Onelio Geatti

Survival after Yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: A European evaluation

A multicenter analysis was conducted to evaluate the main prognostic factors driving survival after radioembolization using yttrium‐90–labeled resin microspheres in patients with hepatocellular carcinoma at eight European centers. In total, 325 patients received a median activity of 1.6 GBq between September 2003 and December 2009, predominantly as whole‐liver (45.2%) or right‐lobe (38.5%) infusions. Typically, patients were Child‐Pugh class A (82.5%), had underlying cirrhosis (78.5%), and had good Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 0‐1; 87.7%), but many had multinodular disease (75.9%) invading both lobes (53.1%) and/or portal vein occlusion (13.5% branch; 9.8% main). Over half had advanced Barcelona Clinic Liver Cancer (BCLC) staging (BCLC C, 56.3%) and one‐quarter had intermediate staging (BCLC B, 26.8%). The median overall survival was 12.8 months (95% confidence interval, 10.9‐15.7), which varied significantly by disease stage (BCLC A, 24.4 months [95% CI, 18.6‐38.1 months]; BCLC B, 16.9 months [95% CI, 12.8‐22.8 months]; BCLC C, 10.0 months [95% CI, 7.7‐10.9 months]). Consistent with this finding , survival varied significantly by ECOG status, hepatic function (Child‐Pugh class, ascites, and baseline total bilirubin), tumor burden (number of nodules, alpha‐fetoprotein), and presence of extrahepatic disease. When considered within the framework of BCLC staging, variables reflecting tumor burden and liver function provided additional prognostic information. The most significant independent prognostic factors for survival upon multivariate analysis were ECOG status, tumor burden (nodules >5), international normalized ratio >1.2, and extrahepatic disease. Common adverse events were: fatigue, nausea/vomiting, and abdominal pain. Grade 3 or higher increases in bilirubin were reported in 5.8% of patients. All‐cause mortality was 0.6% and 6.8% at 30 and 90 days, respectively. Conclusion: This analysis provides robust evidence of the survival achieved with radioembolization, including those with advanced disease and few treatment options. (HEPATOLOGY 2011;)

Localization of parathyroid enlargement: experience with technetium-99m methoxyisobutylisonitrile and thallium-201 scintigraphy, ultrasonography and computed tomography

Technetium-99m methoxyisobutylisonitrile (MIBI), like thallium-201, has recently been introduced as a myocardial perfusion agent and is now also showing very promising results in parathyroid scintigrapy. The results of 201Tl/99mTc-pertechnetate and 99mTc-MIBI/99mTc-pertechnetate subtraction scintigraphy, ultrasonography and computed tomography are presented in a series of 43 patients operated on for hyperparathyroidism. All four imaging modalities were confirmed to be reliable, scintigraphy being the most accurate. Sensitivities ranged from 81% to 95%, that of 99mTc-MIBI being the highest. Moreover this tracer, which has more favourable physical and also biochemical properties, yielded images of superior quality. This allowed localization of the lesion by visual inspection only in as many as 86% of the patients with positive 99mTc-MIBI/99mTc-pertechnetate subtraction scintigraphy. We believe that the higher sensitivity, superior image quality and lower cost of 99mTc-MIBI imaging will make 99mTc-MIBI the new radiopharmaceutical of choice for parathyroid scintigraphy (when one takes into account the stability of labelling with large activities it is possible to perform three or four cardiac studies together with one parathyroid scintigraphic examination using one lyophililzed vial).

The intraperitoneal delivery of radiolabeled monoclonal antibodies: studies on the regional delivery advantage

SummaryThe i.p. delivery of murine monoclonal antibody was compared with i.v. delivery in normal mice and rats, in normal nude mice and in those with i.p. human ovarian carcinoma xenografts. In normal rats, all classes of antibodies and antibody fragments evaluated were cleared from the peritoneal cavity at comparable rates. The regional delivery (Rd1) advantage to the peritoneal cavity following i.p. delivery was thus most dependent on the rate of clearance of the antibody or fragment from the blood stream. Determining the exact i.p. delivery advantage was problematic due to the difficulty in reliably obtaining peritoneal fluid later than 9–10 h after i.p. injection in normal animals. During the first 9 h following i.p. injection, the Rd(0–9/0–9) was, for a murine IgG2ak Fab>F(ab′)2>IgG (at 13.6>10>7.9). Two murine IgMs evaluated differed in Rd(0–9) at 27.1 and 9.2 respectively. When blood levels were extrapolated to infinity, these Rd (0–9/∞) values were considerably lower with the Fab having the highest Rd at 4.67. The i.p. Rd advantage was almost solely due to the i.p. antibody levels seen in the first 24 h after injection, as after that time, blood levels become comparable to those seen following i.v. injection. Normal tissues obtained at sacrifice 5–7 days after i.p. injection. Normal tissues obtained at sacrifice 5–7 days after i.p. or i.v. injection in rats showed comparable levels of radioantibody activity, whether the injection was i.p. or i.v. (except for higher diaphragmatic levels following i.p. delivery). In nude mice with i.p. human-derived ovarian tumors, intact IgG clearance from the peritoneal cavity to the blood was considerably slower than in normal animals, and early i.p. tumor uptake of specific antibody was significantly higher than that following i.v. antibody delivery. With higher early tumor uptake and lower systemic exposure, early tumor/nontumor ratios were significantly greater than those for i.v. delivery, though not beyond 48 h after i.p. injection. This study demonstrates the pharmacokinetic rationale for i.p. monoclonal antibody delivery, especially for agents cleared rapidly from the blood, such as antibody fragments. In addition, definite i.p. delivery benefit for antibody specific to i.p. tumors in the i.p. ovarian cancer system was shown soon after injection. These data regarding i.p. antibody delivery should be useful in rationally planning diagnostic and therapeutic studies involving the i.p. delivery of unmodified and immunoconjugated monoclonal antibodies.

Comparison of the survival and tolerability of radioembolization in elderly vs. younger patients with unresectable hepatocellular carcinoma

BACKGROUND & AIMS The European Network on Radioembolization with Yttrium-90 resin microspheres study group (ENRY) conducted a retrospective study to evaluate the outcomes among elderly (≥ 70 years) and younger patients (<70 years) with unresectable hepatocellular carcinoma (HCC) who received radioembolization at 8 European centers. METHODS Patients with confirmed diagnosis of unresectable HCC who either progressed following resection or locoregional treatment and/or who were considered poor candidates for chemoembolization were evaluated by a multidisciplinary team for radioembolization with (90)Y-resin microspheres (SIR-Spheres; Sirtex Medical). The survival outcome and all adverse events were compared between the two age groups. RESULTS Between 2003 and 2009, 128 elderly and 197 younger patients received radioembolization. Patients in both groups had similar demographic characteristics. Many elderly and younger patients alike had multinodular, BCLC stage C disease, invading both lobes (p = 0.648). Elderly patients had a lower tumor burden, a smaller median target liver volume (p = 0.016) and appeared more likely to receive segmental treatment (p = 0.054). Radioembolization was equally well tolerated in both cohorts and common procedure-related adverse events were predominantly grade 1-2 and of short duration. No significant differences in survival between the groups were found (p = 0.942) with similar median survival in patients with early, intermediate or advanced BCLC stage disease. CONCLUSIONS Radioembolization appears to be as well-tolerated and effective for the elderly as it is for younger patients with unresectable HCC. Age alone should not be a discriminating factor for the management of HCC patients.

An unusual false-positive scan in a patient with pericardial effusion

Uptake of I-131 in the pericardial area is described in an asymptomatic patient who underwent total body scan for recurrent papillary thyroid cancer. Ultrasonography demonstrated a small pericardial effusion that persisted after I-thyroxine therapy was reinstituted. Two I-131 therapeutic doses were given, and follow-up total body scans were performed during the next 6 years. Although tracer accumulation in the neck was eliminated and the serum thyroglobulin level was not elevated, I-131 uptake persisted in pericardial effusion. Despite diligent study, no neoplastic, infectious, or autoimmune etiology could be demonstrated, and we thus classified it as idiopathic pericardial effusion. This phenomenon should be considered when interpreting I-131 scans that show I-131 uptake in the region of the heart.

Nifedipine Can Preserve Renal Function in Patients Undergoing Aortic Surgery with Infrarenal Crossclamping

Sixteen patients diagnosed with an aneurysm of abdominal aorta or Leriche disease underwent elective aortic surgery involving crossclamping of infrarenal aorta (ICC). These patients were randomized into two equal groups and 8 patients were infused with nifedipine starting from the isolation of aorta until the end of surgery (group A) while another 8 patients were infused with low-dose dopamine (group B) over the same surgical course. Plasma endothelin (ET) was measured before the induction of anesthesia, at the beginning and at the end of the clamp period and at the end of the operation. Intraoperatively, creatinine clearance and urinary excretion of PGE2, 6-keto PGF1 alpha and TxB2 were also determined before, during and after aortic crossclamping. Preoperative GFR as well as preinduction cardiac index (CI) and pulmonary capillary wedge pressure (PCWP) of the two groups did not differ. During cross-clamping plasma ET rose significantly in both groups. However, after clamp removal, plasma ET decreased in group A while it remained elevated in group B. Urinary excretion of TxB2, PGE2 and 6-keto PGF1 alpha increased during clamp in both groups, but the ratio of PGE2 + 6-keto PGF1 alpha/TxB2 during and after clamp was significantly higher in group A than in B. Postclamp creatinine clearance decreased in group B, and increased in group A; postoperative value of GFR was unchanged in group A and decreased significantly in group B. In conclusion, infusion of nifedipine, in contrast to dopamine, prevented the decrease of GFR in patients undergoing aortic surgery. This effect could be mediated by a nifedipine modulation of ET vascular synthesis and/or a preferential renal synthesis of vasodilating prostanoids.

An Unusual Adrenal Metastasis Secondary to Hürthle Cell Carcinoma of the Thyroid

A 66-year-old woman with Hürthle cell thyroid carcinoma associated with a right adrenal gland metastasis suspected on a postradioiodine therapy scan, is reported. Histology specimens confirmed the suspicion. Adrenal metastases have never been reported previously in this kind of tumor. On radionuclide imaging, there was marked I-131 uptake in the tumor remnant and its metastases, and the tumor spread through both lymphatic and hematogenous routes, as shown by lymph node, bone, and lung metastases.

Late presentation of metastatic pheochromocytoma: a problem case solved by I-131 MIBG scintigraphy.

A patient presented with recurrent pheochromocytoma 10 years following the apparently successful surgical cure of a right adrenal pheochromocytoma. Conventional medical imaging techniques, (chest radiograph, abdominal ultrasound, and abdominal CT) suggested local recurrence for which surgery was planned. I-131 MIBG scintigraphy revealed disseminated metastatic disease that rendered attempts at surgical cure futile. The patient was treated with three therapeutic doses of I-131 MIBG with good symptomatic palliation and improvement of ome biochemical parameters.

Systemic perfusion: a method of enhancing relative tumor uptake of radiolabeled monoclonal antibodies

We evaluated the feasibility of systemic vascular perfusion with saline (mimicking plasmapheresis) as a method to enhance tumor-specific monoclonal antibody (MoAb) tumor/background ratios. Initially, groups of rats were injected intravenously (i.v.) with 131I-5G6.4 MoAb (murine IgG2aK reactive with ovarian carcinoma). These animals radioactivity levels were determined by dose calibrator and they were imaged before and after perfusion which was conducted at 4 or 24 h post-antibody injection. Animals were sacrificed after perfusion, as were controls, and normal organ radioactivity levels determined. In addition, nude mice bearing HTB77 ovarian cancers subcutaneously were injected i.v. with 131I-5G6.4 MoAb and were imaged before and after systemic perfusion with saline 24 h post-5G6.4 injection. Perfusion in rats dropped whole-body 5G6.4 levels significantly at both perfusion times (P less than 0.0005). The drop in whole-body radioactivity with perfusion was significantly greater for the animals perfused at 4 h post i.v. 5G6.4 antibody injection (48.3 +/- 5.1%) than for those perfused at 24 h post i.v. antibody injection (32.9 +/- 2.9%) (P less than 0.025). In the nude mice with ovarian cancer xenografts, gamma camera images of tumors were visually and quantitatively (by computer image analysis) enhanced by perfusion, with a 2.33-fold greater decline in whole body uptake than in the tumor (P less than 0.05). These studies show that (1) much background antibody radioactivity can be removed using whole-body perfusion with saline, (2) that the decline in whole body activity is larger with 4 than 24 h perfusion and (3) tumor imaging can be enhanced by this approach.(ABSTRACT TRUNCATED AT 250 WORDS)

Concurrent Plummer's disease and parathyroid adenoma. Diagnostic and therapeutic approaches to a difficult clinical problem.

When mild asymptomatic hypercalcemia occurs in a patient with hyperthyroidism, it may or may not be due to concurrent hyperparathyroidism and at times only the control of the hyperthyroidism will resolve the problem. Moreover, the presence of hyperfunctioning thyroid nodules will interfere with TI-201/Tc-99m pertechnetate parathyroid scintigraphy. Initial treatment of hyperthyroidism with I-131 in this situation controls hyperthyroidism and permits successful localization of parathyroid adenomas, which may then be excised—a result that was achieved in three cases.