Increasing Nodule Size Research Articles

Alteration Trend and Overlap Analysis of Positive Features in Different-Sized Benign and Malignant Thyroid Nodules: Based on Chinese Thyroid Imaging Reporting and Data System.

This study aimed to investigate the alteration trends and overlaps of positive features in benign and malignant thyroid nodules of different sizes based on the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS). 1337 patients with 1558 thyroid nodules were retrospectively recruited from November 2021 to December 2023. These nodules were divided into three groups according to maximum diameter: A (≤10 mm), B (10-20 mm), and C (≥20 mm). C-TIRADS positive features were compared between benign and malignant thyroid nodules of different sizes. In addition, the trends of positive features with changes in nodule size among malignant thyroid nodules were analyzed. The incidence of positive features in malignant thyroid nodules was higher than that in benign. As benign nodules grow, the incidence of all positive features showed a linear decreasing trend (Z values were 72.103, 101.081, 17.344, 33.909, and 129.304, P values < 0.001). With the size of malignant thyroid nodules increased, vertical orientation, solid, marked hypoechogenicity, and ill-defined/irregular margins/extrathyroidal extension showed a linear decreasing trend (Z = 148.854, 135.378, 8.590, and 69.239, respectively; P values < 0.05), while suspicious microcalcifications showed a linear increasing trend (Z = 34.699, P<0.001). In terms of overlapping characteristics, group A had a significantly higher overlapping rate than the other two groups, and the overlapping rate of solid indicators remained the highest among all three groups (P < 0.05). Differences in positive features were observed between thyroid nodules of different sizes. Except for suspicious microcalcifications, the incidence of other four positive features decreased with increasing nodule size. In addition, a negative correlation was observed between the overlap rate and nodule size. These results may provide a basis for sonographers to upgrade or downgrade thyroid nodules based on their own experience.

Effect of nodule size and stiffness on phonation threshold and collision pressures in a synthetic hemilaryngeal vocal fold model.

Synthetic vocal fold (VF) replicas were used to explore the role of nodule size and stiffness on kinematic, aerodynamic, and acoustic measures of voiced speech production. Emphasis was placed on determining how changes in collision pressure may contribute to the development of phonotrauma. This was performed by adding spherical beads with different sizes and moduli of elasticity at the middle of the medial surface of synthetic silicone VF models, representing nodules of varying size and stiffness. The VF models were incorporated into a hemilaryngeal flow facility. For each case, self-sustained oscillations were investigated at the phonation threshold pressure. It was found that increasing the nodule diameter increased the open quotient, phonation threshold pressure, and phonation threshold flow rate. However, these values did not change considerably as a function of the modulus of elasticity of the nodule. Nevertheless, the ratio of collision pressure to subglottal pressure increased significantly for both increasing nodule size and stiffness. This suggests that over time, both growth in size and fibrosis of nodules will lead to an increasing cycle of compensatory vocal hyperfunction that accelerates phonotrauma.

Application of Convolution Neural Network Algorithm Based on Multicenter ABUS Images in Breast Lesion Detection.

ObjectiveThis study aimed to evaluate a convolution neural network algorithm for breast lesion detection with multi-center ABUS image data developed based on ABUS image and Yolo v5.MethodsA total of 741 cases with 2,538 volume data of ABUS examinations were analyzed, which were recruited from 7 hospitals between October 2016 and December 2020. A total of 452 volume data of 413 cases were used as internal validation data, and 2,086 volume data from 328 cases were used as external validation data. There were 1,178 breast lesions in 413 patients (161 malignant and 1,017 benign) and 1,936 lesions in 328 patients (57 malignant and 1,879 benign). The efficiency and accuracy of the algorithm were analyzed in detecting lesions with different allowable false positive values and lesion sizes, and the differences were compared and analyzed, which included the various indicators in internal validation and external validation data.ResultsThe study found that the algorithm had high sensitivity for all categories of lesions, even when using internal or external validation data. The overall detection rate of the algorithm was as high as 78.1 and 71.2% in the internal and external validation sets, respectively. The algorithm could detect more lesions with increasing nodule size (87.4% in ≥10 mm lesions but less than 50% in <10 mm). The detection rate of BI-RADS 4/5 lesions was higher than that of BI-RADS 3 or 2 (96.5% vs 79.7% vs 74.7% internal, 95.8% vs 74.7% vs 88.4% external). Furthermore, the detection performance was better for malignant nodules than benign (98.1% vs 74.9% internal, 98.2% vs 70.4% external).ConclusionsThis algorithm showed good detection efficiency in the internal and external validation sets, especially for category 4/5 lesions and malignant lesions. However, there are still some deficiencies in detecting category 2 and 3 lesions and lesions smaller than 10 mm.

Ultrasound Prediction of Segmental Bowel Resection in Women with Rectovaginal Endometriosis: A Single-Center Experience

To retrospectively evaluate the ability of routinely collected preoperative ultrasound data to predict bowel resection during surgery for rectovaginal endometriosis. Patients at the University College London Hospital who underwent surgery for rectovaginal endometriosis during a 6-year period were identified from the prospectively generated hospital (British Society for Gynaecological Endoscopy) database. Imaging data were collected and analyzed to determine associations with the requirement for bowel resection. We evaluated 228 consecutive women undergoing bowel surgery (shave, disc resection, or segmental resection) for rectovaginal endometriosis. The patients in our study underwent surgical resection of rectovaginal endometriosis and interventions included shave, disc resection, and segmental resection of the bowel. All patients underwent a preoperative transvaginal ultrasound to assess the extent of endometriosis. There were 206 rectal shaves (90.4%), 2 disc resections (0.9%), and 20 segmental bowel resections (8.8%). A multivariable analysis demonstrated an association between bowel resection and ≥2 nodules located in the rectovaginal space (odds ratio [OR] 6.85; 95% confidence interval [CI], 1.37-34.2), nodules in the vesicouterine pouch (OR 5.87; 95% CI, 1.03-33.3), and increasing nodule size (OR 2.39 per 1 cm increase per 1 cm diameter increase; 95% CI, 1.56-3.64). Ultrasound findings of endometriotic nodule location, number of nodules, and increasing size are independent predictors of segmental bowel resection at the time of surgery for rectovaginal endometriosis. This highlights the importance of accurate diagnostic evaluation to aid counseling and surgical planning in the preoperative setting for women with rectovaginal endometriosis.

Total laparoscopic hysterectomy in patients with deep endometriosis: Different technical and postoperative considerations, in comparison with a procedure performed for other benign indications

ObjectiveTotal laparoscopic hysterectomy (TLH) may be indicated in patients with deep infiltrative endometriosis (DIE) to treat severe chronic pelvic pain symptoms, recurrences, or co-existing uterine disease. This study discusses the challenges and specific operative and postoperative considerations in patients submitted to TLH and excision of DIE, in comparison with those undergoing a procedure for other benign indications. Materials and methodsPatients undergoing TLH and excision of DIE were included (N = 18, group 1). These were matched with cases, treated with TLH for other benign indications during the same period (2010–2019), at a 2:1 ratio (N = 36, group 2). The two groups were compared with regards to their characteristics, and intraoperative and postoperative data, including operative time, estimated blood loss (EBL), hospital stays, and rates of complications. ResultsIn group 1, median DIE nodule size was 2.5 cm (range: 1.3–4.2). Simple hysterectomy was performed in 10, and a more extended procedure in 8 cases. All nodules were removed from the bowel wall using the shaving technique. Average EBL was significantly higher (p = .027), and duration of surgery and hospital stays longer (p = .003, and p = .0001, respectively), in group 1 vs. group 2. The rates of long-term (L-T) complications were higher in group 1 but not to a significant level (p = .087). Analysis within the DIE group showed that operative time was significantly related to nodule size, type of hysterectomy (p = .021), presence of adenomyosis (p = .041), uterine size ≥12weeks (p = .039), and the occurrence of L-T complications (p = .016). Increasing nodule size and an extended procedure (p = .005) increased significantly the EBL, which had also a significant effect on the risk of L-T complications (p = .006). ConclusionsTLH in DIE patients is a different, complex and potentially more dangerous procedure compared with TLH for other benign indications. Thorough knowledge of retroperitoneal anatomy, a clear operative plan, and excellent laparoscopic skills are necessary for concomitant radical excision of lesions, with low rates of adverse events.

Is patient age associated with risk of malignancy in a ≥4 cm cytologically benign thyroid nodule?

BackgroundCurrent data regarding the risk of malignancy in a large thyroid nodule with benign fine-needle aspiration biopsy(FNAB) is conflicting. We investigated the impact of patient age on the risk of malignancy in nodules≥4 cm with benign cytology. MethodsWe performed a single-institution retrospective review of patients who underwent surgery from 07/2008–08/2019 for a cytologically benign thyroid nodule ≥4 cm. The relationship between malignant histopathology and patient and ultrasound features was assessed with multivariable logistic regression. ResultsOf 474 nodules identified, 25(5.3%) were malignant on final pathology. In patients <55 years old, 21/273(7.7%) nodules were malignant, compared to 4/201(2.0%) in patients ≥55. Patient age ≥55 was independently associated with significantly lower risk of malignancy(OR:0.2,95%CI:0.1–0.7,p = 0.011). Increasing nodule size >4 cm and high-risk ultrasound features were not associated with risk of malignancy(OR:1.0,95%CI:0.7–1.4,p = 0.980, and OR:9.6,95%CI:0.9–107.8,p = 0.066, respectively). ConclusionsPatients <55 years old are 3.7-fold more likely to have a falsely benign FNA biopsy in a nodule≥4 cm.

Thyroid Nodule Size and Prediction of Cancer: A Study at Tertiary Care Hospital in Saudi Arabia.

BackgroundThyroid noduleshave become relatively common in clinical practice,and their prevalence increases with age. The majority of thyroid nodules are benign, with 5-15% being malignant. There are a number of well-established predictors of malignancy in thyroid nodules, but thyroid nodule size has been a cause for concern for many researchers and results of the studies are still controversial about their probability of malignancy. Up to the current knowledge, there is no published study that evaluates if thyroid nodule size is associated with the risk of malignancy in Saudi Arabia, so in this study, we aim to find that.MethodsThis is a retrospective study of 987 patients who underwent thyroid nodule fine-needle aspiration (FNA) and subsequent thyroidectomy for thyroid nodules measuring ≥ 1 cm.ResultsThyroid cancer was more prevalent in males than females, and in patients who were older than or equal to 45 years. Nodular size of 1 - 1.9 cm was more prevalent among cancer patients than in benign cases (p<0.001).ConclusionsThe highest malignancy risk was observed in nodules <2 cm and no increase in malignancy risk for nodules >2 cm. Nevertheless, when examined by type of thyroid malignancy, the rate of follicular carcinoma and other rare malignancy increased with increasing nodule size.

Clinico-pathological profile of solitary pulmonary nodule presenting to a tertiary care hospital-a cross sectional study

Background: The diagnosis, classification and management of a solitary pulmonary nodule (SPN) have always been a challenge for the clinicians and radiologists. All SPNs should be considered malignant until proven otherwise. Malignancy risk rises with increasing nodule size. Hence evaluation of the various clinical and pathological presentations of SPN is essential. Methodology: A hospital-based cross-sectional study was conducted in a tertiary care teaching hospital on 70 cases of SPN. Chest X-ray, CT (Computed Tomography) and bronchoalveolar lavage were used for analysing the SPN. IBM SPSS version 22 was used for statistical analysis. Results: The incidence of SPN in this study was 1.33 per 1000 population. The total number of chest X-rays screened were 5263. The most common risk factors were exposure to PTB (Pulmonary Tuberculosis) or history of PTB (97.1%), followed by smoking (81.4%), history of STD (32.9%). Dry cough was the most common symptom among (20%). In X-ray, in 57.1% of subjects, the upper lobes were involved. Lesions were central in 41.4% while peripheral in 58.6%. The proportion of nodules with 1.1 to 2cm and above 2 cm was 22.85% and 77.15%. No calcification was found in 78.6% of nodules. In SPN the most common final diagnosis was tuberculosis (14.3%) followed by Pneumonia/abscess (8.6%) and Squamous cell carcinoma and Pseudotumor (5.71% each). 20% of SPN were malignant. 11.42% of nodules turned out to be primary lung malignancy while 1.42% were metastasis and 7.1% were small cell carcinoma. Conclusions: SPN is a common incidental and radiologic finding. Some internal features of SPNs can help in differentiating benign from malignant lesions. Despite radiological imaging, still, a large number of nodules have to be described as “indeterminate” and advanced and often more invasive techniques are needed for further work-up. Keywords: Solitary pulmonary nodule (SPN); Malignancy, Incidence; Bronchoalveolar lavage.

Size and Ultrasound Features Affecting Results of Ultrasound-Guided Fine-Needle Aspiration of Thyroid Nodules.

Our goal was to assess the diagnostic efficacy of ultrasound (US)-guided fine-needle aspiration (FNA) of thyroid nodules according to size and US features. A retrospective correlation was made with 1745 whole thyroidectomy and hemithyroidectomy specimens with preoperative US-guided FNA results. All cases were divided into 5 groups according to nodule size (≤5, 5.1-10, 10.1-15, 15.1-20, and >20 mm). For target nodules, static images and cine clips of conventional US and color Doppler were obtained. Ultrasound images were reviewed and evaluated by two radiologists with at least 5 years US working experience without knowing the results of pathology, and then agreement was achieved. The Bethesda category I rate was higher in nodules larger than 15 mm (P < .05). The diagnostic accuracy was best in nodules of 5 to 10 mm in diameter. The sensitivity, accuracy, PPV, and LR for negative US-guided FNA results were better in nodules with a size range of 5 to 15 mm. The specificity, negative predictive value (NPV), and LR for positive results and the Youden index rose with increasing nodule size. Seventeen false-positive and 60 false-negative results were found in this study. The false-negative rate rose with increasing nodule size. However, the false-positive rate was highest in the group containing the smallest nodules. Nodules with circumscribed margins and those that were nonsolid and nonhypoechoic and had no microcalcifications correlated with Bethesda I FNA results. Nodules with circumscribed margins and those that were nonsolid, heterogeneous, and nonhypoechoic and had increased vascularity correlated with false-negative FNA results. Borders correlated with Bethesda I false-negative and false-positive FNA results. Tiny nodules (≤5 mm) with obscure borders tended to yield false-positive FNA results. Large nodules (>20 mm) with several US features tended to yield false-negative FNA results.

Examining the Bethesda criteria risk stratification of thyroid nodules

BackgroundThe Bethesda criteria are proposed for appropriate stratification of malignancy risk in thyroid nodules, but controversy exists regarding their accuracy and reliability in decision making. Additionally, previous studies have suggested higher rates of both malignancy and false negative fine needle aspiration biopsy (FNA) associated with increasing nodule size. This study aims to determine the accuracy of ultrasound (US)-guided FNA using the current Bethesda criteria in surgical practice. We also aimed to investigate the relationship between nodule size and malignancy. MethodsA retrospective analysis of US-guided FNAs by a single surgeon during a 4.5 year period. FNA results using Bethesda criteria were compared to final surgical pathology. Results611 patients with thyroid nodules underwent US-guided FNA. FNA results in 375 subsequently excised thyroid nodules were recorded according to the Bethesda criteria: 192 (51%) benign, 65 (17%) atypia of unknown significance/follicular lesion of undetermined significance (AUS/FLUS), 42 (11%), suspicious for follicular neoplasm (SFN), 17 (5%) suspicious for malignancy (SM), 28 (8%) malignancy, and 31 (8%) non-diagnostic. Malignancy was confirmed by surgical pathology in 15%, 34%, 50%, 88%, 100%, and 39% of the above groups respectively. Sensitivity, specificity, and false-negative rate were 61%, 99%, and 15% respectively. No correlation existed between the size of nodules with indeterminate FNA results and malignancy rate (p=0.89), or size of nodules with non-diagnostic FNA and malignancy rate (p=0.50). ConclusionThe current Bethesda risk stratification system underestimated malignancy rates in benign, indeterminate and non-diagnostic cytopathologic categories in our experience. There was no positive linear correlation between nodule size and malignancy rate in these cytopathologic categories.

Malignancy Rate in Thyroid Nodules Classified as Bethesda Category III (AUS/FLUS)

The Bethesda System for Reporting Thyroid Cytopathology is the standard for interpreting fine needle aspiration (FNA) specimens. The "atypia of undetermined significance/follicular lesion of undetermined significance" (AUS/FLUS) category, known as Bethesda Category III, has been ascribed a malignancy risk of 5-15%, but the probability of malignancy in AUS/FLUS specimens remains unclear. Our objective was to determine the risk of malignancy in thyroid FNAs categorized as AUS/FLUS at a comprehensive cancer center. The management of 541 AUS/FLUS thyroid nodule patients treated at Memorial Sloan-Kettering Cancer Center between 2008 and 2011 was analyzed. Clinical and radiologic features were examined as predictors for surgery. Target AUS/FLUS nodules were correlated with surgical pathology. Of patients with an FNA initially categorized as AUS/FLUS, 64.7% (350/541) underwent immediate surgery, 17.7% (96/541) had repeat FNA, and 17.6% (95/541) were observed. Repeat FNA cytology was unsatisfactory in 5.2% (5/96), benign in 42.7% (41/96), AUS/FLUS in 38.5% (37/96), suspicious for follicular neoplasm in 5.2% (5/96), suspicious for malignancy in 4.2% (4/96), and malignant in 4.2% (4/96). Of nodules with two consecutive AUS/FLUS diagnoses that were resected, 26.3% (5/19) were malignant. Among all index AUS/FLUS nodules (triaged to surgery, repeat FNA, or observation), malignancy was confirmed on surgical pathology in 26.6% [CI 22.4-31.3]. Among AUS/FLUS nodules triaged to surgery, the malignancy rate was 37.8% [CI 33.1-42.8]. Incidental cancers were found in 22.3% of patients. On univariate logistic regression analysis, factors associated with triage to surgery were younger patient age (p<0.0001), increasing nodule size (p<0.0001), and nodule hypervascularity (p=0.032). In patients presenting to a comprehensive cancer center, malignancy rates in nodules with AUS/FLUS cytology are higher than previously estimated, with 26.6-37.8% of AUS/FLUS nodules harboring cancer. These data imply that Bethesda Category III nodules in some practice settings may have a higher risk of malignancy than traditionally believed, and that guidelines recommending repeat FNA or observation merit reconsideration.

Chest Tomosynthesis: Technical and Clinical Perspectives

The recent implementation of chest tomosynthesis is built on the availability of large, dose-efficient, high-resolution flat panel detectors, which enable the acquisition of the necessary number of projection radiographs to allow reconstruction of section images of the chest within one breath hold. A chest tomosynthesis examination obtains the increased diagnostic information provided by volumetric imaging at a radiation dose comparable to that of conventional chest radiography. There is evidence that the sensitivity of chest tomosynthesis may be at least three times higher than for conventional chest radiography for detection of pulmonary nodules. The sensitivity increases with increasing nodule size and attenuation and decreases for nodules with subpleural location. Differentiation between pleural and subpleural lesions is a known pitfall due to the limited depth resolution in chest tomosynthesis. Studies on different types of pathology report increased detectability in favor of chest tomosynthesis in comparison to chest radiography. The technique provides improved diagnostic accuracy and confidence in the diagnosis of suspected pulmonary lesions on chest radiography and facilitates the exclusion of pulmonary lesions in a majority of patients, avoiding the need for computed tomography (CT). However, motion artifacts can be a cumbersome limitation and breathing during the tomosynthesis image acquisition may result in severe artifacts significantly affecting the detectability of pathology. In summary, chest tomosynthesis has been shown to be superior to chest conventional radiography for many tasks and to be able to replace CT in selected cases. In our experience chest tomosynthesis is an efficient problem solver in daily clinical work.

Fast Scanning Tomosynthesis for the Detection of Pulmonary Nodules

: To evaluate the diagnostic performance of fast scanning tomosynthesis in comparison with that of chest radiography for the detection of pulmonary nodules, using multidetector-row computed tomography (MDCT) as the reference, and to assess the association of the true-positive fraction (TPF) with the size, CT attenuation value, and location of the nodules. : The institutional review board approved this study, and written informed consent was obtained from all patients. Fifty-seven patients with and 59 without pulmonary nodules underwent chest MDCT, fast scanning tomosynthesis, and radiography. The images of tomosynthesis and radiography were randomly read by 3 blinded radiologists; MDCT served as the reference standard. Free-response receiver-operating characteristic (FROC) and receiver-operating characteristic (ROC) analyses, Cochran-Armitage trend or Fisher exact test, a conditional logistic regression model, and McNemar test were used. : Both FROC and ROC analyses revealed significantly better performance (P < 0.01) of fast scanning tomosynthesis than radiography for the detection of pulmonary nodules. For fast scanning tomosynthesis, the average TPF and false-positive rate as determined by FROC analysis were 0.80 and 0.10, respectively. For both fast scanning tomosynthesis and radiography, the average TPF increased with increasing nodule size and CT attenuation values, and was lower for subpleural nodules (all P < 0.01). : The diagnostic performance of fast scanning tomosynthesis for the detection of pulmonary nodules was significantly superior to that of radiography. The TPF was affected by the size, CT attenuation value, and location of the nodule, in both fast scanning tomosynthesis and radiography.

Diagnostic Accuracy of Surgeon-Performed Ultrasound-Guided Fine-Needle Aspiration of Thyroid Nodules

There is scant data concerning surgeon-performed thyroid fine-needle aspiration (FNA), and controversy regarding its accuracy in larger nodules. This study aimed to specifically assess accuracy of surgeon-performed ultrasound (US)-guided FNA on a per-nodule basis, with a subanalysis of nodule size. Data of 1,000 surgeon-performed US-guided thyroid FNAs at a single institution from 2000 to 2010 were prospectively collected. Standard clinical information, FNA results using the Bethesda criteria, and final histology were recorded. Fine-needle aspiration results were reported as: cancer (7%), suspicious for cancer (2%), suspicious for follicular neoplasm (17%), atypia of unknown significance (AUS) (1%), benign (67%), and insufficient (6%). Of nodules with FNA results of cancer, suspicious for cancer, suspicious for follicular neoplasm, and atypia of unknown significance, 94% were operated on, with malignancy rates of 97%, 58%, 21%, and 12%, respectively. Of nodules with benign FNA, 26% underwent surgery for associated symptoms, concerning features, or other remote pathology. A total of 56% were followed, and 18% were lost to follow-up. Of nodules with insufficient FNA, 46% had repeat FNA (yielding a diagnosis in 81%), 23% underwent surgery, 21% with hypocellular features were followed, and 9% were lost to follow-up. In size subanalysis, there was no statistically significant difference in risk of malignancy or increased rate of falsely negative FNA with increasing nodule size. The Bethesda system appropriately stratified lesions for risk of malignancy, and repeat FNA had high diagnostic yield in lesions with inadequate FNA. The results suggest no trend toward larger lesions harboring thyroid malignancy nor an increased likelihood of false-negative benign FNA.

Diagnostic lobectomy is not routinely required to exclude malignancy in thyroid nodules greater than four centimetres

Surgical excision has been recommended as a diagnostic test for thyroid nodules ≥ 4 cm, due to the supposedly higher rate of cancer in larger nodules and the higher reported false-negative rates of fine-needle aspiration cytology (FNAC) testing (>10%). The aims of this study are to determine the prevalence of thyroid cancer in nodules ≥ 4 cm, to examine if a relationship between increasing nodule size and malignancy rate was present and to study the accuracy of preoperative FNAC diagnosis. Retrospective analysis of data from patients with thyroid nodules ≥ 4 cm undergoing surgical resection between 1994 and 2008. Malignancy rates, cytology results and indications for surgery were analysed. A total of 223 patients with thyroid nodules ≥ 4 cm underwent thyroid resection between 1994 and 2008. The overall prevalence of thyroid cancer was 7.2% (95% confidence interval (CI): 4.2-11.4%). The malignancy rate did not vary significantly with increasing nodule size. The sensitivity of FNAC was 93.8% (95% CI: 69.8-99.8%), while the specificity of FNAC was 62.2% (95% CI: 54.9-69.2%). The most common indicator for surgery was compression symptoms. A positive FNAC test was the most significant indicator of underlying malignancy, with a likelihood ratio of 2.5 (95% CI: 2.0-3.1). Many patients with large thyroid nodules undergo thyroidectomy for symptom relief alone, regardless of their FNAC results. In such patients where other clinical indicators for thyroidectomy are not present, a benign FNAC result can reassure both patient and surgeon that mandatory surgical excision is not needed to exclude malignancy.

Tumor platinum concentration following intraperitoneal administration of cisplatin versus carboplatin in an ovarian cancer model

Objective Current intraperitoneal (IP) regimens for the treatment of ovarian cancer rely on cisplatin (DDP) whereas intravenous regimens rely on carboplatin (CBDCA). A major question in the field is whether CBDCA can replace DDP for IP treatment. We compared the uptake of IP administered DDP and CBDCA into human ovarian carcinoma nodules of various sizes growing on the peritoneal surface of nu/nu mice. Methods Human 2008 cells expressing GFP were inoculated IP in nu/nu mice. When small tumor nodules became visible by external imaging, a maximum tolerated dose of DDP, or either an equimolar or equitoxic dose of CBDCA, was injected IP. Platinum (Pt) concentration in tumor nodules was measured by inductively coupled plasma mass spectrometry. Results A total of 749 tumors harvested from 33 mice were analyzed for Pt concentration. DDP produced a 3.4-fold higher level of Pt in tumor nodules when compared to an equimolar dose of CBDCA ( p = 0.02). However, when DDP and CBDCA were injected at doses that were equitoxic to the mice, tumor Pt levels were equivalent ( p = 0.63). Although Pt concentrations of equal-sized nodules were highly variable, tumor Pt content (ng Pt/mg tumor) decreased with increasing nodule size following IP DDP, an effect not seen with IP administration of equitoxic doses of CBDCA ( p < 0.001). Conclusions These results suggest that IP CBDCA has comparable or better drug penetration when compared to DDP given at equitoxic doses, and thus provide support for replacing DDP with CBDCA in the IP treatment of patients with ovarian cancer.

Small pulmonary nodules: reproducibility of three-dimensional volumetric measurement and estimation of time to follow-up CT.

To determine reproducibility of volume measurements of small pulmonary nodules on computed tomographic (CT) scans and to estimate critical time to follow-up CT. One hundred fifteen pulmonary nodules for which two thin-section small-field-of-view CT scans were obtained and which were stable during 2-year observation were evaluated. A standard group of 94 nodules (with no or minimal artifact) and an expanded group of 105 nodules (including those with moderate artifacts) were examined. Percentage volume change (PVC) and monthly volumetric growth index (MVGI) were computed for each nodule pair. By using estimates of the variation in PVC in stable nodules as a function of initial diameter, critical time to follow-up CT was estimated; this time is the earliest point at which growth in a nodule of a given size can be reliably identified with repeat CT. The SD of PVC decreased with increasing nodule size from 18.5% in 2-5-mm nodules to 10.6% in 5-8-mm nodules and to 7.47% in 8-10-mm nodules. Inclusion of cases with moderate motion artifacts increased the SD of PVC to 27.4% in 2-5-mm nodules, to 17.1% in 5-8-mm nodules, and to 19.3% in 8-10-mm nodules. Critical time to follow-up CT for nodules detected at baseline screening was 12, 5, and 3 months and 1 month for those with initial sizes of 2, 5, 8, and 10 mm, respectively. For nodules detected at annual repeat screening, it was 4 and 3 months and 1 month for nodules that were 3, 4, and 5 mm or larger in size, respectively. Mean MVGI in 94 standard cases was 0.06%, and standard error was 0.21%. Factors that affect reproducibility of nodule volume measurements and critical time to follow-up CT include nodule size at detection, type of scan (baseline or annual repeat) on which the nodule is detected, and presence of patient-induced artifacts.

Invited commentary

Invited commentary

Follow-Up Evaluation and Clinical Course of Patients with Benign Nodular Thyroid Disease

Reliance on fine-needle aspiration biopsy (FNAB) in determining which patients with a thyroid nodule can be observed depends on a low false-negative rate. The purpose of this study was to determine the false-negative rate of FNAB, the utility of routine repeat FNAB, and the clinical course of patients with benign nodular thyroid disease. The records of all patients with nodular thyroid disease evaluated between June 1990 and May 1998 were reviewed. Patients with a benign FNAB were identified, and nodule size, substernal extension, the results of repeat FNAB, clinical course, histologic diagnosis, and length of follow-up were determined. Of the 341 patients referred with nodular thyroid disease, 121 had a benign FNAB. In 80 patients with a mean nodule size of 3.5 +/- 1.6 cm, clinical follow-up was recommended. The mean duration of follow-up was 20.5 months for 74 patients, and 6 patients were lost to follow-up. Nodule resolution was observed in 7 patients. Repeat FNAB was performed in 45 patients and was benign in 39 (87%), nondiagnostic in 2 (4%), cellular in 3 (7%), and malignant in 1 (2%). Thyroidectomy was performed in the patients with the cellular and malignant aspirates, and the pathology was adenomatous hyperplasia (2), follicular adenoma (1), and papillary carcinoma (1). Thyroidectomy was performed for increasing nodule size and/or compressive symptoms in 41 patients with a mean nodule size of 5.7 +/- 1.9 cm, 19 of whom had substernal extension (P < 0.05). Pathology included benign disease in 39, papillary cancer in 1, and lymphoma arising in Hashimoto's thyroiditis in 1 patient. Given that repeat FNAB was of value in only 1 patient and the false-negative rate for FNAB was only 2.5 per cent, the routine use of repeat FNAB in patients with benign nodular thyroid disease may not be justified. Development of compressive symptoms and diagnosis of unsuspected malignancy in patients with nodule enlargement, including lymphoma in patients with Hashimoto's thyroiditis, underscores the importance of long-term follow-up.

Enhancing effects of carbon tetrachloride in mouse hepatocarcinogenesis

The enhancing effects of 4 or 8 necrogenic doses of carbon tetrachloride (CCl 4) on hepatocarcinogenesis were studied in female B6C3F1 mice previously treated with a single dose of N-nitroso- N-diethylamine (NDEA) at 7 days of age. The CCl 4 treatments were given every other week and started either after weaning or at 18–26 weeks of age, and the animals were observed until 36 weeks of age. The number and size of hepatocellular nodules were then scored and analysed. Hepatocellular nodules were not observed in mice receiving either 4 or 8 CCl 4 treatments without NDEA initiation. Both 4 and 8 CCl 4 treatments promoted NDEA-initiated hepatocarcinogenesis, increasing nodule size but not nodule frequency. Eight CCl 4 doses were more effective than 4 and gave the greatest increase in nodule size when administered from 18 to 32 weeks of age. In an additional experiment, 3 mice bearing hepatocellular nodules induced by a single infantile NDEA treatment were administered CCl 4 once and killed 52 h later. Nine neoplastic nodules were examined and found to be resistant to the CCl 4 induced necrosis, although cells in the nodules were actively dividing at the same rate as in the regenerating surrounding normal liver parenchyma. The ability of a few necrogenic CCl 4 doses to enhance hepatocarcinogenesis may be related to a differential cytotoxicity on neoplastic and normal hepatocytes and to a similar mitogenic stimulus on both cell types.