Joseph M. Collins

Salvage brachytherapy for localized prostate cancer after radiotherapy failure

OBJECTIVES To evaluate the effectiveness and morbidity of salvage brachytherapy for locally recurrent or persistent prostate cancer after radiotherapy failure. METHODS In this retrospective study, 49 patients of median age 73.3 years (range 52.9 to 86.9) with biopsy-proven localized prostate cancer underwent interactive transperineal fluoroscopic-guided and biplane ultrasound-guided brachytherapy with either iodine 125 or palladium 103 after prior radiotherapy failure. Post-treatment follow-up was conducted for a median of 64.1 months (range 26.6 to 96.8) and included clinical assessment of disease status, assays of serum prostate-specific antigen (PSA) levels, and documentation of treatment-related symptoms and complications. Determination of biochemical treatment failure was based on two successive rising PSA values above the post-treatment PSA nadir value. RESULTS The actuarial rate of local prostate cancer control was 98% (95% confidence interval [CI] 94% to 99%). Actuarial disease-specific survival at 3 and 5 years was 89% (95% CI 73% to 96%) and 79% (95% CI 58% to 91%), respectively. At 3 and 5 years, actuarial biochemical disease-free survival was 48% (95% CI 32% to 63%) and 34% (95% CI 17% to 51%), respectively. Post-treatment PSA nadir was found to be a significant predictor of biochemical disease-free survival. Actuarial biochemical disease-free survival of patients who achieved a PSA nadir less than 0.5 ng/mL was 77% (95% CI 53% to 90%) and 56% (95% CI 25% to 78%) at 3 and 5 years, respectively. Of 49 patients, 23 (47%) achieved a post-treatment PSA nadir less than 0.5 ng/mL. The incidence of serious complications after salvage brachytherapy, such as incontinence and rectal complications, was lower than that reported after other types of salvage procedures. CONCLUSIONS Interactive transperineal fluoroscopic-guided and biplane ultrasound-guided brachytherapy is a novel, potentially curative salvage modality for patients in whom prior radiotherapy failed. In a population of patients with poor prognosis, this modality was associated with a high rate of local prostate cancer control and a 34% actuarial rate of biochemical disease-free survival at 5 years. The incidence of major complications after salvage brachytherapy appears to be lower than that after other potentially curative salvage procedures, such as radical prostatectomy and cryoablation. Salvage brachytherapy warrants further investigation.

Integrated genomic characterization reveals novel, therapeutically relevant drug targets in FGFR and EGFR pathways in sporadic intrahepatic cholangiocarcinoma.

Advanced cholangiocarcinoma continues to harbor a difficult prognosis and therapeutic options have been limited. During the course of a clinical trial of whole genomic sequencing seeking druggable targets, we examined six patients with advanced cholangiocarcinoma. Integrated genome-wide and whole transcriptome sequence analyses were performed on tumors from six patients with advanced, sporadic intrahepatic cholangiocarcinoma (SIC) to identify potential therapeutically actionable events. Among the somatic events captured in our analysis, we uncovered two novel therapeutically relevant genomic contexts that when acted upon, resulted in preliminary evidence of anti-tumor activity. Genome-wide structural analysis of sequence data revealed recurrent translocation events involving the FGFR2 locus in three of six assessed patients. These observations and supporting evidence triggered the use of FGFR inhibitors in these patients. In one example, preliminary anti-tumor activity of pazopanib (in vitro FGFR2 IC50≈350 nM) was noted in a patient with an FGFR2-TACC3 fusion. After progression on pazopanib, the same patient also had stable disease on ponatinib, a pan-FGFR inhibitor (in vitro, FGFR2 IC50≈8 nM). In an independent non-FGFR2 translocation patient, exome and transcriptome analysis revealed an allele specific somatic nonsense mutation (E384X) in ERRFI1, a direct negative regulator of EGFR activation. Rapid and robust disease regression was noted in this ERRFI1 inactivated tumor when treated with erlotinib, an EGFR kinase inhibitor. FGFR2 fusions and ERRFI mutations may represent novel targets in sporadic intrahepatic cholangiocarcinoma and trials should be characterized in larger cohorts of patients with these aberrations.

Actuarial disease-free survival after prostate cancer brachytherapy using interactive techniques with biplane ultrasound and fluoroscopic guidance

PURPOSE To evaluate the effectiveness and safety of interactive transperineal brachytherapy under biplane ultrasound and fluoroscopic guidance in patients with localized prostate cancer. METHODS AND MATERIALS Brachytherapy using 125I or 103Pd radioactive seeds either alone or in combination with adjunctive external beam radiotherapy (XRT) was administered to 490 patients at a single institution. Post-treatment follow-up included clinical assessment of disease status, assays of serum prostate-specific antigen (PSA) levels and documentation of treatment-related symptoms and complications. RESULTS Actuarial disease-free survival at 5 yr was 79% (95% CI, 71-85%), and the 5-yr actuarial rate of local control was 98% (95% CI, 94-99%). Post-treatment PSA nadir and pretreatment PSA level were found to be significant predictors of disease-free survival. In patients with a PSA nadir < 0.5 ng/ml, 5-yr disease-free survival was 93% (95% CI, 84-97%), compared with 25% (95% CI, 5-53%) in patients whose PSA nadir was 0.5-1.0 ng/ml and 15% (95% CI, 3-38) in patients with a PSA nadir > 1.0 ng/ml. Brachytherapy was well tolerated with few post-treatment complications. CONCLUSION A broad range of patients with localized prostate cancer can benefit from transperineal brachytherapy with minimal morbidity. A post-treatment PSA nadir below 0.5 ng/ml provides a useful prognostic indicator of favorable long-term outcome.

Contribution of indirect computed tomography venography to computed tomography angiography of the chest for the diagnosis of thromboembolic disease in two United States emergency departments

Summary.  Recent reports suggest that physicians in non‐ambulatory settings can use indirect CT venography (CTV) of the lower extremities immediately following spiral CT angiography (CTA) of the chest to identify patients with a negative CTA who have thromboembolic disease identified on CTV. We sought to determine the frequency of isolated deep venous thrombosis (DVT) discovered on CTV in emergency department (ED) patients with complaints suggestive of pulmonary embolism (PE) yet having a negative CTA. This study was conducted in a suburban and urban ED where patients with symptoms suspicious for PE were primarily evaluated with CTA and CTV. A total of 800 patients were studied, including 360 from the suburban ED and 440 from the urban ED. 88 (11%) patients were diagnosed with thromboembolic disease by CTA, or CTV, or both. Seventy‐three patients had a CTA of the chest that was positive for PE, 42 (5.2%) of whom had evidence of both PE on CTA and DVT on CTV. Fifteen patients (2%, 95% CI = 1–3%) had a negative CTA and were subsequently found to have isolated DVT on CTV, all of whom received anticoagulation therapy. These data suggest that indirect CT venography of immediately following CT angiography of the chest significantly increased the frequency of diagnosed thromboembolic disease requiring anticoagulation in ED patients with suspected PE.

Accuracy of assessment of the extent of examination by experienced colonoscopists

One hundred colonoscopies were done. The colonoscopist noted whether the cecum had been intubated as well as the markers used to make this determination. With the colonoscope in position at maximum penetration, a radiologist independently determined its position using fluoroscopy, with a contrast agent delivered through the colonoscope. The cecum was entered in 86 of 100 cases. The tip of the colonoscope was at the level of the ileocecal valve in nine additional cases; the colonoscopist judged that the cecum was well seen in five of these nine. In one case, the colonoscopist overestimated the extent of the examination when transillumination in the right lower quadrant was the only confirming marker. When the more reliable markers (ileocecal valve, appendiceal orifice, converging indentations of the taenia coli in the cecal pole) were seen, no errors were made. Experienced colonoscopists are accurate in assessing the extent of colonoscopy and fluoroscopic confirmation is not routinely needed. When reliable markers are not seen during the examination, a barium enema, preferably with air contrast, should be done.

Increased prostatic blood flow in response to microwave thermal treatment: preliminary findings in two patients with benign prostatic hyperplasia.

OBJECTIVES To determine the effects on prostate blood flow of heat generated by microwave thermal treatment in patients with benign prostatic hyperplasia. METHODS Prostate blood flow was evaluated by continuous transrectal color Doppler ultrasonography in 2 patients at baseline, after implantation of interstitial needles used for thermal mapping, and during microwave thermal treatment. Temperatures at 30 prostatic, periprostatic, urethral, and rectal sites were continuously monitored. In 1 patient, transrectal prostate compression was applied and the blood flow and temperature response to this maneuver noted. RESULTS Microwave thermal treatment achieved maximum prostate temperatures of 59 degrees C at 5 mm radially from the urethra. Urethral and rectal temperatures remained low. Marked increases occurred in prostate blood flow in response to microwave thermal treatment. These increases were apparent throughout the prostate gland, with the greatest increase in perfusion occurring in the peripheral zone and the posterior half of the transitional zone. After 15 minutes of microwave treatment, peak systolic blood flow increased 99% and 70% in patients 1 and 2, respectively, while end-diastolic blood flow climbed 50% and 112%, respectively. Prostate compression resulted in a prompt quenching of blood flow and an increase in prostate temperature. CONCLUSIONS Based on these preliminary findings in 2 patients, prostate blood flow increases markedly in response to microwave thermal treatment. This compensatory increase in blood flow is likely to be a significant treatment-limiting factor in achieving effective thermoablation.

Gadolinium-enhanced MRI in the evaluation of minimally invasive treatments of the prostate: Correlation with histopathologic findings

OBJECTIVES To explore the use of magnetic resonance imaging (MRI) with gadolinium enhancement as a noninvasive method to image the extent of ablation after minimally invasive treatment. Minimally invasive methods for ablating prostatic tissue have emerged as a viable option in the treatment of prostate disease. As these devices enter the mainstream of patient care, imaging methods that verify the exact location, extent, and pattern of the ablation are needed. METHODS Nineteen patients with prostate cancer were evaluated. All received some type of minimally invasive treatment, post-treatment gadolinium-enhanced MRI sequences, and radical retropubic prostatectomy for histopathologic evaluation. Visual comparisons of gadolinium defects and areas of coagulation necrosis as seen on histopathologic evaluation were made by us. Volumetric and two-dimensional area measurements of the ablation lesions were also compared for correlation between the MRI and histopathologic results. RESULTS Gadolinium-enhanced MRI could be matched to histopathologic findings by visual comparison in 17 of the 19 cases. Surgically distorted histopathologic specimens and a small periurethral lesion caused 2 patients to have MRI and histopathologic results that could not be matched. Complete volumetric measurements were available for 16 of the 19 patients and correlated strongly (r = 0.924). The two-dimensional area data for all patients also showed significant correlation (r = 0.886). CONCLUSIONS Correlation with histopathologic findings showed gadolinium-enhanced MRI to be useful for determining the location, pattern, and extent of necrosis caused within the prostate by minimally invasive techniques. Gadolinium-enhanced MRI gives the urologist a useful tool to evaluate the effectiveness of new minimally invasive therapies.

Esophageal perforation as a complication of esophagogastroduodenoscopy.

Fifty years ago, esophageal perforation was common after rigid upper endoscopy. The arrival of flexible endoscopic instruments and refinement in technique have decreased its incidence; however, esophageal perforation remains an important cause of morbidity and mortality. This complication merits a high index of clinical suspicion to prevent sequelae of mediastinitis and fulminant sepsis. Although the risk of perforation with esophagogastroduodenoscopy alone is only 0.03%, this risk can increase to 17% with therapeutic interventions in the setting of underlying esophageal and systemic diseases. A wide spectrum of management options exist, ranging from conservative treatment to surgical intervention. Prompt recognition and management, within 24 hours of perforation, is critical for favorable outcomes.

Update on intravenous leiomyomatosis: report of five patients and literature review

The objective of this study was to review management and results of surgical therapy of intravenous leiomyomatosis (IVL). A retrospective review of five patients treated at the Mayo Clinic between 2002 and 2012 and a literature review from 1970 to the present were performed. IVL is a rare condition, often overlooked, misdiagnosed or inadequately treated. Despite its benign histological features, invasion of large vessels and cardiac extension can occur and be fatal. Appropriate diagnosis and a radical surgical approach to IVL provide optimal outcomes. Incomplete resection and/or microscopic foci of IVL can lead to recurrence. Surgery should always aim for complete tumor excision and include hysterectomy and bilateral salpingoophorectomy. Radical parametrectomy and intravenous tumor resection may be necessary.

Indolent Enterococcal Abscess Mimicking Recurrent Renal Cell Carcinoma on MR Imaging and PET/CT after Radiofrequency Ablation

A case of asymptomatic enterococcal abscess was found to mimic recurrent renal cell carcinoma (RCC) on gadolinium-enhanced magnetic resonance (MR) imaging and positron emission tomography/computed tomography (CT) 15 months after radiofrequency ablation for RCC. This case illustrates that indolent infection can closely mimic recurrent neoplasm on imaging. The authors suggest that if bacterial and fungal cultures had been performed during the CT-guided biopsy, the subsequent open surgical procedure might have been avoided.