Thomas H. Shawker

Intraoperative Ultrasonographic Localization of Islet Cell Tumors: A Prospective Comparison to Palpation

The purpose of the present study was to evaluate prospectively the value of intraoperative ultrasound scanning (IOUS) in localizing islet cell tumors by comparing results of IOUS to those of palpation during 44 consecutive laparotomies for gastrinoma (36) or insulinoma (8). All patients had preoperative radiographic imaging studies and selective venous sampling for hormones, which guided the subsequent laparotomy. Any suspicious finding by palpation and/or IOUS was resected. Pathologic evidence of islet cell neoplasm served as the reference standard. Five patients were excluded from analysis because neither palpation nor IOUS had suspicious findings and no islet cell tumor was found. Seven pancreatic insulinomas were found in seven patients. IOUS was as sensitive as palpation at localizing insulinomas. Twenty-three pancreatic gastrinomas were found in 19 patients. IOUS was equal to palpation in the ability to localize gastrinomas. Gastrinomas that were successfully imaged by IOUS were significantly larger than gastrinomas that were not imaged. Twelve extrapancreatic gastrinomas were found in nine patients, and palpation was more sensitive than IOUS at localizing these small duodenal wall tumors. Five patients (11%) had their surgical management changed by IOUS. Two patients had pancreatic tumors (one gastrinoma and insulinoma) enucleated that would not have been found without IOUS, and three patients had resections of pathologically proven malignant islet cell tumors based on sonographic findings. All five patients were cured with short follow-up. The present results demonstrate that palpation and IOUS are complementary because IOUS can image tumors that are not palpable and IOUS can provide additional information concerning malignant potential not detected by palpation.

Analysis Of Ultrasound Image Texture Via Generalized Rician Statistics

Tissue signatures are obtained from the first- and second-order statistics of ultrasonic B-scan texture. Laboratory measurements and early clinical results show that the image may be segmented to discriminate between different normal tissues and to detect abnormal conditions based on a multidimensional feature space. These features describe the intrinsic backscatter properties of the tissues imaged and may be used as the basis of an automatic tissue characterization algorithm.

A prospective trial evaluating a standard approach to reoperation for missed parathyroid adenoma.

OBJECTIVES The authors evaluate the results of preoperative imaging protocols and surgical re-exploration in a series of patients with missed parathyroid adenomas after failed procedures for primary hyperparathyroidism. BACKGROUND The success rate is lower and the complication rate is increased in patients undergoing reoperation for primary hyperparathyroidism compared with initial procedures. Scarring and distortion of tissue planes plus the potential for ectopic gland location leads to this worsened outcome. METHODS Two hundred eighty-eight consecutive patients with persistent/recurrent hyperparathyroidism were treated at a single institution after a failed procedure or procedures at outside institutions. Two hundred twenty-two of these patients (77%) were believed to have a missed single adenoma, and these patients underwent 228 operations and 227 preoperative work-ups. Preoperative evaluation consisted of a combination of four noninvasive imaging studies--neck ultrasound, nuclear medicine scan, neck and mediastinal computed tomography scan, and neck and mediastinal magnetic resonance imaging. Based on the noninvasive testing alone, 27% patients underwent surgery whereas the other patients underwent invasive studies, including selective angiography (58%), selective venous sampling for parathyroid hormone (43%), or percutaneous aspiration of suspicious lesions (15%). RESULTS Abnormal parathyroid adenomas were found in 209 of 222 initial procedures and 6 of 6 second procedures, with an overall success rate in terms of resolution of hypercalcemia in 97% (215/222) of patients. The single most common site of missed adenoma glands was in the tracheal-esophageal groove in the posterior superior mediastinum (27%). The most common ectopic sites for parathyroid adenomas are thymus (17%), intrathyroidal (10%), undescended glands (8.6%), carotid sheath (3.6%), and the retroesophageal space (3.2%). The most sensitive and specific noninvasive imaging test is the sestamibi subtraction scan, with 67% true-positive and no false-positive results. The rate of true-positive and false-positive results for ultrasound, computed tomography, magnetic resonance imaging, and technetium thallium scans were 48%/21%, 52%/16%, 48%/14% and 42%/8%, respectively. The incidence of injury to the recurrent laryngeal nerve was 1.3%. CONCLUSIONS A single missed parathyroid adenoma is the most common cause for a failed initial parathyroid operation. Appropriate use of preoperative imaging tests and knowledge of the potential location or parathyroid adenomas can lead to very high cure rates with minimal morbidity.

Localization and surgical treatment of occult insulinomas.

Management of patients with biochemical evidence of insulinoma and negative preoperative imaging studies (occult) tumors is controversial, varying from primarily medical management to aggressive, blind nearly total pancreatectomy to extirpate the tumor. Since 1982, 12 consecutive patients with occult insulinoma underwent preoperative portal venous sampling (PVS) for insulin followed by surgical exploration with intraoperative ultrasound (IOUS). Eleven of twelve patients (92%) had insulinoma removed and were cured. Portal venous sampling correctly predicted the location of the insulinoma in 9 patients (75%) and that no tumor would be found in another patient. A fourfold insulin gradient in the pancreatic tail of one patient correctly predicted that a distal pancreatectomy would remove the insulinoma despite the fact that neither palpation nor IOUS identified any tumor. Intraoperative ultrasound was the single best method to identify occult tumors because it correctly identified 10 of 11 insulinomas that were found, including five pancreatic head tumors that were not palpable. Palpation identified five insulinomas. Of the 10 tumors that were identified during operation by palpation or ultrasound, IOUS identified significantly more (100% versus 50%, p = 0.03) and guided the successful enucleation of each. The results support the strategy of preoperative PVS and operation with IOUS to localize and remove insulinoma in patients with occult tumors. Most tumors (75%) will be correctly localized to a specific pancreatic region by preoperative PVS and identified by IOUS (83%), allowing simple enucleation and biochemical correction of hypoglycemia. Morbid blind pancreatic resections are no longer indicated and long-term medical management of hypoglycemia should be reserved for the occasional patient (8%) who fails preoperative PVS and operation guided by IOUS.

A prospective study of intraoperative methods to diagnose and resect duodenal gastrinomas

ObjectiveThis study determined, prospectively, whether duodenotomy (DX) should be routinely performed in explorations for patients with Zollinger-Ellison syndrome (ZES). Summary Background DataDuodenal gastrinomas are now being found with increasing frequency in patients with Zollinger-Ellison syndrome. The surgical approach used to detect these tumors is controversial. Some recommend intraoperative endoscopy with transillumination (IOE) at surgery, while others recommend routine DX. MethodsBeginning in 1989, the authors prospectively compared the ability of palpation, intraoperative ultrasound (IOUS), IOE, and DX (in that sequence) to detect gastrinomas in 35 consecutive patients with ZES. Each patient also underwent preoperative localization studies. ResultsThirty-three of 35 patients (94%) had tumor detected and excised; duodenal gastrinomas were excised in 27 patients (77%). The average size of the duodenal tumors was 0.8 cm, significantly smaller (p < 0.005) than the pancreatic and lymph node tumors in this series. Standard palpation after a Kocher maneuver identified 19 of the 31 duodenal tumors (61 %) in the 27 patients. IOUS revealed only eight duodenal tumors (26%) and no new lesions. IOE identified 20 duodenal gastrinomas (64%) and 6 new lesions. DX identified 31 duodenal tumors (100%) and 5 additional tumors. The morbidity rate was 17%. One patient had a duodenal fistula after operation (2.8%) and subsequently recovered. No patient died. ConclusionsThese results demonstrate that the duodenum is the most common location for gastrinoma in patients with ZES (77%) and that DX to detect and remove duodenal gastrinomas should be routinely performed in all explorations for patients with ZES.

Hypo-functional SLC26A4 variants associated with nonsyndromic hearing loss and enlargement of the vestibular aqueduct: genotype-phenotype correlation or coincidental polymorphisms?

Hearing loss with enlargement of the vestibular aqueduct (EVA) can be associated with mutations of the SLC26A4 gene encoding pendrin, a transmembrane Cl−/I−/HCO  3− exchanger. Pendrins critical transport substrates are thought to be I− in the thyroid gland and HCO  3− in the inner ear. We previously reported that bi‐allelic SLC26A4 mutations are associated with Pendred syndromic EVA whereas one or zero mutant alleles are associated with nonsyndromic EVA. One study proposed a correlation of nonsyndromic EVA with SLC26A4 alleles encoding pendrin with residual transport activity. Here we describe the phenotypes and SLC26A4 genotypes of 47 EVA patients ascertained since our first report of 39 patients. We sought to determine the pathogenic potential of each variant in our full cohort of 86 patients. We evaluated the trafficking of 11 missense pendrin products expressed in COS‐7 cells. Products that targeted to the plasma membrane were expressed in Xenopus oocytes for measurement of anion exchange activity. p.F335L, p.C565Y, p.L597S, p.M775T, and p.R776C had Cl−/I− and Cl−/HCO  3− exchange rate constants that ranged from 13 to 93% of wild type values. p.F335L, p.L597S, p.M775T and p.R776C are typically found as mono‐allelic variants in nonsyndromic EVA. The high normal control carrier rate for p.L597S indicates it is a coincidentally detected nonpathogenic variant in this context. We observed moderate differential effects of hypo‐functional variants upon exchange of HCO  3− versus I− but their magnitude does not support a causal association with nonsyndromic EVA. However, these alleles could be pathogenic in trans configuration with a mutant allele in Pendred syndrome. Hum Mutat 0, 1–10, 2009.

Intraarterial calcium stimulation and intraoperative ultrasonography in the localization and resection of insulinomas

BACKGROUND Standard imaging studies (computed tomography, magnetic resonance imaging, somatostatin receptor scintigraphy, ultrasonography, and angiography) correctly localize insulinomas in less than 50% of patients and provide no information about the feasibility of enucleation based on proximity of tumor to pancreatic duct. We reviewed our experience with intraarterial calcium stimulation (Ca-Stim) and intraoperative ultrasonography (IOUS) to localize and guide management of insulinomas. METHODS Thirty-six patients (14 men, 22 women, median age 44 years) with insulinomas were treated between August 1989 and June 1996. Preoperative imaging studies were obtained. Patients underwent abdominal exploration with IOUS. Fourteen were evaluated by a surgeon blinded to preoperative imaging results. RESULTS Tumors (4 to 50 mm) were resected by enucleation (67%) or partial pancreatectomy (33%); all were cured. Sensitivities of computed tomography, magnetic resonance imaging, somatostatin receptor scintigraphy, ultrasonography, angiography, and Ca-Stim in localizing insulinomas were 24%, 45%, 17%, 13%, 43%, and 94%, respectively. Tumors were identified by blinded surgical exploration with IOUS in 12 of 14 patients (86%). CONCLUSIONS All insulinomas were identified before operation; however sensitivity of individual noninvasive tests was low (less than 50%). In contrast, Ca-Stim was correct in 94% of cases, thus allowing a focused pancreatic exploration and obviating use of blind distal pancreatectomy. IOUS can then be used to guide safe enucleation.

Hepatic abscess in patients with chronic granulomatous disease.

ObjectiveTo evaluate the clinical presentation, diagnostic procedures, and surgical management of hepatic abscesses in patients with chronic granulomatous disease (CGD). Summary Background DataChronic granulomatous disease is a rare inherited primary immunodeficiency in which phagocytes cannot destroy catalase-positive bacteria and fungi. Defects in the phagocytic cells’ respiratory burst lead to life-threatening infections, including hepatic abscess. These abscesses are recurrent and often multiple and are treated differently from bacterial abscesses in patients without CGD. MethodsBetween 1980 and 2000, 61 cases of hepatic abscess in 22 patients with CGD were treated at the National Institutes of Health. Clinicopathologic features were investigated by retrospective review of the medical records, radiographs, and histopathology. ResultsTwelve of the 61 cases were primary hepatic abscesses. Twenty-nine of the cases were recurrent hepatic abscesses, and 20 cases were persistent hepatic abscesses. The median age at the time of initial hepatic abscess presentation was 14 years. Subjective fever was the most frequent presenting symptom, and the erythrocyte sedimentation rate was elevated in 98% of cases. Fifty-two cases were managed surgically and eight cases were managed with percutaneous drainage. One patient refused surgery. The surgical complication rate was 56%; however, there were no deaths directly related to the hepatic abscesses. Staphylococcus aureus was the most frequent organism identified in culture (88% of positive cultures). Aggressive surgery and antibiotics ultimately resulted in successful treatment of all patients. ConclusionsHepatic abscesses occurring in patients with CGD represent a difficult diagnostic and treatment challenge. Early excision and treatment with antibiotics directed against S. aureus is necessary. General surgeons should be aware of this rare immunodeficiency and should aggressively manage hepatic abscesses in these patients.

A prospective study of hepatic imaging in the detection of metastatic disease.

: This prospective study of 80 patients compared the results of liver scintiscan, ultrasound, and CT scan to the objective findings recorded at laparotomy. Analysis of these data revealed no significant differences in sensitivity, specificity, or accuracy among these three imaging procedures, although a trend toward increased accuracy of the CT scan was noted. In a composite analysis, the accuracy was not improved by combining two or all three of these examinations. A lesion by lesion analysis revealed the inability of any of the three currently used techniques to accurately detect lesions less than 3 cm in diameter.

Blind distal pancreatectomy for occult insulinoma, an inadvisable procedure

BACKGROUND Fasting hypoglycemia with neuroglycopenic symptoms corrected by administration of glucose are the hallmarks for the diagnosis of insulinoma. Surgical resection is the treatment of choice for insulinomas, but localization of these lesions can be challenging. Blind distal pancreatectomy has been advocated for occult insulinomas not detected on imaging studies or during abdominal exploration. With the advent of newer localization techniques, we challenge the wisdom of this approach. STUDY DESIGN The records of patients (multiple endocrine neoplasia excluded) with pathologically proved insulinoma who were screened at our institution or referred to us after a failed blind distal pancreatectomy were reviewed. All records included patient history and results of physical examination and routine blood and urine tests. The diagnosis of insulinoma was confirmed during a supervised fast. Patients with biochemically proved insulinoma underwent localization studies and operation. Studies included CT scans, MRI, transabdominal ultrasound, intraoperative ultrasonography, angiography (more recently, Ca++-stimulated arteriography), and venous sampling. RESULTS From 1970 to 2000, 99 patients (34 men, 65 women; mean age 43 years) underwent operation. All patients with benign tumors (92) were cured after operation. Seventeen patients were referred to the NIH after a failed blind distal pancreatectomy. Of these, 5 were diagnosed as having factitious hypoglycemia. In the other 12 patients a tumor was localized in the pancreatic head. Two patients incorrectly diagnosed with nesidioblastosis after initial surgery were subsequently cured by resection of an insulinoma. CONCLUSIONS The use of preoperative imaging studies, most notably Ca++-stimulated arteriography, and intraoperative ultrasonography permits detection of virtually all insulinomas, including reopcrated cases. When a tumor is not detected, the procedure should be terminated and the patient referred to a center capable of performing advanced preoperative and intraoperative localization techniques. With the preoperative and intraoperative imaging strategies currently available, the use of blind distal pancreatectomy for occult insulinoma should be abolished.