Ofer N. Gofrit

Determination of Renal Stone Composition with Dual-Energy CT: In Vivo Analysis and Comparison with X-ray Diffraction

PURPOSE To preoperatively assess the composition of urinary stones by using dual-energy computed tomography (CT), with postoperative in vitro x-ray diffraction analysis as the reference standard. MATERIALS AND METHODS Institutional review board approval was obtained, and all participants provided written informed consent. Twenty-seven patients aged 50-64 years with renal stones, who were scheduled for stone extraction with percutaneous nephrolithotomy (PCNL), preoperatively underwent nonenhanced single-source dual-energy multidetector CT with 2-mm section thickness, 1-mm increments, 140 kVp, and 250 mAs. Regions of interest were drawn on low- and high-energy images, and low- and high-energy attenuation ratios were calculated for each stone scanned in vivo. The attenuation ratios for the patients were compared with those for an in vitro stone library phantom model of 37 stones with known chemical compositions. After surgery, the extracted stones were analyzed by using x-ray diffraction. The results of in vivo multidetector CT and ex vivo chemical analysis were compared. RESULTS Dual-energy low- and high-energy attenuation ratios measured with the phantom were less than 1.1 for uric acid, 1.1-1.24 for cystine, and greater than 1.24 for calcified stones. Struvite stones had attenuation ratios that overlapped with calcified stone ratios and thus could not be assessed reliably. Four patients had mixed stones (<75% of a single component), and one patient had a struvite stone. Of 27 patients, 22 (82%) (exact confidence interval [CI]: 68%, 92%) received a correct diagnosis with dual-energy CT: all six (100%; exact CI: 54%, 100%) patients with uric acid stones, 15 (79%; exact CI: 62%, 95%) of the 19 patients with calcium stones, and the one (100%) patient with a cystine stone. The patient with a struvite stone did not receive a correct dual-energy CT-based diagnosis. CONCLUSION Dual-energy multidetector CT may enable accurate in vivo characterization of kidney stone composition.

Eardrum perforation in explosion survivors: is it a marker of pulmonary blast injury?

STUDY OBJECTIVES To determine whether isolated eardrum perforation is a marker for concealed blast lung injury in survivors of terrorist bombings. METHODS Survivors who arrived at hospitals after 11 terrorist bombings in Israel between April 6, 1994, and March 4, 1996, were examined otoscopically by ear, nose, and throat specialists. All patients with eardrum perforation underwent chest radiography and were hospitalized for at least 24 hours for observation. The clinical course and final outcome of patients with isolated perforation of the eardrums and of those with other blast injuries were surveyed. RESULTS A total of 647 survivors were examined; 193 (29.8%) of them sustained primary blast injuries, including 142 with isolated eardrum perforation and 51 with other forms of blast injuries (18 with isolated pulmonary blast injury, 31 with combined otic and pulmonary injuries, and 2 with intestinal blast injury). Blast lung injury was promptly diagnosed on admission by physical examination and chest radiography. No patient presenting with isolated eardrum perforation developed later signs of pulmonary or intestinal blast injury (mean 0%; 95% confidence interval, 0% to 2.7%). CONCLUSION Isolated eardrum perforation in survivors of explosions does not appear to be a marker of concealed pulmonary blast injury nor of a poor prognosis. Therefore, in a mass casualty event, persons who have sustained isolated eardrum perforation from explosions may safely be discharged from the emergency department after chest radiography and a brief observation period.

IS THE PEDIATRIC URETER AS EFFICIENT AS THE ADULT URETER IN TRANSPORTING FRAGMENTS FOLLOWING EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY FOR RENAL CALCULI LARGER THAN 10 MM.

PURPOSE We determined whether the thin ureter of the young child transports stone fragments after extracorporeal shockwave lithotripsy (ESWL) as efficiently as the adult ureter does. This determination was done by comparing the outcome after lithotripsy of renal stones greater than 10 mm. between young children and adults. MATERIALS AND METHODS Our study group consisted of 38 children 6 months to 6 years old (median 3 years) with renal stones greater than 10 mm. in diameter. This group was further divided into 3 subgroups according to the longest stone diameter on plain abdominal film. There were 21 children with a renal stone diameter of 10 to 15 mm. (subgroup 1), 8, 16 to 20 mm. (subgroup 2) and 9 greater than 20 mm. (subgroup 3). The control group consisted of 38 adults older than 20 years randomly selected from the local ESWL registry. Each adult was matched with a child regarding stone diameter and localization. The control group was similarly divided into subgroups 1a, 2a and 3a. ESWL was performed with the unmodified Dornier HM-3 lithotriptor (Dornier Medical Systems, Inc., Marietta, Georgia). The stone-free rate, complication rate, and need for tubes, including stent or nephrostomy, and greater than 1 ESWL session were compared. RESULTS The stone-free rate was 95% in the study and 78.9% in the control group (p = 0.086). Stone-free rates were 95%, 100% and 89% in subgroups 1, 2 and 3, and 95%, 65% and 56% in subgroups 1a, 2a and 3a, respectively. There were 10 children and 4 adults who underwent greater than 1 ESWL session (p = 0.14). Then there were 10 children and 6 adults who required a tube before ESWL (p = 0.04), and almost all of them were included in subgroups 3 and 3a. Early complications were rare in both the study and control groups. Late complications had included 2 cases of Steinstrasse in the control and none in the study group. CONCLUSIONS The stone-free rate after ESWL for large renal stones is higher in young children compared to adults with matching stone size. Renal stones greater than 20 mm. often require more than 1 ESWL session. The pediatric ureter is at least as efficient as the adult for transporting stone fragments after ESWL.

Extracorporeal shock wave lithotripsy is highly effective for ureteral calculi in children.

PURPOSE Treatment of ureteral calculi in the pediatric population represents a unique challenge. Extracorporeal shock wave lithotripsy (ESWL*) and ureteroscopy have been advocated for the treatment of such stones. We present our experience with ESWL monotherapy for ureteral stones in children in the last decade. MATERIALS AND METHODS Between 1989 and 1999 we treated 21 boys and 17 girls with a mean age of 8 years (range 8 months to 14 years) with ureteral stones at our institution. Records were reviewed and analyzed for presentation, metabolic and anatomical anomalies, stone size and location, outcome and complications. Average stone size was 9.5 x 6.5 mm. (range 3 to 32). Stones were in the upper ureter in 17 cases, mid ureter in 2 and lower ureter in 19. All patients underwent ESWL with a Dornier HM3 lithotriptor under general anesthesia. Nephrostomies were placed in an anuric infant with bilateral ureteral obstruction and in 2 patients with nonfunctioning kidneys (4 renal units). Ureteral catheters were used in 15 patients for better identification and localization of the stone during ESWL. The catheters were removed immediately postoperatively. RESULTS Of the patients 31 (81.5%) were free of stones after 1 session of ESWL, 5 (13.1%) after 2 and 1 after 3. One patient underwent ureteroscopy for residual fragments after 2 ESWL sessions. The stone-free rate following 1 ESWL session was 100% for ureteral calculi 10 mm. or smaller regardless of location. Of the 12 patients with stones larger than 10 mm. 8 (67%) were free of stones following 1 ESWL session. The overall success rate of ESWL was 97.3%. No child had postoperative urinary infection or ureteral obstruction. CONCLUSIONS ESWL is an efficient and safe modality for the treatment of pediatric ureteral stones.

Lateral Decubitus Position for Percutaneous Nephrolithotripsy in the Morbidly Obese or Kyphotic Patient

BACKGROUND AND PURPOSE Morbidly obese or debilitated patients do not tolerate the prone position used for percutaneous nephrolithotripsy (PCNL) well and may suffer from severe cardiorespiratory compromise in this position. The purpose of this study is to demonstrate a simple way to overcome this difficulty. PATIENTS AND METHODS Two morbidly obese patients, ages 48 and 32 years, with Body Mass Indices of 47.5 and 43.2 and a 68-year old patient severely debilitated by multiple cerebral infarctions, ischemic heart disease, and kyphosis suffered from relatively high renal stone burdens. For PCNL, the patients were placed in the lateral decubitus position. To obtain an anteroposterior projection in this position, the C-arm fluoroscopy unit was tilted to one side and the operating table to the other. Tract dilation, stone fragmentation, and fragment extraction were performed with the patient in this position. RESULTS An attempt to perform PCNL in the prone position in the first patient was aborted because of severe hypoxemia and hypercarbia. In the lateral decubitus position, the procedures were easily performed in all patients without any complications. It was noted that by rotating the C-arm to a perpendicular position, it was possible to perform nephroscopy and use fluoroscopy simultaneously. CONCLUSION We highly recommend using the lateral position for PCNL in morbidly obese patients and in patients suffering from kyphosis. This position is safe and convenient.

The predictive value of multi-targeted fluorescent in-situ hybridization in patients with history of bladder cancer

OBJECTIVES UroVysion (Abbott Molecular Inc., Des Plaines, IL) is a multi-target fluorescent in-situ hybridization (FISH) assay that detects aneuploidy of chromosomes 3, 7, and 17, and loss of the 9p21 locus in exfoliated cells in urine. In this study, we evaluated if UroVysion can predict tumor recurrence in patients with negative cystoscopy and urinary cytology at the time of (FISH) assay. METHODS The study population included patients with history of non-muscle invasive bladder cancer treated by transurethral resection. Follow-up included cystoscopy, barbotage, urinary cytology, and UroVysion testing. Patients were followed for at least 6 months after their initial UroVysion testing. RESULTS A total of 64 patients (37 males) were enrolled into the study. Mean patient age was 62 years (S.D. 13.2 years). Initial highest tumor stage was Ta in 42 patients (65.6%), T1 in 21 patients (33%), and isolated Tis in a single patient. Abnormal UroVysion results were observed in 40 patients (62.5%). After a median follow-up of 13.5 months, 21 patients (33%) developed tumor recurrence (Ta in 13 patients, T1 in 5, and Tis in 3). Recurrent tumors developed in 45% of the patients with abnormal UroVysion test compared with 12.5% of the patients with normal assay (P = 0.01). An abnormal UroVysion result preceded the diagnosis of tumor recurrence in 18/21 cases (86%), including all high-grade recurrences. CONCLUSIONS This data suggest that UroVysion may be a useful tool for predicting tumor recurrence. Cystoscopy may be spared and surveillance intervals widened in patients with history of low grade tumors and a normal UroVysion test.

Raman Molecular Imaging: A Novel Spectroscopic Technique for Diagnosis of Bladder Cancer in Urine Specimens

BACKGROUND Raman molecular imaging (RMI) is an optical technology that combines the molecular chemical analysis of Raman spectroscopy with high-definition digital microscopic visualization. This approach permits visualization of the physical architecture and molecular environment of cells in the urine. The Raman spectrum of a cell is a complex product of its chemical bonds. OBJECTIVE In this work, we studied the possibility of using the Raman spectrum of epithelial cells in voided urine for diagnosing urothelial carcinoma (UC). DESIGN, SETTING, AND PARTICIPANTS Raman signals were obtained from UC tissue, then from UC touch preps obtained from surgical specimens and studied using the FALCON microscope (ChemImage, Pittsburgh, PA, USA), with a×100 collection objective and green laser illumination (532 nm). Then, urine samples were obtained from 340 patients, including 116 patients without UC, 92 patients with low-grade tumors, and 132 patients with high-grade tumors. Spectra were obtained from an average of five cells per slide. MEASUREMENTS Raman spectroscopy of cells from bladder cancer (BCa) tissues and patients. RESULTS AND LIMITATIONS The Raman spectra from UC tissue demonstrate a distinct peak at a 1584 cm(-1) wave shift not present in benign tissues. The height of this peak correlated with the tumors grade. The signal obtained from epithelial cells correctly diagnosed BCa with sensitivity of 92% (100% of the high-grade tumors), specificity of 91%, and a positive predictive value of 94% and a negative predictive value of 88%. The signal correctly assigned a tumors grade in 73.9% of the low-grade tumors and 98.5% of the high-grade tumors. RMI for diagnosis of BCa is limited by the need for specialized equipment and training of laboratory personnel. CONCLUSIONS RMI has the potential to become a powerful diagnostic tool that allows noninvasive, accurate diagnosis of UC.

THE EFFECT OF HALOFUGINONE, AN INHIBITOR OF COLLAGEN TYPE I SYNTHESIS, ON URETHRAL STRICTURE FORMATION: IN VIVO AND IN VITRO STUDY IN A RAT MODEL

PURPOSE Urethral strictures are narrowing of the urethra caused by fibrosis due to excessive collagen production in response to an insult. We evaluated the effects of halofuginone, a potent inhibitor of collagen alpha1(I) gene expression, on experimentally induced urethral strictures in vivo and on rat urethral fibroblasts in vitro. MATERIALS AND METHODS Applying coagulation current to the male rat urethra produced urethral strictures. Halofuginone was given to the animals for 7 days, starting on the day of stricture formation, either orally at 1 and 5 ppm in the diet or by injection of 0.03% halofuginone solution into the urethra. All rats were sacrificed on day 21. Collagen alpha1(I) gene expression was evaluated by in situ hybridization, collagen content by sirius red staining and urethral morphology by urethrogram. RESULTS Coagulation current produced reproducible strictures with a typical urethrogram appearance, which were associated with increases in collagen alpha1(I) gene expression and collagen content at the stricture site. Halofuginone injected into the urethra or orally at 5 ppm normalized the urethrogram and prevented increases in collagen alpha1(I) gene expression and collagen content. Halofuginone at a concentration of 10-8 M. inhibited the collagen secreted by fibroblasts derived from the rat male urethra, which was due to inhibition of the collagen alpha1(I) gene expression. CONCLUSIONS Halofuginone prevented stricture formation and may become an important mode of therapy in the prevention of restenosis during urethral stricture formation.

Renal Cell Carcinoma: Evaluation of the 1997 TNM System and Recommendations for Follow–Up after Surgery

Objective: We evaluated the tumor recurrence pattern after radical or nephron–sparing surgery for localized renal cell carcinoma. Based on this pattern, we suggest a surveillance protocol after surgery. Methods: The outcome of 200 consecutive patients with localized renal cell carcinoma (RCC) that were operated on between January 1982 and December 1997 was evaluated retrospectively. Radical nephrectomy was performed in 155 patients (77.5%), and nephron–sparing surgery in 45 patients (22.5%). The timing and site of disease recurrence were correlated with parameters of the primary tumor. Results: One hundred and twenty–four patients (62%) had pathological stage T1, 26 (13%) had stage T2, and 50 (25%) had stage T3 (41 stage T3a, 8 stage T3b, and 1 stage T3c). The mean follow–up was 47 months (range 6–169 months). Four patients (3.2%) with stage T1, 6 patients (23%) with T2, and 13 patients (26%) with T3 developed recurrent disease. None of the patients with a stage T1 tumor, smaller than 4 cm, had tumor recurrence. There were no recurrences after nephron–sparing surgery compared to 23 recurrences (14.8%) among patients after radical nephrectomy (p = 0.01). Only 1 patient who underwent pulmonary lobectomy for asymptomatic metastases smaller than 2.5 cm, found by routine chest CT, attained long–term survival. Conclusions: The prognosis of patients after radical nephrectomy for renal cell carcinoma, smaller than 4 cm, is excellent and they do not need radiological follow–up. Patients with larger T1 tumors, 4–7 cm in diameter, or a higher stage should be followed with CT of the chest and abdomen done every 6 months for 5 years and then annually. Following partial nephrectomy of small renal tumors periodic renal ultrasonography should be done to rule out local recurrence in the operated kidney.

Hemostatic Agents and Instruments in Laparoscopic Renal Surgery

Control of bleeding is one of the most technically challenging steps in laparoscopic renal surgery, especially partial nephrectomy. Although there is no consensus on how best to approach hemostasis, the options continue to expand. The original method of sutured renorrhaphy is, perhaps, the most effective; however, great skill is needed to avoid prolonged warm ischemia. Tissue sealants and adhesives serve as a barrier to leakage and as a hemostat. The four classes are fibrin sealants, collagen-based adhesives, hydrogel, and glutaraldehyde-based adhesive. Additionally, oxidized cellulose can be applied to the surface of kidney or used as a bolster. Fibrin sealants are self-activating and work best on a dry field. The gelatin matrix agent consists of human-derived thrombin with a calcium chloride solution and bovine-derived gelatin matrix. The fibrinogen required to form a clot comes from autologous blood. Another product is polyethylene glycol-based hydrogel, which acts as a mechanical sealant. The tissue glue consists of bovine serum albumin and glutaraldehyde, which cross-link to each other, as well as to other tissue proteins. Excessive use or spillage around the renal pelvis and ureter may compromise urinary flow. The methylcellulose products, consisting of oxidized cellulose sheets, usually are positioned within a sutured bolster and act in part by providing direct pressure. A number of energy-based technologies also have been utilized. Monopolar cautery consists of a high-frequency electrical current delivered from a single electrode. Care must be taken to avoid injurious current transfer to surrounding structures. With bipolar cautery, hemostasis occurs only between the electrodes. In the argonbeam coagulator, argon, an inert non-flammable gas that clears from the body rapidly, is coupled with an electrosurgical generator. The gas creates a more even distribution of the energy and better sealing of the tissues. There have been a few reports of serious complications, including gas embolism and tension pneumothorax. The holmium:YAG laser simultaneously dissects and coagulates tissue. However, its use may be limited by smoke and by blood splashing onto the camera lens, and the tissue vaporization and liquid could promote tumor-cell spillage. The potassium-titanyl-phosphate (KTP) and diode lasers have shown promise in animal studies. The saline-coupled radiofrequency tool uses a standard electrosurgical generator to deliver energy through the conductive fluid. The fluid keeps the surface temperature much lower, increases the contact area, and reduces char and eschar formation. One caveat for the use of instruments that coagulate and ablate tissue is that they can damage the collecting system. Furthermore, the char can make it difficult to assess margin status. In practice, a combination of instruments, sealants, or both generally is utilized to obtain hemostasis. These multimodality efforts may be especially useful in the patient with compromised renal function. On the other hand, the cost can rise quickly when multiple agents are employed. Combining suturing and hemostatic technology may be the best strategy.