Magnetic Resonance Imaging-Targeted and Systematic Biopsy for Detection of Grade Progression in Patients on Active Surveillance for Prostate Cancer.

PURPOSE: Active surveillance for patients with low and intermediate risk prostate cancers is becoming a more utilized option in recent years. However, the use of magnetic resonance imaging and imaging-targeted biopsy for monitoring grade progression has been poorly studied in this population. We aim to define the utility of magnetic resonance imaging-targeted biopsy and systematic biopsy in an active surveillance population. MATERIALS AND METHODS: Between July 2007 and January 2020, patients with diagnosed prostate cancer who elected active surveillance were monitored with prostate magnetic resonance imaging, imaging-targeted biopsy and standard systematic biopsy. Patients were eligible for surveillance if diagnosed with any volume Gleason grade 1 disease and select Gleason grade 2 disease. Grade progression (Gleason grade 1 to ≥2 disease and Gleason grade 2 to ≥3 disease) for each biopsy modality was measured at 2 years, 4 years and 6+ years. RESULTS: In total, 369 patients had both magnetic resonance imaging-targeted and systematic biopsy and were surveilled for at least 1 year. At 2 years, systematic biopsy, magnetic resonance imaging-targeted biopsy and combined biopsy (systematic+imaging-targeted) detected grade progression in 44 patients (15.9%), 73 patients (26.4%) and 90 patients (32.5%), respectively. Magnetic resonance imaging-targeted biopsy detected more cancer grade progression compared to systematic biopsy in both the low and intermediate risk populations (p <0.001). Of all 90 grade progressions at the 2-year time point 46 (51.1%) were found by magnetic resonance imaging-targeted biopsy alone and missed by systematic biopsy. CONCLUSIONS: Magnetic resonance imaging-targeted biopsy detected significantly more grade progressions in our active surveillance cohort compared to systematic biopsy at 2 years. Our results provide compelling evidence that prostate magnetic resonance imaging and imaging-targeted biopsy should be included in contemporary active surveillance protocols.

PI-RADS® Category as a Predictor of Progression to Unfavorable Risk Prostate Cancer in Men on Active Surveillance.

PURPOSE: We identified baseline imaging and clinical characteristics of patients that may improve risk stratification among patients being evaluated for active surveillance. MATERIALS AND METHODS: From July 2007 to January 2020 patients referred to our institution for prostate cancer were evaluated and those who remained on active surveillance were identified. Men underwent multiparametric magnetic resonance imaging upon entry into our active surveillance protocol during which baseline demographic and imaging data were documented. Patients were then followed and outcomes, specifically progression to Gleason Grade Group (GG)3 or greater disease, were recorded. RESULTS: Of the men placed on active surveillance 344 had at least 1 PI-RADS score documented. For those with an index lesion PI-RADS category of 5, 33% (17/51) had progression to GG3 or greater on active surveillance with a median time to progression of 31 months. When comparing the progression-free survival times and progression rates in each category, PI-RADS category was found to be associated with progression to GG3 or greater on active surveillance (p <0.01). On univariable analysis factors associated with progression included an index lesion PI-RADS category of 5, prostate specific antigen density and the size of the largest lesion. On multivariable analysis only PI-RADS category of 5 and prostate specific antigen density were associated with progression on active surveillance. CONCLUSIONS: PI-RADS lesion categories at baseline multiparametric magnetic resonance imaging during active surveillance enrollment can be used to predict cancer progression to GG3 or greater on active surveillance. This information, along with other clinical data, can better assist urologists in identifying and managing patients appropriate for active surveillance.

Ovarian teratoma in a woodchuck (Marmota monax) with hepatocellular carcinoma: radiologic and pathologic features.

BACKGROUND: Teratomas are germ cell neoplasms composed of a wide variety of tissues. In the woodchuck, only one testicular teratoma has been described in the literature. The objective of this report was to describe the radiologic and pathologic findings in a female woodchuck (Marmota monax) with an ovarian teratoma consisting of mature tissues originating from all three germ layers. CASE PRESENTATION: A 2-year-old female woodchuck that had been infected at birth with woodchuck hepatitis virus and subsequently developed hepatocellular carcinoma was incidentally discovered to have a mobile 6.6 × 4.8 × 4.7 cm abdominal mass on computed tomography (CT) imaging. The tumor was predominantly solid and heterogenous on CT with soft tissue, fat, and areas of dense calcification. The teratoma did not enhance with intravenous contrast administration. On ultrasound, the tumor was solid with heterogeneous echogenicity, reflecting the fat content and areas of calcification. Sonolucent areas were present that may have represented cysts. There was heterogeneously increased signal on T1-weighted magnetic resonance imaging (MRI) and heterogeneous hyperintensity in T2-weighted imaging. Fat was evident within the tumor. At necropsy, the tumor was attached to the distal end of the right uterine horn. Histopathology showed mature tissue types representing all three germ layers. CONCLUSIONS: Ovarian teratoma should be considered in the differential diagnosis of ovarian or abdominal masses in woodchucks. The tumor displayed mature tissue derived from all three germ layers. CT, ultrasound, and MRI findings were presented in detail and matched the typical imaging appearance of teratomas.

Clinical and dosimetric evaluation of recurrent breast cancer patients treated with hyperthermia and radiation.

Background: Treatment for locally recurrent breast cancer poses a significant challenge because the benefits in local control must be weighed against the increased risk of side effects of the treatment. Frequently, patients have been heavily pre-treated with radiation and several types of chemotherapy. Moreover, they often present with large volumes of bulky disease, further complicating management. Hyperthermia can be used to improve the efficacy of radiation, particularly in the setting of recurrent disease. Methods: We reviewed our clinical and dosimetric experience of breast cancer patients who received hyperthermia and radiation for recurrent breast cancer from 2011 to 2017. Thirty-six patients were treated with hyperthermia and radiation. Median follow-up was 11 months. Thirty patients (83.3%) received prior radiotherapy. The most commonly used radiation fraction scheme was 32 Gy in 8 fractions. The median radiation dose at the time of recurrence was 35.5 Gy (range 20-64 Gy). Mild temperature hyperthermia was delivered two times per week. Results: The median repeat radiation volume was 574 cc (range 11-3620 cc). Electrons, conventional photons, and IMRT radiation techniques were used. IMRT was used for large and complex treatment volumes and showed acceptable doses to organs at risk. The overall response rate was 61.1%. Complete response was observed in 17 patients (47.2%), partial response in 5 patients (13.9%), stable disease in 11 patients (30.6%), and progressive disease in 3 patients (8.3%). Twenty-six patients experienced acute grade 1 and 2 toxicities, primarily pain and erythema; and 26 experienced long-term grade 1 and 2 toxicities, mainly hyperpigmentation and lymphedema. Three patients developed new ulcerations that healed with conservative management. One patient developed pulmonary fibrosis resulting in mild dyspnea on exertion. Conclusion: Hyperthermia and radiation provide good local control with a favorable side effect profile. Thermoradiotherapy may be offered to patients with recurrent breast cancer, including those with extensive volumes of disease.

Visualizing the Propagation of Acute Lung Injury.

BACKGROUND: Mechanical ventilation worsens acute respiratory distress syndrome, but this secondary "ventilator-associated" injury is variable and difficult to predict. The authors aimed to visualize the propagation of such ventilator-induced injury, in the presence (and absence) of a primary underlying lung injury, and to determine the predictors of propagation. METHODS: Anesthetized rats (n = 20) received acid aspiration (hydrochloric acid) followed by ventilation with moderate tidal volume (V(T)). In animals surviving ventilation for at least 2 h, propagation of injury was quantified by using serial computed tomography. Baseline lung status was assessed by oxygenation, lung weight, and lung strain (V(T)/expiratory lung volume). Separate groups of rats without hydrochloric acid aspiration were ventilated with large (n = 10) or moderate (n = 6) V(T). RESULTS: In 15 rats surviving longer than 2 h, computed tomography opacities spread outward from the initial site of injury. Propagation was associated with higher baseline strain (propagation vs. no propagation [mean ± SD]: 1.52 ± 0.13 vs. 1.16 ± 0.20, P < 0.01) but similar oxygenation and lung weight. Propagation did not occur where baseline strain was less than 1.29. In healthy animals, large V(T) caused injury that was propagated inward from the lung periphery; in the absence of preexisting injury, propagation did not occur where strain was less than 2.0. CONCLUSIONS: Compared with healthy lungs, underlying injury causes propagation to occur at a lower strain threshold and it originates at the site of injury; this suggests that tissue around the primary lesion is more sensitive. Understanding how injury is propagated may ultimately facilitate a more individualized monitoring or management.

Imaging and Pathologic Evaluation of Cryoablation of Woodchuck (Marmota monax) Hepatocellular Carcinoma.

We characterized cryoablation as a mode of clinical intervention in adult woodchucks with hepatocellular carcinoma (HCC). Woodchucks (n = 4) were infected with woodchuck hepatitis virus at birth and developed LI-RADS-5 hypervascular HCC. At 21 mo of age, they underwent ultrasound (US), contrast-enhanced CT (CECT) imaging, and US-guided subtotal cryoablation (IcePearl 2.1 CX, Galil, BTG) of their largest tumor (Mean HCC volume of 49 ± 9 cm³). Cryoablation was performed using two 10-min freeze cycles, each followed by an 8-min thaw cycle. The first woodchuck developed significant hemorrhage after the procedure and was euthanized. In the other 3 woodchucks, the probe track was cauterized and all 3 completed the study. Fourteen days after ablation, CECT was performed, and woodchucks were euthanized. Explanted tumors were sectioned using subject-specific, 3D-printed cutting molds. Initial tumor volume, the size of the cryoablation ice ball, gross pathology and hematoxylin and eosin-stained tissue sections were evaluated. On US, the edges of the solid ice balls were echogenic with dense acoustic shadowing and average dimensions of 3.1 ± 0.5 × 2.1 ± 0.4 cm and cross-sectional area of 4.7 ± 1.0 cm². On day 14 after cryoablation, CECT of the 3 woodchucks showed devascularized hypo-attenuating cryolesions with dimensions of 2.8 ± 0.3 × 2.6 ± 0.4 × 2.93 ± 0.7 cm and a cross sectional area of 5.8 ± 1.2 cm². Histopathologic evaluation showed hemorrhagic necrosis with a central amorphous region of coagulative necrosis surrounded by a rim of karyorrhectic debris. A rim of approximately 2.5 mm of coagulative necrosis and fibrous connective tissue clearly demarcated the cryolesion from adjacent HCC. Partial cryoablation of tumors produced coagulative necrosis with well-defined ablation margins at 14 d. Cauterization appeared to prevent hemorrhage after cryoablation of hypervascular tumors. Our findings indicate that woodchucks with HCC may provide a predictive preclinical model for investigating ablative modalities and developing new combination therapies.

Primary Total Laryngectomy versus Organ Preservation for Locally Advanced T3/T4a Laryngeal Cancer.

OBJECTIVE: Organ preservation (OP) treatment for advanced laryngeal cancer has increased compared to primary total laryngectomy. Our study compares oncologic and functional outcomes between these approaches. STUDY DESIGN: Retrospective cohort study. SETTING: Single tertiary care institution. METHODS: Retrospective review of patients receiving primary total laryngectomy or OP for laryngeal cancer between 1/1/2000 and 12/31/2018. RESULTS: A total of 118 patients received primary total laryngectomy and 119 received OP. Overall survival was similar between total laryngectomy and OP. When stratified by T stage, disease-free survival was worse among T3 patients receiving OP versus total laryngectomy. In T3 patients, 28 OP patients experienced local recurrence (28.9%) compared to 3 total laryngectomy patients (7.1%; p < 0.01). In total, 20 OP patients with local recurrence received salvage surgery. These patients had similar overall survival to patients who underwent initial total laryngectomy (TL). About 14 OP patients with local recurrence did not receive salvage surgery. About 89 (75.4%) TL patients achieved normal diet as compared to 64 (53.8%) OP patients (p < 0.001). In TL patients, 106 (89.8%) received primary or secondary tracheoesophageal-prosthesis, 82 (77.4%) of whom achieved completely understandable speech. CONCLUSIONS: There was no difference in survival by treatment in T4 patients, possibly because of strict patient selection. However, disease-free survival was worse in T3 patients receiving OP, likely due to a high local recurrence rate. Approximately 40% of patients with local recurrence were not eligible for salvage laryngectomy. TL patients had comparable swallowing and speech outcomes with OP patients. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1122-1131, 2023.

Changes in Magnetic Resonance Imaging Using the Prostate Cancer Radiologic Estimation of Change in Sequential Evaluation Criteria to Detect Prostate Cancer Progression for Men on Active Surveillance.

BACKGROUND: The ability of serial magnetic resonance imaging (MRI) to capture pathologic progression during active surveillance (AS) remains in question. OBJECTIVE: To determine whether changes in MRI are associated with pathologic progression for patients on AS. DESIGN, SETTING, AND PARTICIPANTS: From July 2007 through January 2020, we identified all patients evaluated for AS at our institution. Following confirmatory biopsy, a total of 391 patients who underwent surveillance MRI and biopsy at least once were identified (median follow-up of 35.6 mo, interquartile range 19.7-60.6). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All MRI intervals were scored using the "Prostate Cancer Radiologic Estimation of Change in Sequential Evaluation" (PRECISE) criteria, with PRECISE scores =4 considered a positive change in MRI. A generalized estimating equation-based logistic regression analysis was conducted for all intervals with a PRECISE score of <4 to determine the predictors of Gleason grade group (GG) progression despite stable MRI. RESULTS AND LIMITATIONS: A total of 621 MRI intervals were scored by PRECISE and validated by biopsy. The negative predictive value of stable MRI (PRECISE score <4) was greatest for detecting GG1 to?=?GG3 disease (0.94 [0.91-0.97]). If 2-yr surveillance biopsy were performed exclusively for a positive change in MRI, 3.7% (4/109) of avoided biopsies would have resulted in missed progression from GG1 to?=?GG3 disease. Prostate-specific antigen (PSA) density (odds ratio 1.95 [1.17-3.25], p?=? 0.01) was a risk factor for progression from GG1 to =GG3 disease despite stable MRI. CONCLUSIONS: In patients with GG1 disease and stable MRI (PRECISE score <4) on surveillance, grade progression to?=?GG3 disease is not common. In patients with grade progression detected on biopsy despite stable MRI, elevated PSA density appeared to be a risk factor for progression to?=?GG3 disease. PATIENT SUMMARY: For patients with low-risk prostate cancer on active surveillance, the risk of progressing to grade group 3 disease is low with a stable magnetic resonance image (MRI) after 2?yr. Having higher prostate-specific antigen density increases the risk of progression, despite having a stable MRI.

Combined MRI-targeted Plus Systematic Confirmatory Biopsy Improves Risk Stratification for Patients Enrolling on Active Surveillance for Prostate Cancer.

OBJECTIVE: To evaluate the efficacy of combined MRI-targeted plus systematic 12-core biopsy (Cbx) to aid in the selection of patients for active surveillance (AS). METHODS: From July 2007 to January 2020, patients with Gleason Grade Group (GG) 1 or GG 2 prostate cancer were referred to our center for AS consideration. All patients underwent an MRI and confirmatory combined MRI-targeted plus systematic biopsy (Cbx), and AS outcomes based on Cbx results were compared. Cox regression was used to identify predictors of AS failure, defined as progression to ≥ GG3 disease on follow-up biopsies. RESULTS: Of 579 patients referred for AS, 79.3% (459/579) and 20.7% (120/579) had an initial diagnosis of GG1 and GG2 disease, respectively. Overall, 43.2% of patients (250/579) were upgraded on confirmatory Cbx, with 19.2% (111/579) upgraded to ≥ GG3. For the 226 patients followed on AS, 32.7% (74/226) had benign, 45.6% (103/226) had GG1, and 21.7% (49/226) had GG2 results on confirmatory Cbx. In total, 28.8% (65/226) of patients eventually progressed to ≥ GG3, with a median time to AS failure of 89 months. The median time from confirmatory Cbx to AS failure for the negative, GG1, and GG2 groups were 97, 97, and 32 months, respectively (p < .001). On multivariable regression, only age (hazard ratio 1.06 [1.02-1.11], p < .005) and GG on confirmatory Cbx (hazard ratio 2.75 [1.78-4.26], p < .005) remained as positive predictors of AS failure. CONCLUSION: The confirmatory combined MRI-targeted plus systematic biopsy provides useful information for the risk stratification of patients at the time of AS enrollment.

Mild loss of lung aeration augments stretch in healthy lung regions.

Inspiratory stretch by mechanical ventilation worsens lung injury. However, it is not clear whether and how the ventilator damages lungs in the absence of preexisting injury. We hypothesized that subtle loss of lung aeration during general anesthesia regionally augments ventilation and distension of ventilated air spaces. In eight supine anesthetized and intubated rats, hyperpolarized gas MRI was performed after a recruitment maneuver following 1 h of volume-controlled ventilation with zero positive end-expiratory pressure (ZEEP), FiO2 0.5, and tidal volume 10 ml/kg, and after a second recruitment maneuver. Regional fractional ventilation (FV), apparent diffusion coefficient (ADC) of (3)He (a measurement of ventilated peripheral air space dimensions), and gas volume were measured in lung quadrants of ventral and dorsal regions of the lungs. In six additional rats, computed tomography (CT) images were obtained at each time point. Ventilation with ZEEP decreased total lung gas volume and increased both FV and ADC in all studied regions. Increases in FV were more evident in the dorsal slices. In each lung quadrant, higher ADC was predicted by lower gas volume and by increased mean values (and heterogeneity) of FV distribution. CT scans documented 10% loss of whole-lung aeration and increased density in the dorsal lung, but no macroscopic atelectasis. Loss of pulmonary gas at ZEEP increased fractional ventilation and inspiratory dimensions of ventilated peripheral air spaces. Such regional changes could help explain a propensity for mechanical ventilation to contribute to lung injury in previously uninjured lungs.