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Biomedical subjects

Peter A Pinto

Publications and source records attributed to Peter A Pinto.

At least 19 recordsLinked to original sources
PubMed2026

Integrative Genomic Profiling of Newly Diagnosed Prostate Cancers Progressing on Surveillance.

OBJECTIVE: To identify molecular features associated with earlier progression to definitive therapy amongst patients with localized prostate cancer (PCa) managed on active surveillance (AS). METHODS: We performed a retrospective pilot study of 7 patients with low- to intermediate-risk PCa undergoing serial multiparametric MRI (mpMRI)-targeted biopsies of the same lesion while on AS, who all proceeded to definitive therapy. Time-to-treatment (TTT) was defined as years from first biopsy on AS to definitive therapy. Laser-capture microdissection was used to separate tumor epithelium, benign glands, high-grade prostatic intraepithelial neoplasia, and stroma in each biopsy specimen. DNA from the tumor and matched benign tissue underwent whole-exome sequencing, and RNA from all compartments underwent whole-transcriptome sequencing. Somatic mutations and copy-number alterations were compared across serial biopsies and used to reconstruct phylogenies and quantify clonal complexity. RESULTS: Tumors exhibited substantial intratumoral heterogeneity, and in 3 of 6 paired cases, serial mpMRI-targeted biopsies showed discordant somatic profiles consistent with sampling distinct major clones over time. By contrast, no single gene-level alteration, and few large-scale chromosomal events, were associated with TTT. High clonal complexity, defined as ≥3 subclones, was associated with significantly shorter TTT than low complexity (median 1.9 vs 7.2 years; P = .0082). Exploratory pathway analyses of individual tissue components suggested TTT-associated differences in inflammatory signaling and stromal-epithelial cross-talk. CONCLUSION: In this small, hypothesis-generating cohort, clonal complexity was more closely associated with earlier definitive therapy than individual genomic alterations. Larger prospective studies are needed to validate whether multiomic measures of clonal architecture can improve AS risk stratification.

Humans↗
PubMed2025

Discovery and performance of DNA methylation panels for cancer detection and classification in blood.

Examining DNA in a liquid biopsy for non-invasive cancer detection relies on identifying dilute signal in a high background. This study aims to identify DNA methylation biomarkers for multi-cancer detection. Utilizing large tissue datasets, we apply novel search algorithms to discover confined biomarker panels capable of distinguishing tumor from normal and determining the tissue of origin. We explore the applicability to blood-based testing using targeted methylation sequencing followed by machine learning classification. We present an 8-marker panel, which successfully predicts tumors across 14 types with a 91% average sensitivity, maintaining a low false positive rate (< 0.04%). Additionally, a panel of 39 CpG sites exhibits accuracies ranging from 69% to 98% for identifying tissue of origin. When tested on 114 patient plasma samples (colon, liver, pancreatic, prostate, and stomach cancer), the 8-marker panel obtains an AUC of 0.78 with a 78% sensitivity among 32 early-stage patients (stage I-II), and 60% overall. Using the 39-marker panel in a multi-class classification model selecting only the best match, 54% of tumor samples were on average correctly assigned to the tissue of origin, and up to 80% when allowing more inclusive criteria. Using a limited set of biomarkers, our work contributes to advancing non-invasive cancer diagnostics.

DNA methylation↗
PubMed2006

Mechanisms of disease: the role of heat-shock protein 90 in genitourinary malignancy.

Insight into the molecular biology of cancer has allowed the development of novel therapeutic strategies that target specific oncogenic pathways. Molecular therapeutic strategies are now part of the armamentarium available against urologic malignancy. Among the many targets of interest in urologic cancer, heat-shock protein 90 (HSP90) shows great promise. This molecule has a major role in prostate as well as in renal malignancy. In contrast to other targets, where cancer might escape inhibition via alternative pathways, HSP90 operates at multiple checkpoints in a cancer cell. Its inhibition could, therefore, prove more difficult for neoplastic cells to overcome. Inhibitors of HSP90, such as geldanamycin and its derivatives (17-allylamino-17-demethoxygeldanamycin and 17-dimethylaminoethylamino-17-demethoxygeldanamycin, known as 17AAG and 17DMAG, respectively) are available and have shown activity both in vivo and in vitro. 17AAG is currently being tested for efficacy in humans after having completed phase I trials, while 17DMAG is still in phase I evaluation. Phase II trials of HSP90 inhibitors in urologic malignancy are being conducted in kidney and advanced prostate cancer. Beyond monotherapy, HSP90 inhibitors might also prove to be beneficial in combination therapy with other chemotherapeutic agents in advanced disease. Studies being conducted in prostate cancer will hopefully help to define this potential application better.

Antineoplastic Agents↗
PubMed2005

Metastatic renal cell carcinoma to contralateral ureter presenting as acute obstructive renal failure after radical nephrectomy.

Metastatic renal cell carcinoma commonly involves the lungs, bone, liver, adrenal glands, and brain. Less commonly affected organs include the gallbladder, thyroid, and pancreas. Even metastatic spread to the contralateral kidney and the bladder has been reported. Computed tomography is the standard imaging technique to evaluate for contralateral involvement. One of the disadvantages of computed tomography as a screening modality is its difficulty in identifying small ureteral lesions. We report a rare case of metastatic renal cell carcinoma in the contralateral ureter presenting as acute obstructive renal failure after radical nephrectomy.

Acute Disease↗
PubMed2005

Management of von Hippel-Lindau-associated kidney cancer.

Von Hippel-Lindau disease (VHL) is an autosomal-dominant inherited condition that predisposes patients to develop renal cysts and tumors, most commonly in the second to fourth decades of life. Renal cysts and tumors have historically been a major cause of disease-related morbidity and mortality, so urologists are often called on to manage patients with VHL. Knowledge of the extrarenal manifestations of VHL (hemangioblastomas of the central nervous system and retina, endolymphatic sac tumors, pancreatic cysts, epididymal and broad-ligament cysts, and pheochromocytomas) and integration of nonurologic specialties into management teams for VHL patients will help to achieve successful outcomes. Screening for renal manifestations of VHL, by regular imaging of the abdomen, begins late in the second decade of life. Because renal tumors in VHL can be multifocal and bilateral, management can be complex. Radical nephrectomy removes all tissue at risk for forming renal tumors; however, this necessitates renal replacement therapy. In an effort to control cancer effectively while preserving native renal function and minimizing intervention, some researchers have proposed an observational strategy. Patients are screened until the largest tumor reaches 3 cm in diameter, at which time operative intervention is recommended. Nephron-sparing surgery is undertaken, whenever technically feasible, with the goal of removing all tumors in that renal unit. The role of minimally invasive technologies is currently being evaluated in selected patients with VHL renal masses. Elucidation of molecular pathways associated with VHL renal tumors may facilitate development of effective medical treatments for these lesions in the future.

Humans↗
PubMed2004

Telerounding and patient satisfaction after surgery.

BACKGROUND: Technologic advances in communications have facilitated the development and diffusion of telemedicine. Most applications have focused on remote outpatient management of medical conditions. We assessed the impact of introducing remote video conferencing during the immediate postoperative period (telerounds) on patient-reported satisfaction with their hospitalization. STUDY DESIGN: Between October 2002 and June 2003,85 patients undergoing elective laparoscopic or percutaneous urologic procedures were enrolled in a trial testing the impact of telerounds on patients' satisfaction with their hospitalization. Participants were entered into one of three postoperative care arms: standard once-daily attending bedside rounds; standard once-daily attending level bedside rounds plus one afternoon telerounding visit; or a substitution of one daily bedside round with a robotic telerounding visit. Participants completed a validated patient satisfaction survey 2 weeks after hospital discharge. RESULTS: Eighty-five individuals (100% response rate) completed the questionnaire. With responses dichotomized to "excellent" or "other," patients in the telerounding arm demonstrated statistically substantial improvements in ratings of examination thoroughness, quality of discussions about medical information, postoperative care coordination, and attending physician availability. Patients in the robotic telerounding arm indicated considerably higher satisfaction with regard to physician availability. After adjusting for age differences, ratings of each of the previously listed aspects of care remained notably improved in the telerounding arm. CONCLUSIONS: Telerounding either as an additional visit or as a substituted bedside visit is associated with increased patient satisfaction in postoperative care. This type of interaction appears to acceptably facilitate physician communication with hospitalized patients.

Female↗
PubMed2004

Complications of abdominal urologic laparoscopy: longitudinal five-year analysis.

OBJECTIVES: To analyze complications of abdominal laparoscopic surgery of the urinary tract at a single institution during a 5-year period. METHODS: From 1996 to 2000, we identified 894 abdominal laparoscopic procedures performed at a single institution: 600 nephrectomies (live donor, simple, radical, nephroureterectomy, and partial), 112 pyeloplasties, 61 renal biopsies, 35 retroperitoneal lymph node dissections, 31 renal cyst ablations, 18 adrenalectomies, and 37 other abdominal procedures. The charts were retrospectively reviewed for complications, which were classified as operative, postoperative, or medical. Complications were correlated with patient age and American Society of Anesthesiologists score. Statistical analysis was performed with Fisher's exact test and chi-square tests. RESULTS: A total of 118 complications (13.2%) occurred. Two patients (0.2%) died. As a result of operative complications, the procedure of 13 patients (1.5%) was converted to an open one. As a result of postoperative complications, 13 (1.5%) underwent operative and 6 (0.7%) nonoperative intervention. The most common intraoperative complications were vascular (n = 23), adjacent organ (n = 10), and bowel (n = 9) injuries. The most common postoperative complications were neuromuscular pain (n = 12), hematoma (n = 11), urine leak (n = 7), and wound infection (n = 7). The differences in the annual complication rates for all procedures did not attain statistical significance (P = 0.5). Among all procedures, excluding live donor nephrectomy, complications of any kind correlated with a greater patient American Society of Anesthesiologists score (P = 0.01). CONCLUSIONS: Rather than decreasing, the overall incidence of laparoscopic complications did not change significantly during a 5-year period at our institution. The factors contributing to this observation likely included the progression of inexperienced individual surgeons through the learning curve, the introduction of new, more sophisticated laparoscopic procedures, and stable rates of patient comorbidity. This experience may represent the average complication rate for urologic laparoscopy at a large-volume, academic training center.

Adrenalectomy↗
PubMed2004

Laparoscopic-assisted renal autotransplantation.

OBJECTIVES: To report our experience with laparoscopic nephrectomy and autotransplantation for the management of a variety of conditions with significant loss of healthy ureteral tissue or ureteral length. Renal autotransplantation has been described as an effective method for addressing this problem, avoiding the need for nephrectomy or complex ureteral replacement. In an effort to decrease the morbidity associated with traditional autotransplantation we elected to perform laparoscopic procurement of the kidney. METHODS: Four patients underwent laparoscopic nephrectomy using a transperitoneal four-port technique and subsequent autotransplantation into the iliac fossa for the treatment of proximal ureteral avulsion (2 patients), ureteral malignancy, and ureteral stricture. All patients had less than 5 cm of viable ureter. RESULTS: All procedures were performed without intraoperative complications. All renal scans on postoperative day 1 demonstrated good perfusion. None of the patients had a postoperative rise in serum creatinine. On postoperative day 1, the mean creatinine value was 0.95 mg/dL. Three patients had an uneventful postoperative course. One patient, however, had loss of the graft because of renal vein thrombosis on postoperative day 7. She was later found to have an undiagnosed thrombophilic disorder (decreased levels of antithrombin III) and to have a recent history of oral contraceptive use. CONCLUSIONS: Laparoscopic nephrectomy with renal autotransplantation is a feasible minimally invasive alternative to treat patients who have significant ureteral loss. This approach avoids the need for an upper abdominal or flank incision, resulting in decreased morbidity. The initial follow-up studies indicated stable renal function. Additional long-term observation is currently under way.

Adult↗
PubMed2004

Urethral stricture after pancreas-kidney transplantation due to polypoid urethritis.

Urologic complications are common after pancreas-kidney transplantation using bladder drainage. We report a case of urethral stricture caused by polypoid urethritis occurring 4 years after simultaneous pancreas-kidney transplantation. Endoscopic exploration revealed irregular, ragged-appearing urethral mucosa. The diagnosis of polypoid urethritis was confirmed histopathologically.

Adult↗
PubMed2004

Laparoscopic partial nephrectomy: effect of warm ischemia on serum creatinine.

PURPOSE: Laparoscopic partial nephrectomy (LPN) has been shown to be a safe and effective option for small renal tumors. However, limited data are available regarding the effect of warm ischemic time on postoperative renal function. We assessed the effect of variable durations of warm ischemia on long-term renal function in patients undergoing LPN. MATERIALS AND METHODS: A total of 118 patients with a single, unilateral, sporadic renal tumor and normal contralateral kidney underwent LPN from August 1998 to November 2002. Patients were divided into 3 groups based on warm ischemic time, namely group 1-no renal occlusion in 42, group 2-warm ischemia less than 30 minutes in 48 and group 3-warm ischemia greater than 30 minutes in 28. All 3 groups were assessed for changes in serum creatinine 6 months after LPN. Additionally, renal remnants were examined with cross-sectional imaging. RESULTS: At a median followup of 28 months (range 6 to 56) median creatinine had not statistically increased postoperatively. None of the 118 patients progressed to renal insufficiency or required dialysis after LPN. CONCLUSIONS: Based on postoperative serum creatinine warm ischemia time up to 55 minutes does not significantly influence long-term renal function after LPN. Thus, during LPN efforts to minimize warm ischemia are important but they should not jeopardize cancer control, hemostasis or collecting system closure.

Adult↗
PubMed2004

Extraosseous (extramedullary) plasmacytoma of the adrenal gland.

Plasmacytomas are clonal proliferations of atypical plasma cells that manifest a localized osseous or extraosseous growth pattern. Although many represent solitary lesions of bone, fewer arise in extraosseous (extramedullary) tissues. We report a case of a primary extraosseous plasmacytoma of the adrenal gland. Magnetic resonance imaging (MRI) with contrast revealed a 3.5-cm, right adrenal mass with heterogeneous enhancement. Although the mass was small and nonfunctioning, concern for malignancy based on MRI findings prompted laparoscopic resection. Histologic and immunohistochemical findings were consistent with a plasmacytoma. This is the third reported case, to our knowledge, of a primary plasmacytoma of the adrenal gland. The present case is unique in that a contrast MRI was performed, which showed heterogeneous enhancement of the mass, providing further evidence beyond heterogeneous hyperintensity on T2-weighted images for a possible malignant process. Another unique feature is that a biopsy specimen of the lesion was taken, although it was nondiagnostic.

Adrenal Cortex Neoplasms↗
PubMed2003

Management of recurrent urethral fistulas after hypospadias repair.

OBJECTIVES: To report on our experience in the management of recurrent urethrocutaneous fistulas in order to understand the etiology and outcome of secondary repair of the failed fistula closure. METHODS: We reviewed the records of 28 patients between 28 months and 19 years of age, who underwent surgery between January 1990 and December 1998. In all patients, urethrocutaneous fistulas developed postoperatively, and the number of operations for their closure ranged from 2 to 15 attempts. In 17 children, a single large fistula was present, and in 11 children, multiple fistulas were present. The causes of failure were believed to be the awkward fistula site in 12 (coronal fistulas), urethral diverticula in 7, and distal urethral strictures in 4. In 5 children, the cause of fistula formation was unclear. RESULTS: The 12 coronal fistulas were converted into coronal hypospadias. Thereafter, the urethral plate was tubularized using a wider strip (Thiersch tube) with (n = 3) or without (n = 9) a relaxing midline incision (Reddy-Snodgrass). Of the 12 repairs, 11 were successful; 1 child developed wound separation, resulting in a megameatus that was subsequently corrected. In 7 children, the cause of the fistula was a urethral diverticulum, which was excised and closed in multiple layers. All were successful (voiding well and no stricture or fistula). In 4 children (1 with multiple fistulas), the distal urethra was stenotic, and repair of the fistula included repair of the stricture using an island onlay flap in 2 and a buccal mucosal graft in 2. All 4 patients achieved a successful outcome. Dartos flaps were used to cover the repair in 18 patients, and tunica vaginalis flaps were used in 6 children. CONCLUSIONS: Recurrent urethral fistula after hypospadias repair may be a manifestation of another problem, such as urethral stricture and/or urethral diverticulum. Intraoperative calibration of the distal urethra and distension of the repaired hypospadias to search for a diverticulum are recommended. Coronal fistulas are best repaired by converting them into coronal hypospadias, followed by tubularization of the urethral plate with or without a dorsal midline relaxing incision. In resurfacing the operative site, the traditional transposition flaps (Y-V and advancement) may be unreliable, because their vascularity may be compromised by previous surgery. The hairless scrotal island or rotation scrotal flap is more reliable for these cases.

Adolescent↗
PubMed2003

Bipolar needle electrocautery for laparoscopic partial nephrectomy without renal vascular occlusion in a porcine model.

OBJECTIVES: To report a novel method of accomplishing laparoscopic lower pole partial nephrectomy in an acute porcine model using a bipolar needle electrode without the need for renal arterial occlusion. METHODS: Six animals (12 renal units) underwent laparoscopic polar nephrectomy using the bipolar needle electrode. After complete laparoscopic mobilization of the lower pole of the kidney, the bipolar needle electrode was repeatedly inserted full-thickness into the renal parenchyma and applied transversely, creating regional ischemia to the entire lower pole without renal vascular occlusion. The specimen was then amputated using laparoscopic scissors. RESULTS: For the 12 laparoscopic partial nephrectomies, the mean operative time was 39 +/- 30 minutes, and the mean blood loss was 90 +/- 112 mL. Of the 12 cases, 10 (83%) were performed successfully with the bipolar needle electrocautery as the only source of hemostasis and without the need for ancillary hemostatic measures. Two of the procedures (17%) required temporary arterial control for hemostasis. For the successful procedures, the mean operative time was 29 +/- 4 minutes, and the mean blood loss was 48 +/- 11 mL. Histologic analysis of the specimens demonstrated coagulative necrosis between 2 and 4 mm from the line of the surgical incision. CONCLUSIONS: Bipolar needle electrocautery is a promising device that can be used to facilitate laparoscopic partial nephrectomy with minimal blood loss and without the need for renal arterial occlusion and warm ischemia. Additional studies are required to optimize the delivery parameters of this device.

Animals↗
PubMed2003

Laparoscopic procurement model for living donor liver transplantation.

BACKGROUND/AIMS: Noting the contribution to renal transplantation by the introduction of the laparoscopic approach to donor nephrectomy, we investigated the possibility of performing a laparoscopic hepatic lobe procurement with the goal of performing a live donor liver transplantation. We describe our technique and determine its feasibility for such a goal. METHODS: The surgical technique was developed over a series of 12 adult female pigs and adapted in two human cadavers. The technique included pneumoperitoneum with CO2, mobilization of the liver, and transection of the parenchyma into right and left lobes with a laparoscopic cavitron ultrasonic aspirator. The vascular inflow and outflow structures (hepatic artery, portal vein, hepatic veins) of the anatomical specimen being procured were preserved undisturbed during the hepatic transection. No temporary vascular occlusion techniques were utilized. The vascular structures were stapled and sectioned just prior to removal of the specimen. RESULTS: Hepatic lobectomies were successfully performed laparoscopically. Vascular and biliary structures were preserved to allow for subsequent transplantation. Operative time from establishment of pneumoperitoneum to lobe procurement was under 4 h. CONCLUSIONS: This study demonstrates the feasibility of laparoscopic living donor procurement for liver transplantation, from both a technical and a physiological perspective.

Animals↗
PubMed2003

Normal and variant arterial supply of the liver and gallbladder.

The vascular supply of the liver and gallbladder is characterized by a striking degree of polymorphism. The occurrence of variants that differ from the usual pattern is both surprisingly common and unpredictable. Knowledge of this variable anatomy is particularly important during surgical interventions in which preoperative imaging studies are not available, such as in organ procurements. In this report we consider various anatomical arterial configurations, and describe an unusual variant.

Arteries↗