Positron emission tomography for predicting recurrence in stage I lung adenocarcinoma: standardized uptake value corrected by mean liver standardized uptake value

Objective: F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) has become an important staging tool for patients with lung cancer, and determination of the standardized uptake value (SUV) is probably the most widely used method for evaluating patients. Although SUV is recognized as a powerful surrogate marker for lung cancer outcomes, SUV standardization and reproducibility in clinical practice remain major concerns. The aim of this study was to evaluate the corrected SUV as a universal marker for lung cancer recurrence. Methods: We conducted a case–control study in our institute. From May 2004 to February 2010, 141 patients with pathological stage IA and IB adenocarcinomas underwent PET-computed tomography scanning and SUV determination. The corrected SUV was defined as the SUV index, which was calculated as the ratio of tumor SUV_max to liver SUV_mean. We examined the association between disease-free survival and several clinicopathological factors, including the SUV index. Results: The 3-year overall survival rate after surgery was 94.3% and the 3-year disease-free survival rate was 90.4%. Univariate analysis showed that male gender (p = 0.04), smoking (p = 0.02), and SUV index (p < 0.01) were independent predictive factors for recurrence. Multivariate analysis showed that the SUV index was significantly associated with a high risk for recurrence (p = 0.03). No patient with an SUV index <1.0 experienced a recurrence. Conclusions: The SUV index is a significantly predictive and reproducible factor for recurrence in pathological stage I lung cancers. Patients with an SUV index <1.0 were more likely to have a good prognosis. Additional multi-institutional studies are needed to confirm these study results.     

Contribution of 18F-fluorodeoxyglucose positron emission tomography to the diagnosis of early pancreatic carcinoma

Background/Purpose  Pancreatic carcinoma has a poor prognosis, and early detection is essential to allow potentially curative resection. Despite the wide array of diagnostic tools available, the detection of small pancreatic tumors remains difficult. The aim of this study was to investigate the contribution of ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) to the diagnosis of early pancreatic cancer. Methods  FDG-PET was performed in 56 patients with pancreatic cancer who underwent curative surgery. The standardized uptake value (SUV) for FDG was calculated in each patient and the relationships between the SUV and various clinicopathological factors were analyzed. Results  The tumors ranged from 0.8 to 6.5 cm in diameter. When the cutoff value for the SUV was set at 2.5, 51 of the 56 patients (91%) had a positive FDG-PET study. The SUV did not show a significant difference in relation to tumor differentiation or pTS and pT factors. There was also no correlation between the SUV and the maximum tumor diameter (r = 0.22; P = 0.1). Five tumors had an SUV below the cutoff value, and all of these lesions had intermediate or scirrhous stroma rather than medullary stroma. Conclusions  These results indicate that FDG-PET is useful for the detection of small early pancreatic cancers.     

Positron-emission tomography with 18F-2-fluoro-2-deoxy-D-glucose (18FDG-PET) in the diagnosis of retroperitoneal lymph-node metastases from testicular tumors

Summary In 1991, this prospectively designed study was started to assess the potentials of positron emission tomography with ¹⁸FDG in the diagnostic workup for the detection of lymph node metastases in testicular cancer, since there were no data available concerning this subject at this time. In 54 patients (27 patients with pure seminoma, 27 patients with non-seminomatous tumors) ¹⁸FDG-PET results were compared with the findings obtained with abdominal computed tomography, serum level of tumor markers (AFP, β -HCG), and the histopathological findings after primary or post-chemotherapy retroperitoneal lymph node dissection. In 21 patients with pure seminoma (clinical stage I according to the Lugano classification) ¹⁸FDG-PET results were identical with those of the abdominal computed tomography, so PET does not add relevant informations in this group of patients. In 7 patients presenting with non-seminomatous testicular cancer (stage I), PET was not able to detect the existing micrometastases in 4 patients. In 1/7 case PET examination showed a suspicious focal lesion, this lymph node had 2 micrometastases within inflammatory changes. In 1/7 patient ¹⁸FDG-PET definitely revealed metastatic lesions, while the CT scans where judged to be unobtrusive and tumor marker levels were within the normal range. In the 4 patients with pure seminomas stage II B and II C (N = 6), that have undergone retroperitoneal lymph node dissection following chemotherapy, ¹⁸FDG-PET correctly predicted absence of tumor in 3 out of these 4, and in 1/4 patient the benign nature of a persistent large tumor after two cycles of polychemotherapy was correctly identified wich eventually turned out to be a ganglioneuroma. This lesion falsely was classified as malignant tumor with abdominal computed tomography, and in 2/4 patients post-chemotherapy residual retroperitoneal lesions in the CT scans could not be assessed exactly whether or not malignant tumor was present. In 20 patients presenting with non-seminomatous testicular cancer (stage II and III) ¹⁸FDG-PET was able to demonstrate therapeutic effects of chemotherapy by showing decreasing tracer activity in those regions, that had hypermetabolic foci prior to chemotherapy. It became evident in testicular cancer that there is a single entity which is not characterized by increased glucose metabolism, the mature teratoma. In lesions detected by abdominal computed tomography which do not present increased ¹⁸FDG uptake, mature teratoma as well as scar/necrosis or rare other tumors with normal glucose metabolism can be supposed, but additional characteristics based on different ¹⁸FDG uptake were not observed. In 1/20 case post-chemotherapy PET scan detected a hypermetabolic lesion, which was suspicious for metastatic spread, but in the histopathological examination this lesion was identified as inflammatory tissue reaction. Based on the data reported here in ¹⁸FDG-PET cannot be considered a standard diagnostic tool in the staging examinations in testicular cancer. It is of clinical relevance in patients who present residual tumor after chemotherapy. In this situation ¹⁸FDG-PET is helpful in deciding whether or not a residual mass post-chemotherapy contains active tumor. ¹⁸FDG-PET can not replace retroperitoneal lymph node dissection for staging purposes.      

Evaluation of 18F-2-deoxy-2-fluoro-<Emphasis Type="SmallCaps">d</Emphasis>-glucose Positron Emission Tomography for Gastric Cancer

Positron emission tomography (PET) with ¹⁸F-2-deoxy-2-fluoro-d-glucose (FDG) has been investigated as a means of detecting certain primary tumors and their metastatic disease in recent years. The aim of this study was to compare the performance of FDG-PET and operative assessment with formal pathologic staging. Altogether, 85 patients had undergone surgical treatment for gastric cancer with curative intent, with FDG-PET preoperatively. The results using FDG-PET were compared with those using computed tomography (CT); they were also correlated with the pathologic findings. For quantitative analysis, the regional tumor uptake was measured by the standard uptake value (SUV) using a region of interest technique. Using FDG-PET, the primary tumor was visualized in 75.2% of patients. A comparison of the FDG uptake and the clinicopathologic findings showed that there was a significant association between FDG uptake and the depth of invasion, the size of the tumor, and lymph node metastasis. FDG-PET scans had less accuracy for diagnosing locoregional lymph nodes than CT because of a significant lack of sensitivity (23.3% vs. 65.0%). The survival rate for patients with high FDG uptake (SUV > 4) was significantly lower than that for those with low FDG uptake (SUV < 4) (p < 0.05). FDG-PET was successful in detecting the primary gastric cancer lesion but not for finding early-stage gastric cancers. Detection of nodal metastasis also was not possible by FDG-PET. However, FDG-PET appears to provide important additional information concerning the aggressiveness of the tumor and the prognosis in patients with gastric cancer.     

Comparison of Uptake Characteristics and Prognostic Value of <Superscript>201</Superscript>Tl and <Superscript>18</Superscript>F-FDG in Esophageal Cancer

Background Patients with esophageal cancer often undergo ²⁰¹Tl myocardial imaging for preoperative risk evaluation, thereby providing an excellent opportunity to assess tumor handling of ²⁰¹Tl. We thus compared the characteristics of ²⁰¹Tl and ¹⁸F-FDG uptake by esophageal cancer and further investigated their prognostic values. Methods The study included 100 newly diagnosed esophageal cancer patients who underwent preoperative ²⁰¹Tl SPECT and ¹⁸F-FDG PET exams. Tumor to mediastinal uptake (T/M) ratio and retention index (RI) of ²⁰¹Tl, tumor ¹⁸F-FDG pSUV, tumor size, location, and stage were assessed. Survival analysis was performed for disease-free survival using the Kaplan–Meier method. Cox proportional hazard models were used to determine independent risk factors. Results ²⁰¹Tl SPECT and ¹⁸F-FDG PET visualized the primary tumor in 85/100 (85.0%) and 91/100 (91.0%) patients, respectively (p = 0.03). There were close correlations between early and delayed ²⁰¹Tl T/M ratios (r = 0.83, p < 0.0001) and between T/M ratios and ¹⁸F-FDG pSUV (r = 0.56 and 0.57, respectively, both p < 0.0001). Both T/M ratios and ¹⁸F-FDG pSUV correlated significantly with tumor stage (ρ = 0.45, 0.40, and 0.59, respectively, all p < 0.0001). Survival analysis revealed tumor size, ²⁰¹Tl negative tumors, ¹⁸F-FDG negative tumors, delayed ²⁰¹Tl T/M ratio, RI, stage, and ¹⁸F-FDG pSUV to be significant univariate predictors for disease-free survival. Multivariate survival analysis showed stage (p = 0.02) to be a significant independent prognostic predictor. Conclusions In patients with esophageal cancer, assessment of tumor ²⁰¹Tl uptake, as with ¹⁸F-FDG, may provide potentially useful information regarding tumor characteristics. Presented in part at the 51st Annual Meeting of the Society of Nuclear Medicine, Philadelphia, PA, USA, June 19–23, 2004.     

Predicting neo‐adjuvant chemotherapy response and progression‐free survival of locally advanced breast cancer using textural features of intratumoral heterogeneity on F‐18 FDG PET/CT and diffusion‐weighted MR imaging

Predicting response to neo‐adjuvant chemotherapy (NAC) and survival in locally advanced breast cancer (LABC) is important. This study investigated the prognostic value of tumor heterogeneity evaluated with textural analysis through F‐18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and diffusion‐weighted imaging (DWI). We enrolled 83 patients with LABC who had completed NAC and curative surgery. Tumor texture indices from pretreatment FDG PET and DWI were extracted from histogram analysis and 7 different parent matrices: co‐occurrence matrix, the voxel‐alignment matrix, neighborhood intensity difference matrix, intensity size‐zone matrix (ISZM), normalized gray‐level co‐occurrence matrix (NGLCM), neighboring gray‐level dependence matrix (NGLDM), and texture spectrum matrix. The predictive values of textural features were tested regarding both pathologic NAC response and progression‐free survival. Among 83 patients, 46 were pathologic responders, while 37 were nonresponders. The PET texture indices from 7 parent matrices, DWI texture indices from histogram, and 1 parent matrix (NGLCM) showed significant differences according to NAC response. On multivariable analysis, number nonuniformity of PET extracted from the NGLDM was an independent predictor of pathologic response (P = .009). During a median follow‐up period of 17.3 months, 14 patients experienced recurrence. High‐intensity zone emphasis (HIZE) and high‐intensity short‐zone emphasis (HISZE) from PET extracted from ISZM were significant textural predictors (P = .011 and P = .033). On Cox regression analysis, only HIZE was a significant predictor of recurrence (P = .027), while HISZE showed borderline significance (P = .107). Tumor texture indices are useful for NAC response prediction in LABC. Moreover, PET texture indices can help to predict disease recurrence.     

Activated Akt and Erk Expression and Survival After Surgery in Pancreatic Carcinoma

Background Long-term survival of surgically resectable pancreatic cancer patients is uncommon. The epidermal growth factor receptor (EGFR) and the phosphoinositol-3-kinase pathways are often activated in pancreatic cancer, and an understanding of their role in resected cases may help refine adjuvant therapy. Methods We investigated the expression of EGFR, Erk, Akt, and their phosphoforms (p-) in pancreatectomy specimens and correlated these with survival. Thirty-nine consecutive surgically resected pancreatic adenocarcinoma cases were included. Immunohistochemical staining of paraffin-embedded blocks was performed by using monoclonal antibodies against EGFR, Erk, p-Erk, Akt, and p-Akt. A standard immunoperoxidase technique was used to detect the avidin-biotin peroxidase complex. Immunostaining was visually scored with the histoscore method by two surgical pathologists. Results Patient characteristics were as follows: 17 men and 22 women; median age, 66 years; and American Joint Committee on Cancer stage I, 5 patients; stage II, 4 patients; stage III, 27 patients; and stage IV, 3 patients. The tumor was World Health Organization grade 1 in 4, grade 2 in 17, and grade 3 in 18 cases. Adjuvant therapies were chemotherapy (n = 6), radiotherapy (n = 1), and chemoradiotherapy (n = 17). Immunohistochemistry revealed positive expression of EGFR in 30.8%, Erk in 92.3%, p-Erk in 45.9%, Akt in 71.8%, and p-Akt in 20.5% of cases. On univariate analyses, tumor grade (P = .0098), p-Akt (P = .0003), and p-Erk (P = .0052) expression correlated with survival. On multivariate analyses, age (P = .0002; hazard ratio [HR], 1.8), grade (P = .00318; HR, 3.0), Akt (P = .0433; HR, .4), p-Akt (P = .0002; HR, .2), and p-Erk (P = .0003; HR, 3.5) expression correlated significantly with survival. Conclusions p-Erk and p-Akt expression may have prognostic and therapeutic implications in pancreatic cancer.     

Preoperative Positron Emission Tomography with Fluorine-18-Fluorodeoxyglucose is Predictive of Prognosis in Patients with Hepatocellular Carcinoma after Resection

Background: Hepatocellular carcinomas (HCCs) accumulate fluorine-18 fluorodeoxyglucose (FDG) to various degrees. The standardized uptake values (SUVs) of FDG-positron emission tomography (PET) in high-grade HCCs are significantly higher than those in low-grade HCCs. Aim: The aim of this study was to evaluate the possible usefulness of FDG-PET in predicting the prognosis of HCC patients after resection. We analyzed the relationship between the tumor to non-tumor SUV ratios (SUV ratio) and surgical outcome in 31 patients. Results: Of the 31 cases of HCC studied, seven (23%) exhibited SUV ratios greater than 2, as the cutoff value. The percentage of patients with poorly differentiated HCC was greater in the higher SUV ratio group (SUV ratio >2) than in the lower SUV ratio group (SUV ratio <2) (57 vs. 32%). The overall survival was significantly longer in the lower SUV ratio group than in the higher SUV ratio group (5-year-survival rate: 63 vs. 29% P = 0.006) (median survival time: 2310 vs.182 days). Conclusion: The SUV ratio was related significantly to disease-related death as well as other predictive factors, including the number of tumors, the size, stage, and involvement of vessels, and the involvement of the capsule. Consequently, we conclude that the SUV ratio provides information of prognostic relevance in patients with HCC before surgery.     

18F-FDG PET在胰腺癌患者预后评估中的价值

目的 评估18F-FDG PET判断胰腺癌患者预后的价值.方法 回顾性分析54例胰腺癌病例资料.取所有病例PET检查的标准摄取值(standard uptake value,SUV)平均值4为截断点分组,A组22例(SUV≤4),B组32例(SUV＞4),分析两组患者的预后.结果 A组1、3年生存率为68.18%、34.91%;B组1、3年生存率为33.61%、11.95%,两组生存率比较差异有统计学意义(P=0.01);Cox回归分析提示肿瘤分期和SUV是胰腺癌患者预后的独立危险因素.结论 18F-FDG PET在判断胰腺癌预后方面有一定的价值.     

Whole-Body [18F]FDG PET in the Management of Metastatic Brain Tumours

Summary Background To determine its roles in the diagnosis and the systemic evaluation of metastatic brain tumours, whole-body positron emission tomography (PET) using [¹⁸F]FDG was performed in 20 consecutive patients. Methods  All patients were thought to be suffering or needing to be differentiated from metastatic brain tumours. Nine patients had multiple brain lesions; six were older and showed a rim-enhancing lesion with surrounding oedema; seven had homogeneously enhancing periventricular lesion(s) on computed tomography (CT) and/or magnetic resonance (MR) imaging, thought to be central nervous system lymphomas. Two patients had skull mass(es) and two patients had a solid mass suspected to be, respectively, a haemorrhagic metastasis and a metastatic malignant melanoma. All of them received whole-body [¹⁸F]FDG PET and conventional systemic work-up for metastasis in order to compare the results of the two methods. Results  Metastatic brain tumours were diagnosed on whole-body [¹⁸F]FDG PET in eleven patients who had extracranial and intracranial hypermetabolic lesions. In nine of these, a conventional work-up also detected primary lesions which on whole-body [¹⁸F]FDG PET were seen to be hypermetabolic foci. Systemic lymph node metastases were detected by whole-body [¹⁸F]FDG PET only in two patients and histological diagnosis was possible by biopsy of lymph nodes rather than of brain lesions. In the remaining nine patients who had only intracranial hypermetabolic foci, histological diagnosis was made by craniotomy or stereotactic biopsy. It was confirmed that seven of nine patients were suffering from a primary brain tumour and two from metastatic carcinoma. None of the nine showed evidence of systemic cancer on conventional work-up. Histological diagnoses of the primary brain tumours were four cases of primary central nervous system lymphoma and one each of multifocal glioblastoma, Ewing's sarcoma, and cavernous angioma.  Patients felt no discomfort during the whole-body [¹⁸F]FDG PET procedure and there were no complications. The false negative rate in [¹⁸F]FDG PET and in conventional work-up was 15.4% and 30.7% respectively. There were no false positives on either [¹⁸F]FDG PET or conventional work-up. Conclusion  It is suggested that whole-body [¹⁸F]FDG PET is a safe, reliable, and convenient method for the diagnosis and systemic evaluation of patients thought to be suffering or needing to be differentiated from a metastatic brain tumour.     

Preoperative Evaluation of Pancreatic Masses with Positron Emission Tomography Using 18F-fluorodeoxyglucose: Diagnostic Limitations

Identification of pancreatic cancer in patients presenting with an enlarged pancreatic mass is a major diagnostic problem. Positron emission tomography (PET) using the radiolabeled glucose analogue ¹⁸F-fluorodeoxyglucose (FDG) has been suggested to provide excellent accuracy for noninvasive determination of suspicious pancreatic masses. We conducted a prospective study to verify these results. Forty-two patients admitted for pancreatic surgery underwent PET scanning. Image analysis was based on visual film evaluation and quantification of regional tracer uptake. PET imaging was visually analyzed by three observers blinded for the results of other diagnostic tests; they qualitatively graded the scans using a five-point scale (I = low to V = high) for the presence and intensity of focal FDG uptake. Diagnosis was proven by histology (n= 38) or follow-up (n= 4). Furthermore, the results of PET were compared with helical computed tomography (CT) and conventional ultrasonography (US), done during the routine diagnostic workup before pancreatic cancer surgery. Regarding only the results with scores of IV and V as positive for representing definite malignancy yielded a sensitivity of 71% and a specificity of 64% for film reading. Quantification of regional tracer uptake contributed no significant diagnostic advantage for differentiation between benign and malignant tumors. Helical CT revealed a sensitivity of 74% and a specificity of 45.5% and abdominal US 56% and 50%, respectively. We concluded that PET imaging provides only fair diagnostic accuracy (69%) for characterizing enlarged pancreatic masses. PET does not allow exclusion of malignant tumors. In doubtful cases, the method must be combined with other imaging modalities, such as helical CT. The results indicate that the number of invasive procedures is not significantly reduced by PET imaging.     

Postoperative morbidity and long-term survival after pancreaticoduodenectomy with superior mesenterico-portal vein resection

The role of superior mesenteric-portal vein resection (SM-PVR) for vein invasion or tumor adherence during pancreatoduodenectomy (PD) is still under debate. We investigated morbidity, mortality, and long-term survival in patients who underwent PD with or without SM-PVR. Between July 1994 and December 2004, 222 PD (78% pylorus preserving, 19% Whipple, and 3% total pancreatectomy) were performed for malignant disease. Fifty-three patients (24%) had PD with SM-PVR. Sixty-eight percent of the venous resections were performed as wedge excisions and 32% as segmental resections. Long-term survival was analyzed in 165 patients with pancreatic (n=110), ampullary (n=33), or distal bile (n=22) duct cancer using univariate (log-rank) and multivariate (Cox regression) methods. In patients undergoing PD with SM-PVR and conclusive histologic examination of the resected vein specimen (n=42), 60% had true tumor involvement of the venous wall, whereas 40% had no proven tumor infiltration. In the complete study group, negative resection margins were obtained in 69% of patients with SM-PVR and in 79% of patients without SM-PVR (P=0.09). Median duration of surgery was 500 minutes (SM-PVR) versus 440 minutes (no SM-PVR; P<0.001). Volume of intraoperatively transfused blood was 600 ml (median) in both groups. Postoperative surgical complications/mortality occurred in 23%/3.8% (SM-PVR) versus 35%/4.1% (no SM-PVR); P=0.09/0.9. Analysis of long-term survival in all 165 patients included 41 with SM-PVR. Five-year survival rates were 15% in cancer of the pancreatic head, 22% in ampullary cancer, and 24% in distal bile duct cancer (P=0.02). Long-term survival was not influenced by the need for SM-PVR in any of the different tumor entities. In multivariate analysis, a positive resection margin (P<0.01, relative risk [RR]: 1.8, 95% confidence interval [CI]: 1.2–2.7), a histologically undifferentiated tumor (P=0.01, RR: 1.7, 95% CI: 1.1–2.5), and the tumor entity (P<0.01) were significant predictors of survival. Univariate survival analysis of the 110 patients with cancer of the pancreatic head revealed that a histologically undifferentiated tumor (P=0.05) and positive resection margins (P=0.02) were associated with a poorer survival. In multivariate analysis, the resection margin (P=0.02, RR: 5.1, 95% CI: 1.1–2.8) and a histologically undifferentiated tumor (P=0.05, RR: 3.8, 95% CI: 1.0–2.5) significantly influenced survival. After PD, perioperative morbidity and long-term survival in patients with SM-PVR were similar to those of patients without vein resection. In case of tumor adherence or infiltration, combined resection of the pancreatic head and the vein should always be considered in the absence of other contraindications for resection. Initial results were presented at the Forty-Fourth Annual Meeting of The Society for Surgery of the Alimentary Tract, Orlando, Florida, May 18–21, 2003 (poster).     

Positron-emission tomography as a prognostic tool for early-stage lung cancer

BACKGROUND: Positron-emission tomography (PET) shows tissue metabolic activity in the form of the standard uptake value (SUV). This study examines the prognostic value of the SUV for early-stage lung cancer. METHODS: A retrospective review of 187 patients undergoing PET for potential lung cancer. Data collected included patient demographics, tumor pathology, and survival information. Data were correlated with PET results to determine if a prognostic relationship exists. RESULTS: The sensitivity and specificity of PET for detecting malignant lesions were 98% and 24%. Malignant lesions had a higher SUV than benign lesions (5.9 +/- 6.2 versus 2.2 +/- 1.8, P < .0001). The average SUV of well-differentiated tumors was 2.6 +/- 3.1 versus 5.9 +/- 5.5 for other tumors (P = .010). There was a strong correlation between tumor stage and SUV (analysis of variance, P < .0001). There was no difference in tumor SUV for survivors versus nonsurvivors. CONCLUSIONS: The SUV correlates with prognostic indicators, such as tumor stage and grade. The SUV alone was not an independent predictor of survival.     

Acute exacerbation of interstitial lung disease with lung cancer after surgery: evaluation with 2-[18]-fluoro-2-deoxy-d-glucose positron emission tomography

Purpose

Interstitial lung disease (ILD) has been associated with primary lung cancer and an increased risk of postoperative acute exacerbation (AE). The effectiveness of 2-[18]-fluoro-2-deoxy-d-glucose (¹⁸F-FDG) positron emission tomography (PET) for staging lung cancer is well established. This study investigates the association of FDG uptake on PET in patients with AE of ILD.

Methods

The subjects of this retrospective study were 1309 patients with lung cancer, who underwent pulmonary resection at Shizuoka Cancer Center between September, 2002 and January, 2011. ILD was diagnosed with chest computed tomography in 95 patients, 81 of whom underwent ¹⁸F-FDG PET before surgery. Six patients suffered from AE after surgery (AE group), while the remaining 75 (non-AE group) did not. We investigated the clinico-pathological findings and the results of FDG uptake on PET using the value of the I/M ratio, which is the ratio of the peak of standardized uptake value (SUV) of the ILD area to the mean SUV of the mediastinum.

Results

There was no significant difference in clinico-pathological findings, but a significance difference in the I/M ratio (P = 0.0102).

Conclusion

The FDG uptake in PET may be a predictive factor for AE of ILD in patients who have undergone lung cancer surgery.     

Prognostic Significance of Vascular Endothelial Growth Factor Expression and Microvessel Density in Esophageal Squamous Cell Carcinoma: Comparison With Positron Emission Tomography

Background This study investigated whether the expression of vascular endothelial growth factor (VEGF) in a primary tumor and the intratumoral microvessel density (MVD) were independent prognostic factors in patients with an esophageal squamous cell carcinoma (SCC) in comparison with positron emission tomography (PET) by using ¹⁸F-fluorodeoxyglucose (FDG) and stage. Methods Fifty-one patients with a newly diagnosed esophageal SCC who underwent preoperative FDG-PET and esophagectomy with intent to cure were enrolled in this study. The VEGF expression level, the intratumoral MVD, and the Ki-67 labeling index were evaluated by using immunohistochemical staining. Only significant variables in the univariate survival analysis were examined by multivariate survival analysis with the Cox proportional hazards model. Result Cancer-related deaths occurred in 17 of 51 patients during the follow-up. Univariate survival analysis showed that the pathologic stage, pNM, maximum standardized uptake value of the primary tumor, tumor length on PET, number of PET-positive lymph nodes, PET stage, Ki-67 labeling index, intratumoral MVD, and the presence of VEGF expression were significant prognostic predictors for the overall survival. Multivariate analysis revealed that the pathologic stage, number of PET-positive nodes (0, 1, 2, or ≥3), intratumoral MVD (cutoff, 60/mm²), and presence of VEGF expression were independent significant prognostic predictors for overall survival. Conclusion In addition to the pathologic stage, the intratumoral MVD, the presence of VEGF expression, and the number of FDG-PET–positive nodes were independent prognostic predictors in patients with an esophageal SCC undergoing curative surgery.     

High Expression of Plasminogen Activator Inhibitor-2 (PAI-2) is a Predictor of Improved Survival in Patients with Pancreatic Adenocarcinoma

Objective Recent findings suggest that the urokinase-type plasminogen activator (uPA), its receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and -2 (PAI-2) play key roles in cancer invasion. Summary Background Data The prognostic value of components of this system is well established in breast cancer. However, little is known of its involvement in pancreatic cancer (PC). Methods Quantitative real-time polymerase chain reaction (Q-RT-PCR) was used on tissue-banked specimens and immunohistochemistry (IHC) on paraffin specimens was used to measure expression of uPA, uPAR, PAI-1, and PAI-2 proteins in 46 PC and 12 cystadenoma specimens. Results were related to survival using Cox’s proportional hazards testing. Results Increased expression of uPA, uPAR, and PAI-1 in PC tissue were independently associated with a higher Union Internationale Contre le Cancer [International Union Against Cancer (UICC)] tumor stage (P < 0.001) and were intercorrelated (P < 0.001). Overexpression of uPAR indicated reduced survival (P = 0.03). Conversely, PAI-2 messenger ribonucleic acid (mRNA) overexpression, which occurred in 21 of 46 tumors, negatively correlated with tumor size (P = 0.008) and survival (P < 0.007) but not with uPA, uPAR, or tumor stage. There was good agreement between PAI-2 mRNA value and IHC score (P < 0.001). Using Cox’s stepwise analysis, PAI-2 mRNA value (HR = 0.24; P = 0.001) and UICC tumor stage (HR = 2.014; P = 0.001) independently predicted survival. An IHC score for PAI-2 of 3+ or 4+ also independently predicted improved survival (HR = 2.72; P = 0.025). Conclusions The uPA/uPAR/PAI-1 system is activated in advanced pancreatic cancer and may account for the tumor’s aggressive behavior, whereas PAI-2 expression appears to be independent of uPA/uPAR/PAI-1 and is associated with improved prognosis. Because of its intercorrelation with mRNA expression, PAI-2 IHC may be used as an indicator of survival.     

Prognostic Significance of the Immediate Early Response Gene X-1 (IEX-1) Expression in Pancreatic Cancer

Background The immediate early response gene X-1 (IEX-1) is a stress-inducible protein that is involved in the regulation of cell proliferation and apoptosis. The aim of this study was to evaluate the prognostic significance of IEX-1 expression in pancreatic cancer. Methods IEX-1 protein expression was examined on paraffin-embedded specimens from 78 patients with pancreatic ductal adenocarcinoma using immunohistochemistry. The relationships between the IEX-1 expression and other clinicopathological parameters and patient survival were evaluated. A similar analysis was conducted in a subgroup of 48 patients, who underwent a macroscopically curative resection with detailed information on the pathological findings. Results Among 78 pancreatic cancer patients, 41 patients (53%) were positive for IEX-1 staining. In a multivariate analysis, curative operation (P < .001), pathological stage I–III (P = .001), and positive IEX-1 expression (P = .002) were significantly favorable factors for survival. In a subgroup of 48 patients undergoing a macroscopically curative surgery, IEX-1 expression was positive in 28 patients (58%). A significant negative correlation was observed between the IEX-1 expression and serosal (P = .032) or arterial (P = .040) invasion of tumors. A multivariate analysis demonstrated limited local invasion (pT1-3, P = .021), negative lymph node involvement (pN0, P < .001), and positive IEX-1 expression (P = .004) to be significantly favorable factors for survival. Conclusions The positive IEX-1 expression in tumor tissues may be associated with a better prognosis in pancreatic cancer. An immunohistochemical assessment of IEX-1 expression may therefore be helpful for predicting patient prognosis in this disease.     

18F-FDG Uptake at Initial Staging of the Adrenocortical Cancers: A Diagnostic Tool but Not of Prognostic Value

Background

Adrenocortical carcinoma (ACC) is a rare cancer for which little level evidence exists to guide management. ¹⁸F-FDG PET (¹⁸F-fluorodeoxyglucose positron emission tomography) is an increasingly used diagnostic tool in patients with suspicious or indeterminate adrenal tumors. In some other solid tumors, ¹⁸F-FDG PET may offer prognostic information that can guide optimal patient treatment. The aim of the present study was to evaluate whether preoperative ¹⁸F-FDG PET based on SUVs assessments has a prognostic value in ACC patients.

Methods

A retrospective analysis was performed in patients who underwent ¹⁸F-FDG PET/CT for the evaluation of ACC. Inclusion criteria were an unequivocal diagnosis of ACC; all data from primary diagnosis available; ¹⁸F-FDG PET/CT performed prior to surgery or other treatment of the primary tumor; a minimum of 6-months follow-up for surviving patients. All ¹⁸F-FDG PET/CT procedures were reinterpreted in a blind fashion.

Results

Thirty-seven patients (23 without metastasis [M0], 14 with metastasis [M1]) fulfilled the study criteria. Median uptake values were tumor standardized uptake values (SUV)_max = 11 (range: 3–56) and a tumor/liver SUV_max ratio = 4.2 (range: 1.3–15). Median follow-up was 20 months. Although classic risk factors (tumoral stage, Weiss score) were associated with poor outcome, there was no correlation between primary tumor FDG uptake with overall survival (OS) and disease free survival (DFS) in M0 patients and with overall survival in M1 patients. ¹⁸F-FDG uptake correlated inconsistently with sinister histological features, such as atypical mitoses or necrosis.

Conclusions

At initial staging, primary tumor FDG uptake in ACC patients does not correlate with OS and DFS at 2 years. Patient prognosis and treatment strategy should not be based on uptake values.     

18F‐FDG‐PET/CT predicts early tumor recurrence in living donor liver transplantation for hepatocellular carcinoma

The prognosis including ¹⁸F‐fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F‐FDG‐PET/CT) for the early recurrence for hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) was not well established. Consecutive patients who underwent ¹⁸F‐FDG‐PET/CT and subsequent LDLT for HCC from March 2005 to June 2011 were enrolled. The 191 patients with a median follow‐up of 26.1 months were evaluated. There were 20 patients (10.5%) with early recurrence (≤6 months), 18 patients (9.4%) with late recurrence (>6 months), and 153 patients (80.1%) with no recurrence. Fifty‐five patients (28.8%) displayed increased PET/CT tumor uptake. Three‐year overall and disease‐free survival for PET/CT‐positive patients were 65.5% and 57.1%, respectively, while PET/CT‐negative patients showed respective values of 89.8% and 86.8% (P = 0.001 vs. P < 0.001). Tumor variables associated with PET/CT‐positive finding were preoperative AFP level, Milan, UCSF criteria, maximum tumor size, total tumor size, differentiation, vascular invasion, and serosal invasion. PET/CT‐positive status was identified as an independent prognostic factor for disease‐free survival influencing early recurrence in multivariable analysis (HR 3.945, 95% CI 1.196–13.016, P = 0.024). ¹⁸F‐FDG‐PET/CT is an independent and significant predictor of early tumor recurrence in LDLT for HCC.     

Positron Emission Tomography Detection of Distant Metastatic or Synchronous Disease in Patients with Locally Advanced Rectal Cancer Receiving Preoperative Chemoradiation

Background Patients with locally advanced rectal cancer may present with synchronous distant metastases. Choice of optimal treatment—neoadjuvant chemoradiation versus systemic chemotherapy alone—depends on accurate assessment of distant disease. We prospectively evaluated the ability of [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography (PET) to detect distant disease in patients with locally advanced rectal cancer who were otherwise eligible for combined modality therapy (CMT). Methods Ninety-three patients with locally advanced rectal cancer underwent whole-body [¹⁸F]FDG PET scanning 2–3 weeks before starting CMT. Sites other than the rectum, mesorectum, or the area along the inferior mesenteric artery were considered distant and were divided into nine groups: neck, lung, mediastinal lymph node (LN), abdomen, liver, colon, pelvis, peripheral LN, and soft tissue. Two nuclear medicine physicians blinded to clinical information used PET images and a five-point scale (0–4) to determine certainty of disease. A score greater than 3 was considered malignant. Confirmation was based on tissue diagnosis, surgical exploration, and subsequent imaging. Results At a median follow-up of 34 months, the overall accuracy, sensitivity, and specificity of PET in detecting distant disease were 93.7%, 77.8%, and 98.7% respectively. Greatest accuracy was demonstrated in detection of liver (accuracy = 99.9%, sensitivity = 100%, specificity = 98.8%) and lung (accuracy = 99.9%, sensitivity = 80%, specificity = 100%) disease; PET detected 11/12 confirmed malignant sites in liver and lung. A total of 10 patients were confirmed to have M1 stage disease. All 10 were correctly staged by pre-CMT PET; abdominopelvic computed tomography (CT) scans accurately detected nine of them. Conclusion Baseline PET in patients with locally advanced rectal cancer reliably detects metastatic disease in liver and lung. PET may play a significant role in defining extent of distant disease in selected cases, thus impacting the choice of neoadjuvant therapy. An erratum to this article can be found at