoles and/or crinophagic vacuoles.

Primary sphincter repair in anorectal trauma.

Two patients who sustained severe anorectal trauma from "fist fornication" were treated by irrigation, colostomy, drainage, antibiotics, and primary repair of the rectum and anal sphincters without complications. Both had complete return of continence. Primary sphincter repair is advocated for these and similar anorectal injuries.

Inositol trisphosphate production and amylase secretion in mouse pancreatic acini.

Dispersed mouse pancreatic acini prelabelled with (3H)-myoinositol generated (3H)-inositol trisphosphate (3H-IP3), (3H)-IP2 and (3H)-IP1 in response to both cholinergic and cholecystokinin analogues. The generation of (3H)-IP3 was very rapid, reaching a maximal value within 5 seconds following hormone stimulation. Stimulation with 10(-3)M carbachol increased (3H)-IP3 to a value which was 13 times that found in unstimulated acini. These results indicate that the mechanism of stimulus-secretion coupling in mouse pancreatic acini may proceed by a mechanism similar to many other systems, including rat pancreatic acini. This sequence includes hormone-stimulated phosphatidylinositol turnover and Ca2+ mobilization, i.e. secretagogue-stimulated generation of IP3 which induces the subsequent release of intracellular Ca2+. These observations differ from those recently reported by Hokin-Neaverson and Sadeghian (J. Biol. Chem. 259: 1346, 1984), in which no hormone stimulated IP3 generation was detected in mouse pancreatic acini.

Intracellular Ca2+ levels and amylase secretion in Quin 2-loaded mouse pancreatic acini.

Dispersed mouse pancreatic acini were loaded with the Ca2+-sensitive fluorescence probe Quin 2. Stimulation with carbamylcholine or cholecystokinin-octapeptide (CCK-OP) resulted in a rapid increase in Quin 2 fluorescence, which returned to a lower and sustained plateau level within 2 min of secretagogue stimulation. The magnitude of the initial rise in fluorescence intensity and of amylase secretion were closely related to the concentration of agonist used. Maximal fluorescence changes and amylase secretion were noted with 1 X 10(-5) M carbamylcholine and 1 X 10(-9) M CCK-OP, whereas both responses were half maximal in the presence of 5 X 10(-7) M carbamylcholine and approximately 1 X 10(-10) M CCK-OP. The resting cytosolic free Ca2+ concentration, as measured by the intensity of Quin 2 fluorescence, was calculated to be 1.03 +/- 0.12 X 10(-7) M. Cytosolic free Ca2+ rose to 1.3 +/- 0.3 X 10(-6) M after addition of 1 X 10(-5) M carbamylcholine and 1.25 +/- 0.21 X 10(-6) M following 1 X 10(-9) M CCK-OP. Amylase secretion, but not the Quin 2 fluorescence response, was attenuated at higher secretagogue concentrations. Both secretagogue-induced Quin 2 fluorescence and amylase secretion were inhibited by secretagogue antagonists. Removal of Ca2+ from the extracellular medium resulted in a 48.8 +/- 2.0% reduction of carbamylcholine-induced Quin 2 fluorescence. Following addition of carbamylcholine, CCK-OP was unable to stimulate a second increase in Quin 2 fluorescence without the intervening addition of a cholinergic antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of cyclic AMP-dependent protein kinase-induced changes in the kinetic properties of hepatic pyruvate kinase by the specific cyclic AMP antagonist, the (Rp)-diastereomer of adenosine cyclic 3',5'-phosphorothioate.

The effects of the diastereomers of adenosine cyclic 3',5'-phosphorothioate, (Sp)- and (Rp)-cAMPS, on the kinetic properties of pyruvate kinase were studied in hepatocytes isolated from fed rats. Incubation of the cells with the cAMP-dependent protein kinase agonist, (Sp)-cAMPS, produced a concentration-dependent increase in S0.5 for phosphoenolpyruvate, but had no effect on Vmax. The (Sp)-cAMPS-treated enzyme was more sensitive to inhibition by alanine and ATP and, under the same conditions, was less responsive to activation by fructose-1,6-bisphosphate when assayed at a subsaturating phosphoenolpyruvate concentration. Incubation of the hepatocytes with only the cAMP-dependent protein kinase antagonist, (Rp)-cAMPS, produced no change in any kinetic parameters, but did suppress the (Sp)-cAMPS- or glucagon-induced increase in the S0.5 for phosphoenolpyruvate with IC50 values of 10 microM and 5 microM (Rp)-cAMPS. (Rp)-cAMPS is exerting an effect on the kinetic properties of pyruvate kinase through inhibition of cAMP-dependent protein kinase.