Total Neoadjuvant Therapy Significantly Increases Complete Clinical Response.

BACKGROUND: Increased experience with total neoadjuvant therapy for rectal cancer suggests significantly more tumor regression and increased rates of complete clinical response as measured by pathological complete response and clinical complete response. OBJECTIVE: This study aimed to assess outcomes after total neoadjuvant therapy versus standard neoadjuvant chemoradiotherapy for patients with locally advanced rectal cancer. DESIGN: This is a retrospective cohort study. SETTINGS: A database of patients with rectal cancer from 2015 to 2019 at a large integrated health care system was reviewed. PATIENTS: Demographics of the 2 groups revealed no significant difference in clinical stage or patient characteristics. Of 465 patients, 66 patients underwent total neoadjuvant therapy and 399 underwent standard neoadjuvant chemoradiotherapy. Fifty-six patients underwent consolidation chemotherapy, and 10 underwent induction chemotherapy. MAIN OUTCOME MEASURES: Complete clinical response, disease-free survival, proctectomy-free survival, and organ preservation rates were the main outcome measures. RESULTS: Complete clinical response was achieved in 36 patients (58.1%) versus 59 patients (14.8%; p < 0.001), favoring the total neoadjuvant therapy group. Three-year overall survival was similar between groups (85.6% standard neoadjuvant chemoradiotherapy versus 86.0% total neoadjuvant therapy). Three-year distant metastasis-free survival was 67.4% in the total neoadjuvant therapy group compared to 77.7% in the standard neoadjuvant chemoradiotherapy group. Three-year proctectomy-free survival was 44% in the total neoadjuvant therapy group compared to 6% in the standard neoadjuvant chemoradiotherapy group. Twenty-two patients (37.3% of complete clinical responders) in the standard neoadjuvant chemoradiotherapy group elected to pursue organ preservation, whereas 31 patients (86.1% of complete clinical responders) from the total neoadjuvant therapy group chose organ preservation. LIMITATIONS: This study is limited by its retrospective nature with a shorter follow-up of 3 years. CONCLUSIONS: Total neoadjuvant therapy for rectal cancer significantly increased complete clinical response. This allowed patients to have greater organ preservation with no significant difference in overall survival or disease control. See Video Abstract at http://links.lww.com/DCR/B934 . LA TERAPIA NEOADYUVANTE TOTAL AUMENTA SIGNIFICATIVAMENTE LA RESPUESTA CLNICA COMPLETA: ANTECEDENTES:La mayor experiencia con la terapia neoadyuvante total para el cáncer de recto sugiere una regresión tumoral significativamente mayor y mayores tasas de respuesta clínica completa, medidas por respuesta patológica completa y respuesta clínica completa.OBJETIVO:Este estudio evaluó los resultados después de la terapia neoadyuvante total versus la quimiorradioterapia neoadyuvante estándar para pacientes con cáncer de recto localmente avanzado.DISEÑO:Este es un estudio de cohorte retrospectivo.ESCENARIO:Se revisó una base de datos de pacientes con cáncer de recto de 2015 a 2019 en un sistema de salud integrado grande.PACIENTES:La demografía de los dos grupos no revela diferencias significativas en el estadio clínico o las características de los pacientes. De 465 pacientes, 66 pacientes recibieron terapia neoadyuvante total y 399 quimiorradioterapia neoadyuvante estándar. Cincuenta y seis se sometieron a quimioterapia de consolidación mientras que 10 pacientes a quimioterapia de inducción.PRINCIPALES MEDIDAS DE RESULTADO:Se midieron la respuesta clínica completa, la sobrevida libre de enfermedad, la sobrevida libre de proctectomía y las tasas de preservación de órgano.RESULTADOS:Se logró una respuesta clínica completa en 36 pacientes (58.1 %) frente a 59 pacientes (14.8 %) (p < 0,001) a favor del grupo de terapia neoadyuvante total. La sobrevida general a tres años fue similar entre los grupos (85.6 % quimiorradioterapia neoadyuvante estándar frente a 86.0 % terapia neoadyuvante total). La sobrevida libre de metástasis a distancia a los tres años fue del 67.4 % en el grupo de terapia neoadyuvante total y del 77.7 % en el grupo de quimiorradioterapia neoadyuvante estándar. La sobrevida sin proctectomía a los tres años fue del 44 % en el grupo de terapia neoadyuvante total frente al 6 % en el grupo de quimiorradioterapia neoadyuvante estándar. Veintidós pacientes (37.3 % con respuesta clínica completa) en el grupo de quimiorradioterapia neoadyuvante estándar optaron por la preservación de órgano, mientras que 31 pacientes (86.1 % respuesta clínica completa) del grupo de terapia neoadyuvante total eligieron la preservación de órgano.LIMITACIONES:Este estudio es un estudio retrospectivo con un seguimiento más corto de 3 años.CONCLUSIONES:La terapia neoadyuvante total para el cáncer de recto aumentó significativamente la respuesta clínica completa. Esto permitió a los pacientes tener una mayor preservación de órgano sin diferencias significativas en la sobrevida general o el control de la enfermedad. Consulte Video Resumen en http://links.lww.com/DCR/B934 . (Traducción-Dr. Jorge Silva Velazco ).

Peripheral Thyroid Nodule Calcifications on Sonography: Evaluation of Malignant Potential.

OBJECTIVE. The purpose of this study is to assess the association of thyroid cancer with sonographic features of peripheral calcifications. MATERIALS AND METHODS. We retrospectively reviewed patients who had a total of 97 thyroid nodules with peripheral calcifications who underwent ultrasound-guided fine-needle aspiration from 2008 to 2018. Three board-certified radiologists evaluated the nodules for features of peripheral calcifications: the percentage of the nodule involved by peripheral calcifications, whether the calcifications were continuous or discontinuous, the visibility of internal components of the nodule, and the presence of extrusion of soft tissue beyond the calcifications. The correlation of peripheral calcification parameters with the rate of thyroid nodule malignancy was evaluated. In addition, the interobserver agreement between readers was assessed with Cohen kappa coefficient. RESULTS. Of the 97 nodules with peripheral calcifications, 27% (n = 26) were found to be malignant on biopsy. The continuity of peripheral calcifications, visibility of internal components, and extrusion of soft tissue beyond the calcification rim showed no significant association with benign or malignant nodules. Readers had good agreement on peripheral calcification continuity (κ = 0.63; 95% CI, 0.53-0.73) and moderate agreement on internal component visibility (κ = 0.43; 95% CI, 0.35-0.51) and percentage of the nodule involved by rim calcifications (κ = 0.52; 95% CI, 0.44-0.59). There was fair agreement for extranodular soft-tissue extrusion (κ = 0.32, 95% CI, 0.24-0.39). CONCLUSION. Peripheral rim calcifications are highly associated with malignancy. However, specific peripheral rim calcification features do not aid in distinguishing benign from malignant nodules, which may in part be caused by high interobserver variability.

Contrast-Enhanced Transrectal Ultrasound for Follow-up After Focal HIFU Ablation for Prostate Cancer.

The optimal strategy for imaging after focal therapy for prostate cancer is evolving. This series is an initial report on the use of contrast-enhanced transrectal ultrasound (TRUS) in follow-up of patients after high-intensity focused ultrasound (HIFU) hemiablation for prostate cancer. In 7 patients who underwent HIFU hemiablation, contrast-enhanced TRUS findings were as follows: (1) contrast-enhanced TRUS clearly showed the HIFU ablation defect as a sharply marginated nonenhancing zone in all patients; (2) contrast-enhanced TRUS identified suspicious foci of recurrent enhancement within the ablation zone in 2 patients, facilitating image-guided prostate biopsy, which showed prostate cancer; and (3) contrast-enhanced TRUS findings correlated with multiparametric magnetic resonance imaging and biopsy histologic findings.

Contrast-Enhanced Transrectal Ultrasound in Focal Therapy for Prostate Cancer.

PURPOSE OF REVIEW: Contrast-enhanced transrectal ultrasound (CeTRUS) is an emerging imaging technique in prostate cancer (PCa) diagnosis and treatment. We review the utility and implications of CeTRUS in PCa focal therapy (FT). RECENT FINDINGS: CeTRUS utilizes intravenous injection of ultrasound-enhancing agents followed by high-resolution ultrasound to evaluate tissue microvasculature and differentiate between benign tissue and PCa, with the latter demonstrating increased enhancement. The potential utility of CeTRUS in FT for PCa extends to pre-, intra- and post-operative settings. CeTRUS may detect PCa, facilitate targeted biopsy and aid surgical planning prior to FT. During FT, the treated area can be visualized as a well-demarcated non-enhancing zone and continuous real-time assessment allows immediate re-treatment if necessary. Following FT, the changes on CeTRUS are immediate and consistent, thus facilitating repeat imaging for comparison during follow-up. Areas suspicious for recurrence may be detected and target-biopsied. Enhancement can be quantified using time-intensity curves allowing objective assessment and comparison. Based on encouraging early outcomes, CeTRUS may become an alternative imaging modality in prostate cancer FT. Further study with larger cohorts and longer follow-up are needed.

Versatile utilization of real-time intraoperative contrast-enhanced ultrasound in cranial neurosurgery: technical note and retrospective case series.

OBJECTIVE: Intraoperative contrast-enhanced ultrasound (iCEUS) offers dynamic imaging and provides functional data in real time. However, no standardized protocols or validated quantitative data exist to guide its routine use in neurosurgery. The authors aimed to provide further clinical data on the versatile application of iCEUS through a technical note and illustrative case series. METHODS: Five patients undergoing craniotomies for suspected tumors were included. iCEUS was performed using a contrast agent composed of lipid shell microspheres enclosing perflutren (octafluoropropane) gas. Perfusion data were acquired through a time-intensity curve analysis protocol obtained using iCEUS prior to biopsy and/or resection of all lesions. RESULTS: Three primary tumors (gemistocytic astrocytoma, glioblastoma multiforme, and meningioma), 1 metastatic lesion (melanoma), and 1 tumefactive demyelinating lesion (multiple sclerosis) were assessed using real-time iCEUS. No intraoperative complications occurred following multiple administrations of contrast agent in all cases. In all neoplastic cases, iCEUS replicated enhancement patterns observed on preoperative Gd-enhanced MRI, facilitated safe tumor debulking by differentiating neoplastic tissue from normal brain parenchyma, and helped identify arterial feeders and draining veins in and around the surgical cavity. Intraoperative CEUS was also useful in guiding a successful intraoperative needle biopsy of a cerebellar tumefactive demyelinating lesion obtained during real-time perfusion analysis. CONCLUSIONS: Intraoperative CEUS has potential for safe, real-time, dynamic contrast-based imaging for routine use in neurooncological surgery and image-guided biopsy. Intraoperative CEUS eliminates the effect of anatomical distortions associated with standard neuronavigation and provides quantitative perfusion data in real time, which may hold major implications for intraoperative diagnosis, tissue differentiation, and quantification of extent of resection. Further prospective studies will help standardize the role of iCEUS in neurosurgery.

Contrast-enhanced ultrasound (CEUS) of cystic and solid renal lesions: a review.

Incidentally detected renal lesions have traditionally undergone imaging characterization by contrast-enhanced computer tomography (CECT) or magnetic resonance imaging. Contrast-enhanced ultrasound (CEUS) of renal lesions is a relatively novel, but increasingly utilized, diagnostic modality. CEUS has advantages over CECT and MRI including unmatched temporal resolution due to continuous real-time imaging, lack of nephrotoxicity, and potential cost savings. CEUS has been most thoroughly evaluated in workup of complex cystic renal lesions, where it has been proposed as a replacement for CECT. Using CEUS to differentiate benign from malignant solid renal lesions has also been studied, but has proven difficult due to overlapping imaging features. Monitoring minimally invasive treatments of renal masses is an emerging application of CEUS. An additional promising area is quantitative analysis of renal masses using CEUS. This review discusses the scientific literature on renal CEUS, with an emphasis on imaging features differentiating various cystic and solid renal lesions.

Quantitative assessment of solid renal masses by contrast-enhanced ultrasound with time-intensity curves: how we do it.

PURPOSE: To discuss the evaluation of the enhancement curve over time of the major renal cell carcinoma (RCC) subtypes, oncocytoma, and lipid-poor angiomyolipoma, to aid in the preoperative differentiation of these entities. Differentiation of these lesions is important, given the different prognoses of the subtypes, as well as the desire to avoid resecting benign lesions. METHODS: We discuss findings from CT, MR, and US, but with a special emphasis on contrast-enhanced ultrasound (CEUS). CEUS technique is described, as well as time-intensity curve analysis. RESULTS: Examples of each of the major RCC subtypes (clear cell, papillary, and chromophobe) are shown, as well as examples of oncocytoma and lipid-poor angiomyolipoma. For each lesion, the time-intensity curve of enhancement on CEUS is reviewed, and correlated with the enhancement curve over time reported for multiphase CT and MR. CONCLUSIONS: Preoperative differentiation of the most common solid renal masses is important, and the time-intensity curves of these lesions show some distinguishing features that can aid in this differentiation. The use of CEUS is increasing, and as a modality it is especially well suited to the evaluation of the time-intensity curve.

Contrast-Enhanced Sonography for Monitoring Neoadjuvant Chemotherapy in Soft Tissue Sarcomas.

Neoadjuvant chemotherapy is a mainstay in treating soft tissue sarcomas. Soft tissue sarcomas can show an increase in size and central necrosis, with a decrease in the viable tumor, as an initial response to neoadjuvant chemotherapy. Thus, the maximum tumor diameter may not reliably assess the response to this therapy. Contrast-enhanced sonography may address this limitation. We evaluated 4 patients with soft tissue sarcomas by contrast-enhanced sonography, performed concomitantly with conventional imaging (computed tomography, magnetic resonance imaging, or positron emission tomography). Quantitative analysis was also performed on 1 sarcoma. A viable, enhancing tumor versus tumor necrosis was nearly identical on contrast-enhanced sonography and conventional imaging. Preliminary results demonstrate potential for contrast-enhanced sonographic monitoring of soft tissue sarcomas during neoadjuvant chemotherapy.

Pre-embolization evaluation of high-flow priapism: magnetic resonance angiography of the penis.

PURPOSE: High-flow priapism is often a sequela of perineal trauma resulting in an arteriocavernosal fistula (ACF) between a cavernosal artery and lacunar spaces of the penis. We report our experience utilizing magnetic resonance angiography (MRA) in addition to color Doppler Sonography (CDS) in the workup and treatment planning of 4 patients with high-flow priapism. METHODS: All patients had suspected high-flow priapism diagnosed by clinical exam and CDS and underwent MRA of the penis prior to sub-selective arterial embolization (SSAE) of the feeding vessel(s). RESULTS: While CDS is valuable in diagnosing and lateralizing high-flow priapism, it does not provide clear anatomic delineation of the number and origin of feeding vessels. MRA provided demonstration of the fistula, demonstrated bilateral ACF supply in 2 patients, and afforded three-dimensional display of the feeding vessels which facilitated pre-embolization planning. CONCLUSIONS: In all four cases, MRA was an effective tool for displaying arterial and venous anatomy, localizing the ACF, and planning subsequent SSAE. MRA influenced management in two out of 4 patients by demonstrating bilateral feeding vessels to their ACFs that required bilateral SSAE.

Use of MR imaging to determine preservation of the neurovascular bundles at robotic-assisted laparoscopic prostatectomy.

PURPOSE: To determine whether findings at preoperative endorectal coil magnetic resonance (MR) imaging influence the decision to preserve neurovascular bundles and the extent of surgical margins in robotic-assisted laparoscopic prostatectomy (RALP). MATERIALS AND METHODS: This study was approved by the investigational review board and was compliant with the HIPAA; the requirement to obtain informed consent was waived. The authors prospectively evaluated 104 consecutive men with biopsy-proved prostate cancer who underwent preoperative endorectal coil MR imaging of the prostate and subsequent RALP. MR imaging was performed at 1.5 T between January 2004 and April 2008 and included T2-weighted imaging (n = 104), diffusion-weighted imaging (n = 88), dynamic contrast-enhanced imaging (n = 51), and MR spectroscopy (n = 91). One surgeon determined the planned preoperative extent of resection bilaterally on the basis of clinical information and then again after review of the final MR imaging report. The differences in the surgical plan before and after review of the MR imaging report were determined and compared with the actual surgical and pathologic results by using logistic regression analysis. Continuous and ranked variables underwent Pearson and Spearman analysis. RESULTS: After review of MR imaging results, the initial surgical plan was changed in 28 of the 104 patients (27%); the surgical plan was changed to a nerve-sparing technique in 17 of the 28 patients (61%) and to a non-nerve-sparing technique in 11 (39%). Seven of the 104 patients (6.7%) had positive surgical margins. In patients whose surgical plan was changed to a nerve-sparing technique, there were no positive margins on the side of the prostate with a change in treatment plan. CONCLUSION: Preoperative prostate MR imaging data changed the decision to use a nerve-sparing technique during RALP in 27% of patients in this series.

Multifunctionality of prostatic acid phosphatase in prostate cancer pathogenesis.

The role of human prostatic acid phosphatase (PAcP, P15309|PPAP_HUMAN) in prostate cancer was investigated using a new proteomics tool termed signal sequence swapping (replacement of domains from the native cleaved amino terminal signal sequence of secretory/membrane proteins with corresponding regions of functionally distinct signal sequence subtypes). This manipulation preferentially redirects proteins to different pathways of biogenesis at the endoplasmic reticulum (ER), magnifying normally difficult to detect subsets of the protein of interest. For PAcP, this technique reveals three forms identical in amino acid sequence but profoundly different in physiological functions, subcellular location, and biochemical properties. These three forms of PAcP can also occur with the wildtype PAcP signal sequence. Clinical specimens from patients with prostate cancer demonstrate that one form, termed PLPAcP, correlates with early prostate cancer. These findings confirm the analytical power of this method, implicate PLPAcP in prostate cancer pathogenesis, and suggest novel anticancer therapeutic strategies.

Multifunctionality of Prostatic Acid Phosphatase in Prostate Cancer Pathogenesis.

The role of human prostatic acid phosphatase (PAcP, P15309|PPAP_HUMAN) in prostate cancer was investigated using a new proteomic tool termed signal sequence swapping (replacement of domains from the native cleaved amino terminal signal sequence of secretory/membrane proteins with corresponding regions of functionally distinct signal sequence subtypes). This manipulation preferentially redirects proteins to different pathways of biogenesis at the endoplasmic reticulum, magnifying normally difficult to detect subsets of the protein of interest. For PAcP this technique reveals three forms identical in amino acid sequence but profoundly different in physiological functions, subcellular location, and biochemical properties. These three forms of PAcP can also occur with the wild-type PAcP signal sequence. Clinical specimens from patients with prostate cancer demonstrate that one form, termed PLPAcP, correlates with early prostate cancer. These findings confirm the analytical power of this method, implicate PLPAcP in prostate cancer pathogenesis, and suggest novel anticancer therapeutic strategies.

Quantitative magnetic resonance imaging (q-MRI) for the assessment of soft-tissue sarcoma treatment response: a narrative case review of technique development.

Soft-tissue sarcomas are a heterogeneous class of tumors that exhibit varying degrees of cellularity and cystic degeneration in response to neoadjuvant chemotherapy. This creates unique challenges in the radiographic assessment of treatment response when relying on conventional markers such as tumor diameter (RECIST criteria). In this case series, we provide a narrative discussion of technique development for whole tumor volume quantitative magnetic resonance imaging (q-MRI), highlighting cases from a small pilot study of 8 patients (9 tumors) pre- and post-neoadjuvant chemotherapy. One of the methods of q-MRI analysis (the "constant-cutoff" technique) was able to predict responders versus non-responders based on percent necrosis and viable tumor volume calculations (p = 0.05), respectively. Our results suggest that q-MRI of whole tumor volume contrast enhancement may have a role in tumor response assessment, although further validation is needed.

Pictorial review: Renal ultrasound.

Ultrasound (US) is the first-line imaging modality for evaluating azotemic patients for urinary obstruction and renal size. US is also valuable for distinguishing congenital variants and simple cystic lesions from renal masses. Doppler US is effective in detection of renal calculi and evaluation of vascular pathology. Unfortunately, renal US is limited in distinguishing causes of medical renal disease. The kidneys have a complex internal architecture with a highly variable appearance on US. This article illustrates non-neoplastic renal conditions, including normal and embryological variants, parenchymal, cystic, and vascular diseases. Renal infections, calcifications, and trauma and fluid collections are also discussed, with an emphasis on distinguishing US features and pathophysiology.

Contrast-Enhanced Ultrasound of Spermatic Cord and Retroperitoneal Liposarcoma.

Liposarcoma is the most common paratesticular scrotal malignancy. Ultrasound is the conventional imaging modality for evaluating scrotal masses. Contrast-enhanced ultrasound (CEUS) can provide complementary information by identifying distinct enhancement patterns. We present CEUS findings of 2 concurrent soft tissue masses in 1 patient: a spermatic cord well-differentiated liposarcoma and a retroperitoneal dedifferentiated liposarcoma. We review the Doppler ultrasound, computed tomography, and histopathologic appearances of low- versus high-grade liposarcomas in addition to the utility of CEUS with quantitative analysis in potentially grading liposarcomas.

Ureteral tumor thrombus from renal cell carcinoma extending into bladder.

Tumor thrombus from renal cell carcinoma (RCC) usually occurs within the renal vein. We present the first report of a tumor thrombus from RCC extending from the kidney down the ureter and into the lumen of the bladder. This case both: (1) provides evidence for growth of RCC along the urinary tract, and (2) poses a staging dilemma.

Hepatic Kaposi Sarcoma Revisited: An Important but Less Commonly Seen Neoplasm in Patients With Acquired Immunodeficiency Syndrome.

Hepatic Kaposi sarcoma (KS) is the most commonly seen hepatic neoplasm in patients with acquired immunodeficiency syndrome (AIDS), found in 34% of patients in an autopsy series. However, the incidence of hepatic KS has significantly declined since the advent of highly active antiretroviral therapy and is not as commonly seen on imaging. We present a case of hepatic KS in a patient with AIDS, which was initially mistaken for hepatic abscesses on computed tomography. We discuss the computed tomography, grayscale ultrasound, and contrast-enhanced ultrasound appearance of hepatic KS and how to distinguish this hepatic neoplasm from other common hepatic lesions seen in patients with AIDS.

Intra-arterial contrast-enhanced ultrasound (IA CEUS) for localization of hepatocellular carcinoma (HCC) supply during transarterial chemoembolization (TACE): a case series.

Transarterial chemoembolization (TACE) is a proven catheter-based locoregional therapy for treatment of hepatocellular carcinoma (HCC). Drug-eluting bead TACE involves delivering micrometer-sized particles preloaded with doxorubicin directly to the tumor via its arterial blood supply and results in vascular embolization with intra-tumoral drug release. Effective therapy requires mapping of the tumor arterial supply, which in some cases cannot be accomplished with conventional angiographic techniques alone. Contrast-enhanced ultrasound (CEUS) is an imaging technique which utilizes microbubble contrast agents to demonstrate blood flow and tissue perfusion, enabling tumor visualization in real time. CEUS with intravenous contrast administration is well established for evaluation of HCC. Intra-arterial (IA) CEUS, on the other hand, is an emerging technique that allows more selective evaluation of the arterial supply to the tumor. The three cases in this report illustrate the utility of intra-procedural IA CEUS during TACE. Specifically, IA CEUS aided TACE in cases where the HCC showed poor arterial enhancement, an extrahepatic arterial supply, and a portal venous supply, respectively.