Discordance of intraoperative frozen section analysis with definitive histology of sentinel lymph nodes in breast cancer surgery: complementary axillary lymph node dissection is irrelevant for subsequent systemic therapy.

BACKGROUND: In breast cancer surgery, intraoperative frozen section (FS) analysis of sentinel lymph nodes (SLNs) enables axillary lymph node dissection (ALND) during the same operative procedure. In case of discordance between a "negative" FS analysis and definitive histology, an ALND as a second operation is advocated since additional lymph node metastases may be present. The clinical implications of the subsequent ALND in these patients were evaluated. MATERIALS AND METHODS: Between November 2000 and May 2008, 879 consecutive breast cancer patients underwent surgery including sentinel lymph node biopsy (SLNB) with intraoperative FS analysis of 2 central cuts from axillary SLNs. Following fixation and serial sectioning, SLNs were further examined postoperatively with hematoxylin and eosin (H&E) and immunohistochemical techniques. For patients with a discordant FS examination, the effect of the pathology findings of the subsequent ALND specimen on subsequent nonsurgical therapy were evaluated. RESULTS: FS analysis detected axillary metastases in the SLN(s) in 200 patients (23%), while the definitive pathology examination detected metastases in SLNs in another 151 patients (17%). A complementary ALND was performed in 108 of the 151 patients with discordant FS. Additional tumor positive axillary lymph nodes were found in 17 patients (16%), leading to "upstaging" in 7 (6%). Subsequent nonsurgical treatment was adjusted in 4 patients (4%): all 4 had more extensive locoregional radiotherapy; no patient received additional hormonal and/or chemotherapy. CONCLUSION: Discordance between intraoperative FS analysis and definitive histology of SLNs is common. In this selection of patients, a substantial proportion had additional lymph node metastases, but postsurgical treatment was rarely adjusted based on the findings of the complementary ALND.

The impact on post-surgical treatment of sentinel lymph node biopsy of internal mammary lymph nodes in patients with breast cancer.

BACKGROUND: Since the introduction of the sentinel lymph node (SLN) biopsy in breast cancer patients there is a renewed interest in lymphatic drainage to the internal mammary (IM) chain nodes. We evaluated the frequency of lymphatic drainage to the IM chain, the rate of SLNs that contain metastases and the clinical implications of IM LN metastases. METHODS: Between June 1999 and April 2005 506 consecutive patients underwent SLN biopsy as a staging procedure for clinically T1-2N0 breast cancer. In all patients preoperative lymphoscintigraphy was combined with the intraoperative use of a gammaprobe. In patients with IM SLNs visualized on lymphoscintigraphy, LNs were extirpated through an intercostal parasternal incision. RESULTS: SLNs were visualized by preoperative lymphoscintigraphy in 99% of all patients (502/506): axillary SLNs in 499 patients (99%), ipsilateral IM LNs in 109 patients (22%). In 85 patients with visualized IM SLNs the IM nodes could be removed (78%). In 20 of the latter 85 patients IM SLNs contained metastases (24%). IM metastases were associated with axillary LN metastases (P < 0.001). In 17 patients IM metastases led to extension of the radiotherapy field, while additional (adjuvant) systemic therapy was given in six patients. CONCLUSION: SLNs in the IM chain are common in breast cancer patients and can be extirpated in the majority of these patients. The proportion of patients in whom radiotherapeutic treatment was adjusted due to IM LN metastases was substantial. We advocate retrieval of IM SLNs when visualized by preoperative lymphoscintigraphy.

[Minimally-invasive parathyroidectomy: a good operative procedure for primary hyperparathyroidism even without the use of intraoperative parathyroid-hormone assessment or a gamma probe]. / Minimaal invasieve parathyreoïdectomie: ook zonder het gebruik van intraoperatieve parathormoonmeting of gammaprobe een goede behandeling voor primaire hyperparathyreoïdie.

OBJECTIVE: To evaluate the results of minimally-invasive parathyroidectomy without the use of intraoperative parathyroid-hormone assessment or a gamma probe. DESIGN: Retrospective. METHODS: In 2 community hospitals in the Netherlands, 49 patients with primary hyperparathyroidism in whom preoperative investigations had shown a solitary adenoma underwent minimally-invasive surgery by the lateral neck approach. In total 9 men and 40 women with an average age of 58 years (limits: 25-84) underwent this procedure. More extensive preoperative investigations were carried out at the Mesos Medisch Centrum (n = 29) including neck CT in 76% of patients as well as ultrasonography, and scintigraphy. At the Diakonessenhuis (n = 20) scintigraphy was the preferred method of adenoma localisation. Intraoperative parathyroidhormone assessment and a gamma probe were not used in the operative procedure. At the Diakonessenhuis intraoperative frozen-section investigations were done. RESULTS: In 44 of the 49 patients (90%) minimally-invasive parathyroidectomy resulted in normocalcaemia. In the remaining 5 patients a second procedure was necessary--a conventional neck exploration and also resulted in normocalcaemia. In 2 of these patients the adenomas had been missed during first procedure by the surgeon, while in 3 other patients preoperative examinations were falsely positive in the sense that the adenoma proved to be present but in an area other than that indicated by preoperative imaging. Permanent recurrent laryngeal-nerve paralysis complicated the postoperative course in 2 patients. The success rate of the minimally-invasive operation was the same for both groups. CONCLUSION: Without the use of intraoperative parathyroid-hormone assessment or a gamma probe minimally-invasive parathyroidectomy was successful in 90% of patients.

Detection of malignant breast tumours in dense breast tissue: results of 99mTc-tetrofosmin scintimammography related to surgery.

AIMS: To assess the contribution of 99mTechnetium tetrofosmin (99mTc-TF) scintimammography for staging of breast lesions in patients with a suspicious or non-diagnostic mammogram to reduce unnecessary surgical procedures in future. METHODS: Fifty patients with suspicious physical examinations and/or mammography underwent 99mTc-TF breast imaging. RESULTS: Scintimammography with 99mTc-TF was positive in 37 patients (36 true positive, one false positive) and negative in 13 patients (12 true negative, one false negative). The detection of a malignant tumour by 99mTc-TF was independent of the density of the breast tissue. In 33 patients with a malignant breast tumour 99mTc-TF was diagnostic with respect to axillary status, but in four out of 19 patients with a histologically positive axillary lymph node status, tumour involvement remained undetected by scintigraphy. Moreover, in four patients, scintimammography revealed an additional discrete area of increased 99mTc-TF uptake, which proved to be second primary breast cancers. CONCLUSIONS: 99mTc-TF scintimammography appears to be an accurate diagnostic test in patients with a symptomatic breast lesion and a non-diagnostic mammogram, also in those patients with dense breast tissue. This procedure may also have potential for the detection of second primary breast cancers in an early stage.

Technetium-99m-sestamibi uptake in axillary lymph node metastases in breast cancer patients.

In a prospective study the value of technetium-99m-sestamibi scintigraphy (MIBI scintigraphy) in staging axillary lymph node involvement in breast cancer patients was established. The study comprised 36 cases. The results of the staging were compared with physical and histological examination. MIBI scintigraphy had a sensitivity of 91% and a total accuracy of 81%. These percentages demonstrate the potential value of this technique; larger series will be needed to confirm our results.

Evaluation of the Singh index for measuring osteoporosis.

We studied the reliability of the Singh classification of trabecular bone structure in the proximal femur as a measure of osteoporosis, using kappa statistics. Radiographs of fractures of the femoral neck or trochanteric region in 80 consecutive patients were assessed by six observers. The interobserver variation was large; only three of 72 radiographs were given the same classification by all six observers and the kappa values ranged from 0.15 to 0.54. the intraobserver variation showed substantial strength of agreement; kappa values ranged from 0.63 to 0.88. In 77 patients dual-energy X-ray absorptiometry was used to measure bone mineral density. The results were compared with those of the Singh classification: we found no correlation.

Postprandial reversal of the portal venous flow in a patient with liver cirrhosis.

The case of a 61-year-old man with alcoholic liver cirrhosis and a hepatocellular carcinoma is presented. He was examined with duplex Doppler before and after a meal. In the fasting state a sluggish hepatopetal portal venous flow was found. After the meal a pendulating flow and then hepatofugal flow were found. The magnitude and direction of flow alternated synchronously with the action of the heart, suggesting a significant role for the hepatic artery in the postprandial reversal of portal venous flow. One year after this examination the patient died from the complications of decompensated cirrhosis and liver failure. At autopsy a large hepatocellular carcinoma was detected.

Blunted postprandial reaction of portal venous flow in chronic liver disease, assessed with duplex Doppler: significance for prognosis.

To establish the effects of a meal on portal venous flow and the prognostic value of this parameter, 46 patients with chronic liver disease and 28 healthy subjects were examined with duplex Doppler before and after a meal. The measurements were completed in 40 patients and 21 healthy subjects. Postprandial portal venous diameter, blood velocity and quantitative flow were measured for 60 min. Mean baseline values were: 11.4 mm versus 10.2 mm (p = 0.019), 10.8 cm.s-1 versus 13.4 cm.s-1 (p = 0.015) and 668 ml.min-1 versus 646 ml.min-1 (p = 0.7) respectively. Spleen size was 15.0 cm versus 10.6 cm (p = 0.0001) respectively. Postprandial diameter, velocity and flow increased significantly in patients and controls (p = 0.0001 for all). Mean postprandial flow could best be described by a polynomial equation with a parabolic curve. Patients' curves were more blunted than controls', with significantly different regression constants (p = 0.025 and p = 0.029). All subjects were followed up for survival and variceal haemorrhage. The mean follow-up time was 47 months. Early maximum postprandial velocity (p = 0.041) and large spleen size (p = 0.002) were significantly related to an unfavourable prognosis for survival. Early maximum velocity was also related to increased variceal haemorrhage. This study shows that postprandial portal venous flow is blunted in patients with chronic liver disease. Postprandial portal venous flow may have prognostic significance.

The value of ultrasound in the evaluation of palpable breast tumours: a prospective study of 400 cases.

In a prospective study, 400 palpable breast tumours were examined to establish the value of ultrasound. 174 Carcinomas were diagnosed by histological examination. The sensitivity of ultrasound examination in detecting malignancy was 96.6%, the specificity 94.2%. Ultrasound examination of a palpable breast tumour is reliable in differentiating between benign and malignant tumours.

Portal venous flow and follow-up in patients with liver disease and healthy subjects. Assessment with duplex Doppler.

The evolution of portal venous flow in non-end-stage chronic liver disease with portal hypertension was assessed in 59 patients and compared with that in 55 control subjects and by means of duplex Doppler measurements by a single observer. All patients were prospectively followed up, and a repeated measurement was performed in a subgroup of 23 patients. The mean (+/- SD) portal venous diameter and velocity of patients versus controls were 11.2 (+/- 2.0) mm versus 10.1 (+/- 1.4) mm (p < 0.0005) and 11.0 (+/- 4.2) cm/sec versus 13.9 (+/- 4.1) cm/sec (p < 0.0005). The portal venous flow did not differ: 671 (+/- 291) ml/min versus 652 (+/- 203) ml/min. Diagnosis, Child class, and grade of varices did not influence the portal flow. Patients were followed up during a median (+/- SD) time of 47 (+/- 17) months. Nineteen (32%) patients died, and 14 (23%) had a variceal hemorrhage. Survival and hemorrhage were not correlated with the portal venous flow. Subsequent measurements in 23 patients showed a significant decrease in portal venous flow in 5 patients who died during follow-up. This was not found in the patients who survived. It is concluded that portal venous flow in chronic liver disease with portal hypertension is stable for a long time in the evolution of chronic liver disease. The existence of a 'portostat' is postulated. Only in the terminal stage of liver disease can a reduction of the portal venous flow be detected.

[Ultrasonographic study of the palpable breast tumor is very useful]. / Echografisch onderzoek van de palpabele mammatumor zeer waardevol.

OBJECTIVE: To determine the value of ultrasonographic examination in the assessment of palpable breast tumours, with special reference to the distinction between benign and malignant tumours. DESIGN: Prospective ultrasonographic study; the results of the ultrasonographic examination were compared retrospectively with those of mammographic examination. SETTING: Diakonessenhuis, Utrecht. METHOD: In 282 successive patients, 300 palpable breast tumours were examined ultrasonographically in the period from December 1989 to May 1992 and the findings were compared with those of morbid-anatomical examination (histological examination in solid tumours, cytological examination in cysts). The results of ultrasonographic and mammographic examination of 241 tumours were compared. RESULTS: Of the 300 palpable tumours examined ultrasonographically, 297 were included in the study (122 carcinomas and 175 benign lesions). The sensitivity of ultrasonography was 97.5%, its specificity 92.6%. The predictive value of a positive test result was 90.2%. When the results of ultrasonography and mammography were compared for 204 tumours, the sensitivity of ultrasonography proved to be 97.4% and its specificity 91.0%; for mammography, these figures were 91.3% and 75.3%, respectively. CONCLUSION: Ultrasonography of palpable breast tumours can be a highly reliable diagnostic method, particularly with a view to distinguishing between malignant and benign lesions.

Duplex Doppler measurements of portal venous flow in normal subjects. Inter- and intra-observer variability.

We investigated the variability of quantitative duplex Doppler measurements of portal flow. Measurements were validated in vitro using a flow phantom. The measured flow Q (ml/min), is related to the actual phantom output P (ml/min) according to the following formula: Q = 1.08 (P + 44) (r = 0.998). To estimate inter- and intra-observer variance, 38 subjects without portal hypertension were examined in two groups. Two observers examined the first group of subjects (n = 19), from a routine daily ultrasound schedule. Significant differences were found in mean +/- S.D. portal flow (692 +/- 182 ml/min vs. 613 +/- 185 ml/min, p = 0.04) and mean +/- S.D. velocity (15.3 +/- 3.9 cm/s vs. 13.2 +/- 2.6 cm/s, p = 0.01). The combined inter- and intra-observer coefficient of variation (S.D.) was 24% (158 ml/min), 9% (0.92 mm) and 24% (3.4 cm/s) for portal flow, diameter and velocity respectively. Non-systematic components of variance were the largest. Patient characteristics, age, sex, height, weight and body surface area did not influence measurement variations. In the second group of healthy volunteers (n = 19), where variance in measurements over 3 consecutive days was comparable to the combined variance in the first group, the non-systematic variance component was also the largest. We conclude that quantitative duplex Doppler measurements of portal venous flow are mainly subject to non-systematic variability. A coefficient of variation of 24% can be expected in diagnostic measurements in a single patient. Examination by a single observer is advisable. The value of this technique lies in the analysis of pathophysiological mechanisms in portal flow changes in large groups of subjects.

Locating and marking non-palpable, mammographically suspicious breast lesions with the aid of ultrasound.

Most non-palpable, mammographically suspicious breast lesions can be located by ultrasound (47 of 58 lesions in our series). We found that it was possible in 26 of 28 cases to mark these lesions prior to operation under ultrasound guidance thus simplifying the operating procedure.

[Little extra information with ultrasonic studies of the axillary glands in patients with breast carcinoma]. / Weinig extra informatie door echografisch onderzoek van de okselklieren bij patiënten met een mammacarcinoom.

In order to establish the value of ultrasound examination of the axillary lymph nodes on the presence of lymph node metastases of carcinoma of the breast a prospective survey was carried out in 100 consecutive patients with a carcinoma of the breast on which a lymph node dissection was performed. In the survey the results of the ultrasound examination were compared with the results of the physical and pathological examinations. Although the sensitivity of the ultrasound examination was higher (60%) than that of the physical examination (33%) the ultrasound examination proved insufficiently reliable.

Ultrasonographic detection of the patellar plica in the knee.

In 39 knees of 38 patients, an ultrasonographic investigation of the patellofemoral space was performed to detect a plica synovialis. By arthroscopic control, we found a sensitivity for the ultrasonographic method of 92% and a specificity of 73%. The method, materials, and results are discussed in this paper.

False-positive subtraction scintigram of the parathyroid glands due to metastatic tumor.

A focus of increased uptake on a 201Tl minus 99mTc subtraction scintigram of the parathyroid glands was found in a patient with persistent hypercalcemia. This area was not caused by an abnormal parathyroid gland but by an enlarged lymph node containing metastatic tissue from an adenocarcinoma of the ovary.

Detection and localization of lower extremity deep venous thrombosis with radionuclide venography.

Radionuclide venography has been performed in 180 patients for evaluation of the lower extremity deep venous system. 21 of these patients suffered from a pelvic vein thrombosis, in 5 out of these patients a systemic-portal shunting of blood has been discovered. Also the collateral circulation in the patients with a lower extremity deep venous thrombosis has been clearly shown. Radionuclide venography is a relatively simple method of thrombus detection in the pelvic veins and the lower extremity deep venous system.