The effect of parathyroidectomy on bone fracture risk in patients with primary hyperparathyroidism.

BACKGROUND: Parathyroidectomy may increase bone density in primary hyperparathyroidism (PHPT), but it is unclear whether fracture risk is decreased. HYPOTHESIS: Parathyroidectomy decreases fracture risk. DESIGN: Retrospective cohort study with median follow-up of 6.5 years. SETTING: Twelve regional hospitals in California. PATIENTS: One thousand five hundred sixty-nine patients with PHPT. INTERVENTIONS: Parathyroidectomy or observation. Main Outcome Measure Fracture-free survival. RESULTS: Mean initial calcium, parathyroid hormone, and creatinine levels were 11.2 mg/dL (2.8 mmol/L), 123.0 pg/mL, and 0.9 mg/dL (79.6 micromol/L), respectively. Parathyroidectomy was performed in 452 (28.8%) patients, and 1117 (71.2%) were observed. The 10-year fracture-free survival after PHPT diagnosis was 73% in patients treated with parathyroidectomy compared with 59% in those observed (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.38-0.73; P < .001). Parathyroidectomy decreased the 10-year hip fracture rate by 8% (P = .001) and the upper extremity fracture rate by 3% (P = .02). Parathyroidectomy was independently associated with a decreased fracture risk (HR, 0.68; 95% CI, 0.47-0.98), whereas female sex (HR, 1.82; 95% CI, 1.19-2.80) and increased creatinine level (HR per 1-mg/dL [88.4-micromol/L] increment, 2.05; 95% CI, 1.22-3.46) remained independently associated with an increased fracture risk. Age of 50 years or older (HR, 1.62; 95% CI, 0.99-2.66), initial parathyroid hormone level (HR, 1.00; 95% CI, 0.99-1.02), and calcium level (HR, 1.02; 95% CI, 0.75-1.37) were not independently associated with fracture risk after adjusting for all other variables. CONCLUSIONS: Parathyroidectomy is associated with a decreased risk of fracture in PHPT. The largest decrease was in hip fractures. Parathyroidectomy should be considered for all patients with PHPT to reduce fracture risk, regardless of age or calcium or parathyroid hormone levels.

Understanding and interpreting serum protein electrophoresis.

Serum protein electrophoresis is used to identify patients with multiple myeloma and other serum protein disorders. Electrophoresis separates proteins based on their physical properties, and the subsets of these proteins are used in interpreting the results. Plasma protein levels display reasonably predictable changes in response to acute inflammation, malignancy, trauma, necrosis, infarction, burns, and chemical injury. A homogeneous spike-like peak in a focal region of the gamma-globulin zone indicates a monoclonal gammopathy. Monoclonal gammopathies are associated with a clonal process that is malignant or potentially malignant, including multiple myeloma, Waldenstrom's macroglobulinemia, solitary plasmacytoma, smoldering multiple myeloma, monoclonal gammopathy of undetermined significance, plasma cell leukemia, heavy chain disease, and amyloidosis. The quantity of M protein, the results of bone marrow biopsy, and other characteristics can help differentiate multiple myeloma from the other causes of monoclonal gammopathy. In contrast, polyclonal gammopathies may be caused by any reactive or inflammatory process.

Ex vivo lymphatic mapping: a technique to improve pathologic staging in colorectal cancer.

Sentinel lymph node (SLN) biopsy is widely used for solid tumors and has been proposed for use in staging colorectal cancer (CRC). Few studies have examined the ex vivo lymphatic mapping (EVLM) technique for staging CRC. We hypothesized that EVLM is technically feasible, sensitive, accurate, and improves the staging of CRC. After standard resection for colorectal cancer, 1 mL of isosulfan blue dye was injected circumferentially around the tumor. Blue-stained nodes were dissected separately and examined by hematoxylin and eosin (H&E) and immunohistochemical (IHC) stains. Routine pathologic evaluation was performed on all other harvested lymph nodes. Forty patients underwent 43 cancer resections with EVLM from July 2000 to December 2003. SLN were identified in 39 of 43 (91%) specimens. The mean number of SLN obtained was 1.9 (range, 0-5). Pathologic evaluation demonstrated nodal metastasis in 16 of 39 (39%) specimens. The SLN was tumor-positive in 9 of these 16 (56%) patients. The overall accuracy of EVLM was 82%. Two patients (9%) with H&E node negative disease were upstaged when found to have micrometastases by IHC staining. In conclusion, EVLM is technically possible in 90 per cent of patients with CRC. Although overall accuracy was high, the SLN status correlated poorly with the true nodal status of the CRC. However, EVLM improves pathologic staging in 9 per cent of patients and therefore may be of value in CRC.

Benefits of early feeding and early hospital discharge in elderly patients undergoing open colon resection.

BACKGROUND: Recent studies have demonstrated a reduction in hospital stay and postoperative complications in elderly patients undergoing laparoscopy-assisted colectomy, and have attributed the shorter stays and reduced morbidity to the laparoscopic approach. We questioned whether the improved outcomes in these studies were a result of the laparoscopic procedure alone or a result of early postoperative feeding and early hospital discharge. We hypothesized that early feeding in elderly patients undergoing open colorectal resection results in a short hospital stay and favorably affects postoperative morbidity. STUDY DESIGN: Patients aged 70 years and older who were undergoing elective open colon resection were placed on an early postoperative feeding protocol. The early feeding protocol consisted of clear liquids on postoperative day 2, regular diet on postoperative day 3, and discharge to home as tolerated. The main outcomes measurements included early feeding tolerance, hospital stay, postoperative morbidity, and requirement for postoperative assisted care. RESULTS: There were 87 study patients (42 men and 45 women, mean age 77 years). The most common operation was right hemicolectomy (53%). Overall 78 of 87 patients (89.6%) tolerated early feeding. Five patients (5.7%) initially tolerated a diet but required readmission for ileus. Nine patients (10.4%) did not tolerate early feeding initially. The mean hospital stay for all patients was 3.9 days. There were 15 postoperative complications in 13 patients (14.9%), the most common of which was urinary retention. There were no deaths, anastomotic leaks, abscesses, or pneumonia. Only 3 of 86 patients (3.5%) who were previously independent required assisted care after colectomy. CONCLUSIONS: In elderly patients undergoing elective open colon resection, early feeding results in a short hospital stay and low postoperative morbidity. These results are comparable to those reported for laparoscopy-assisted colectomy.

Vaccinations in pregnancy.

Adult immunization rates have fallen short of national goals partly because of misconceptions about the safety and benefits of current vaccines. The danger of these misconceptions is magnified during pregnancy, when concerned physicians are hesitant to administer vaccines and patients are reluctant to accept them. Routine vaccines that generally are safe to administer during pregnancy include diphtheria, tetanus, influenza, and hepatitis B. Other vaccines, such as meningococcal and rabies, may be considered. Vaccines that are contraindicated, because of the theoretic risk of fetal transmission, include measles, mumps, and rubella; varicella; and bacille Calmette-Guerin. A number of other vaccines have not yet been adequately studied; therefore, theoretic risks of vaccination must be weighed against the risks of the disease to mother and fetus. Inadvertent administration of any of these vaccinations, however, is not considered an indication for termination of the pregnancy.

Axillary dissection is not required for all patients with breast cancer and positive sentinel nodes.

HYPOTHESIS: Sentinel node (SN) biopsy for breast cancer enhances staging sensitivity, often demonstrating only micrometastases (<2 mm) or isolated, keratin-positive cells. When SN metastasis is present, the value of additional axillary dissection is unclear and not all patients benefit from axillary lymph node dissection (ALND). DESIGN: Prospective cohort study, median 32-month follow-up. SETTING: Multidisciplinary breast cancer centers. PATIENTS: Forty-six women having SN metastases diagnosed between May 1, 1996, and September 1, 2001, who refused ALND or were recommended to omit ALND owing to serious comorbid conditions. INTERVENTIONS: Isosulfan blue dye-directed SN biopsy. Axillary lymph node dissection was not performed. Standard breast irradiation was given. Adjuvant systemic therapy was provided as determined by an oncologist. Interval clinical evaluation was performed. MAIN OUTCOME MEASURE: Axillary and systemic failure rates. RESULTS: Mean patient age was 61.6 years (age range, 36-92 years). Mean tumor size was 1.65 cm (range, 0.4-5.5 cm). Thirty-five (76%) of 46 tumors were ductal carcinomas and 39 (87%) of 45 were estrogen receptor-positive. A mean of 2.6 SNs were identified (median, 2; range, 1-7). Thirty-nine patients (85%) had a single positive SN; the remaining 7 patients (15%) had 2 positive SNs. Seven patients (15%) had macrometastases (>2 mm); 16 (35%) had micrometastases (<2 mm); and 23 (50%) had cellular metastases. Only 16 positive SNs (35%) were seen on hematoxylin-eosin staining, while 30 SNs (65%) had positive immunohistochemical staining. There have been no axillary recurrences. One patient (2%) developed distant metastases during follow-up (range, 4-61 months). CONCLUSIONS: Patients with SN metastases who did not have ALND had a low incidence of regional failure. To confirm this observation, we suggest that patients with SN metastases are ideal candidates for trials evaluating the necessity of ALND.

Does tumor burden limit the accuracy of lymphatic mapping and sentinel lymph node biopsy in colorectal cancer?

PURPOSE: Sentinel lymph node (SLN) biopsy is a widely accepted method for staging breast cancer and melanoma, and it has recently been proposed as a means of improving staging in colorectal cancer. However, lymphatic mapping in colorectal cancer has been plagued by studies demonstrating high false-negative rates. The purpose of this study was to evaluate possible mechanisms for high false-negative rates after SLN biopsy in colorectal cancer. We hypothesized that poor accuracy may be due to bulky tumor or complete replacement of lymph nodes by tumor. PATIENTS AND METHODS: Patients with colorectal adenocarcinoma underwent standard colorectal resection with lymphatic mapping. At operation, 1 mL of isosulfan blue dye was injected at the tumor site, using either an in vivo or an ex vivo technique. Routine pathological evaluation was performed. The sentinel node was examined by hematoxylin and eosin stains, and if these results were negative, by cytokeratin immunohistochemistry. The patient's age, operation type, tumor stage, tumor diameter, method of SLN detection, presence of palpable nodes, and pathological description of nodes completely replaced by tumor were recorded. RESULTS: Fifty patients (mean age, 62.8, 50% men) undergoing colorectal cancer resection underwent 51 lymphatic mapping procedures. Right- and left-sided colorectal resections were almost equally distributed (48% vs 42%). SLNs were successfully identified in 47 of 51 specimens (92%). The mean number of SLNs obtained from each specimen was 1.5 (range, 1-5). Routine pathological evaluation demonstrated lymph node metastasis in 20 of the 47 patients (43%) who had an SLN identified. The SLN was positive for metastasis in 10 of these 20 patients (50%). Ten of 20 patients with metastatic disease had a negative SLN, resulting in a false-negative rate of 50%. The false-negative rate was significantly higher in patients undergoing left-sided procedures versus right-sided procedures. Differences among gender, tumor stage, tumor diameter, method of SLN detection, presence of palpable nodes, and pathological description of nodes completely replaced by tumor were not associated with a higher false-negative rate. DISCUSSION: Identification of the SLN in colorectal cancer is technically possible in more than 90% of patients. However, SLN status correlates poorly with the true nodal status of the colorectal cancer, and the false-negative rate is 50%. This high false-negative rate is not clearly explained by extensive tumor burden, and it was also independent of gender, tumor stage, and type of lymphatic mapping technique. However, staging accuracy was lower in patients who underwent left-sided colorectal resection. Further studies are needed to clarify the limitations of lymphatic mapping in colorectal cancer.

The effect of cisapride on the success of early feeding after elective open colon resection.

Early postoperative feeding after open colon resection has been shown to be safe and effective. However, approximately 13 per cent of patients fail to tolerate it. We hypothesized that the use of promotility agents may decrease failure of early postoperative feeding after elective open colectomy. As part of a consecutive case series metoclopramide or cisapride was administered to patients undergoing open colectomy as part of an early feeding protocol. The early feeding protocol consisted of instituting a clear liquid diet on postoperative day (POD) 2, followed by a regular diet on POD 3. One hundred fifty-one patients received early-feeding without promotility agents (Group I). The next 49 patients were treated with metoclopramide (Group II), and 31 patients received cisapride (Group III). In Group I 20 of 151 patients (13.2%) failed early feeding, and the mean hospital stay was 3.77 days (range 3-11 days). In Group II seven of 49 patients (14.2%) failed early postoperative feeding, and the mean hospital stay was 3.67 days (range 3-8 days). Group III had no patients who failed to tolerate early feeding, and the mean hospital stay was 3.32 days (range 3-5 days). There were no anastomotic leaks or abdominal abscesses in any group. No cardiac arrhythmias were associated with cisapride. A decrease in early feeding failure was observed with cisapride, administration.