Prognostic role of early 18-FDG PET/CT during neoadjuvant chemotherapy for resectable adenocarcinoma of the esophagus and esophagogastric junction.

We prospectively investigated whether metabolic response assessed by 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (PET/CT) early in the course of neoadjuvant chemotherapy is predictive of survival in patients with adenocarcinoma of the esophagus and esophagogastric junction. PET/CT was performed before and in the third week after the initiation of the first cycle of neoadjuvant chemotherapy, which consisted of epirubicin, cisplatin, and 5-fluorouracil or capecitabine. The metabolic response was defined as a relative decrease in the peak standardized uptake value (SUL) of the tumor by ≥35% or total lesion glycolysis (TLG) by ≥66%. The associations of metabolic response with overall survival (OS) and disease-free survival (DFS) were investigated using Kaplan-Meier curves and multivariable Cox regression analysis. Among 126 recruited patients, the early metabolic response was assessed in 107 patients (90 of them underwent surgical resection). The five-year OS and DFS rates of all patients were 28% and 27%, respectively. No difference was found in OS (p=0.10 for SUL, p=0.08 for TLG) or DFS (p=0.50 for SUL, p=0.20 for TLG) between metabolic responders and non-responders. Post hoc analysis of the patients with a follow-up PET/CT within 16 days showed that metabolic response reflected by SUL predicted OS (p=0.03). We concluded that metabolic response assessed by PET/CT after the first cycle of neoadjuvant chemotherapy does not predict survival in patients with adenocarcinoma of the esophagus and esophagogastric junction. However, proper timing of the follow-up PET/CT may affect the prognostic ability of the early metabolic response.

FDG-PET/CT lymph node staging after neoadjuvant chemotherapy in patients with adenocarcinoma of the esophageal-gastric junction.

OBJECTIVES: The aim of the analysis was to assess the accuracy of various FDG-PET/CT parameters in staging lymph nodes after neoadjuvant chemotherapy. METHODS: In this prospective study, 74 patients with adenocarcinoma of the esophageal-gastric junction were examined by FDG-PET/CT in the course of their neoadjuvant chemotherapy given before surgical treatment. Data from the final FDG-PET/CT examinations were compared with the histology from the surgical specimens (gold standard). The accuracy was calculated for four FDG-PET/CT parameters: (1) hypermetabolic nodes, (2) large nodes, (3) large-and-medium large nodes, and (4) hypermetabolic or large nodes. RESULTS: In 74 patients, a total of 1540 lymph nodes were obtained by surgery, and these were grouped into 287 regions according to topographic origin. Five hundred and two nodes were imaged by FDG-PET/CT and were grouped into these same regions for comparison. In the analysis, (1) hypermetabolic nodes, (2) large nodes, (3) large-and-medium large nodes, and (4) hypermetabolic or large nodes identified metastases in particular regions with sensitivities of 11.6%, 2.9%, 21.7%, and 13.0%, respectively; specificity was 98.6%, 94.5%, 74.8%, and 93.6%, respectively. The best accuracy of 77.7% reached the parameter of hypermetabolic nodes. Accuracy decreased to 62.0% when also smaller nodes (medium-large) were taken for the parameter of metastases. CONCLUSIONS: FDG-PET/CT proved low sensitivity and high specificity. Low sensitivity was based on low detection rate (32.6%) when compared nodes imaged by FDG-PET/CT to nodes found by surgery, and in inability to detect micrometastases. Sensitivity increased when also medium-large LNs were taken for positive, but specificity and accuracy decreased.

FLT-PET in previously untreated patients with low-grade glioma can predict their overall survival.

BACKGROUND: Low-grade gliomas (LGG) of the brain have an uncertain prognosis, as many of them show continuous growth or upgrade over the course of time. We retrospectively investigated the role of positron emission tomography with 3'-deoxy-3'-[18F]fluorothymidine (FLT-PET) in the prediction of overall survival and event free survival in patients with untreated LGG. No such information is yet available in the literature. MATERIAL AND METHODS: Forty-one patients with previously untreated LGG underwent 55 FLT-PET investigations during their follow-up because of subjective complaints, objective worsening of clinical conditions, equivocal findings or progression on magnetic resonance imaging. The time interval before referral for neurosurgical or radiation treatment was considered to be event free survival, the interval until death as overall survival, respectively. Standardized uptake values (SUV) were measured, and a 3-point scale of subjective assessment was also applied. ROC analysis was used to define cut-off values. The log rank test was used for comparison of Kaplan-Meier survival curves. RESULTS: Eight patients (a total of 9 FLT-PET studies performed) died during follow-up. Progression leading to referral to therapy was recorded in 24 patients (a total of 33 FLT-PET studies). With a cut-off value of SUV(mean) = 0.236, a median overall survival of 1.007 days was observed in the test positive subgroup while median overall survival for the test negative subgroup was not achieved (p = 0.0002), hazard ratio = 17.6. Subjective assessment resulted in hazard ratio 11.5 (p = 0.0001). Only marginal significance (p=0.0562) was achieved in prediction of event free survival. CONCLUSIONS: Increased FLT uptake in previously untreated patients with LGG is a strong predictor of overall survival. On the other hand, prediction of event free survival was not successful in our cohort, probably because of high prevalence of patients who needed treatment due to symptoms caused by a space-occupying lesion without respect to the proliferative activity of the tumour.

Nontuberculous mycobacterial infection after therapy with temsirolimus for metastatic renal cell carcinoma.

We describe the case of a patient with metastatic renal cell carcinoma (mRCC) who developed a nontuberculous mycobacteria (NTM)-related pulmonary nodule during therapy with the mammalian target of rapamycin (mTOR) inhibitor temsirolimus. After discontinuation of temsirolimus treatment, a small pulmonary nodule with increased glucose uptake was detected on a positron emission tomography (PET) scan. A lung resection carried out to confirm and treat the suspected solitary metastasis of RCC yielded the surprising finding of a caseating granuloma containing NTM. A single PET-positive nodule presents a significant differential diagnostic dilemma in the setting of mRCC treated with mTOR inhibitors. Although the treatment of mRCC with temsirolimus can lead to immunosuppression and opportunistic infections, there is no report to our knowledge on the occurrence of NTM infections in mRCC patients treated with mTOR inhibitors. These infections should be included in the differential diagnosis of lung nodules. Interestingly, there is strong preclinical evidence pointing to direct and indirect antimycobacterial activity of mTOR inhibitors. We therefore hypothesize that while the seeding of NTM can occur during temsirolimus therapy due to T-lymphocyte suppression, the infection may only become active after the discontinuation of mTOR inhibitor treatment.

The analysis of factors affecting the threshold on repeated 18F-FDG-PET/CT investigations measured by the PERCIST protocol in patients with esophageal carcinoma.

BACKGROUND: When applying the PET Response Criteria in Solid Tumors protocol, a threshold value based on standardized uptake value corrected to lean body mass (SUL) in liver parenchyma, or in the blood pool, is used: to metabolically specify a measurable lesion; to calculate metabolic tumor volume (mTV) and its product total lesion glycolysis (TLG); and as a limit for response measurement. The problem with using changes in glucose metabolism as a marker for response to therapy is its reproducibility on test-retest examinations. Therefore, before the evaluation of tumor treatment response, we verified our diagnostic protocol for homogeneity using the PET Response Criteria in Solid Tumors quality parameters. In addition, we analyzed the effect of the time span between examinations on the average value of SUL (SUL MEAN) in liver parenchyma at three different points: first at baseline (BL), after the first course of chemotherapy (ChT1), and finally after finishing therapy (ChT3). We also analyzed the influence of SUL MEAN variation on mTV and TLG. METHODS: Eighty-four patients with esophageal cancer were prospectively examined at BL using 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG)-PET/CT; 53 of 84 patients were examined after ChT1, 47 of 84 after ChT3, and 41 of 84 underwent all three examinations. Coefficient of variance (CV) and relative differences (RDw) were assessed for test-retest liver SUL values. The influence of liver SUL MEAN to mTV and TLG was modeled on BL examinations by artificial changes in liver SUL MEAN by ± 20%. RESULTS: No significant differences were found in test-retest liver SUL MEAN values. Comparing BL with ChT1, BL with ChT3, and ChT1 with ChT3, the CV of the liver SUL MEAN was 10.4, 10.7, and 10.3%; nevertheless, in 34.0, 38.3, and 36.6% of these examinations, respectively, the liver average SUL MEAN values exceeded the limit for inclusion in the study; that is, the difference was less than ± 0.3 U and ± 20%. The corresponding CV of blood background was 14.9, 16.5, and 17.2%. The artificial decrease of -20% in the liver SUL MEAN resulted in an increase of +43.6% in mTV and of +20.4% in TLG, whereas an increase of +20% in the liver SUL MEAN resulted in a decrease of -20.6% in mTV and -11.9% in TLG. CONCLUSION: SUL MEAN values in reference tissues (liver parenchyma or descending aorta) measured before chemotherapy did not differ significantly from those measured during chemotherapy. The CV of liver SUL MEAN was comparable to that seen in published data, but some patients had to be excluded from the study because of the individual variability of their mean liver SUL MEAN, which consequently hinders the clinical usage of mTV and TLG. Even in the standardized protocol, all potential sources of variability should be minimized.

Clinical outcomes of patients with nonseminomatous germ cell tumours and negative postchemotherapy positron emission tomography.

Univariate and multivariate analyses were carried out to identify factors associated with the failure of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) to correctly predict relapse-free survival in patients with nonseminomatous germ cell tumours. Ninety-three patients with negative postchemotherapy FDG-PET scan were analyzed in the retrospective study. The FDG-PET result was validated by long-term follow-up and, in some patients, by resection of the residual tumour mass. The negative predictive value of FDG-PET was 81.7%. Higher tumour marker levels and nodal stage at diagnosis, presence of residual mass, and teratoma or teratocarcinoma in the primary histology were associated with FDG-PET failure.

Prognostic and diagnostic accuracy of [18F]FDG-PET/CT in 190 patients with carcinoma of unknown primary.

PURPOSE: The aim of the study was to determine the accuracy of [(18)F]fluorodeoxyglucose (FDG) PET/CT in the search for the primary and the presence of a malignancy. The prognostic value of FDG-PET/CT information was tested. METHODS: A total of 190 patients were retrospectively analysed: 82 with histologically proven metastases (HPM) and 108 with clinical suspicion of the presence of a malignancy (CSM). The sensitivity and specificity were determined. Overall survival was calculated to evaluate the prognostic value of the FDG-PET/CT findings. RESULTS: In the search for the primary, the sensitivity and specificity were 62.0% and 81.9%, respectively. In the search for the presence of a malignancy, the sensitivity and specificity were 93.6% and 85.7%, respectively. Between the HPM and CSM groups, no significant difference in sensitivity and specificity was found either in the search for the primary or in the search for the presence of a malignancy. No significant difference in the sensitivity and specificity was found between 78 patients who were investigated by contrast-enhanced FDG-PET/CT and the remaining patients. A significantly shorter overall survival was found among patients with positive FDG-PET/CT findings compared with patients with negative findings (p = 0.00001); no significant difference in survival was found between the HPM and the CSM group (p = 0.770). CONCLUSION: FDG-PET/CT imaging is very helpful in the search for the presence of a malignancy in patients with carcinoma of unknown primary syndrome. FDG-PET/CT is less accurate in identifying exactly the site of a primary. Discovery of a hypermetabolic lesion was associated with the worst survival rate.

Gunshot liver trauma with disruption of the right hepatic duct managed by surgery, radiology, and endoscopy: a case report.

During the process of treating a complicated gunshot wound of an upper limb, chest, abdomen, and spine, there appeared--sometime after the initial treatment--a necrosis of the right hepatic duct in the bullet path within the liver. Although laparotomy was the life-saving operation during the first and second period, the final diagnosis and solution were based on bypassing the defect, i.e., a combination of a percutaneous and endoscopic approach. The efficiency of this method was also proved by an examination carried out 1 year after the end of the treatment.