Damien Huglo

Supernumerary Parathyroid Glands: Frequency and Surgical Significance in Treatment of Renal Hyperparathyroidism

Supernumerary parathyroid glands (SPGs) are found in 13% of random autopsies. The high incidence of SPGs could explain the persistence or trigger recurrence of renal hyperparathyroidism after surgery. The aim of this study was to assess the frequency and clinical relevance of SPG in patients operated on for renal hyperparathyroidism (HPT). In this retrospective study we reviewed the medical records of 290 patients with renal HPT who were initially treated in our department. We examined the anatomic and pathologic findings during cervical surgical exploration and the outcome of HPT during follow-up. SPGs were identified in 87 patients (30%) during the initial cervicotomy, corresponding to intrathymic parathyroid cell islets (one to four) in 70 cases and to extrathymic SPG in 17 patients. Among 260 patients available for follow-up, 11 experienced persistent HPT (4%), and 34 developed recurrent HPT (13%). A total of 25 patients were reoperated on, and SPGs were responsible for 4 of 8 cases of persistent HPT and 4 of 17 cases of recurrent HPT, representing an overall frequency of 32%. The anatomic distribution of SPGs found during reoperations included thymus, retroesophageal grove, carotid sheath, and mediastinum. SPGs are thus present in 30% of patients with renal HPT and are situated mainly in the thymus. Thymectomy should be performed routinely during the first surgical exploration to prevent recurrences arising from anterior mediastinal glands. SPGs were also responsible for 32% of persistent or recurrent HPT. In that setting, frankly ectopic SPGs are not rare, and preoperative imaging appears highly desirable prior to embarking on surgical reexploration.

High Rates of Durable Responses With Anti-CD22 Fractionated Radioimmunotherapy: Results of a Multicenter, Phase I/II Study in Non-Hodgkin's Lymphoma

PURPOSE Fractionated radioimmunotherapy targeting CD22 may substantially improve responses and outcome in non-Hodgkins lymphoma (NHL). PATIENTS AND METHODS A multicenter trial evaluated two or three weekly infusions of yttrium-90 ((90)Y) epratuzumab tetraxetan (humanized anti-CD22 antibody) in 64 patients with relapsed/refractory NHL, including 17 patients who underwent prior autologous stem-cell transplantation (ASCT). Objective (OR) and complete responses (CR/complete response unconfirmed [CRu]), as well as progression-free survival (PFS), were determined. RESULTS At the maximum total (90)Y dose of 45 mCi/m(2) (1,665 MBq/m(2)), grade 3 to 4 hematologic toxicities were reversible to grade 1 in patients with less than 25% bone marrow involvement. The overall OR rate and median PFS for all 61 evaluable patients was 62% (CR/CRu, 48%) and 9.5 months, respectively. Patients without prior ASCT obtained high OR rates of 71% (CR/CRu, 55%) across all NHL subtypes and (90)Y doses, even in poor-risk categories (refractory to last anti-CD20-containing regimen, 73% [CR/CRu, 60%]; bulky disease: 71% [CR/CRu, 43%]). Patients with prior ASCT received lower doses, but achieved an OR rate of 41% (CR/CRu, 29%). For patients with follicular lymphoma (FL), OR rates and median PFS increased with total (90)Y-dose, reaching 100% (CR/CRu, 92%) and 24.6 months, respectively, at the highest dose levels (> 30 mCi/m(2) total (90)Y-dose [1,110 MBq/m(2)]). Further, patients with FL refractory to prior anti-CD20-containing regimens achieved 90% (nine of 10 patients) OR and CR/CRu rates and a median PFS of 21.5 months. CONCLUSION Fractionated anti-CD22 radioimmunotherapy provides high total doses of (90)Y, yielding high rates of durable CR/CRus in relapsed/refractory NHL, resulting in 20 mCi/m(2) x 2 weeks as the recommended dose for future studies.

Ineffectiveness of ¹⁸F-fluorodeoxyglucose positron emission tomography in the evaluation of tumor response after completion of neoadjuvant chemoradiation in esophageal cancer.

Objective:To evaluate the role of 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in the assessment of tumor response after the completion of neoadjuvant chemoradiation (CRT) in patients with locally advanced resectable esophageal cancer. Background:After primary CRT, a noninvasive evaluation of the tumor response could help in the treatment decision to identify patients who may benefit from surgery. Whether FDG-PET provides clinically relevant information remains questionable. Methods:Operable patients with locally advanced esophageal cancer (clinically staged T3 N0-1 M0) were enrolled in this prospective study. The complete treatment plan included neoadjuvant CRT (cisplatin + 5-fluorouracil/45 Gy) followed 6 to 8 weeks later by a transthoracic en bloc esophagectomy. Morphological evaluation combined with FDG-PET was performed 2 weeks before the start of CRT and 4 to 6 weeks after the completion of CRT. Intratumoral pre- and posttreatment FDG-standardized uptake values (SUV1, SUV2, percentage change) were assessed. These variables were correlated with pathological and morphologic responses and survival. Investigators were blinded to the FDG-PET results unless they revealed metastatic disease. Results:Of 60 total patients, 46 underwent the complete treatment plan (median age: 60.1 years; adenocarcinoma: 25 patients; squamous cell cancer: 21 patients). A major pathological response occurred in 45.7% of patients and was associated with a favorable outcome (P = 0.057). Neoadjuvant CRT led to a significant reduction in intratumoral FDG-uptake (P < 0.001). No significant association was seen between a pathological response (either complete or major) and the FDG-PET results (P > 0.280). The SUV2 value was correlated with a morphological response and the possibility to perform an R0 resection (P < 0.018; receiver operating characteristic curve analysis: SUV2 threshold = 5.5). No significant association was found between metabolic imaging and recurrence or survival. Conclusions:FDG-PET does not effectively correlate with pathological response and long-term survival in patients with locally advanced esophageal cancer undergoing neoadjuvant CRT followed by surgery. (Registered on the www.e-cancer RECF0350.)

Comparison of technetium-99m methoxyisobutylisonitrile and gallium-67 citrate scanning in the assessment of lymphomas

The aim of this study was to compare the value of scintigraphy using technetium-99m methoxy-isobutylisonitrile (MIBI) with that of scintigraphy using gallium-67 citrate in the assessment of Hodgkins disease and non-Hodgkins lymphoma and to relate these results with those of CT scan and MRI. Fifty-eight patients were included either for a follow-up examination or for monitoring of their treatment. Twenty-three residual masses were studied. A whole-body scan was performed, followed by single-photon emission computed tomography (SPET) 20 min after injection of 740 MBq of99mTc-MIBI and 72 h after injection of 185 MBq of67Ga citrate. The overall sensitivity of99mTc-MIBI and67Ga citrate was 71% and 68%, respectively, and the overall specificity was 76% and 44%, respectively. For residual masses, the sensitivity was 44% with both tracers and the specificity was 80% with99mTc-MIBI and 53% with67Ga citrate. The positive predictive values were 85% and 68% and the negative predictive values were 59% and 44%, respectively. The signal-to-background ratio was 1.5 for99mTc-MIBI and 2 for67Ga citrate. At present,99mTc-MIBI cannot replace67Ga citrate in the assessment of lymphomas.

A New Method for Volume Segmentation of PET Images, Based on Possibility Theory

18F-fluorodeoxyglucose positron emission tomography (18FDG PET) has become an essential technique in oncology. Accurate segmentation and uptake quantification are crucial in order to enable objective follow-up, the optimization of radiotherapy planning, and therapeutic evaluation. We have designed and evaluated a new, nearly automatic and operator-independent segmentation approach. This incorporated possibility theory, in order to take into account the uncertainty and inaccuracy inherent in the image. The approach remained independent of PET facilities since it did not require any preliminary calibration. Good results were obtained from phantom images [percent error =18.38% (mean) ±9.72% (standard deviation)]. Results on simulated and anatomopathological data sets were quantified using different similarity measures and showed the method was efficient (simulated images: Dice index =82.18% ±13.53% for SUV =2.5 ). The approach could, therefore, be an efficient and robust tool for uptake volume segmentation, and lead to new indicators for measuring volume of interest activity.

Questionability of the benefits of routine laparotomy as the surgical approach for pheochromocytomas and abdominal paragangliomas

BACKGROUND Improvement of preoperative imaging of pheochromocytomas and abdominal paragangliomas may render routine laparotomy questionable as the surgical approach of choice for these lesions. METHODS We studied the records of 100 patients with chromaffin tumors who underwent abdominal exploration. The disease was familial in 28 patients and was malignant in 19. Seventy-five patients had intraadrenal disease (bilateral in 13). Computed tomography (CT), metaiodobenzylguanidine (MIBG) scintigraphy, and magnetic resonance imaging (MRI) were performed since 1979, 1984, and 1987 in 97, 73, and 43 patients, respectively. False-positive and false-negative results were defined as any discrepancy between imaging results and surgical findings. RESULTS Overall accuracy of preoperative localization was 85% with CT scan, 77% with MIBG scintigraphy, and 86% with MRI. In unilateral pheochromocytoma, accuracy was 94% with CT scan, 80% with MIBG scintigraphy, and 96% with MRI. When all three studies were performed (n = 38), overall accuracy was 97% and only one extraadrenal tumor in a patient with familial pheochromocytoma was overlooked. CONCLUSIONS The outstanding accuracy of available imaging techniques questions the strategy of routine laparotomy for sporadic and seemingly benign pheochromocytomas, favoring more elective approaches such as the posterior approach or laparoscopy.

Comparison of somatostatin analogue and metaiodobenzylguanidine scintigraphy for the detection of carcinoid tumours

The purpose of this prospective study was to compare the ability of radiolabelled somatostatin analogue (RSA) and metaiodobenzylguanidine (MIBG) scintigraphy to display carcinoid tumours. Forty patients were studied after radiological assessment based on clinical symptomatology. These patients had radiologically demonstrated tumours (n=28), resected tumours discovered to be of the carcinoid type (n=5) or clinically and biologically suspected carcinoid tumours (n=7). They underwent indium-111 DTPA-pentetreotide or iodine-123-Tyr-3-octreotide and131I-MIBG scintigraphy. The results were compared with those of complementary surgical or morphological examinations and analysed according to the site of the tumour and the symptomatology. In the case of 31 patients with a total of 55 tumoral sites, the sensitivity of the initial radiological assessment, of RSA and of MIBG was 96%, 86% and 64%, respectively, for the detection of at least one tumour per patient, but 51%, 85% and 51%, respectively, for the total number of sites. No site was detected solely by MIBG. The concordance between RSA and MIBG was better when all sites were considered (kappa index+0.44) than for only extrahepatic abdominal tumoral sites (kappa index+0.095). Abdominal, thoracic or bone marrow tumours were more easily detected with RSA than with MIBG. Hepatic invasion (21 cases) was more easily detected by radiology (sensitivity 100%) than by RSA and MIBG, both of which displayed a sensitivity of 80%, but with differences in uptake intensity. Tumour detection using MIBG was more significantly linked with flush (P<0.01) than with diarrhoea (P>0.10). In the assessment of carcinoid tumours, RSA scintigraphy should be carried out initially (just after hepatic ultrasonography) and supplemented by MIBG, as comparison of the studies serves to guide therapeutic options and might be valuable for prognosis.

Efficacy of iodine-131 6β-methyl-iodo-19-norcholesterol scintigraphy and computed tomography in patients with primary aldosteronism

Abstract. In order to define the role of scintigraphy in determining the aetiology of primary aldosteronism, 41 patients were examined by computed tomography (CT) scan and adrenal scintigraphy using iodine-131 6β-methyl-iodo-19-norcholesterol with the dexamethasone suppression test. Hormonal and scintigraphic examinations were conducted while avoiding interference by medical treatment. The aetiological diagnosis was established by taking account of the clinical context, the endocrine profile, and CT scan and scintigraphic data, as well as possible hormone assays after catheterization of the adrenal veins (12 cases) and postoperative pathology data (14 cases). The aetiological diagnoses established were Conn’s adenoma (insensitive to angiotensin II) in 12 cases, idiopathic hyperplasia in 11 and macronodular hyperplasia (with functional autonomy of the nodules) in 18. Unilateral and bilateral lesions were correctly distinguished by scintigraphy in 92% of cases as compared with only 58% using CT scan alone; this was because the CT scan appearance was normal in 3/12 cases of adenoma and because a single nodule was visible in 2/11 cases of idiopathic hyperplasia and in 12/18 cases of macronodular hyperplasia. It is concluded that scintigraphy using noriodocholesterol with the dexamethasone suppression test should be performed systematically in conjunction with hormonal tests and adrenal CT scan in all cases of primary aldosteronism, as part of a strategy aimed not only at detecting adenoma but also at determining whether the hyperfunctional lesions are bilateral.

Evaluation of response to fractionated radioimmunotherapy with 90Y-epratuzumab in non-Hodgkin’s lymphoma by 18F-fluorodeoxyglucose positron emission tomography

FDG-PET imaging has been proven to be more accurate than conventional imaging for assessment of lymphoma response to therapy. This study evaluates the usefulness of FDG-PET for predicting response to radioimmunotherapy in patients with refractory lymphoma. The results suggest that positive FDG-PET findings 6 weeks after radioimmunotherapy predict significantly earlier relapse. Background The study aimed to evaluate FDG-PET imaging for early prediction of response to radioimmunotherapy in patients with non-Hodgkin’s lymphoma. Design and Methods Twenty-seven patients from a large ongoing, multicenter, phase I/II trial of fractionated radioimmunotherapy using anti-CD22 90Y-epratuzumab underwent FDG-PET imaging. They also underwent assessment by conventional diagnostic methods that included chemotherapy at baseline and six weeks post-radioimmunotherapy, and every three months until progression. Responses evaluated from conventional methods were classified using International Workshop Response Criteria as complete response, unconfirmed CR, partial response, stable disease, or progression of disease. FDG-PET images were evaluated visually and were classified as complete response, partial response or progression of disease. The gold standard was histology and follow-up. Results A total of 81 paired imaging studies were obtained post-radioimmunotherapy (including 3 patients after retreatment) and evaluated as complete response (n=34), partial response (n=24) or progression of disease (n=23) by FDG-PET, and complete response (n=12), unconfirmed complete response (n=31), partial response (n=15), stable disease (n=8) or progression of disease (n=15) by conventional methods. Of the 31 responses evaluated as unconfirmed complete response by conventional methods, 20 (65%) were classified as negative for disease (complete response) by PET while the other 11 (35%) were positive for disease (7 partial response and 4 progression of disease). Among 22 assessable PET images acquired at six weeks post-radioimmunotherapy, the mean time-to-progression was 15.6 months when PET was negative for disease (complete response), compared with 5.4 months when PET was positive (partial response or progression of disease) (p=0.008). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET six weeks after radioimmunotherapy were 86%, 63%, 80%, 71% and 77% respectively, compared with 36%, 87%, 83%, 44% and 55% respectively using conventional methods. Conclusions A positive assessment of disease by PET acquired six weeks after radioimmunotherapy corresponded with a shorter time to progression.

Drop of Total Liver Function in the Interstages of the New Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Technique: Analysis of the "Auxiliary Liver" by HIDA Scintigraphy.

To induce rapid hepatic hypertrophy and to reduce posthepatectomy liver failure (PHLF), associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been recently developed for patients with a limited future remnant liver (FRL). Nevertheless, high morbidity rates and mortality up to 12 % were reported. As a potential explanation of the poor outcome of ALPPS, little is known about the improvement in FRL function in the interstages period that was shown to be determinant for ALPPS outcome. Here, we report a new technique of evaluation of the liver function in the setting of ALPPS using sequential hepatobiliary scintigraphy (HBS) using Technetium-99m labeled Hepatobiliary IminoDiacetic Acid (HIDA) compounds ((99m)Tc-mebrofenin) with single photon emission computed tomography. Five patients (53–80 years of age) scheduled for extended hepatectomy underwent ALPPS for colorectal liver metastases (N 1⁄4 4) in 4 cases and gallbladder carcinoma (N 1⁄4 1) after giving informed consent. The colorectal liver metastases’ patients had received extensive chemotherapy (6–25 cures). The first stage of ALPPS was preceded by portal vein embolization in 3 patients with an anticipated FRL to body weight ratio 0.5%, including 2 salvage ALPPS due to almost-nil hypertrophy after portal vein embolization. All patients had sequential determinations of FRL and total liver volumes by computed tomography volumetric measurement combined with functional assessment by HBS as previously described, in the immediate preoperative period of stage 1 and between the 2 stages after a delay of 5 to 7 days following the first stage in 4 patients and 11 days in the elderly patient who badly tolerated the liver partition. HBS results were reported as the mebrofenin uptake of the total liver and FRL (TLU and RLU; %/min m). The increase in FRL function was compared with the volume increase, with increase rates expressed as relative increases (ie, postoperative FRL— preoperative FRL/preoperative FRL). Preoperatively, the median FRL to body weight ratio was 0.43% (0.3%–0.5%). Hepatic biological parameters remained near