Sara Apter

Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients

Purpose: Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) has shown promising results in metastatic melanoma patients. Although objective response rates of over 50% have been reported, disadvantages of this approach are the labor-intensive TIL production and a very high drop-out rate of enrolled patients, limiting its widespread applicability. Previous studies showed a clear correlation between short TIL culture periods and clinical response. Therefore, we used a new TIL production technique using unselected, minimally cultured, bulk TIL (Young-TIL). The use of Young-TIL is not restricted to human leukocyte antigen (HLA)-A2 patients. The purpose of this study is to explore the efficacy and toxicity of adoptively transferred Young-TIL following lympho-depleting chemotherapy in metastatic melanoma patients, refractory to interleukin-2 and chemotherapy. Experimental Design: Young-TIL cultures for 90% of the patients were successfully generated, enabling the treatment of most enrolled patients. We report here the results of 20 evaluated patients. Results: Fifty percent of the patients achieved an objective clinical response according to the Response Evaluation Criteria in Solid Tumors, including two ongoing complete remissions (20+, 4+ months) and eight partial responses (progression-free survival: 18+, 13+, 10+, 9, 6+, 4, 3+, and 3 months). All responders are currently alive. Four additional patients showed disease stabilization. Side effects were transient and manageable. Conclusion: We showed that lympho-depleting chemotherapy followed by transfer of short-term cultured TIL can mediate tumor regression in 50% of metastatic melanoma with manageable toxicity. The convincing clinical results combined with the simplification of the process may thus have a major effect on cell therapy of cancer. Clin Cancer Res; 16(9); 2646–55. ©2010 AACR.

Intussusception in adults: CT diagnosis

PURPOSE Intussusception in adults is nowadays usually diagnosed on computed tomography (CT), as CT is often the first modality for the investigation of prolonged abdominal pain from which these patients suffer. We wish to present the CT, clinical and pathological findings of 16 adult patients with intussusception seen over a 5-year period. MATERIALS AND METHODS The abdominal scans of 16 patients with intussusception were reviewed. Special attention was directed to the location of the mass, its shape and fat content, possible underlying pathology and dilatation of the bowel proximally. The findings were correlated with clinical and pathological data. RESULTS Eight men and eight women, aged 34-81 years, were studied. The most frequent indication for CT was prolonged abdominal pain. CT findings included an inhomogeneous soft tissue mass, target or sausage-shaped, depending on the angle of the CT beam vs. the intussusception, with a fatty component in 14 of the 16. Intussusception was enteroenteric (six), ileocolic (three), or colocolic (seven). Complete small bowel obstruction was present only in one case and some bowel dilatation in three. The underlying pathology could be diagnosed on CT in only two cases of lipoma. Nine patients had an underlying malignant process, eight of them unsuspected. Of the other five, two had coeliac disease, two were classified as idiopathic and one had a necrotic polyp of undetermined pathology. CONCLUSION Intussusception on CT presented a characteristic mass lesion containing fat stripes in almost all patients. Obstruction was rarely seen. Malignant lesions were the most common cause and therefore early diagnosis and prompt intervention are essential.

Adoptive Transfer of Tumor-Infiltrating Lymphocytes in Patients with Metastatic Melanoma: Intent-to-Treat Analysis and Efficacy after Failure to Prior Immunotherapies

Purpose: Adoptive cell transfer (ACT) using autologous tumor-infiltrating lymphocytes (TIL) was reported to yield objective responses in about 50% of metastatic patients with melanoma. Here, we present the intent-to-treat analysis of TIL ACT and analyze parameters predictive to response as well as the impact of other immunotherapies. Experimental Design: Eighty patients with stage IV melanoma were enrolled, of which 57 were treated with unselected/young TIL and high-dose interleukin-2 (IL-2) following nonmyeloablative lymphodepleting conditioning. Results: TIL cultures were established from 72 of 80 enrolled patients. Altogether 23 patients were withdrawn from the study mainly due to clinical deterioration during TIL preparation. The overall response rate and median survival was 29% and 9.8 months for enrolled patients and 40% and 15.2 months for treated patients. Five patients achieved complete and 18 partial remission. All complete responders are on unmaintained remission after a median follow-up of 28 months and the 3-year survival of responding patients was 78%. Multivariate analysis revealed blood lactate-dehydrogenase levels, gender, days of TIL in culture, and the total number of infused CD8+ cells as independent predictive markers for clinical outcome. Thirty-two patients received the CTLA-4-blocking antibody ipilimumab prior or post TIL infusion. Retrospective analysis revealed that nonresponders to ipilimumab or IL-2 based therapy had the same overall response rate to ACT as other patients receiving TIL. No additional toxicities to TIL therapy occurred following ipilimumab treatment. Conclusion: Adoptive transfer of TIL can yield durable and complete responses in patients with refractory melanoma, even when other immunotherapies have failed. Clin Cancer Res; 19(17); 4792–800. ©2013 AACR.

Polysplenia syndrome detected in adulthood: report of eight cases and review of the literature.

Abstract.Background: To present the computed tomographic (CT) features of the abdominal anomalies consistent with polysplenia syndrome in adults. Awareness of these abnormalities may avoid misdiagnosing characteristic findings as separate pathological processes. Methods: Imaging studies, mainly abdominal CT scans, of eight patients were reviewed. Attention was directed to the location of the multiple spleens, stomach, and liver and to the possible presence of a short pancreas, malrotation of the intestine, and venous anomalies. We also reviewed the CT findings of 15 adult patients described in the literature. Results: Three men and five women underwent CT for various unrelated conditions. The most common findings were multiple spleens along the greater curvature of the stomach, which were located in the right upper quadrant in six patients. The inferior vena cava was seen on the left side in seven subjects, with azygos/hemiazygos continuation in six. A preduodenal portal vein was present in seven subjects. The liver was in the midline in four patients and on the left side in two. A short pancreas was seen in four patients, intestinal nonrotation in five, and dextrocardia in two. The prevalence of these anomalies was similar to that of the reviewed cases. Conclusions: CT proved to be an excellent imaging modality in the diagnosis of the abdominal anomalies. Some of these (a short pancreas, multiple spleens, and azygos continuation) can simulate pathological processes. Hence the importance of recognizing these CT findings as part of a syndrome.

Minimally Cultured or Selected Autologous Tumor-infiltrating Lymphocytes After a Lympho-depleting Chemotherapy Regimen in Metastatic Melanoma Patients

Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) and high-dose interleukin-2 (IL-2), after nonmyeloablative chemotherapy, has been shown to result in tumor regression in half of refractory metastatic melanoma patients. In the present study, we describe 2 separate clinical protocols. Twelve patients were treated with “Selected”-TIL, as previously reported and 8 patients with the modified version of “Young”-TIL. Selected-TIL protocol required the establishment of multiple T-cell cultures from 1 patient and in vitro selection of cultures secreting interferon-γ upon antigenic stimulation. In contrast, Young-TIL are minimally cultured T cells with superior in vitro features that do not require further selection. Two of 12 Selected-TIL patients experienced objective clinical responses (1 complete response, 1 partial response). Out of 8 treated Young-TIL patients, 1 experienced complete response, 2 partial response, and 4 patients had disease stabilization. Twenty-one of 33 enrolled Selected-TIL patients were excluded from the protocol, mainly as cultures failed the interferon-γ selection criteria or due to clinical deterioration, compared with only 3 Young-TIL patients. Expected bone marrow suppression and high-dose IL-2 toxicity were transient. There was no treatment-related mortality. This study vindicates the feasibility and effectiveness of TIL technology and calls for further efforts to implement and enhance this modality. The use of minimally cultured, unselected Young-TIL enables the treatment of most enrolled patients. Although the cohort of Young-TIL patients treated so far is rather small and the follow-up short, the response rate is encouraging.

CT findings of the chest in adults with aspirated foreign bodies.

Abstract The aim of this study was to assess the imaging findings in adult patients with tracheobronchial foreign body aspiration. Nineteen patients (11 men and 8 women; age range 26–89 years) with foreign-body aspiration were retrospectively reviewed. Nine

Urinomas caused by ureteral injuries: CT appearance

AbstractBackground: We report the computed tomographic (CT) features of urinomas caused by ureteral injuries which are often not clinically suspected, causing delay in diagnosis. Methods: CT studies of 12 patients with ureteral injury were reviewed. Ureteral injuries were iatrogenic in 9 patients and traumatic in the remaining three. CT was performed between 2 and 139 days (average = 33 days) after the insult. The most common presenting symptoms were severe abdominal pain and fever. All CT studies were performed before and after intravenous contrast administration. In 11 of 12 cases, delayed scanning was added 15 min to 5 h later. Results: The sites of injury were the proximal ureter in two patients, the middle ureter in three, the distal ureter in two, and the ureteral anastomosis in five. The urinomas appeared as confined water-density fluid collections in seven patients, as free fluid (urinary ascites) in two, and as both in three. Extravasation of contrast from the ureter was observed on early scans in six patients and on delayed scanning only in the other six. The density of the opacified urinoma measured 80–200 HU. Ipsilateral hydronephrosis was observed in seven patients. Ureteral injuries were treated conservatively in eight patients and surgically in four. Conclusion: Ureteral injuries after iatrogenic or penetrating trauma often are diagnosed with considerable delay. The presence of ascites or localized fluid collections in symptomatic patients after abdominal surgery or penetrating trauma should raise the possibility of a ureteral injury and prompt delayed scanning.

Imaging of mucocoele of the appendix with emphasis on the CT findings: A report of 10 cases

AIM Mucocoele of the appendix denotes an obstructive dilatation of the appendiceal lumen due to abnormal accumulation of mucus. It is sometimes associated with pseudomyxoma peritonei, which predicts a malignant origin. We present the CT findings and additional imaging studies of 10 patients with neoplastic appendiceal mucocoele and discuss the clinical implications. MATERIALS AND METHODS Abdominal CT findings from 10 patients with appendiceal mucocoele were reviewed. Barium enema, US and MRI were additionally performed in three patients. There were five men and five women aged 45-80 years. Special attention was directed to the shape and nature of the mass, its relation to the caecum and the presence of ascites or peritoneal implants, as well as possible additional ovarian tumours in female patients. RESULTS The mucocoele was an incidental finding in five patients. They were either spherical or elongated cystic lesions, attached to the wall of the caecum, six of them with mural calcification. Ascites were present in six patients and hypodense large peritoneal implants representing pseudomyxoma peritonei in four. Pathologically the series included five cases of cystadenoma (in one, a malignant pseudomyxoma peritonei subsequently developed), four cases of cystadenocarcinoma and one villous adenoma (this patient later developed pseudomyxoma peritonei). Pseudomyxoma peritonei was found in five cases. Three women had associated ovarian cystic tumour. CONCLUSION The appearance of an appendiceal mucocoele is quite characteristic and can be diagnosed on CT. CT can also depict additional findings suggesting pseudomyxoma peritonei. In women with an appendiceal mucocoele the ovaries should be examined closely for cystic tumour and vice versa.

Gossypiboma in the Early Post-operative Period: A Diagnostic Problem

A gossypiboma (a retained surgical sponge) usually has the characteristic appearance on CT of a soft tissue mass with air-bubbles and a whirl-like pattern. This finding may be confused in the early post-operative period with an abscess, especially when a fistula is present. We describe two patients, in whom this diagnosis was initially missed. A soft tissue mass containing air-bubbles in the early post-operative period with or without a fistula should include a retained pad, in the differential diagnosis.

Coronary calcium by spiral computed tomography predicts cardiovascular events in high-risk hypertensive patients.

Objective The ability of coronary artery calcium (CAC) to predict coronary events has been shown in several studies. We aimed to investigate the hypothesis that CAC as assessed by dual slice spiral computed tomography (DSCT), is an independent risk factor for cardiovascular events in hypertensive patients. Methods We followed 446 participants of INSIGHT (International Nifedipine Study Intervention as Goal for Hypertension Therapy) calcification study, for the incidence of cardiovascular events as a function of CAC and other factors. All were hypertensive, without coronary artery disease (CAD), ages > 55 years and with at least one more major cardiovascular risk factor. All underwent a baseline DSCT and were followed for a mean period of 3.8 ± 0.4 years. All events were documented while the scheduled visits and confirmed by the INSIGHT critical event committee. Results Follow-up was conducted on all participants. 294 patients (66%) had CAC at baseline. Forty-seven patients experienced a first cardiovascular event: acute myocardial infarction (MI), 16; sudden cardiac death, two; unstable angina resulting in revascularization, 14; stroke, 15. The incidence of first cardiovascular events was 3.7 times higher among those who had CAC at baseline than among those who had no CAC (14.5% (41 of 294) versus 3.9% (6 of 152)). Patients who experienced an event were more likely to be males, had had higher prevalence of peripheral vascular disease, longer duration of hypertension, and had higher levels of systolic blood pressure (SBP), glucose, creatinine and uric acid. Adjusting for these covariates, CAC (total coronary calcium score (TCS) > 0) independently predicted cardiovascular events with an odds ratio (OR) of 2.76 [95% confidence interval (CI) 1.09–6.99, P = 0.032]. Conclusion The presence of CAC predicts cardiovascular events in high-risk asymptomatic hypertensive patients.