Di-indenopyridines as topoisomerase II-selective anticancer agents: Design, synthesis, and structure-activity relationships.

Topoisomerases are key molecular enzymes responsible for altering DNA topology, thus they have long been considered as attractive targets for novel chemotherapeutic agents. Topoisomerase type II (Topo II) catalytic inhibitors embrace a fresh perspective meant to get beyond drawbacks caused by topo II poisons, such as cardiotoxicity and secondary malignancies. Based on previously reported 5H-indeno[1,2-b]pyridines, here we presented new twenty-three hybrid di-indenopyridines along with their topo I/IIα inhibitory and antiproliferative activity. Most of the prepared 11-phenyl-diindenopyridines showed negligible topo I inhibitory activity, showing selectivity over topo II. Among the series, we finally selected compound 17, which displayed 100 % topo IIα inhibition at 20 µM concentration and comparable antiproliferative activity against the tested cell lines. Through competitive EtBr displacement assay, cleavable complex assay, and comet assay, compound 17 was finally determined as a non-intercalative catalytic topo IIα inhibitor. The findings in this study highlight the significance of phenolic, halophenyl, thienyl, and furyl groups at the 4-position of the indane ring in the design and synthesis of di-indenopyridines as potent catalytic topo IIα inhibitors with remarkable anticancer effects.

A Case of Adenomyosis Showing Size Reduction in a Follicular Lymphoma Patient Receiving Chemotherapy With R-Bendamustine.

ABSTRACT: We describe a case of adenomyosis that reduced in size in a patient with lymphoma on receiving chemotherapy. A 48-year-old woman with worsening left flank pain was diagnosed with follicular lymphoma. [ 18 F]FDG PET/CT revealed multiple hypermetabolic lymph nodes in the bilateral cervical, axillary, mediastinal, mesenteric, retroperitoneal, iliac, and inguinal regions. In addition, adenomyosis with mild hypermetabolism was demonstrated on [ 18 F]FDG PET/CT. The size and metabolism of adenomyosis decreased after chemotherapy with R-bendamustine; in addition, along with decrease in estradiol levels, the patient experienced amenorrhea and hot flushes. The patient was diagnosed with chemotherapy-induced early menopause.

Assessment of Instability in Thoracolumbar Burst Fractures Using a New Bone Scan Scoring System.

Background and Objectives: Unstable thoracolumbar burst fractures require surgical management as they can result in neurological deficits if left untreated. This study aimed to evaluate whether a new bone scan scoring system could accurately assess instability in thoracolumbar burst fractures. Materials and Methods: Fifty-two patients with thoracolumbar burst fractures who underwent bone scans and magnetic resonance imaging prior to surgery between January 2015 and August 2017 at Ulsan University Hospital were selected for inclusion. Instability was determined by clinical assessment and imaging, and the Thoracolumbar Injury Classification and Severity score was determined. Bone scans were visually evaluated using a new bone scan scoring system. Bone scan findings of vertebral body (BB) and posterior column (BP) were scored separately and were summed to produce BTS {BTS (total score) = BB (body score, 5 points) + BP (posterior score, 2 points)}. The diagnostic performance of the scoring system for identifying unstable then thoracolumbar burst fractures were assessed. Results: Of the 52 thoracolumbar burst fractures, 34 (65.4%) were unstable and 31 (59.6%) had a Thoracolumbar Injury Classification and Severity score ≥ 5. The diagnostic performance of using BTS ≥ 4 to identify unstable thoracolumbar burst fractures and those with a Thoracolumbar Injury Classification and Severity score ≥ 5 was as follows: sensitivity, 61.8% and 58.1%; specificity, 94.4% and 81.0%; positive predictive value, 95.5% and 81.8%; and negative predictive value, 56.7% and 56.7%, respectively. Conclusions: The proposed bone scan scoring system has a high specificity and positive predictive value for identifying thoracolumbar burst fractures that are unstable or have a Thoracolumbar Injury Classification and Severity score ≥ 5. This scoring system may help to inform decisions regarding surgical management.

Clinicopathologic Characteristics Associated with Prognosis in Ocular Extranodal Marginal Zone B Cell Lymphoma.

Background and Objectives: Extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT) type is the most common subtype of the ocular adnexal lymphoma. Despite its excellent prognosis, some patients experience partial remission or progressive disease. We aimed to evaluate clinicopathologic differences in the treatment responder group by comparing complete remission (CR) and non-complete remission (non-CR). Materials and Methods: This study retrospectively reviewed 48 patients who were diagnosed with ocular adnexal MALT lymphoma at Ulsan University Hospital between March 2002 and August 2018. Patients who were followed up for less than 6 months were excluded. Histologic and clinical features were analyzed. The patients were divided into two groups: CR and non-CR. Results: Among the 48 patients, 33 achieved CR and 15 achieved non-CR during the median follow-up period of 40.00 months (range, 7-109 months). In univariable analysis, more patients tend to undergo treatment in the CR group, and post-radiotherapy (post-RT) SUVmax, PET and serum lactate dehydrogenase (LDH) levels were higher in the non-CR group (p = 0.043, p = 0.016, and p = 0.042, respectively). In a multivariable analysis, only application of treatment, including radiotherapy or chemotherapy with immunotherapy, was related to CR (odd ratio 7.301, 95% confidence interval 1.273-41.862, p = 0.026). In subgroup analysis according to the site of involvement, none of the variables were significant except for the post-RT SUVmax of PET and level of serum LDH in the non-conjunctiva group (p = 0.026, and p = 0.037, respectively). Seven (14.6%) patients had a recurrence, and those with a recurring site other than the primary site had a higher Ki-67 labeling index, although it was not statistically significant (9.56% vs. 18.00%, p = 0.095). Conclusions: Although belonging to the early stages, the non-CR rate was high in patients with high serum LDH levels, and recurred patients had higher Ki-67. Thus, considering active treatment is recommended in this group of patients.

Feasibility of robotic thyroidectomy via hairline incision using da Vinci single port system: Initial experience with 40 consecutive cases.

BACKGROUND: This study aimed to introduce our robotic technique, which can minimize dissection extent using the da Vinci SP robotic system via hairline incision. METHODS: Forty patients underwent robotic thyroidectomy using the da Vinci SP robotic system via a hairline incision between February 2020 and April 2021 at Ulsan University Hospital. All procedures were performed successfully by one surgeon using the SP robotic system. RESULTS: Hemithyroidectomies were performed in 32 patients and total thyroidectomies in eight patients. Central neck dissection was performed in 32 patients. The overall mean operative time was 140.2 ± 50.7 min, and the mean console time was 74.0 ± 42.7 min. All patients were discharged on the second or third day after operation without any complications. CONCLUSIONS: Robotic thyroidectomy using the SP robotic system via hairline incision is technically feasible and safe, with a shorter incision length when compared with that of the Xi system.

Smad4 and p53 synergize in suppressing autochthonous intestinal cancer.

BACKGROUND: Smad4 and p53 mutations are the most common mutations in human colorectal cancers (CRCs). We evaluated whether and how they are synergistic in intestinal carcinogenesis using novel autochthonous mouse models. METHOD: To recapitulate human CRCs, we generated Villin-Cre;Smad4F / F ;Trp53F / F mice. We then compared the intestinal phenotype of Villin-Cre;Smad4F / F ;Trp53F / F mice (n = 40) with Villin-Cre;Smad4F / F (n = 30) and Villin-Cre;Trp53F / F mice (n = 45). RESULTS: Twenty-week-old Villin-Cre;Smad4F / F ;Trp53F / F mice displayed spontaneous highly proliferative intestinal tumors, and 85% of mice developed adenocarcinomas. p21 was downregulated in the intestinal mucosa in Villin-Cre;Smad4F / F ;Trp53F / F mice than in Villin-Cre;Smad4F / F and Villin-Cre;Trp53F / F mice. Villin-Cre;Smad4F / F ;Trp53F / F mice displayed multistep intestinal tumorigenesis and Wnt activation. Long-term CWP232291 (small-molecule Wnt inhibitor) treatment of Villin-Cre;Smad4F / F ;Trp53F / F mice suppressed intestinal tumorigenesis and progression. CWP232291 treatment downregulated cancer stem cell (CSC) tumor markers including CD133, Lgr-5, and Sca-1. CWP232291 treatment reduced the CSC frequency. Small-molecule Wnt inhibitors reduced intestinal CSC populations and inhibited their growth, along with Bcl-XL downregulation. Furthermore, BH3I-1, a Bcl-XL antagonist, increasingly inhibited intestinal CSCs than bulk tumor cells. CONCLUSION: Smad4 loss and p53 loss are synergistic in autochthonous intestinal carcinogenesis, by downregulating p21 and activating Wnt/ß-catenin pathway.

Amyloid Arthropathy and Pseudomyopathy Associated With Multiple Myeloma Detected by 18F-Florapronol Amyloid PET/CT.

ABSTRACT: We report a case of amyloid arthropathy and pseudomyopathy with multiple myeloma, detected by amyloid PET/CT using 18F-florapronol. Bone scintigraphy and 18F-FDG PET/CT in a multiple myeloma patient revealed uneven soft tissue uptakes, especially at periarticular areas. The joint capsule and intermuscular fascia showed enhancement on CT, whereas muscle enzymes were normal. These suggested amyloid arthropathy with pseudomyopathy. 18F-Florapronol amyloid PET/CT showed extensive soft tissue uptakes. Amyloid arthropathy and pseudomyopathy were confirmed after biopsy. This is the first report of amyloid PET/CT aiding in the diagnosis of unusual presentation of systemic amyloidosis.

Identification of new halogen-containing 2,4-diphenyl indenopyridin-5-one derivative as a boosting agent for the anticancer responses of clinically available topoisomerase inhibitors.

Based on previous reports on the significance of halogen moieties and the indenopyridin-5-one skeleton, we designed and synthesized a novel series of halogen (F-, Cl-, Br-, CF3- and OCF3-)-containing 2,4-diphenyl indenopyridin-5-ones and their corresponding -5-ols. Unlike indenopyridin-5-ols, most of the prepared indenopyridin-5-ones with Cl-, Br-, and CF3- groups at the 2-phenyl ring conferred a strong dual topoisomerase I/IIα inhibitory effect. Among the series, para-bromophenyl substituted compound 9 exhibited the most potent topoisomerase inhibition and antiproliferative effects, which showed dependency upon the topoisomerase gene expression level of diverse cancer cells. In particular, as a DNA minor groove-binding non-intercalative topoisomerase I/IIα catalytic inhibitor, compound 9 synergistically promoted the anticancer efficacy of clinically applied topoisomerase I/IIα poisons both in vitro and in vivo, having the great advantage of alleviating poison-related toxicities.

4-Flourophenyl-substituted 5H-indeno[1,2-b]pyridinols with enhanced topoisomerase IIα inhibitory activity: Synthesis, biological evaluation, and structure-activity relationships.

A series of fluorinated and hydroxylated 2,4-diphenyl indenopyridinols were designed and synthesized using l-proline-catalyzed and microwave-assisted synthetic methods for the development of new anticancer agents. Adriamycin and etoposide were used as reference compounds for the evaluation of topo IIα inhibitory and anti-proliferative activity of the synthesized compounds. Exploring the structure-activity relationships of 36 prepared compounds and biological results, most of the compounds with ortho- and para-fluorophenyl at 4-position of indenopyridinol ring displayed strong topo IIα inhibition. In addition, the majority of the ortho- and meta-fluorophenyl substituted compounds 1-24 displayed strong anti-proliferative activity against DU145 prostate cancer cell line compared to the positive controls. Interestingly, compound 4 possessing ortho-phenolic and ortho-fluorophenyl group at 2- and 4-position, respectively of the central pyridine ring showed high anti-proliferative activity (IC50 = 0.82 µM) against T47D human breast cancer cell line, while para-phenolic and para-fluorophenyl substituted compound 36 exhibited potent topo IIα inhibitory activity with 94.7% and 88.6% inhibition at 100 µM and 20 µM concentration, respectively. A systematic comparison between the results of this study and the previous study indicated that minor changes in the position of functional groups in the structure affect the topo IIα inhibitory activity and anti-proliferative activity of the compounds. The findings from this study will provide valuable information to the researchers working on the medicinal chemistry of topoisomerase IIα-targeted anticancer agents.

Acute Abdominal Pain due to Accessory Splenic Infarction in an Adult: A Case Report.

Accessory spleens are common congenital anatomic variations that are usually asymptomatic. On the other hand, they can be clinically significant if complicated by hemorrhage, torsion, or infarction. This paper describes a case of an infarcted accessory spleen in a 30-year-old male who presented with abdominal pain. Abdominal CT and MRI revealed an isolated mass, 4.5 cm in size, in the perisplenic area. An infarcted accessory spleen was suspected. The patient underwent laparoscopic accessory splenectomy. Histopathology identified the mass as splenic tissue that had undergone ischemic necrosis. A definitive diagnosis of an infarcted accessory spleen was made, and the patient was discharged on day 5 after surgery symptom-free.

Anticancer Activity of Indeno[1,2-b]-Pyridinol Derivative as a New DNA Minor Groove Binding Catalytic Inhibitor of Topoisomerase IIα.

Topoisomerase IIα has been a representative anti-cancer target for decades thanks to its functional necessity in highly proliferative cancer cells. As type of topoisomerase IIα targeting drugs, topoisomerase II poisons are frequently in clinical usage. However, topoisomerase II poisons result in crucial consequences resulted from mechanistically induced DNA toxicity. For this reason, it is needed to develop catalytic inhibitors of topoisomerase IIα through the alternative mechanism of enzymatic regulation. As a catalytic inhibitor of topoisomerase IIα, AK-I-191 was previously reported for its enzyme inhibitory activity. In this study, we clarified the mechanism of AK-I-191 and conducted various types of spectroscopic and biological evaluations for deeper understanding of its mechanism of action. Conclusively, AK-I-191 represented potent topoisomerase IIα inhibitory activity through binding to minor groove of DNA double helix and showed synergistic effects with tamoxifen in antiproliferative activity.

Should Total Thyroidectomy Be Recommended for Patients with Familial Non-medullary Thyroid Cancer?

BACKGROUND: It is unknown whether familial non-medullary thyroid cancer (FNMTC) has more aggressive clinical features and a worse prognosis than sporadic non-medullary thyroid cancer (SNMTC). METHODS: We retrospectively reviewed 2894 patients with differentiated thyroid cancer who underwent primary thyroidectomy, identified 391 FNMTC cases, and compared the prevalence, surgical extension, and clinicopathologic features of FNMTC and SNMTC. RESULTS: A family history of thyroid cancer was noted in 391 patients (13.5%), with 85% having two affected relatives and 15% with ≥3 affected relatives. A sibling was affected in 52.9% of cases, and in 47.1%, both parent and child were affected. There were no significant between-group differences in sex, age, tumor size, extrathyroidal extension, or central lymph node metastases. Significantly more patients with FNMTC exhibited multifocal disease (p = 0.020) or benign nodules (p = 0.015). Lateral neck lymph node metastases were noted in 6.6% (SNMTC) and 9.7% (FNMTC, p = 0.021) of patients. Multifocality and combined benign masses were more frequently observed in patients with FNMTC in multivariate analysis. In the FNMTC group, seven experienced disease recurrence, with no mortality noted during follow-up. CONCLUSIONS: FNMTC is not more aggressive than SNMTC; however, FNMTC should be treated with total thyroidectomy because of the increased disease multifocality and the presence of benign nodules. Lateral neck lymph node metastases were more likely in patients with FNMTC, although we could not estimate prognosis. All patients with thyroid cancer should be checked for family disease history and undergo preoperative ultrasonography to determine the extent of node dissection and the need for total thyroidectomy.

Clinicopathological characteristics of primary central nervous system lymphoma with low 18F-fludeoxyglucose uptake on brain positron emission tomography.

Primary central nervous system lymphoma (PCNSL) typically shows a strong uptake of F-fludeoxyglucose (FDG) imaged by positron emission tomography (PET). Uncommonly, PCNSL demonstrates a low uptake on FDG PET. We investigated the clinicopathological characteristics of the unusual cases of PCNSL with low FDG uptake.We retrospectively enrolled 104 consecutive patients with newly diagnosed PCNSL who underwent baseline brain FDG PET. The degree of FDG uptake of PCNSL was visually scored by 4 grades (0, ≤contralateral white matter; 1, >contralateral white matter and contralateral gray matter). Grades 0-2 were considered as PCNSL with low uptake. We investigated association of low uptake of PCNSL with the following clinicopathological factors: age, sex, steroid treatment, lactate dehydrogenase level, cerebrospinal fluid protein level, condition of PET scanning, immunohistochemical markers (cluster of differentiation 10 [CD10], B-cell lymphoma 6 [BCL-6], B-cell lymphoma 2 [BCL-2], multiple myeloma oncogene 1 [MUM1], Epstein-Barr virus [EBV] protein, and Ki67), location of lesions, tumor size, multiplicity of lesions, involvement of deep brain structures, and cystic or necrotic appearance of lesions.Of the 104 patients with PCNSL, 14 patients (13.5%) showed PCNSL with low FDG uptake on PET. Among various clinicopathological factors, MUM1 negativity was the only factor associated with low FDG uptake PCNSL by univariate (P = .002) and multivariate analysis (P = .007).This study suggests that the different clinicopathological characteristics between patients with high uptake and low uptake of PCNSL on FDG PET is closely associated with lack of MUM1, a protein known to be a crucial regulator of B-cell development and tumorigenesis.

Small Animal PET Imaging of hTERT RNA-Targeted HSV1-tk Gene Expression with Trans-Splicing Ribozyme.

Background: Trans-splicing ribozymes (TSR) are useful anticancer agents targeting cancer-specific transcripts and replacing the RNA to induce anticancer gene expression specifically and selectively in cancer cells. Similar to other gene therapy methods, it is also important to evaluate the transgene expression for target specificity and ribozyme activity. Materials and Methods: In this study, the authors performed in vivo small animal positron emission tomography (PET) imaging and biodistribution assay to evaluate human telomerase reverse transcriptase (hTERT) RNA-targeting-specific TSR, which directs the expression of herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene selectively in hTERT-positive tumors through targeted RNA replacement of the hTERT transcript. Results: The hTERT RNA-targeted HSV1-tk expression with TSR was monitored by PET imaging with 124I labeled 2'-fluoro-2'-deoxy-1-ß-D-arabinofuranosyl-5-iodouracil, which is one of the thymidine derivatives acting as substrates for HSV1-tk, in hTERT-positive tumor-bearing mice. Conclusions: Imaging of hTERT RNA-targeted HSV1-tk expression by TSR could be used in the development of advanced gene therapy using tumor-specific TSR.

Clinical Utility of 18F-Florbetaben PET for Detecting Amyloidosis Associated With Multiple Myeloma: A Prospective Case-Control Study.

PURPOSE: The aims of this study were to evaluate the diagnostic performance of F-florbetaben PET/CT for detecting amyloid deposits in patients with multiple myeloma (MM) and to identify the optimal PET analysis method. METHODS: Fourteen patients with MM were prospectively enrolled (6 with amyloidosis, 8 control subjects). Dynamic imaging of the kidneys was performed for 20 minutes, and the retention ratio was obtained. At 90 minutes after injection, PET was performed. All images were assessed qualitatively and quantitatively, and the SUVmax, SUVmean, and SUVratio were obtained. Variables were compared between the amyloidosis group and the control group. Amyloid deposition was confirmed according to international consensus guidelines. RESULTS: Tracer uptake was abnormal in all patients with amyloidosis. The visual detection rate was excellent (100%) in the heart, stomach, and tongue but limited in the kidneys (50%) and poor (0%) in the esophagus, liver, and colon. F-florbetaben PET/CT identified 13 unexpected cases of abnormal uptake, confirming further amyloid deposition. Both spherical and manual volumes of interest showed similar diagnostic performance when evaluating amyloidosis in target organs. There was no significant difference in diagnostic performance between the SUVmax, SUVmean, and SUVratio. CONCLUSIONS: F-florbetaben PET/CT can accurately detect systemic amyloid deposits in patients with MM. F-florbetaben PET/CT was particularly useful in the heart, stomach, and tongue but of limited value in the esophagus, liver, and colon. F-florbetaben PET/CT can provide clinical information on organ involvement and could replace pathologic examination for diagnosis of amyloidosis in the future.

Chronic Vasitis After Mesh Herniorrhaphy: A Potential Cause of False Positive Results in 18F-FDG PET/CT Studies.

We report two cases of supra-scrotal vasitis incidentally detected in patients who had undergone mesh herniorrhaphy. PET/CT in patients undergoing lymphoma work-up and health check-up revealed hypermetabolic dilatation of vas deferens in the external iliac area. There were no symptoms, and blood test results did not indicate acute inflammation. Interestingly, both had undergone herniorrhaphy for inguinal hernia. Herniorrhaphy is reported to cause vasal complications such as obstruction or inflammation, although most are asymptomatic and probably under-reported. Chronic vasitis after herniorrhaphy may be a potential cause for false positive findings on F-FDG PET/CT in patients undergoing work-up for various oncological indications.

Development of 64Cu-NOTA-Trastuzumab for HER2 Targeting: A Radiopharmaceutical with Improved Pharmacokinetics for Human Studies.

The purpose of this study was to develop 64Cu-labeled trastuzumab with improved pharmacokinetics for human epidermal growth factor receptor 2 (HER2). Methods: Trastuzumab was conjugated with SCN-Bn-NOTA and radiolabeled with 64Cu. Serum stability and immunoreactivity of 64Cu-NOTA-trastuzumab were tested. Small-animal PET imaging and biodistribution studies were performed in a HER2-positive breast cancer xenograft model (BT-474). The internal dosimetry for experimental animals was determined using the image-based approach with the Monte Carlo N-particle code. Results:64Cu-NOTA-trastuzumab was prepared with high radiolabeling yield and radiochemical purity (>98%) and showed high stability in serum and good immunoreactivity. Uptake of 64Cu-NOTA-trastuzumab was highest at 48 h after injection as determined by PET imaging and biodistribution results in BT-474 tumors. The blood radioactivity concentrations of 64Cu-NOTA-trastuzumab decreased biexponentially with time in both mice with and mice without BT-474 tumor xenografts. The calculated absorbed dose of 64Cu-NOTA-trastuzumab was 0.048 mGy/MBq for the heart, 0.079 mGy/MBq for the liver, and 0.047 mGy/MBq for the spleen. Conclusion:64Cu-NOTA-trastuzumab was effectively targeted to the HER2-expressing tumor in vitro and in vivo, and it exhibited a relatively low absorbed dose due to a short residence time. Therefore, 64Cu-NOTA-trastuzumab could be applied to select the right patients and right timing for HER2 therapy, to monitor the treatment response after HER2-targeted therapy, and to detect distal or metastatic spread.

More accurate than MRI measurement of tumor size in breast cancer by using the peri-tumoral halo uptake layer method of the 18F-FDG PET/CT scan.

OBJECTIVE: To evaluate the reliability of a method using the peri-tumoral halo layer (PHL) for assessing tumor size in breast cancer patients on the fluorine-18-fluorodeoxy glucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan compared to MRI and pathology. SUBJECTS AND METHODS: Among 121 patients with breast cancer who underwent both 18F-FDG PET/CT and MRI between March 2013 and June 2016, 59 patients were included in this study. Exclusion criteria were as follows: history of neoadjuvant therapy, history of pre-operative mammotome, insufficient pathologic/radiologic size report, clustered tumor, positive tumor resection margin, 18F-FDG non-avid tumor. The PHL was examined by two nuclear medicine physicians. Tumor sizes (longest diameters) on 18F-FDG PET/CT were estimated using margins defined as the inner line of the PHL. Pathologic tumor sizes were utilized as reference standards. RESULTS: The PHL of each tumor was most commonly designated as the 20%-30% band of the maximum standardized uptake value (SUVmax) it exhibited an inverse correlation with tumor SUVmax. Tumor size on 18F-FDG PET/CT showed a more linear correlation with pathology than that on MRI (r2=0.91 vs 0.65). In Bland-Altman analysis, 18F-FDG PET/CT showed significantly lower bias in size difference relative to pathology, compared with MRI (0.6±9.6cm vs. -1.9±17.3cm). Fluorine-18-FDG PET/CT showed more accurate T staging with pathology, especially in T3 cases, than MRI. CONCLUSION: A method of tumor size determination, using PHL on 18F-FDG PET/CT, showed more linear relationship and smaller size differences with pathology than MRI (average 0.6 vs. 1.9cm). It provides sufficient reliability and reproducibility for measuring tumor size in breast cancer.

Clinical impact of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography in patients with resectable pancreatic cancer: diagnosing lymph node metastasis and predicting survival.

PURPOSE: To evaluate the diagnostic accuracy of fluorine-18-fluorodeoxyglucose PET/computed tomography (F-FDG PET/CT) for lymph node (LN) metastasis and the prognostic significance of F-FDG PET/CT LN parameters in patients with resectable pancreatic cancer. PATIENTS AND METHODS: Patients with resectable pancreatic cancer who underwent staging F-FDG PET/CT between May 2007 and September 2016 were retrospectively enrolled and analyzed through medical record and image re-evaluation. The diagnostic accuracy of F-FDG PET/CT in predicting LN metastasis was evaluated and compared with that of contrast-enhanced abdominal computed tomography (CECT). Prognostic variables, including LN parameters assessed by F-FDG PET/CT [standardized uptake value (SUV)LN and LN/tumor SUV ratio], that affect disease-free survival (DFS) and overall survival (OS) were evaluated by regression analysis. RESULTS: When predicting LN metastasis, F-FDG PET/CT showed greater sensitivity, positive predictive value, negative predictive value, and accuracy than CECT. Among prognostic factors affecting DFS, PET-positive LN (P=0.008), and LN/tumor SUV ratio (P=0.003) were found to be significant by regression analysis. Among the variables affecting OS, lymphovascular invasion (P=0.018) and the LN/tumor SUV ratio (P=0.046) were found to be significant. CONCLUSION: F-FDG PET/CT showed higher diagnostic accuracy in predicting LN metastasis than CECT in patients with resectable pancreatic cancer. Only the LN/tumor SUV ratio of F-FDG PET/CT was an independent prognostic variable in both DFS and OS.