Claire E. Bender

Percutaneous Removal of Kidney Stones: Review of 1,000 Cases

We report the results of 1,000 consecutive patients who underwent percutaneous removal of renal and ureteral stones. Removal was successful for 98.3 per cent of the targeted renal stones and 88.2 per cent of the ureteral stones. Complications, evolution and technique are discussed. Percutaneous techniques are an effective way to handle the majority of renal calculi and these techniques will continue to be important as shock wave lithotripsy becomes more widespread in the United States.

Dissolution of Cholesterol Gallbladder Stones by Methyl Tert-Butyl Ether Administered by Percutaneous Transhepatic Catheter

We treated 75 patients with symptomatic cholesterol gallstones by dissolving the stones with methyl tert-butyl ether (MTBE) instilled into the gallbladder through a percutaneous transhepatic catheter. The MTBE was continuously infused and aspirated manually four to six times a minute, for an average of five hours per day for one to three days; the treatment was monitored by fluoroscopy. The placement of the catheter and the administration of MTBE caused few side effects or complications, and treatment did not have to be stopped in any patient for this reason. In 72 patients there was complete dissolution of stones or more than 95 percent dissolution. Among 21 patients who were completely free of stones after treatment, 4 had recurrence of stone formation 6 to 16 months later. The other 51 patients had residual debris, which spontaneously cleared completely in 15 patients within 6 to 35 months; only 7 with persisting debris have had symptoms. Five of the initial 6 patients treated, but only 1 of the next 69 patients, have required surgery during follow-up periods of 6 to 42 months. We conclude that the dissolution of gallstones by MTBE delivered through a percutaneous transhepatic catheter is a useful alternative to surgery in selected patients with symptomatic cholesterol stones. Further study will be necessary to establish the long-term effectiveness of this treatment and its appropriate role in the management of the various types of gallstones.

External radiation therapy and transcatheter iridium in the treatment of extrahepatic bile duct carcinoma

PURPOSE/OBJECTIVE Review survival, prognostic factors, and patterns of failure in patients with extrahepatic bile duct (EHBD) carcinoma treated with external beam irradiation (EBRT) and transcatheter iridium. METHODS AND MATERIALS The charts of 24 patients with EHBD cancer treated with EBRT and transcatheter boost were reviewed. All patients had transhepatic biliary tubes or endoprostheses placed. Two patients underwent hemihepatectomy with hepaticojejunostomy formation but had residual disease. Two patients had biopsy proven adenopathy. Five patients had Grade 1 adenocarcinoma, nine Grade 2, six Grade 3, and one Grade 4 disease. Median EBRT dose was 50.4 Gy delivered in 1.8 Gy/day fractions. Median transcatheter boost at 1 cm radius was 20 Gy. Nine patients received concomitant 5-Fluorouracil (5-FU) during EBRT. RESULTS Median survival was 12.8 months (range 7.5 months to 9 years). Overall 2- and 5-year survival rates were 18.8 and 14.1%, respectively (three disease-free survivors > or =5 years). One patient is still alive without relapse 10 years from diagnosis and 5 years after liver transplantation for liver failure (no cancer in specimen, underlying sclerosing cholangitis). Two additional long-term survivors had no evidence of relapse 6.9 and 8.2 years after diagnosis. Histologic grade, lymph node status, cystic, hepatic, common hepatic or common bile duct involvement, surgical resection, radiation therapy dose, and chemotherapy did not significantly effect survival due to the number of patients analyzed. There was a trend towards improved survival with the addition of 5-FU chemotherapy (5-year survival in two of nine patients, or 22%). Eight of 24 patients (33%) demonstrated radiographic evidence of local recurrence. Distant metastases developed in 6 of 24 (25%) patients. The most common complications were tube related cholangitis (50%) and gastric/duodenal ulceration or bleeding (42%). CONCLUSION External beam irradiation combined with a transcatheter boost can result in long-term survival of patients with EHBD cancer. Both distant metastases and local recurrence develop in 25-30% of patients despite irradiation. Survival may be improved by using chemotherapy in combination with EBRT to impact disease relapse (local and distant). Because there may be a dose response with irradiation, survival may also be improved by increasing the dose of radiation delivered by transcatheter boost. A Phase II trial is being developed using a combination of 45-50 Gy EBRT with concomitant 5-FU delivered by protracted venous infusion followed by a 25-30 Gy transcatheter boost.

Analysis of failure following curative irradiation of gallbladder and extrahepatic bile duct carcinoma

Twenty patients with carcinoma of the gallbladder (GB-4 patients) or extrahepatic bile ducts (EHBD-16 patients) received radiation therapy with curative intent between January, 1980 and December, 1982. All 20 received 4500-5000 rad in 180-200 rad fractions to the tumor and regional lymph nodes. A 1000 to 1500 rad external beam boost was delivered in 180-200 rad fractions in 10 patients who received external beam alone or concomitant 5-Fluorouracil (5-FU). Three of the four GB and 5 of the 16 EHBD patients received a transcatheter boost with 192-Iridium (192Ir) to a dose of 2000-2500 rad calculated at a 0.5-0.1 cm radius. An additional 2 patients with EHBD lesions received an intraoperative electron (IORT) boost of 1500-2000 rad in one fraction calculated to the 90% isodose. Survival and patterns of failure were analyzed by site and treatment method. All four patients with GB carcinoma are dead of disease at 5 1/2, 6, 9 and 10 months from the date of diagnosis respectively. Three of the four developed diffuse peritoneal carcinomatosis. Five of the 16 patients with EHBD carcinoma are alive with a median follow-up of 18 months (range 6-23 months). Four of the 5 patients received a transcatheter 192Ir or IORT boost and all are without evidence of disease. Four of 9 patients who had a subtotal resection with transection of tumor, dilatation of the bile ducts with probes or curettement of the bile ducts developed either diffuse peritoneal carcinomatosis (3 patients) or a recurrence in the surgical scar (2 patients). Local failure was documented in 3 of the nine patients treated with external beam alone +/- 5-FU, and has been documented in one of the seven patients who received an IORT or transcatheter 192Ir boost. Further experience is necessary to determine whether this aggressive treatment will result in long-term disease-free survival in these patients.

Analysis of failure after curative irradiation of extrahepatic bile duct carcinoma

Thirty-four patients with subtotally resected or unresectable carcinoma of the extrahepatic bile ducts received radiation therapy; a minimum of 45 Gy (external beam) to the tumor and regional lymph nodes ± 5-fluorouracil (5-FU). Seventeen patients received an external beam boost of 5 to 15 Gy to the tumor, and a specialized boost was used in the remaining 17 patients (iridium-192 transcatheter seeds in 10 and intraoperative radiation therapy [IORTJ with electrons in seven). The median time to death in all 34 patients was 12 months (range, 4 to 98 months). The only patients who survived longer than 18 months were those either with gross total or subtotal resection before external irradiation (2 of 6) or who received specialized boosts (192Ir, 3 of 10; IORT, 3 of 7). Local failure was documented in 9 of 17 patients who received external beam irradiation alone ± 5-FU, 3 of 10 patients who received an 192Ir boost, and 2 of 6 patients who received an IORT boost with curative intent.

Cholangiopancreatography, sphincterotomy, and common duct stone removal via Roux-en-Y limb enteroscopy

An enteroscopic method that uses a pediatric colonoscope provides an alternative approach to the diagnostic and management problems arising in the setting of a Roux-en-Y limb hepaticojejunostomy or biliary diversion. Three patients with Roux-en-Y limb reconstructions who experienced recurrent cholangitis, recurrent pancreatitis, or choledocholithiasis in whom the technique was used are presented. The technique, which uses colonoscopic principles, is discussed along with the combined use of percutaneous transhepatic assistance. Enteroscopy of a Roux-en-Y limb is technically feasible and expands the diagnostic and management approach to biliary and pancreatic disease involving this postoperative anatomic condition.

Sodium Iodide Symporter (NIS)-Mediated Radiovirotherapy for Pancreatic Cancer

OBJECTIVE We have previously shown the therapeutic efficacy of an engineered oncolytic measles virus expressing the sodium iodide symporter reporter gene (MV-NIS) in mice with human pancreatic cancer xenografts. The goal of this study was to determine the synergy between MV-NIS-induced oncolysis and NIS-mediated (131)I radiotherapy in this tumor model. MATERIALS AND METHODS Subcutaneous human BxPC-3 pancreatic tumors were injected twice with MV-NIS. Viral infection, NIS expression, and intratumoral iodide uptake were quantitated with (123)I micro-SPECT/CT. Mice with MV-NIS-infected tumors were treated with 0, 37, or 74 MBq (131)I and monitored for tumor progression and survival. Additional studies were performed with stable NIS-expressing tumors (BxPC-3-NIS) treated with 0, 3.7, 18.5, 37, or 74 MBq of (131)I. RESULTS Mice treated with intratumoral MV-NIS exhibited significant tumor growth delay (p < 0.01) and prolonged survival (p = 0.02) compared with untreated mice. Synergy between MV-NIS-induced oncolysis and NIS-mediated (131)I ablation was not seen; however, a significant correlation was observed between NIS-mediated intratumoral iodide localization (% ID/g) and peak tumor volume reduction (p = 0.04) with combination MV-NIS and (131)I therapy. Stably transduced NIS-expressing BxPC-3 tumors exhibited rapid regression with > or = 18.5 MBq (131)I. CONCLUSION Delivery of (131)I radiotherapy to NIS-expressing tumors can be optimized using micro-SPECT/CT imaging guidance. Significant hurdles exist for NIS as a therapeutic gene for combined radiovirotherapy in this human pancreatic cancer model. The lack of synergy observed with MV-NIS and (131)I in this model was not due to a lack of radiosensitivity but rather to a nonuniform intratumoral distribution of MV-NIS infection.

Quantitative Molecular Imaging of Viral Therapy for Pancreatic Cancer Using an Engineered Measles Virus Expressing the Sodium-Iodide Symporter Reporter Gene

OBJECTIVE Our objectives were to, first, determine the oncolytic potential of an engineered measles virus expressing the sodium-iodide symporter gene (MV-NIS) for intratumoral (i.t.) therapy of pancreatic cancer and, second, evaluate NIS as a reporter gene for in vivo monitoring and quantitation of MV-NIS delivery, viral spread, and gene expression in this tumor model. MATERIALS AND METHODS Cultured human pancreatic cancer cells were infected with MV-NIS. Light microscopy, cell viability, and iodide uptake assays were used to confirm viral infection and NIS gene expression and function in vitro. Human pancreatic tumor xenografts were established in mice and infected via i.t. MV-NIS injections. NIS-mediated i.t. iodide uptake was quantitated by (123)I micro-SPECT/CT. i.t. MV-NIS infection was confirmed by immunohistochemistry of excised pancreatic xenografts. The oncolytic efficacy of MV-NIS was determined by measurement of tumor growth and mouse survival. RESULTS Infection of human pancreatic cancer cell lines with MV-NIS in vitro resulted in syncytia formation, marked iodide uptake, and ultimately cell death. Tumor xenografts infected with MV-NIS concentrated radioiodine, allowing serial quantitative imaging with (123)I micro-SPECT/CT. i.t. MV-NIS therapy of human pancreatic cancer xenografts resulted in a significant reduction in tumor volume and increased survival time of the treated mice compared with the control mice. CONCLUSION MV-NIS efficiently infects human pancreatic tumor cells and results in sufficient radioiodine uptake to enable noninvasive serial imaging and quantitation of the intensity, distribution, and time course of NIS gene expression. MV-NIS also shows oncolytic activity in human pancreatic cancer xenografts: Tumor growth is reduced and survival is increased in mice treated with the virus.

In Vivo Quantitation of Intratumoral Radioisotope Uptake Using Micro-Single Photon Emission Computed Tomography/Computed Tomography

PurposeThis study was undertaken to determine the ability of micro-single photon emission computed tomography (micro-SPECT)/computed tomography (CT) to accurately quantitate intratumoral radioisotope uptake in vivo and to compare these measurements with planar imaging and micro-SPECT imaging alone.ProceduresHuman pancreatic cancer xenografts were established in 10 mice. Intratumoral radioisotope uptake was achieved via intratumoral injection of an attenuated measles virus vector expressing the NIS gene (MV-NIS). On various days after MV-NIS injection, 123I planar and micro-SPECT/CT imaging was performed. Tumor activity was determined by dose calibrator measurements and region-of-interest (ROI) image analysis. Agreement and reproducibility of tumor activity measurements were assessed by Bland–Altman plots and Lin’s concordance correlation coefficient (CCC).ResultsIntratumoral radioisotope uptake was detected in all mice. Scatterplots demonstrate strong agreement (CCC = 0.93) between micro-SPECT/CT ROI image analysis and dose calibrator tumor activity measurements. The differences between dose calibrator activity measurements and those obtained with ROI image analysis of micro-SPECT alone and planar imaging are less accurate and more variable (CCC = 0.84 and 0.78, respectively).ConclusionsMicro-SPECT/CT can be used to accurately quantify intratumoral radioisotope uptake in vivo and is more reliable than planar or micro-SPECT imaging alone.

Imaging-Assisted Percutaneous Biopsy of the Thoracic Spine

Confirmation of tissue pathologic changes often is necessary before appropriate therapy can be instituted for lesions of the thoracic spine. Plain film roentgenography and computed tomography provide the key information needed for the percutaneous biopsy procedure. The location and type of bone involvement (lytic or sclerotic) and the presence or absence of a soft tissue mass determine the imaging technique and the choice of needle to use for safe and accurate performance of the procedure. In 26 patients with thoracic spinal or paraspinal lesions (or both), biopsy was done with use of fluoroscopic or computed tomographic guidance. The overall accuracy was 90%. Pneumothorax occurred in two patients. Percutaneous biopsy is a rapid, safe technique for diagnosis of lesions of the thoracic spine.