Sharjeel Usmani

Predictors of non-sentinel lymph node metastasis in breast cancer patients with positive sentinel lymph node (Pilot study).

BACKGROUND Sentinel Lymph Node Biopsy (SLNB) procedure was found to be an accurate method of staging the axilla in patients with early stage breast cancer. The standard of care for breast cancer patients with positive SLN metastasis includes complete Axillary Lymph Node Dissection (ALND). However, in 40-70% of patients, the SLN is the only involved axillary node. Factors predicting non SLN metastasis should be identified in order to define subgroups of patients with positive SLN in whom the axilla may be staged by SLNB alone. OBJECTIVES To identify the factors predicting metastatic involvement of the non-SLNs in breast cancer patients having SLN metastasis. PATIENTS AND METHODS Data were collected and analyzed from 80 patients with early stage invasive breast cancer (T1, T2, N0, M0) who underwent SLNB at the Surgical Oncology Department, Kuwait Cancer Control Center (KCCC) between November 2004 and February 2009. SLNB was performed using a combined technique (radioactive colloid, and blue dye) in the majority of cases. In some cases, only one technique was used. Complete ALND was performed in the case of failure of SLN identification and in patients with positive SLN. Multiple variables (patient, tumor, and SLN characteristics) were tested as possible predictors of nonsentinel lymph node metastasis. RESULTS The mean age of patients at diagnosis was 46.6years. The median tumor size was 2cm. The SLN identification rate was 96.2% (77 out of 80 patients). The SLN was positive in 24 patients (31%), and half of these showed evidence of capsular invasion. The median number of SLNs removed was two. The median number of positive SLNs was one. The incidence of non-SLN metastasis associated with positive SLN was 50% (12 out of 24 patients). Lymphovascular invasion was found to be the only factor associated with non-SLN metastases. In addition, two trends were observed, though they did not reach the statistical significance: the first is that the majority of patients having capsular invasion of the SLN (8 out of 12 patients, 67%) had positive non-SLN metastasis, and the second is that the patients having more than one SLN metastasis were more likely to have non-SLN metastasis (4 out of 5, 80%). CONCLUSION In the current pilot study, only the lymphovascular invasion in the area of the primary tumor was found to be significantly related to the nonsentinel lymph node metastasis. There was a tendency toward higher incidence of nonsentinel lymph node metastasis associated with the number of positive SLN and capsular invasion of SLN, though this did not reach the statistical significance. This could be attributed to the small number of patients recruited. Further evaluation of the predictors of nonsentinel lymph node metastasis on a larger number of patients is required. The validation of these predictors in prospective studies may enable approximately half of early stage breast cancer patients with positive SLN to be staged with SLNB alone while avoiding the morbidity of unnecessary ALND.

The clinical utility of combining pre-operative axillary ultrasonography and fine needle aspiration cytology with radionuclide guided sentinel lymph node biopsy in breast cancer patients with palpable axillary lymph nodes.

PURPOSE Clinically palpable lymph nodes (CPLN) are usually considered a contraindication to sentinel lymph node biopsy (SLNB) but one third of these patients are node negative. The aim of the present study is to evaluate the clinical usefulness of combining SLNB and preoperative axillary ultrasonography (AUS) with FNAC in patients with clinically palpable but indeterminate axillary lymph nodes. MATERIALS AND METHODS Fifty three patients with primary breast cancer and CPLN (mean age, 51.6 years; median age 51 years; age range, 28-73 years) were included in the study. All patients underwent AUS and fine needle aspiration (FNAC) followed by SLNB in FNAC negative patients (Group A). Patients with proven metastasis subsequently had axillary lymph node dissection (ALND) (Group B). Standard SLN scintigraphy was performed 2-4h before surgery by injecting Tc-99m labeled nano-colloid intra-dermally in the periareolar region. RESULTS Nodal metastases were documented at FNAC in 26 (49%) of the 53 patients with subsequent ALND (Group B). All 27 patients (51%) with negative FNAC results (Group A) underwent SLNB, which revealed metastasis in 6 (11%) patients. The remaining 21 (40%) patients were tumor negative and all these patients remain disease free during the follow-up period of 12-36 months with NPV of 100%. SLN was identified in all patients (100% success rate). Preoperative AUS sensitivity was 78%, specificity 76%, PPV 83%, NPV 69% and accuracy 77% (p=0.001). In comparison, ultrasound guided FNAC sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 81%, 100%, 100%, 78%, 89% respectively (p=0.001). CONCLUSIONS The inaccuracy of clinical assessment allows widening of indication of SLNB. Preoperative ultrasonography and guided FNAC can help in selecting the patients suitable for ALND or SLNB. Patients who are FNAC positive can proceed to ALND whilst FNAC negative samples can undergo SLNB. This combination strategy may be helpful in avoiding unnecessary ALND.

Minimally Invasive Radionuclide-Guided Parathyroidectomy Using 99mTc-Sestamibi in Patients with Primary Hyperparathyroidism: A Single-Institution Experience

Objective: To evaluate the efficacy and usefulness of 99mTc-sestamibi scintigraphy and gamma probe localization of parathyroid glands in patients with primary hyperparathyroidism and establish radio-guided minimally invasive parathyroidectomy at Hussain Makki Al Jumma Center for Specialized Surgery, Kuwait. Subjects and Methods: Twelve patients with primary hyperparathyroidism (mean age: 48 ± 14 years; median age: 46 years; age range: 29–68 years) were evaluated. The diagnosis of hyperparathyroidism was established by elevated serum calcium and parathyroid hormone levels. All patients had a well-defined parathyroid lesion on previous standard 99mTc-sestamibi scintigraphy with or without ultrasound study. All had a normal thyroid gland, no history of familial hyperparathyroidism or multiple endocrine neoplasia nor any history of previous neck irradiation. On the day of surgery, patients were injected with 740 MBq (20 mCi) of 99mTc -sestamibi followed by a half-hour-delayed single standard pinhole view of the neck. A skin marker was placed on the basis of maximum count intensity during gamma probe localization. Patients were then sent for radio-guided minimally invasive parathyroidectomy. Results: The preoperative localization of the affected gland was successful in all cases using a gamma probe and 99mTc -sestamibi scintigraphy. The pathological parathyroid tissue was localized and successfully removed with the gamma probe. The histopathological diagnosis was parathyroid adenoma in 11 cases and hyperplasia in the remaining one. All patients remained disease and symptom free at 12-month follow-up. Conclusions: Our initial experience with intraoperative use of a gamma probe to carry out minimally invasive parathyroidectomy was a useful, easy and safe procedure for treating patients with primary hyperparathyroidism.

Three-Phase 99mTc MDP Bone Scintigraphy and SPECT-CT in Sinus Tarsi Syndrome.

Sinus tarsi syndrome is a pain in the lateral side of the hind foot that is responsive to injection of local anesthetic agents. We report a case of a 42-year-old man who presented with pain over the lateral aspect of the right foot. Laboratory investigations and x-ray were normal. Bone scintigraphy showed hyperemia and increase tracer uptake in right hind foot. SPECT-CT localizes this uptake at the inferior aspect of the talus and superior aspects of the calcaneus. Diagnosis of sinus tarsi syndrome was made on the basis of history, clinical examination, and bone scintigraphy findings. Local conservative therapy was initiated.

Tc-99m-methoxy isobutyl isonitrile scintimammography: imaging postexcision biopsy for residual and multifocal breast tumor.

Objectives The interpretation of mammogram in a postsurgical breast can be extremely complex and difficult because masses, calcifications, and architectural distortion can mimic cancer. Scintimammography has been proposed because it is not affected by these morphological changes and can potentially be used in patients after excision biopsy to assess any residual tumor, other foci of disease (multifocal disease). Materials and methods The population comprised of 21 patients (mean age: 47.80 years, median age: 50 years, and age range: 26–77 years) evaluated for suspected residual breast cancer after excision biopsy. All patients received a 740–1000 MBq bolus IV injection of Tc-99m-methoxy isobutyl isonitrile (MIBI) preferably in pedal vein. At 5–10 min after injection, planar images were obtained in prone lateral and supine anterior positions using dual head &ggr; camera. MIBI uptake was scored as follows: 1 – as normal uptake (compared with contralateral side), 2 – focal low-intense uptake (equivocal), and 3 – focal high-intense uptake (positive). All patients had histopathology for tissue diagnosis. Results Of the 21 patients evaluated, scintimammography planar was found true positive in 13 and true negative in six. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 92.85, 85.71, 92.85, 85.71, and 90.47%, respectively (P<0.001). Scintimammography detected 2/2 multifocal disease. Conclusion In patients after excision biopsy, scintimammography with Tc-99m-MIBI is valuable in assessing residual or multifocal disease. Scintimammography has high positive predictive value and may influence planning further management.

The role of fluorine-18 fluorodeoxyglucose positron emission tomography in patients with mycosis fungoides.

Purpose: The aim of the present study is to evaluate the possible role of fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) in the management of mycosis fungoides (MF). Materials and Methods: Nineteen patients (mean age, 40.6 years; median age 41 years; 16 males and 3 females) with risk of secondary lymph node (LN) involvement (those with large cell transformation, tumors, erythroderma, or enlarged LNs on physical examination) were included in the study. All patients underwent PET-CT scan by injecting 0.06 mCi/kg of F18 FDG. The maximum standard uptake value (SUVmax) was recorded for each patient. Results: The 18F-FDG PET-CT was positive in 15 patients. PET-CT detected local cutaneous disease in 13 cases. The range of SUVmax is 2.8–14.1. Out of 19 patients, hypermetabolic adenopathy is found in 9 patients and visceral involvement in one. Conclusions: Although the study population is small our findings suggests that 18F-FDG PET-CT can detect cutaneous and extracutaneous lesions in MF and may guide biopsies especially in patients with risk of secondary LN involvement.

Role of serial quantitative gallium-67 tumor uptake in assessing response rates for chemotherapy in lymphoma patients.

PurposeTo evaluate in serial gallium-67 scans (GS) the role of semiquantitative tumor-to-background (Tm/Bg) and tumor-to-liver ratios in assessing response rates to chemotherapy, in Hodgkins disease and non-Hodgkins lymphoma. Materials and methodsTwenty-seven consecutive patients (15 Hodgkins disease and 12 non-Hodgkins lymphoma patients) with an average age of 30 (range, 5–60) years underwent GS at prechemotherapy, early chemotherapy (after first cycle), and postchemotherapy. Average tumor, background, and liver region of interest counts obtained and Tm/Bg, tumor-to-liver, and liver region to background ratios were derived for each patient on serial GS. All patients were assessed by visual and quantitative GS and followed up clinically for more than 7 years. ResultsAt early visual GS, 70% (19 of 27) of the patients showed rapid response, 15% (four of 27) showed delayed response (negative at post-GS), and 15% showed no response. Mean early-GS Tm/Bg ratio of disease-free patients (1±0.04) was significantly different from relapsed (1.4±0.2) (P<0.025) and progressive disease (1.8±0.7) patients. A significant difference was noted (P<0.01) in serial paired comparisons of Tm/Bg ratios between pretherapy and early-therapy scans in relapsed patients, whereas progressive disease patients showed no significant change during the same time. At early-GS, 15 patients showed quantitative rapid response (Tm/Bg ratio 1.04), nine patients showed quantitative delayed response (Tm/Bg ratio >1.04 with significant serial change between pretherapy and early-therapy GS), and three patients showed quantitative no response (Tm/Bg ratio >1.04 with nonsignificant serial change between pretherapy and posttherapy GS). ConclusionQuantitative GS is an effective tool in the detection of early response to chemotherapy. Quantitative response rates after the first cycle can more reliably identify patients who are most likely to be disease-free or relapse after first-line therapy or those that will show no response to therapy as compared with visual analysis alone.

Hybrid SPECT/CT Imaging in the Management of Differentiated Thyroid Carcinoma

Differentiated thyroid cancer (DTC) has a good prognosis overall; however, lifelong follow-up is required for many cases. Radioiodine planar imaging with iodine-123 (I-123) or radioiodine-131 (I-131) remains the standard in the follow-up after initial surgery and ablation of residual thyroid tissue using I-131 therapy. Radioiodine imaging is also used in risk-stratifying and for staging of thyroid cancer, and in long-term follow-up. Unfortunately, the lack of anatomical detail on planar gamma camera imaging and superimposition of areas presenting with increased radioiodine uptake can make accurate diagnosis and localization of radioiodine-avid metastatic disease challenging, leading to false positive results and potentially to over-treatment of patients. Hybrid SPECT/CT allows precise anatomical localization and superior characterization of foci of increased tracer uptake when compared to planar imaging. This, in turn, allows the differentiation of pathological and physiological uptake, increasing the accuracy of image interpretation and ultimately improving the accuracy of DTC staging and subsequent patient management. In this review, we look at the unique and emerging role that SPECT/CT plays in the management of DTC, illustrated by examples from our own clinical practice.

Scintimammography in conjunction with ultrasonography for local breast cancer recurrence in post-mastectomy breast

The aim of this study was to compare the usefulness of (99)Tc(m)-methoxy-isobutyl-isonitrile (MIBI) scintimammography and ultrasonography, alone and in combination, for the detection of chest wall recurrence in the post-mastectomy breast. A total of 41 consecutive post-mastectomy patients (mean age 46.6 years; median age 45 years) with clinical suspicion of breast cancer recurrence were evaluated. For scintimammography all patients received a 740-900 MBq iv injection of (99)Tc(m)-MIBI; planar images were taken 5-10 min post-injection followed by supine single photon emission CT. Breast ultrasonography was performed in each patient using a 7.5 MHz transducer. Both MIBI uptake and ultrasound findings were documented using standard protocols. All patients had fine needle aspiration cytology biopsy (FNAC), core biopsy or excision biopsy for final tissue diagnosis. Of the 41 patients, 24 had true positive signs of local breast cancer recurrence upon ultrasonography, 10 were diagnosed as true negatives, a sensitivity of 86%, specificity 77%, positive predictive value (PPV) 89%, negative predictive value (NPV) 71% and accuracy 83% (p = 0.001). By comparison, scintimammography findings were found to be true positive in 25 patients and true negative in 12 patients - sensitivity 89%, specificity 92%, PPV 96%, NPV 80% and accuracy 90% (p = 0.001). Using a combination of these two modalities, the combined sensitivity was 100%, specificity 77%, PPV 90%, NPV 100% and accuracy 93%. The high NPV of the two studies in combination implies a potential use of this approach to exclude recurrent disease in patients with a low initial index of suspicion and/or when histology is indeterminate.

Prediction of cardiac events in patients having left bundle-branch block with/without chest pain using dipyridamole technetium-99m-sestamibi myocardial perfusion imaging.

Objective: To determine the prognostic value of myocardial perfusion scintigraphy with dipyridamole stress in patients with preexisting left bundle-branch block (LBBB) with or without chest pain. Subjects and Methods: Seventy-six patients, mean age 53 ± 10 years, with preexisting LBBB underwent technetium-99m-sestamibi perfusion imaging with dipyridamole infusion protocol (0.56 mg/kg). Stress and rest single photon emission computed tomography (SPECT) images were interpreted by consensus of 2 experienced nuclear medicine physicians and classified as low-risk scans (normal myocardial perfusion scan, small reversible/small fixed defect) and high-risk scans (large, severe, fixed or reversible defect and dilated left ventricle cavity). The patients were followed up for 24 ± 8 months and occurrences of hard cardiac events (infarction or cardiac death) were noted. Results: Of the 76 patients, 52 (68%) had low-risk scans and the remaining 24 (32%) had high-risk scans. In the low-risk group, 1 (1.9%) cardiac death and 2 (3.8%) cases of nonfatal myocardial infarction occurred, while in the high-risk group, 5 (20.8%) suffered cardiac death, and 3 (12.5%) nonfatal myocardial infarction. Overall survival rate was 98.1% in the low-risk group compared with 79.2% in the high-risk group with a significant difference of p = 0.034. Negative predictive value of normal myocardial perfusion scintigraphy for the occurrence of death was 100%. No significant difference in survival rate among patients with or without chest pain (p = 0.31) was observed. Conclusions: Myocardial perfusion imaging with dipyridamole provided important prognostic information in patients with LBBB; it was useful in stratifying the patients according to cardiovascular morbidity and mortality, and would thus allow the clinician to provide early treatment especially in the high-risk category.