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M D Stone

Publications and source records attributed to M D Stone.

At least 37 records · Page 2Linked to original sources

Determinants of remission of Paget's disease of bone.

Bisphosphonates are a safe and effective treatment for Paget's disease of bone, but little information is available about the factors influencing the duration of remission so obtained. We assessed 60 patients with Paget's disease treated with disodium pamidronate (APD). The mean duration of remission was 9.5 months (range 3-25). The major influences were the initial pretreatment alkaline phosphatase (ALP; r = -4.6, p < 0.0001), minimum posttreatment ALP (r = -0.51, p < 0.0001), and the rate of response of bone turnover to the first dose of APD (r = 0.61, p < 0.0001). Multiple linear regression showed that the initial response to treatment was the most significant influence. Also, despite a minimum ALP within the normal range, the duration of remission varied considerably (4-25 months). This may be due to the difficulties in applying a population-based normal range to individuals.

Aged↗

New therapeutic possibilities in primary invasive breast cancer.

OBJECTIVE: Current therapy for small invasive breast cancer, particularly when discovered mammographically, was re-examined. Axillary dissection may be avoided when lymph node metastases incidence is low (< 10%) or when primary cancer features determine adjuvant therapy. Radiation therapy may be avoided when risk of recurrence is very low. SUMMARY BACKGROUND DATA: Recent studies by the Surveillance, Epidemiology, and End Results program (SEER) have shown increases in small invasive breast cancers (< 1 cm) attributable to mammographic screening. The incidence of axillary metastases in mammographically discovered small cancers (< 1 cm) may be less than 10%. Follow-up data from the Breast Cancer Detection Demonstration Project (BCDDP) indicate a disease-free survival rate exceeding 95% at 8 years if the cancer was discovered mammographically. METHODS: Maximum diameter and lymph node metastases of invasive breast cancer diagnosed between 1969 and 1988 were analyzed and compared to cases diagnosed between 1929 and 1968. One hundred thirty patients have been treated without either axillary dissection or radiation therapy since 1980. RESULTS: The mean and median diameters of invasive breast cancers decreased to 2.31 and 2.0 cm, respectively, between 1984 and 1988; 13% were less than 1 cm in diameter. Only 13% of patients had axillary metastases if the primary cancer was 1 cm or less in diameter in the last 10 years; 71% had only 1 or 2 nodes involved. Isolated local recurrence, total local recurrence, and distant metastases were unchanged when radiated and nonirradiated patients were compared. Axillary nodal recurrence was decreased in irradiated patients because the lower half of the axilla was treated. CONCLUSION: In selected patients with very small invasive breast cancers detected by mammography, breast conservation without axillary dissection or radiation therapy may be used. Entirely outpatient treatment markedly reduces morbidity and cost, and furthers the gains from screening programs.

Axilla↗

Acute changes in calcium homeostasis during treatment of primary hyperparathyroidism with risedronate.

We administered risedronate, a potent oral bisphosphonate, to patients with mild primary hyperparathyroidism in order to 1) determine if we could normalize the serum calcium concentration in the short term, and 2) analyze changes in the homeostatic mechanisms responsible for maintaining hypercalcemia in this patient population. When administered for 7 days, risedronate reduced fasting serum calcium concentrations without significant toxicity in patients with primary hyperparathyroidism. The decrease in serum calcium was accompanied by evidence of inhibition of bone resorption, as assessed by measurement of urinary hydroxyproline, increased serum immunoreactive PTH concentrations, enhanced renal tubular reabsorption of calcium, and a progressive decrease in serum alkaline phosphatase. Serum PTH was partially suppressed by an oral calcium load in untreated patients as well as in patients treated with risedronate. Although patients treated with risedronate had normal fasting serum calcium levels, serum calcium values in these normocalcemic patients were labile after oral ingestion of calcium. After daily calcium intake of 2 g, serum calcium levels in risedronate-treated patients were similar to those in untreated patients with primary hyperparathyroidism, suggesting that there are likely to be fluctuations in serum calcium in risedronate-treated patients with normal fasting serum calcium during postprandial periods. These studies show that risedronate lowers fasting serum calcium during short term treatment. However, further studies are required to determine whether the lability in serum calcium in these patients after an oral calcium load has clinical significance, and whether longer term treatment would maintain serum calcium in the normal range.

Administration, Oral↗

Technical and biological factors in disease-free survival after hepatic resection for colorectal cancer metastases.

Careful patient selection for hepatic resection of colorectal cancer metastases is essential to improve current poor results. Carcinoembryonic antigen level and number of metastases were significant preoperative prognostic indicators of 5-year disease-free survival in patients selected clinically for hepatic surgery. Surgical margin, weight of hepatic tissue resected, carcinoembryonic antigen level, and flow cytometry were significant postoperative prognostic indicators. Patients with a carcinoembryonic antigen level less than 200 ng/mL, 1-cm surgical margins, and less than 1,000 g of liver tissue removed had a greater than 50% estimated 5-year disease-free survival rate. If the metastases were diploid on flow cytometry, an additional survival advantage may have been gained. Inadequate surgical margins led to high rates of liver-only recurrence. Nonhepatic recurrence was unrelated to surgical margins. Intraoperative liver examination by ultrasound during primary colon cancer resection and adjuvant chemotherapy may offer earlier selection of biologically appropriate patients and improved outcome; both recommendations require clinical trials.

Adult↗

Bisphosphonate space measurement in Paget's disease of bone treated with APD.

The bisphosphonate space (BPS) is a quantitative measurement of skeletal uptake of 99mTc-HMDP. We measured BPS in 36 patients with Paget's disease of bone, both before and 6 months after treatment with intravenous APD (disodium pamidronate) infusions. BPS fell after treatment, but proportionally less than serum alkaline phosphatase (ALP) and fasting urinary hydroxyproline/creatinine (HYPRO). There was no dose-response relationship between the dose of APD given and the percentage reduction in ALP and HYPRO at 6 months. Log dose of APD/pretreatment BPS, however, predicted the percentage reduction in ALP and HYPRO very well, and from the respective regression equations it was possible to predict the dose of APD needed to achieve normal values of ALP and HYPRO. In the 10 patients who achieved a normal ALP and 9 patients a normal HYPRO after more than 6 months treatment with APD (range 7-18 months), the predicted dose of APD agreed closely with the actual dose. In conclusion, our data support the idea that log dose APD/pretreatment BPS is a valid predictor of biochemical response in Paget's disease.

Alkaline Phosphatase↗

A neuroendocrine cause of oncogenic osteomalacia.

All definite cases of oncogenic osteomalacia have, until now, been classified as mesenchymal tumours. We report here a case of oncogenic osteomalacia caused by a spinal tumour. Microscopically, it resembled the mixed connective tissue variant of previously described phosphaturic tumours. Immunohistochemical studies, however, showed the tumour cells to be positive for low molecular weight cytokeratin (CAM 5.2), S100 protein, PGP 9.5, and synaptophysin. Electron microscopy demonstrated neurosecretory granules. The histopathological findings strongly suggest that this is a neuroendocrine tumour.

Adult↗

Comparison of low-dose intramuscular and intravenous salcatonin in the treatment of primary hyperparathyroidism.

The treatment of hypercalcaemia with low-dose salcatonin (100 U/d), administered either as a single intramuscular bolus or as a continuous intravenous infusion for five days, was examined in two groups of 10 patients with primary hyperparathyroidism, in a randomized open parallel study. Both the peak (0.31 +/- 0.035 mmol/L v 0.13 +/- 0.034 mmol/L) and overall (0.073 +/- 0.016 mmol/L v 0.018 +/- 0.016 mmol/L) hypocalcaemic responses were greater in the infusion group. The peak reduction in serum calcium occurred on day 2 of treatment after which there was a progressive attenuation of response. All the differences between the two methods of administration wer due to renal rather than bony effects of salcatonin. Possible causes of progressive resistance to treatment included reductions in sodium excretion and serum phosphate. It is concluded that low-dose salcatonin administered as a continuous infusion was more effective than the same dose given as a bolus. The kidney played a pivotal role both in the cause of the hypercalcaemia and in the response to treatment, including the rapid development of resistance which limits the use of salmon calcitonin in primary hyperparathyroidism to short-term reduction of serum calcium.

Alkaline Phosphatase↗

The role of surgical resection of liver metastases in colorectal carcinoma.

While hepatic resection of colorectal carcinoma, metastatic to the liver, is a suitable and effective treatment, it nevertheless remains applicable only to a highly selective group of patients. Even within this highly selective group of patients only a minority will survive 5 years disease-free indicating the increased sophistication needed to understand the biological factors that control outcome. It is clear that the good results come from biological suitability and not temporal acceleration of the detection process. Appropriate patients after careful selection and sophisticated diagnostic studies should be subjected to exploration and attempted hepatic resection. A preliminary prognostic scoring system has been presented to illustrate the usefulness of this approach.

Aftercare↗

Surgical therapy for recurrent liver metastases from colorectal cancer.

Forty percent of patients whose disease recurs after hepatic resection for liver metastases from colorectal cancer initially will have liver-only metastases. We have retrospectively reviewed our experience with repeated surgical treatment for liver-only recurrence after previous hepatic resection for colorectal metastases. Repeated hepatic procedures were performed with no mortality in 10 patients. Intraoperative ultrasound allowed identification of three unsuspected metastases and determination of unresectability of two metastases during 11 procedures. Three patients were free of disease at 31, 41, and 48 months from the first hepatic procedure and at 15, 31, and 43 months from the second procedure. Five patients have remained free of hepatic disease. Patients whose initial metastases were less than 6 cm in diameter and had single liver recurrences after hepatic resection appeared to be the best candidates for further surgical therapy. These data and a review of the literature suggest that surgical treatment of recurrent liver metastases from colorectal cancer can be performed safely, and it is associated with long-term disease-free survival in up to 38% of highly selected patients.

Aged↗

Treatment of Paget's disease with intermittent low-dose infusions of disodium pamidronate (APD).

Disodium pamidronate (APD) is a potent inhibitor of bone resorption, with less risk of defective mineralization than earlier bisphosphonates. We assessed the response to six spaced low-dose intravenous infusions of APD given at intervals of approximately 6 weeks followed by weekly infusions if bone turnover remained abnormal. Three groups of 10 patients were studied, each group receiving infusions of 15, 30, or 45 mg. Hydroxyproline excretion fell by 62% and alkaline phosphatase was reduced by 72%, with no difference between the dose levels. A total of 21 patients (70%) achieved normal levels of bone turnover, indicating that low-dose infusions of APD are a safe and effective treatment for Paget's disease.

Alkaline Phosphatase↗

Potentiation of calcitonin by corticosteroids during the treatment of the hypercalcaemia of malignancy.

Some patients treated for the hypercalcaemia of malignancy develop renal tubular resistance to the effects of calcitonin which is independent of concurrent changes in sodium excretion. This type of resistance can be overcome by the addition of corticosteroids. In other patients apparent renal resistance to calcitonin is a consequence of reduced sodium excretion and is unaffected by corticosteroids.

Aged↗

A model of reversible obstructive jaundice in the rat.

A model of reversible, extrahepatic biliary obstruction is described. Vessel loop blockade of the biliary tree results in obstructive jaundice while removal of the exteriorized vessel loop provides internal biliary drainage without subsequent laparotomy. This technique combined with a system for chronic venous infusion and arterial blood sampling in the unrestrained rat is ideal for long-term metabolic studies of obstructive jaundice. Male Fisher 344 rats (275-350 g) underwent either the combined procedure of total biliary tract blockade and vascular access or sham operation. Mean serum bilirubin was significantly elevated (12.7 +/- 8.9 mg/dl) in the experimental group and following relief of biliary obstruction significantly dropped below 1 mg/dl in all animals except one. Concomitant changes in alkaline phosphatase, glutamate oxaloacetate transaminase, and glutamate pyruvate transaminase were seen. Experimental and control rats initially lost weight following laparotomy; however, mean body weight stabilized by the 5th postoperative day and was similar in both groups on the 10th postoperative day. This combined procedure is a simple, effective and reproducible method of obstructive jaundice.

Alanine Transaminase↗

Techniques of lumpectomy and axillary dissection.

Preservation of the breast with a good or excellent cosmetic appearance is achievable in most patients. Careful attention to the details of surgical technique allows these procedures to be carried out easily and comfortably for the patient and the surgeon alike.

Anesthesia↗

Selection of breast-preservation therapy for primary invasive breast carcinoma.

Breast-preservation treatment for primary breast cancer should not be used for all women. Women frequently excluded from consideration for such treatment or who choose not to have it may be elderly and not concerned about cosmetic appearance or live at a distance so that 6 weeks of daily trips to radiotherapy would be inconvenient or even impossible. Also, if radiotherapeutic expertise or facilities are not available, a breast-preservation program is difficult. In Massachusetts, a full course of just over 6000 cGy (4500 cGy to the whole breast and a 1600-cGy local boost) costs roughly $6000. Thus, breast preservation is more expensive than mastectomy even with reconstruction, as patients still frequently require a hospital admission with general anesthesia for an axillary dissection. Although insurance policies cover such expenses, patients who do not have insurance or have inadequate coverage may find the extra expense of the breast-preservation technique burdensome or impossible. Women with a small breast and a proportionately large cancer may have an unsatisfactory cosmetic outcome after appropriate lumpectomy. The cosmetic result in such patients frequently cannot be predicted beforehand; this fact adds emphasis to the need for a two-step process of lumpectomy and then re-evaluation of the cosmetic outcome as well as pathologic features for decisions regarding breast preservation. Finally, women may have strikingly different attitudes toward breast preservation than expected by the surgeon. For some women, the urge to preserve the breast is so strong that they will accept virtually any risk to achieve this option, whereas for other women, the constant anxiety about a recurrence or undergoing radiation therapy is traumatic enough that they readily accept mastectomy. In our referral surgical oncology practice, roughly 60% of patients are currently treated with breast-preservation techniques; the remainder undergo mastectomy, with immediate reconstruction in approximately three fourths of the cases. The proportion of patients who elect to have breast preservation depends greatly on local medical customs and attitudes; the radiotherapeutic skills available; women's attitudes, which frequently are dependent on the local press and publicity; and the surgeon's interest and enthusiasm for such a program. There is no appropriate proportion of patients who should be treated by breast-preservation techniques, but clearly, the proportion of patients so treated increases with experience, acceptability, publicity, and availability. Thus, the selection of breast-preserving therapy for individual patients is a result of an extraordinary array of factors that need to be considered in each patient.(ABSTRACT TRUNCATED AT 400 WORDS)

Breast↗

Work of breathing: reliable predictor of weaning and extubation.

During the course of a critical illness, many patients become ventilator dependent. The standard assessment criteria are not always accurate in predicting potential for extubation. This investigation was designed to analyze whether the work of breathing (WOB) was a more reliable predictor of ventilator dependence. Twenty consecutive ventilator-dependent patients were prospectively studied. Nineteen required ventilator support for greater than 2 wk and all were considered ventilator dependent because of their inability to tolerate weaning trials. The oxygen consumption (VO2) and resting energy expenditure were measured using a metabolic gas monitor. Respiratory mechanics and arterial blood gas measurements were obtained, and the deadspace to tidal volume ratio (VD/VT) was calculated. The WOB was determined by the difference in VO2 between spontaneous and mechanical ventilation, and expressed as a percentage of VO2 during mechanical ventilation. Five of eight patients with a WOB less than 15% (mean 1.9) were extubated within 2 wk of study, while none of 12 patients with a WOB greater than or equal to 15% (mean 34) were able to be extubated in this period. The differences in the WOB between the two groups were statistically significant (p less than .01), while there was no significant difference in mechanics, PaCO2, VD/VT or measured resting energy expenditure. These data support the use of WOB determinations in evaluating extubation potential. Using a reference value for the WOB of 15%, this study had a sensitivity of 100% and a specificity of 80%. This proved to be of greater predictive value than traditional criteria.

Aged↗

Experience with transplantation in the treatment of liver cancer.

Thirteen patients with hepatic tumors, from the Boston Center for Liver Transplantation, have been transplanted among a total of 169 recipients. Ten were transplanted primarily for tumor, while three other patients harbored incidental tumors. Two perioperative deaths occurred (15%). Eight patients had hepatocellular carcinoma, one hepatoblastoma and four bile duct (Klatskin) tumors. Two of the bile duct cancers recurred with patient deaths at 9 and 10 months. The remaining nine patients are alive from between 1 month and 36 months postoperatively. A selected review of the literature allowed analysis of follow-up on 185 patients transplanted for tumor. Overall, the proportion of patients transplanted for tumor was 16%. Fifty-two percent of patients had hepatocellular carcinomas (HCC), 24% cholangiocarcinomas, 10% other primary liver tumors, and 14% metastatic hepatic tumors. Median survival for HCC was 1 year; 90-day mortality was 30%. Actuarial survival for 1, 2 and 3 years was 49%, 37% and 30% respectively. Fibrolamellar HCC and incidental HCC had significantly better results than other HCC. Tumor recurrence was present in 72% of autopsies after 90 days. Transplantation for HCC has satisfactory results in selected patients and may be improved by adjuvant chemotherapy. The median survival with cholangiocarcinomas was 8 months; 90-day mortality was 40%. Actuarial survival for 1 year was 36%. Recurrence was present in 100% of autopsies after 90 days. Survival after transplantation for this tumor was similar to that observed in patients not undergoing surgical treatment. Median survival for 18 other primary hepatic tumors was 16 months. Transplantation in carefully selected patients with these other primary tumors appears warranted. Although experience overall with transplantation for metastatic disease has been relatively unfavorable, each histological type must be considered independently.

Adult↗

Liver resection. Preoperative and postoperative care.

Liver resection is an increasingly common procedure. Despite a wide variety of indications, the preoperative and postoperative care required is similar. Experience with liver resection and transplantation has brought to light the significant alterations in fluid and electrolytes, hemostasis, metabolism, and pulmonary function that may result. A thorough understanding of these changes is required to minimize the morbidity and mortality rates of these procedures. Postoperative hepatic failure is a devastating complication, and careful patient selection is required to avoid this. More work is needed to identify better methods of evaluating functional hepatic reserve.

Age Factors↗