Phase I study of immunotherapy of hepatic metastases of colorectal carcinoma by direct gene transfer.
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Biomedical subjects
Publications and source records attributed to J W Charboneau.
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Intraoperative color Doppler sonography is emerging as a useful procedure for evaluating renal arteries during transaortic renal endarterectomy or bypass grafting. Technical difficulties encountered during surgical renal revascularization, such as intimal defects or flaps, partial or complete thrombosis, and anastomotic stenosis of the renal artery, can be difficult to defect and evaluate. Intraoperative color Doppler sonography allows evaluation at a time when the problem is often correctable. We have been performing intraoperative sonographic studies of the renal artery for several years and have studied 151 vessels. In this pictorial essay, we present some of our observations on these cases.
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A retrospective review of 211 computed tomographic (CT)-guided and 58 ultrasound (US)-guided biopsies of pancreatic lesions performed between 1985 and 1989 was undertaken to evaluate the accuracy of diagnosis and the number of complications. Combined CT and US accuracy in the diagnosis of malignancy was 93%. CT-guided biopsies had an accuracy of 86%, and US-guided biopsies had an accuracy of 95%. Accuracy was higher with larger masses (> 3.0 cm, 92%; < or = 3 cm, 81%) and larger needle sizes (16-19 gauge, 92%; 20-22 gauge, 85%) and when the mass was located in the body or tail of the pancreas (93%) rather than the head (84%). Major complications developed in three cases (1.1%). No biopsy-related deaths occurred. Needle passage through the gastrointestinal tract, including the colon, did not cause complications.
BACKGROUND: Between 1927 and 1992, 313 patients have undergone surgery for insulinoma(s) at our institution, 12% of which were reoperations. We retrospectively reviewed all cases (n = 39) of reoperative surgery for persistent hyperinsulinism to identify changing patterns in surgical approach, morbidity, and outcome and to evaluate the influence of preoperative and intraoperative localization studies. METHODS: The diagnosis of endogenous hyperinsulinism has evolved from satisfying Whipple's triad to documenting concomitant hypoglycemia and endogenous hyperinsulinemia. Thirty-nine patients were divided into two groups for comparison: those treated before localization studies were available (1927 to 1967) (n = 17) and those treated since that time (n = 22). Initial operations were also compared with reoperations among these 39 patients. RESULTS: There were 26 women and 13 men (mean age, 42 years). There was at least one positive preoperative localization study in 16 of 22 patients (73%). Intraoperative ultrasonogram and careful palpation successfully identified 10 of 11 tumors in the reoperative setting. Blind or completion pancreatectomies were common before 1967 (10 of 17 patients). Since 1967, 14 of 22 patients have undergone enucleation of their primary tumor. Operative morbidity increased from 21% to 58% with reoperation but decreased from 65% to 29% (p = 0.026) when comparing the preangiography to the postangiography eras. The development of iatrogenic diabetes mellitus occurred in 13 patients (33%) after reoperation. Forty-one percent had diabetes before 1967 and 27% since that time (p = not significant). Thirty-four of 36 patients (94%) without malignant tumors were cured by reoperation. There was one operative death. Survival for patients who underwent completion or total pancreatectomy was significantly reduced (p = 0.003). CONCLUSIONS: Reoperations for persistent hyperinsulinism can be highly successful in experienced hands. These reoperations, however, are associated with increased morbidity and iatrogenic diabetes. With experience and the use of selected localization studies, first-time failures can be avoided in most cases thus reducing the need for reoperations and its inherent sequelae.
Eighty-three patients with radiographically opaque renal stones were evaluated prospectively with ultrasound and compared to KUB (kidneys, ureters, bladder) with tomograms (KUB/T) to further define the use of ultrasound in the evaluation of renal calculi. The presence or absence and the size, number, and location of stones were analyzed and correlated for each modality. Ultrasound detected the presence of renal stones in 77 of 83 (93%) patients. However, all of the stones were detected on ultrasound in only 60% of these patients. Thirty percent (80 of 269) of the papillary-calyceal stones seen on KUB/T were missed on US; 66% of the stones missed measured 2 mm or less. Although ultrasound can be used for detection of intrarenal stones, KUB/T is a more accurate imaging examination for determination of size and number of small stones.
BACKGROUND: An occult insulinoma refers to a biochemically proven tumor with an anatomic site that remains indeterminate before operation. The amount of radiologic localization for such patients is debatable. METHODS: Sixty-five patients with sporadic insulinomas were surgically treated at the Mayo Clinic between January 1980 and December 1990. True occult tumors were present in 31% of these patients (n = 20). Thirty-eight negative preoperative localization studies were performed, with 10 patients undergoing more than one study. A benign adenoma was found in 19 patients when they underwent exploratory operation, whereas one patient had malignant disease with hepatic metastases. Thirteen patients underwent intraoperative ultrasonography with a 7.5 MHz real-time high-resolution transducer. RESULTS: Solitary lesions were successfully removed either by enucleation or by distal pancreatectomy in all 19 patients with benign disease. CONCLUSIONS: This high success rate in the management of occult insulinomas suggests that extensive preoperative radiologic investigation is neither indicated nor cost-effective.
We have described previously that the gallbladder responds abnormally to infusions of cholecystokinin octapeptide (CCK-8) in patients with irritable bowel syndrome (IBS). To confirm these results and to examine the possible mechanisms, patients with IBS and predominant symptoms of diarrhea or constipation were compared with matched controls. During infusions of CCK-8 at one of three doses, the response of the gallbladder was measured ultrasonographically. The levels of CCK-8 reached in the peripheral circulation and degradation of the peptide in vitro and in vivo were used to evaluate metabolism of cholecystokinin. We confirmed that the gallbladders of patients with IBS responded abnormally to CCK-8; however, the differences were not due to any prereceptor event. Instead, this abnormality in IBS must be explained by an atypical response at the level of the target tissues.
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Somatostatin (SS) receptor status was investigated in the tumor tissues from 62 patients with carcinoid tumors and 15 patients with islet cell carcinomas using receptor autoradiography techniques with two different iodinated somatostatin analogues as radioligands, a [Leu8, DTrp22, Tyr25]somatostatin-28 and a somatostatin octapeptide, Tyr3-octreotide. The carcinoid tumors were either primaries (n = 32) or metastases (n = 43), sampled as surgical specimens or as small needle liver biopsies. Fifty-four of 62 carcinoid patients had SS receptor-positive tumors (87%). All 15 islet cell carcinoma patients had positive tumors (4 primaries, 11 metastases), i.e., 3 vipomas, 3 insulinomas, 2 glucagonomas, 1 gastrinoma, 2 polyfunctional tumors, and 4 nonfunctioning tumors. Saturation and competition experiments on tissue sections revealed saturable, high affinity binding sites pharmacologically specific for bioactive SS analogues. In a majority of the tumors, the receptors were densely distributed and were always homogeneously found in the whole tumor. All except two tumors were labeled with both radioligands. Multiple liver metastases (n = 16) from three different patients were all shown to contain a comparable amount of receptors. SS receptors could be demonstrated even in very small tissue samples of liver metastases obtained by percutaneous liver biopsies (mean weight, 6.8 mg). The majority of the eight SS receptor-negative carcinoids were mainly bronchial carcinoids (n = 5), usually poorly differentiated. On the contrary, SS receptor-positive cases were never found to be anaplastic. All tumors except one from patients pretreated with octreotide (3 days to 3.8 years) were SS receptor positive. In the majority of carcinoids or islet cell carcinomas, the SS receptor status correlated with the in vivo biochemical response (hormone inhibition) to octreotide. These data demonstrate (a) the high prevalence of SS receptors in the primary tumors of both carcinoids and islet cell carcinomas, (b) their presence in metastases as well, (c) their continuous expression even during long term octreotide therapy, (d) the possibility of measuring SS receptors in percutaneous needle liver biopsies, and (e) the evidence of their functionality. This study therefore suggests that tumoral SS receptors may be the likely molecular basis for octreotide action and may be an important parameter for predicting the therapeutic efficacy of SS analogues in carcinoids and islet cell carcinomas.
Endorectal ultrasonography is a valuable imaging method for examination of the rectum and perirectal tissues. We assessed 50 patients with known rectal carcinoma prospectively by using a 7.0-MHz endorectal transducer to determine the depth of invasion of the rectal wall by tumor and the presence of lymphadenopathy. Tumors were staged by using the Astler-Coller modification of the Dukes staging system, and the results were compared with histologic staging of the surgical specimen. Ultrasonography had an accuracy of 80%, a sensitivity of 92%, and a specificity of 76% for detection of invasion of the perirectal fat. Ultrasonography was sensitive in the detection of perirectal lymphadenopathy but was not specific in distinguishing benign from malignant nodes.
This study was performed to determine the long-term outcome of renal transplantation in 54 patients with end-stage renal failure secondary to autosomal dominant polycystic kidney disease (ADPKD) and in 107 patients with renal diseases other than ADPKD or diabetes mellitus matched by gender, age, year of transplantation, and source of the allograft. The overall patient survival and patient survival with a functioning first renal allograft were similar in both groups. Infection and cardiovascular accidents were the leading causes of early and late death in both groups. No cause of death was greatly overrepresented in the ADPKD group. Serious complications from extrarenal manifestations of ADPKD following renal transplantation included a ruptured intracranial aneurysm in one patient, a dissection of the ascending thoracic aorta in one patient, and infected hepatic cysts in two patients. Neoplasia (other than skin or cervical) occurred in four ADPKD patients and in one control patient and included one lymphoma in each group. Two ADPKD and one control patient had monoclonal gammopathies of undetermined significance. No complications related to the retention of native kidneys were detected in 12 ADPKD patients with a mean follow-up of 3 years. Cysts were observed in the renal allografts of some patients in both groups at autopsy and in a prospective computed tomography (CT) study of the allograft. However, we failed to detect a significant difference in the occurrence and number of the cysts between ADPKD and control patients.
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The mirror-image artifact, which has been previously described in gray-scale sonographic imaging, is also readily visualized with both spectral and color Doppler flow imaging. In 10 consecutive healthy subjects, a mirror image of the subclavian artery was readily apparent at gray-scale, spectral Doppler, and color Doppler sonography. An experimental in vitro model was constructed to demonstrate that the lung apex, which is located immediately posterior to the subclavian artery, acts as the highly reflective acoustic interface to form this artifact. Knowledge of the presence of the mirror-image artifact should be helpful to the radiologist and sonographer in avoiding misinterpretation of this important pitfall in both spectral and color Doppler flow imaging of the subclavian region, where there is a plethora of branching vessels.
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