[MICRO- AND ULTRASTRUCTURAL RECONSTRUCTION OF THE RAT SUBMANDIBULAR GLAND IN THE LATE STAGES OF EXPERIMENTAL TYPE 2 DIABETES MELLITUS].

Electron microscopic investigations of the animals' submandibular gland, conducted in 6 weeks of the experiment, established that ultrastructural changes increase in glandular cells of terminal secretory units in comparison with early period of the experiment. Serocytes have osmiophilic, rather small or picnotic nuclei. Perinuclear spaces of karyolemma are uneven, external nuclear membrane forms local protrusions. Electron density of the karyoplasm is significant, appearing homogenous, nuclei are not observed. Evident submicroscopic changes in blood capillaries of the submandibular gland in experimental diabetes mellitus indicate the impairment of blood-tissue barrier and transcapillary exchange. Deep destructive modifications of all branches of microcirculatory blood flow of the submandibular gland are observed in 8-week course of experimental diabetes mellitus. As compared with the 6th week of investigation, a reliable slight dilation of organ artery diameter, dilation of the diameter of interlobular arterioles, dilation of the diameter of intralobular (precapillary) arteriole and dilation of the capillary diameter were observed. Dilation, as compared to 6th weeks of the experiment, of postcapillary venules was observed. Compared to the indices of the 6th weeks of the experiment, an index of trophic activity of the submandibular gland tissuereaches its maximum meaning and an index of packing density of the capillaries reaches its minimum meaning. Capillary network loses delicate, tortuous pattern and often breaks due to destruction of the capillary component. Arteriovenous anastomoses dilate and blood from the arterioles flows into the venous bed avoiding destructed capillaries. Venules are dilated; thin-walled, retained fragments of the capillaries are significantly dilated in some areas. Swelling of connective tissue stroma and significant swelling of the interstitium are observed. Walls of the capillaries and venules are deformed. The walls of the arterioles are thickened due to plasmorrhagia, sclerosis and hyalinosis.

Long-term regional control in the observed neck following definitive chemoradiation for node-positive oropharyngeal squamous cell cancer.

Traditionally, patients treated with chemoradiotherapy for node-positive oropharyngeal squamous cell carcinoma (N+ OPSCC) have undergone a planned neck dissection (ND) after treatment. Recently, negative post-treatment positron-emission tomography (PET)/computed tomography (CT) imaging has been found to have a high negative predictive value for the presence of residual disease in the neck. Here, we present the first comprehensive analysis of a large, uniform cohort of N+ OPSCC patients achieving a PET/CT-based complete response (CR) after chemoradiotherapy, and undergoing observation, rather than ND. From 2002 to 2009, 302 patients with N+ OPSCC treated with 70 Gy intensity-modulated radiation therapy and concurrent chemotherapy underwent post-treatment clinical assessment including PET/CT. CR was defined as no evidence of disease on clinical examination and post-treatment PET/CT. ND was reserved for patients with

Fluoro-deoxy-glucose positron emission tomography for evaluation of indeterminate lung nodules: assigning a probability of malignancy may be preferable to binary readings.

OBJECTIVE: To assess the diagnostic value of fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) using standard uptake values (SUV) in the differential diagnoses of indeterminate pulmonary nodules. Specifically, we assessed the probability of malignancy for various SUV ranges, and compared the diagnostic efficacy of SUV with and without correction for partial volume effects on the basis of lesion size. METHODS: The FDG-PET scans performed on 158 patients with biopsy-proven pulmonary lesions seen on computed tomography (CT) scan were retrospectively reviewed. Histopathological confirmation was obtained to establish the diagnosis of the lesions. A region of interest (ROI) was drawn for each lesion, and FDG uptake was quantified (SUV(raw)). The SUV(raw) values were normalized for the "size" of the pulmonary lesions measured on CT (SUV(size)). Sensitivity and specificity of FDG-PET for pulmonary lesions <2 cm in diameter or > or =2 cm in diameter were determined at SUV cutoff values of 2.5. The areas under the receiver-operating characteristic (ROC) curve for SUV(raw) and SUV(size) regarding the presence of malignancy were compared for statistical differences. The frequency of malignant lesions for each range of SUVs was obtained to produce the probability of cancer (POC). RESULTS: The mean SUV(raw) was 3.17 +/- 2.76 and 9.18 +/- 6.72 for benign and malignant lesions, respectively. When a SUV(raw) value of 2.5 was used as a cutoff, sensitivity and specificity were 89% and 51%, respectively, for all lesion sizes. The sensitivity and specificity at a cutoff SUV(raw) of 2.5 for lesions less than 2 cm in diameter were 75% and 72%, respectively, and 92% and 41% for lesions 2 cm or greater, respectively. The sensitivity and specificity at a cutoff SUV(size) of 2.5 were 88% and 42%, respectively. The area under the ROC curves for SUV(raw) and SUV(size) was 0.816 and 0.743, respectively (P value 0.034). When the SUV(raw) was divided into three groups, the probability of malignancy was 26% when the SUV(raw) was <2, 57% for 2 < or = SUV(raw) < 6, and 89% for SUV(raw) > or = 6. CONCLUSIONS: The FDG-PET is a reasonably accurate and useful tool for characterizing the nature of indeterminate pulmonary lesions, although the specificity was not as high as that reported in the literature, probably owing in part to our patient population and selection bias. Our data suggest that reporting the results of PET studies as a probability rather than as positive or negative for malignancy would be more useful for further management decision making. Correction of SUVs for tumor size did not improve accuracy.

Temporal relation between temperature change and FDG uptake in brown adipose tissue.

OBJECTIVES: It has been reported that the prevalence of (18)F fluorodeoxyglucose (FDG) uptake in brown adipose tissue (BAT) is related to outdoor temperature, i.e., more frequent during the colder periods of the year. The purpose of this study was to assess the temporal relationship between BAT FDG uptake and temperature. We correlated the prevalence of BAT with average temperatures (divided into five temperature ranges) of seven different durations. METHODS: One thousand four hundred ninety-five consecutive FDG Positron emission tomography (PET) studies in 1,159 patients (566 male and 593 female, mean age = 60.4 years) were retrospectively reviewed. FDG uptake with distinct patterns compatible with BAT was identified by a consensus of two readers. The local daily average temperature from January 2000 to November 2003 (beginning 60 days before the date of first PET scan) were obtained, and 2-, 3-, 7-, 14-, 30-, and 60-day average temperatures before the date of a PET study were calculated. The prevalence of BAT FDG uptake was correlated with these various average temperatures. RESULTS: The daily, 2-day, 3-day, and 7-day average temperature had an inverse relation with the prevalence of BAT, i.e., the lower the temperature, the higher prevalence of BAT. When the temperature was averaged over 14 days or longer, this inverse relationship between the temperature and the prevalence of BAT was no longer preserved. CONCLUSIONS: Our data suggest that increased FDG uptake in BAT occurs more often as an acute response to cold weather (1-7 days) rather than to prolonged periods of average cold weather.

Appearance of descended superior parathyroid adenoma on SPECT parathyroid imaging.

UNLABELLED: An ectopic superior parathyroid adenoma (SPA) descends inferoposteriorly and can migrate to the posterior mediastinum. It often appears on sestamibi planar parathyroid imaging as an inferior lesion, which can be misleading to inexperienced surgeons. Its correct identification before surgery will be of great help for correct surgical planning. We assessed the appearance of descended SPA on SPECT imaging. METHODS: Sestamibi SPECT imaging studies performed on 103 patients who had parathyroid adenomas with their origin and locations confirmed by surgery and histology were retrospectively reviewed. Abnormal foci seen on the SPECT images were grouped as to location relative to the thyroid gland as superior (S), middle (M), and inferior (I). The proximity between the focus and the thyroid on the sagittal SPECT images was graded from 0 to 2 with 2 being widely separated. RESULTS: Of the 103 SPECT studies, 89 were positive. Eleven of the 89 visualized foci were at the S level: all were SPA. Ten foci were at the M level, including 6 SPA and 4 inferior parathyroid adenomas (IPA). There were 68 foci at the I level; none (0%) of 56 in the I0 location, 2 (25%) of 8 foci in the I1 location, and all (100%) of 4 abnormal foci in the I2 location were descended SPAs. CONCLUSION: The more posteriorly located the abnormal focus, the higher the probability of descended SPA. Recognition of the characteristic appearance of descended SPA on SPECT imaging can have a significant impact on the surgical approach and prevent failed neck exploration.

Patterns of red marrow in the adult femur.

PURPOSE: Conversion of red marrow (RM) to fatty marrow in the skeleton of the lower extremities begins at the distal end, ie, feet, and progresses proximally with distal bone marrow (ie, tibia) being converted more rapidly than proximal bone marrow (ie, femur). However, in an individual long bone, conversion begins in the diaphysis and progresses both distally and proximally (more rapidly toward the distal side). In a normal adult's femur, RM is present in the proximal one third or less. Reconversion of fatty marrow to RM is reported to occur in the reverse order of conversion. We assessed the frequency of various patterns of RM in the adult femur on In-111 leukocyte scans for a better understanding of the bone marrow regeneration process in individual long bones. METHODS: The patterns of marrow activity in the femur shown on In-111 leukocyte scans performed in 354 adults were divided into a) RM limited to the proximal one third or less, b) to the proximal two thirds, c) to the proximal one third and distal one third with no activity in the middle shaft, and d) in the entire femur. RESULTS: There were 207 patients with pattern A, 91 pattern B, 14 pattern C, and 42 pattern D. CONCLUSIONS: A considerably higher number of adults showed pattern B than pattern C. This suggests that regeneration of diaphyseal marrow precedes that of the distal marrow in an individual long bone or possibly that conversion of the latter precedes the former, which is different from that proposed in the literature.

Appearance of intrathymic parathyroid adenomas on pinhole sestamibi parathyroid imaging.

OBJECTIVES: Ectopic inferior parathyroid adenomas (PAs) are frequently located in the anterior mediastinum, quite often in the thymus gland. Correct preoperative localization is particularly helpful for surgical planning. Clinical follow up has shown that most intrathymic adenomas were visualized on pinhole views and located closer to the thyroid than expected. We reviewed the typical appearance of intrathymic PA on pinhole views. METHODS: We retrospectively reviewed sestamibi pinhole parathyroid imaging performed on 163 patients with primary hyperparathyroidism and final diagnoses established by surgery, histology, intraoperative PTH monitoring, and clinical follow up. Studies showing focal increased activity in the lower pole region of the thyroid were selected and divided into 2 groups, group A (foci that are visually not separable from the thyroid) and group B (foci that are completely separated from the thyroid), and correlated with the final diagnoses. RESULTS: Of the 163 patients, 102 had 103 clearly abnormal foci in the lower pole region (bilateral lower pole foci in one study). There were 93 foci in group A and 10 foci in group B. Of the 93 foci in group A, there were 80 normally situated inferior PA, 6 descended superior PA, 3 intrathyroidal PA, one hyperplastic parathyroid gland, one thyroid adenoma, one unidentified, and one intrathymic PA. Of the 10 foci in group B, 3 were eutopic inferior PA and 7 were intrathymic PA. CONCLUSION: Focal increased activity completely separated from the lower pole of thyroid (regardless of the distance of separation) on sestamibi pinhole images indicates a high probability of intrathymic parathyroid adenoma.

Concomitant paravertebral FDG uptake helps differentiate supraclavicular and suprarenal brown fat uptake from malignant uptake when CT coregistration is not available.

OBJECTIVES: Fluorine-18 fluorodeoxyglucose (F-18 FDG) uptake in brown adipose tissue (BAT) in the supraclavicular, superior mediastinal, paravertebral, and suprarenal/perinephric regions has been recognized. Of these 4 areas, uptake in the supraclavicular, mediastinal, and suprarenal areas may be difficult to differentiate from malignancy for those who interpret PET images only without CT coregistration or fusion. We assessed the prevalence and concomitance of F-18 FDG uptake in these 4 BAT regions. METHODS: A total of 1495 F-18-FDG PET studies were reviewed. Distinct patterns compatible with BAT uptake in the 4 regions were graded and correlated with each other. RESULTS: Of the 1495 studies, supraclavicular uptake was seen in 40 (2.7%), paravertebral uptake in 29 (1.9%), mediastinal uptake in 23(1.5%), and suprarenal uptake in 11 (0.7%). Of the 40 studies showing supraclavicular uptake, paravertebral uptake was also seen in 27 (68%), mediastinal uptake in 23 (58%), and suprarenal uptake in 11 (28%). Alternatively, of the 29 studies showing paravertebral uptake, all but 2 studies (93%) also had concomitant supraclavicular uptake. No studies showed isolated mediastinal or suprarenal uptake. All studies with mediastinal uptake also had supraclavicular uptake, and all studies with suprarenal uptake also had paravertebral uptake. CONCLUSIONS: Virtually all of mediastinal and suprarenal BAT uptake was associated with supraclavicular and paravertebral uptake, respectively. Nearly all paravertebral uptake coexisted with supraclavicular uptake. Even when CT coregistration is not available, concomitant paravertebral uptake can help differentiate suprarenal uptake and somewhat less typical supraclavicular BAT uptake from malignant uptake, and concomitant supraclavicular uptake can help differentiate mediastinal uptake from malignant uptake.

Lymphoscintigraphy and triangulated body marking for morbidity reduction during sentinel node biopsy in breast cancer.

Current trends in patient care include the desire for minimizing invasiveness of procedures and interventions. This aim is reflected in the increasing utilization of sentinel lymph node biopsy, which results in a lower level of morbidity in breast cancer staging, in comparison to extensive conventional axillary dissection. Optimized lymphoscintigraphy with triangulated body marking is a clinical option that can further reduce morbidity, more than when a hand held gamma probe alone is utilized. Unfortunately it is often either overlooked or not fully understood, and thus not utilized. This results in the unnecessary loss of an opportunity to further reduce morbidity. Optimized lymphoscintigraphy and triangulated body marking provides a detailed 3 dimensional map of the number and location of the sentinel nodes, available before the first incision is made. The number, location, relevance based on time/sequence of appearance of the nodes, all can influence 1) where the incision is made, 2) how extensive the dissection is, and 3) how many nodes are removed. In addition, complex patterns can arise from injections. These include prominent lymphatic channels, pseudo-sentinel nodes, echelon and reverse echelon nodes and even contamination, which are much more difficult to access with the probe only. With the detailed information provided by optimized lymphoscintigraphy and triangulated body marking, the surgeon can approach the axilla in a more enlightened fashion, in contrast to when the less informed probe only method is used. This allows for better planning, resulting in the best cosmetic effect and less trauma to the tissues, further reducing morbidity while maintaining adequate sampling of the sentinel node(s).

Using the intraoperative hand held probe without lymphoscintigraphy or using only dye correlates with higher sensory morbidity following sentinel lymph node biopsy in breast cancer: a review of the literature.

BACKGROUND: There are no studies that have directly investigated the incremental reduction in sensory morbidity that lymphoscintigraphy images (LS) and triangulated body marking or other skin marking techniques provide during sentinel lymph node biopsy (SLNB) compared to using only the probe without LS and skin marking or using only dye. However, an indirect assessment of this potential for additional sensory morbidity reduction is possible by extracting morbidity data from studies comparing the morbidity of SLNB to that of axillary lymph node dissection. METHODS: A literature search yielded 13 articles that had data on sensory morbidity at specific time points on pain, numbness or paresthesia from SLNB that used radiotracer and probe or used only dye as a primary method of finding the sentinel node (SN). Of these, 10 utilized LS, while 3 did not utilize LS. By matching the data in studies not employing LS to the studies that did, comparisons regarding the percentage of patients experiencing pain, numbness/paresthesia after SLNB could be reasonably attempted at a cutoff of 9 months. RESULTS: In the 7 studies reporting on pain after 9 months (> 9 months) that used LS (1347 patients), 13.8% of patients reported these symptoms, while in the one study that did not use LS (143 patients), 28.7% of patients reported these symptoms at > 9 months (P < 0.0001). In the 6 studies reporting on numbness and/or paresthesia at > 9 months that used LS (601 patients), 12.5% of patients reported these symptoms, while in the 3 studies that did not use LS (229 patients), 23.1% of patients reported these symptoms at > 9 months (P = 0.0002). Similar trends were also noted for all these symptoms at < or = 9 months. CONCLUSION: Because of variations in techniques and time of assessing morbidity, direct comparisons between studies are difficult. Nevertheless at a minimum, a clear trend is present: having the LS images and skin markings to assist during SLNB appears to yield more favorable morbidity outcomes for the patients compared to performing SLNB with only the probe or performing SLNB with dye alone. These results are extremely pertinent, as the main reason for performing SLNB itself in the first place is to achieve reduced morbidity.

Focally increased activity in the lateral aspect of the mid cervical spine on bone scintigraphy is almost always benign in nature.

OBJECTIVES: Abnormal bone scan findings in the spine are often nonspecific. The confidence level for the differential diagnosis between metastases and benign or degenerative changes may vary depending on their appearance, location or intensity. The recognition of a specific pattern for certain benign conditions and its subcategorization will increase the credibility of bone scan interpretation while retaining a high level of sensitivity. We report one such finding, focally increased activity on the lateral side of the cervical spine on the posterior view, most common at the C3-C5 level ("mid-cervical-lateral-focus"). METHODS: Of 481 patients with various cancers who had at least 2 whole-body bone scans, 6 months or more apart, 41 patients were judged to show this characteristic "mid-cervical-lateral-focus" on at least one scan. Final diagnosis (metastasis vs. benign) for each "mid-cervical-lateral-focus" was made based on clinical grounds and serial bone scans. RESULTS: The bone scan showed definite multiple metastases in 15 patients, and the differential diagnosis for the "mid-cervical-lateral-focus" was already clinically irrelevant in these patients. Nevertheless, the "mid-cervical-lateral-focus" was finally judged to be benign in 14 of these 15 patients and in all remaining 26 patients without other obvious metastases. The only "mid-cervical-lateral-focus" judged to be a metastatic focus was not only clinically redundant, but also the most intense among all the "mid-cervical-lateral-foci." in this series (too intense to be interpreted as benign). CONCLUSION: The typical "mid-cervical-lateral-focus" pattern is extremely unlikely to represent metastases (virtually 0% in patients without other obvious metastases). This knowledge helps exclude metastases on bone scans.

Extremely indirect dermal lymphatic channels: value of areolar-cutaneous junction injection technique for breast lymphoscintigraphy.

This case describes a patient who initially had peri-excisional injections of radiocolloid around a lumpectomy site that failed to visualize sentinel nodes during lymphoscintigraphy. After additional areolar-cutaneous junction injections, extremely indirect dermal lymphatic pathways were evident with resultant drainage to two sentinel nodes, both of which contained disease. Hybrid combination injections of radiotracer during sentinel lymph node biopsy is gaining in popularity. This case illustrates the validity of the hybrid injection techniques and the demonstrated accuracy despite seemingly disconnected and extremely tortuous pathways as demonstrated in the figure.

Whole abdominal radiotherapy in the adjuvant treatment of patients with stage III and IV endometrial cancer: a gynecologic oncology group study.

OBJECTIVE: To evaluate toxicity, survival, and recurrence-free interval in women with loco-regionally advanced endometrial carcinoma treated with postoperative whole abdominal radiation therapy. METHODS: Whole abdominal irradiation with pelvic plus or minus para-aortic boost was initiated within 8 weeks of total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic washings, and selective pelvic and para-aortic node sampling in eligible, consenting patients. RESULTS: Of 180 evaluable patients entered on the study with surgically staged III and IV endometrial carcinoma maximally debulked to less than 2 cm, 77 had typical endometrial adenocarcinoma and 103 had high-risk histology, either papillary serous or clear cell carcinoma. Patients with typical endometrial adenocarcinoma were significantly younger and had significantly fewer poorly differentiated cancers. Proportionally, there were twice as many non-Whites with high-risk histologies as non-Whites with typical endometrial adenocarcinoma. Forty-five percent of patients with typical endometrial adenocarcinomas had positive pelvic nodes compared to 51% of those with high-risk histologies. Both histologic groups had similar distribution for performance status, para-aortic node positivity, site and extent of disease, and International Federation of Gynecology and Obstetrics (FIGO) stage. The frequency of severe or life-threatening adverse effects among 174 patients evaluable for radiation toxicity included 12.6% with bone marrow depression, 15% GI, and 2.2% hepatic toxicity. The recurrence-free survival rates were 29% and 27% (at 3 years) for the typical endometrial adenocarcinoma and high-risk histologies, respectively. The survival rates were 31% and 35%, respectively. No patient with gross residual disease survived. CONCLUSION: Whole abdominal irradiation in maximally resected advanced endometrial carcinoma has tolerable toxicity, and it is suggested that the outcome may be improved by this adjunctive treatment in patients with completely resected disease.

Areolar-cutaneous junction injection boosts activity in sentinel node by more than 50 times compared to perilesional injection: implications for morbidity reduction.

The combination of concurrently administered perilesional radiotracer injections and areolar-cutaneous junction radiotracer injections during one imaging session in the detection of sentinel nodes (SN) in breast cancer is new. A case is presented where the perilesional injections of radiotracer produced a faint node. Subsequently, 45 minutes later, the same patient received an injection of radiotracer at the areolar-cutaneous junction, which "boosted" the activity in the original SN by more than 50 times. This case illustrates the marked improvement in SN counts that can occur with the addition of areolar-cutaneous junction injections to perilesional injections. The perilesional component of this hybrid injection technique maintains the ability to visualize internal mammary and extra-axillary SN. Even more importantly, these "hotter" nodes have significant implications for morbidity reduction, the main goal of sentinel lymph node biopsy in itself.

Reducing exposure from 57Co sources during breast lymphoscintigraphy by optimizing energy windows and other suggested enhancements of acquisition and the display of images.

UNLABELLED: We set out to measure the reduction in exposure attained by using a weak 57Co sheet source with optimal energy windows. METHODS: Two groups of 10 lymphoscintigraphy studies were analyzed. Group 1 consisted of 10 studies obtained with a stronger source of 57Co, 59 MBq (1.6 mCi) at the time of data acquisition, with transmission images acquired at 3 energy windows of 115-129, 130-134, and 135-150 keV. Group 2 consisted of 10 studies with a weaker sheet source of 57Co, 11 MBq (0.3 mCi). Transmission images were acquired at 3 energy windows of 112-132, 130-134, and 135-150 keV. Same-sized regions of interest (ROIs) were drawn on the patient's torso (PT) and on the nonattenuated image of the transmission source itself (TS), all 1-min images. The counts in each ROI obtained over 1 min and the ratios between the TS ROI and the PT ROI were calculated for all of the energies. Dosimetry calculations based on measured exposure rates and the activity of the sheet sources were used to calculate the patient equivalent dose at 30 cm. RESULTS: For the 57Co energy window, group 1 had an average ROI count of 1,955 in the TS region and 135 counts in the PT region. The average ratio of TS/PT was 15.4. Similarly, group 2 had an average ROI count of 646.4 in the TS region and 91.2 counts in the PT region. The average ratio of TS/PT was 8.6. The relative "outlining performance," when comparing the 57Co and 99mTc windows, showed an average improvement when using the 57Co window of 4.4 and 5.8 times for group 1 and group 2, respectively (TS/PT at 57Co window)/(TS/PT at 99mTc window). Estimates of the patient equivalent dose per study were 2.30 microSv for the stronger 57Co flood source and 0.46 microSv for the weaker 57Co flood source, a 5-fold reduction in equivalent dose. Technologists received less than half of the above doses. CONCLUSION: Use of expanded, separate energy windows optimized for the primary 122-keV photon of 57Co greatly improves transmission scan image quality compared with the standard 140-keV 99mTc windows used for the delineation of the sentinel node. This markedly reduces exposure for all, by allowing the use of a weaker source, and can save time.