CD40 Agonists Alter the Pancreatic Cancer Microenvironment by Shifting the Macrophage Phenotype toward M1 and Suppress Human Pancreatic Cancer in Organotypic Slice Cultures.

Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. Results: CD163+ (predominant in M2 macrophages) and FOXP3+ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163+ expression had shorter overall survival than those with low CD163+ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR+ (predominant in M1 macrophages) and a decrease in CD163+ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR+ and decrease CD163+ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Anticancer Effect of Statins in Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma.

The anticancer effect of statins is drawing attention. However, it is unclear whether statin use reduces the risk of hepatocellular carcinoma (HCC) recurrence in patients who undergo liver transplantation (LT) for HCC. Consecutive patients who underwent LT for HCC between 1995 and 2019 were enrolled. The effects of statins on HCC recurrence and mortality were compared between statin user and statin nonuser groups. We performed the analyses in a variety of ways, including inverse probability treatment weighting (IPTW) methods to balance any confounders and the landmark method to avoid immortal time bias. A total of 430 patients were enrolled, among whom 323 (75.1%) were statin nonusers and 107 (24.9%) were statin users. During a median of 64.9 months (IQR, 26.1-122.6 months) of follow-up, 79 patients (18.4%) had HCC recurrence and 111 (25.8%) died. Among those who died, 53 (47.7%) were identified as HCC-related mortalities. Statin use was a predictor of HCC recurrence (adjusted hazard ratio [HR], 0.3; 95% confidence interval [CI], 0.1-0.6; P = 0.002), all-cause mortality (adjusted HR, 0.3; 95% CI, 0.2-0.5; P < 0.001), and HCC-related mortality (adjusted HR, 0.4; 95% CI, 0.2-0.9; P = 0.03). The effects of statin use on clinical outcomes were also identified through IPTW analysis. There was a dose-dependent relationship between statin use and HCC recurrence. The anticancer effect of statins on HCC recurrence was consistently significant across multivariable-stratified and sensitivity analyses. Statin use significantly reduced the risk of HCC recurrence and improved the survival of patients who underwent LT for HCC.

Development and External Validation of Survival Prediction Model for Pancreatic Cancer Using Two Nationwide Databases: Surveillance, Epidemiology and End Results (SEER) and Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP).

Background/Aims: Several prediction models for evaluating the prognosis of nonmetastatic resected pancreatic ductal adenocarcinoma (PDAC) have been developed, and their performances were reported to be superior to that of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. We developed a prediction model to evaluate the prognosis of resected PDAC and externally validated it with data from a nationwide Korean database. Methods: Data from the Surveillance, Epidemiology and End Results (SEER) database were utilized for model development, and data from the Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP) database were used for external validation. Potential candidate variables for model development were age, sex, histologic differentiation, tumor location, adjuvant chemotherapy, and the AJCC 8th staging system T and N stages. For external validation, the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) were evaluated. Results: Between 2004 and 2016, data from 9,624 patients were utilized for model development, and data from 3,282 patients were used for external validation. In the multivariate Cox proportional hazard model, age, sex, tumor location, T and N stages, histologic differentiation, and adjuvant chemotherapy were independent prognostic factors for resected PDAC. After an exhaustive search and 10-fold cross validation, the best model was finally developed, which included all prognostic variables. The C-index, 1-year, 2-year, 3-year, and 5-year time-dependent AUCs were 0.628, 0.650, 0.665, 0.675, and 0.686, respectively. Conclusions: The survival prediction model for resected PDAC could provide quantitative survival probabilities with reliable performance. External validation studies with other nationwide databases are needed to evaluate the performance of this model.

Huge intrameniscal cyst successfully treated by open debridement and combined arthroscopic and open repair: a case report.

BACKGROUND: Meniscal cysts are not uncommon in clinical practice, with reported incidence rates varying from 1 to 22%. Most meniscal cysts are parameniscal cysts, which are created by extravasation of synovial fluid through the meniscal tear into the adjacent soft tissue. In contrast, intrameniscal cysts in which the fluid collects in the meniscus are very rare. We encountered a teenager with a huge intrameniscal cyst accompanied by a small vertical meniscal tear in the red-white zone of the upper surface of the medial meniscus. A literature search revealed no information regarding the appropriate treatment methods and results for this type of lesion. CASE PRESENTATION: A 14-year-old boy presented to our outpatient clinic because of right knee pain that had been present for the previous 2 months. The patient participated in Hapkido, but had no specific trauma history. Magnetic resonance imaging revealed a huge intrameniscal cyst located in the central parenchyma of the posteromedial corner of the medial meniscus. In addition, one sagittal slice on MRI revealed a vertical tear in the red-white zone of the upper surface of the medial meniscus. The presence of such a tear accompanied by a huge intrameniscal cyst is very unusual. The patient was treated via arthroscopic inside-out meniscal suture repair and open cystic debridement with additional meniscocapsular suturing. During 4 years of magnetic resonance imaging follow-up, the lesion has completely disappeared and the meniscus has successfully recovered its normal form. CONCLUSIONS: Our treatment method may be considered as the first choice for young patients who require surgical treatment for large intrameniscal cysts with accompanying small vertical meniscal tears.

Patella-patellar tendon angle decreases in patients with infrapatellar fat pad syndrome and medial patellar plica syndrome.

PURPOSE: Infrapatellar fat pad (IPFP) syndrome and medial patellar plica (MPP) syndrome are two recognized causes of anterior knee pain. However, diagnosing these syndromes is challenging without arthroscopic examination. The aim of this study was to evaluate sagittal patellar tilt in patients with IPFP syndrome or MPP syndrome by measuring the patella-patellar tendon angle (PPTA) in affected patients. METHODS: Eighty-three patients with anterior knee pain who underwent diagnostic arthroscopy that confirmed isolated IPFP or MPP syndrome from 2011 to 2016 were included in this retrospective study. Patients were divided into Group A (IPFP syndrome, n = 44) and Group B (MPP syndrome, n = 39). The control group included 78 patients without knee pathology who underwent magnetic resonance imaging (MRI) of the knee during the study period. Radiographic measurements, including PPTA, IPFP area, patellar height, axial patellar alignment, patellar tilt, sulcus angle, and lateral trochlear inclination, were made on MRI images by two experienced sports medicine orthopedists. RESULTS: The mean PPTA in each knee-pathology group was significantly smaller than that in the control group (Group A: 137.3° ± 4.9°; Group B: 138.1° ± 3.2°; control group, 141.4° ± 2.9°). There was no significant difference between groups for any other radiographic parameter evaluated. CONCLUSION: The PPTA was significantly smaller in patients with IPFP syndrome or MPP syndrome than in healthy controls. Therefore, sagittal patellar tilt should be included in the routine evaluation of patients with anterior knee pain. Evaluation of PPTA may help to diagnose IPFP syndrome or MPP syndrome. LEVEL OF EVIDENCE: Level IV.

Surgical Outcomes of Hepatocellular Carcinoma With Bile Duct Tumor Thrombus: A Korea-Japan Multicenter Study.

OBJECTIVE: To identify optimal surgical methods and the risk factors for long-term survival in patients with hepatocellular carcinoma accompanied by macroscopic bile duct tumor thrombus (BDTT). SUMMARY BACKGROUND DATA: Prognoses of patients with hepatocellular carcinoma accompanied by BDTT have been known to be poor. There have been significant controversies regarding optimal surgical approaches and risk factors because of the low incidence and small number of cases in previous reports. METHODS: Records of 257 patients from 32 centers in Korea and Japan (1992-2014) were analyzed for overall survival and recurrence rate using the Cox proportional hazard model. RESULTS: Curative surgery was performed in 244 (94.9%) patients with an operative mortality of 5.1%. Overall survival and recurrence rate at 5 years was 43.6% and 74.2%, respectively. TNM Stage (P < 0.001) and the presence of fibrosis/cirrhosis (P = 0.002) were independent predictors of long-term survival in the Cox proportional hazards regression model. Both performing liver resection equal to or greater than hemihepatectomy and combined bile duct resection significantly increased overall survival [hazard ratio, HR = 0.61 (0.38-0.99); P = 0.044 and HR = 0.51 (0.31-0.84); P = 0.008, respectively] and decreased recurrence rate [HR = 0.59 (0.38-0.91); P = 0.018 and HR = 0.61 (0.42-0.89); P = 0.009, respectively]. CONCLUSIONS: Clinical outcomes were mostly influenced by tumor stage and underlying liver function, and the impact of BDTT to survival seemed less prominent than vascular invasion. Therefore, an aggressive surgical approach, including major liver resection combined with bile duct resection, to increase the chance of R0 resection is strongly recommended.

Clinicopathologic analysis of intraductal papillary neoplasm of bile duct: Korean multicenter cohort study.

BACKGROUND: IPNB is very rare disease and most previous studies on IPNB were case series with a small number due to low incidence. The aim of this study is to validate previously known clinicopathologic features of intraductal papillary neoplasm of bile duct (IPNB) based on the first largest multicenter cohort. METHODS: Among 587 patients previously diagnosed with IPNB and similar diseases from each center in Korea, 387 were included in this study after central pathologic review. We also reviewed all preoperative image data. RESULTS: Of 387 patients, 176 (45.5%) had invasive carcinoma and 21 (6.0%) lymph node metastasis. The 5-year overall survival was 80.9% for all patients, 88.8% for IPNB with mucosal dysplasia, and 70.5% for IPNB with invasive carcinoma. According to the "Jang & Kim's modified anatomical classification," 265 (68.5%) were intrahepatic, 103 (26.6%) extrahepatic, and 16 (4.1%) diffuse type. Multivariate analysis revealed that tumor invasiveness was a unique predictor for survival analysis. (p = 0.047 [hazard ratio = 2.116, 95% confidence interval 1.010-4.433]). CONCLUSIONS: This is the first Korean multicenter study on IPNB through central pathologic and radiologic review process. Although IPNB showed good long-term prognosis, relatively aggressive features were also found in invasive carcinoma and extrahepatic/diffuse type.

Recurrence of common bile duct stones following laparoscopic common bile duct exploration: a multicenter study.

BACKGROUND: Recurrence of common bile duct stone (CBDS) is not common after laparoscopic common bile duct exploration (LCBDE). This study aimed to investigate the risk factors of recurrence of CBDS after LCBDE. METHODS: Patients who underwent LCBDE between January 2001 and December 2018 in four teaching hospitals of The Catholic University of Korea were included. The operation, fluoroscopy, and endoscopic retrograde cholangiopancreatography records were investigated retrospectively. The primary outcome of this study was the independent risk factors for recurrence of CBDS. RESULTS: A total of 230 patients were included in this study. Thirty-one patients had recurrence of CBDS. In univariate analysis, CBDS size (>9 mm) (P = 0.003), multiple stones (≥2) (P = 0.031), stone size (≥1.5 cm) (P = 0.041), CBD diameter (≥12 mm) (P = 0.005), CBD dilatation (≥10 mm) (P = 0.02), prior history of laparoscopic cholecystectomy (P = 0.002) were associated with recurrence. After multivariable logistic regression, CBDS size (>9 mm) (OR 4.67, 95% CI 1.35-16.18, P = 0.011), CBD dilatation (≥10 mm) (OR 5.66, 95% CI 1.47-21.82, P = 0.012), and prior history of laparoscopic cholecystectomy (AOR 3. 90, 95% CI 1.34-11.37, P = 0.013) were associated with recurrence. CONCLUSIONS: Stone size >9 mm, CBD diameter ≥10 mm, and prior history of laparoscopic cholecystectomy were risk factors for recurrence of CBDS after LCBDE.

Randomized controlled study of the effect of octreotide on pancreatic exocrine secretion and pancreatic fistula after pancreatoduodenectomy.

BACKGROUND: Octreotide is known to decrease the rate of postoperative complication after pancreatic resection by diminishing exocrine function of the pancreas. The aim of this study was to evaluate the effect of octreotide in decreasing exocrine excretion of pancreas and preventing pancreatic fistula. MATERIALS AND METHODS: Prospective randomized trial was conducted involving 59 patients undergoing pancreaticoduodenectomy for either malignant or benign tumor, 29 patients were randomized to receive octreotide; 30 patients allotted to placebo. All pancreaticojejunal anastomosis was performed with external stent of negative-pressured drainage and the amount of pancreatic juice through the external stent was measured until postoperative 7th day. Pancreatic fistula was recorded. RESULTS: There were no differences in demographics, pancreatic texture and pancreatic duct diameter between the octreotide and placebo group. The median output of pancreatic juice was not significantly different between both groups during 7 days after surgery. When the patients were stratified according to the diameter of pancreatic duct (duct ≤5 mm, > 5 mm), there were no significant differences in daily amount of pancreatic juice, however, when stratified according to pancreatic texture, median output of pancreatic juice was significantly lower in patients with hard pancreas compared with those with soft pancreas from 5 day to 7 day after surgery (p < 0.05). No significant differences in pancreatic fistula and postoperative complications were found between the octreotide and placebo groups. CONCLUSIONS: Prophylactic octreotide is not effective to inhibit the exocrine secretion of the remnant pancreas and does not decrease the incidence of pancreatic fistula after pancreaticoduodenectomy.

Improved functional outcome after early reduction in Bosworth fracture-dislocation.

BACKGROUND: Bosworth described an unusual fracture-dislocation of the ankle with fixed posterior fracture-dislocation of the fibula. Previous epidemiological data on the prevalence and characteristics of patients with Bosworth ankle fractures have been limited. Bosworth fracture-dislocations are often missed in patients with ankle fractures. We investigated the outcomes of missed diagnosis and the prevalence of Bosworth fracture-dislocation in patients with ankle fractures. METHODS: We conducted a retrospective analysis of inpatients aged 15 years and older with an ankle fracture, who underwent surgery between 2007 and 2016 in 4 Korean hospitals. The patient demographics, risk factors, fracture characteristics, treatment data, outcomes, and complications were analyzed. RESULTS: We reviewed 3405 hospital admissions for ankle fractures. During the study period, Bosworth fracture-dislocations were diagnosed in 51 cases. The prevalence of Bosworth fracture-dislocations (n=51) was 1.62% among patients with ankle fractures who were enrolled in this study (n=3140). Emergency surgery was performed within 24h of injury in 36 cases (group A) and delayed surgery was performed in 15 cases (group B). The mean patient age at admission was 35.97 (standard deviation [SD], 1.643) years in group A and 34.33 (SD, 2.296) years in group B. Men were more commonly affected than women, with a 32:19 ratio. Most of the patients with Bosworth fracture-dislocations were young adults with high-energy trauma. The most frequent mechanism of trauma was falling down stairs (n=27, 52.94%), followed by traffic accidents. Patient outcomes were significantly better in group A than in group B. CONCLUSION: The prevalence of Bosworth fracture-dislocations was higher than expected. If unrecognized, it can result in inappropriate treatment and permanent disability. With accurate diagnosis and prompt treatment, excellent results can usually be obtained. LEVEL OF CLINICAL SIGNIFICANCE: 4.

Organotypic slice cultures of pancreatic ductal adenocarcinoma preserve the tumor microenvironment and provide a platform for drug response.

BACKGROUND: /Objective: The conventional models currently used to evaluate various anti-tumor therapeutic agents are not sufficient for representing human pancreatic ductal adenocarcinoma (PDA), which has a unique tumor microenvironment. We aimed to produce an organotypic slice culture model from human PDA that resembles the in vivo situation and to evaluate the responses of PDA slices to established cytotoxic drugs. METHODS: PDA tissues were obtained from 10 patients who underwent pancreatic resection. The tissues were sliced by a vibratome, and the tumor slices were then cultured. The viability of tumor slices during slice culture was evaluated using H&E and immunohistochemical staining, and stromal cells were demonstrated. The effects of cytotoxic drugs on PDA cell lines and slices were analyzed. RESULTS: Tumor slices maintained their surface areas and tissue viability for at least five days during culture. Preserved proliferation and apoptosis in tumor slices were observed by the expression of Ki-67 and cleaved caspase-3. Stromal cells including macrophages (CD68+ and CD163+), T cells (CD3+, CD8+, and FOXP3+), and myeloid cells (CD11b+) were present throughout the culture period. Staurosporine, gemcitabine, and cisplatin treatment of PDA cell lines and tumor slices exerted proportional cytotoxic effects in terms of MTT viability, tumor cell number, and Ki-67 and cleaved caspase-3 expression. CONCLUSIONS: Organotypic human PDA slice cultures preserved their viability and tumor microenvironment for at least five days during slice culture. PDA slice culture appears to be a feasible preclinical test model to assess the response to anti-tumor agents.

Small cell carcinoma of the gallbladder: a case report.

Small cell carcinoma (SCC) of the gallbladder is an extremely rare tumor. Despite aggressive and varied treatments, its prognosis is poor. A 70-year-old woman undergoing treatment for pneumonia was detected with a gallbladder mass. Radical cholecystectomy was performed and the pathology revealed small cell carcinoma. There were metastases in 2 lymph nodes, scoring T2N1M0, stage IIIB (AJCC 7th). The patient has survived thus far, with subsequent chemotherapy. SCC of the gallbladder has an extremely low incidence and poor prognosis. In some cases, radical surgery with chemotherapy or radiation therapy could increase survival rate of patients.

The Optimal Suture Site for the Repair of Posterior Horn Root Tears: Biomechanical Evaluation of Pullout Strength in Porcine Menisci.

PURPOSE: There are few studies on biomechanical evaluation of suture points in repair of root tears. The purpose of this study was to determine the point of greatest pullout strength for root tear repair. MATERIALS AND METHODS: A total of 120 fresh porcine medial menisci were obtained. The red-red and red-white zones of the meniscus were divided by two lines designated as lines A and B (groups A and B). Groups A and B were further divided into three groups each by dividing lines A and B into three points: 3, 5, and 7 mm from the meniscal ligament root insertion. Vertical meniscal repair was performed on each point. The pullout failure strength was tested using a biaxial servohydraulic testing machine. RESULTS: The average maximal load at failure was significantly greater in group A than group B (87.65 vs. 62.93; p<0.001) The average length at maximal load failure was greater in group A than group B (4.35 vs. 3.2; p<0.001). Among the subgroups of 3, 5, and 7 mm in both groups A and B, 7 mm showed the greatest maximal load (p<0.001). CONCLUSIONS: The pullout strength was statistically significantly greater in group A than group B and in the 7 mm subgroup than the 3 and 5 mm subgroups. Thus, the 7 mm subgroup in group A showed the greatest pullout strength.

Clinical Features of Male Breast Cancer: Experiences from Seven Institutions Over 20 Years.

PURPOSE: Breast cancer treatment has progressed significantly over the past 20 years. However, knowledge regarding male breast cancer (MBC) is sparse because of its rarity. This study is an investigation of the clinicopathologic features, treatments, and clinical outcomes of MBC. MATERIALS AND METHODS: Clinical records of 59 MBC patients diagnosed during 1995-2014 from seven institutions in Korea were reviewed retrospectively. RESULTS: Over a 20-year period, MBC patients accounted for 0.98% among total breast cancer patients, and increased every 5 years. The median age of MBC patientswas 66 years (range, 24 to 87 years). Forty-three patients (73%) complained of a palpable breast mass initially. The median symptom duration was 5 months (range, 1 to 36 months). Mastectomy was performed in 96% of the patients. The most frequent histology was infiltrating ductal carcinoma (75%). Ninety-one percent of tumors (38/43) were estrogen receptor-positive, and 28% (11/40) showed epidermal growth factor receptor 2 (HER-2) overexpression. After curative surgery, 42% of patients (19/45) received adjuvant chemotherapy; 77% (27/35) received hormone therapy. Five out of ten patients with HER-2 overexpressing tumors did not receive adjuvant anti-HER-2 therapy, while two out of four patients with HER-2 overexpressing tumors received palliative trastuzumab for recurrent and metastatic disease. Letrozole was used for one patient in the palliative setting. The median overall survival durations were 7.2 years (range, 0.6 to 17.0 years) in patients with localized disease and 2.9 years (range, 0.6 to 4.3 years) in those with recurrent or metastatic disease. CONCLUSION: Anti-HER-2 and hormonal therapy, except tamoxifen, have been underutilized in Korean MBC patients compared to female breast cancer patients. With the development of precision medicine, active treatment with targeted agents should be applied. Further investigation of the unique pathobiology of MBC is clinically warranted.

Suction Drain Tip Culture after Spine Surgery: Can It Predict a Surgical Site Infection?

STUDY DESIGN: Retrospective clinical study. PURPOSE: To assess the diagnostic value of suction drain tip culture in patients undergoing primary posterior spine surgery. OVERVIEW OF LITERATURE: To date, the diagnostic value of suction drain tip culture for predicting surgical site infection (SSI) has not been firmly established in orthopedic or spinal surgery. METHODS: In total, 133 patients who underwent primary posterior spine surgery from January 2013 to April 2015 were included in this retrospective study. Patients diagnosed with infective disease or condition was excluded. The suction drain tip was cut off approximately 5 cm from its far end. The sample was sent to the microbiological laboratory of the hospital for culture analysis. Any signs of infection, such as wound discharge or dehiscence, fever, chills, or chronic pain, were recorded. The culture outcome, identification of bacteria, and postoperative transition of the serum C-reactive protein level were also recorded in all patients. The wounds were followed up for a minimum of 3 months. RESULTS: A positive drain tip culture was found in 48 patients (36.1%), of whom, 6 developed SSI. The sensitivity of drain tip culture for SSI after primary posterior spine surgery was 60.0%, and the specificity was 65.9%. The association between the incidence of positive suction tip culture and SSI was not statistically significant. Among the 48 positive drain tip cultures, there was no significant association between the occurrence of SSI and virulence of isolated bacteria. There was no significant association between drain tip culture positivity and the duration of drainage, or between the rate of SSI and duration of drainage. CONCLUSIONS: Suction drain tip culture analysis is a poor predictor of SSI after primary posterior spine surgery. Routine use of a drain tip culture is not supported by the results of this study.

Usefulness of Ultrasound-Guided Lower Extremity Nerve Blockade in Surgery for Patellar Fracture.

PURPOSE: To evaluate the usefulness of ultrasound-guided nerve blockade in patellar fracture surgery. MATERIALS AND METHODS: Twenty-three patients who underwent metal fixation under ultrasound-guided lower extremity blockade after diagnosis of patellar fracture from July 2011 to June 2012 were enrolled in this study. Under ultrasound guidance, femoral nerve, lateral femoral cutaneous nerve, obturator nerve, and sciatic nerve blockades were performed. For evaluation of anesthesia, interference with overall surgery, such as intraoperative knee pain and tourniquet pain, was checked. Individual anesthetic complications, satisfaction with nerve blocks, and choice of future anesthesia method were investigated. RESULTS: Nineteen patients underwent surgery without any pain and 4 patients with mild pain. Satisfaction was excellent in 17 patients, good in 5, and unsatisfactory in 1. No complications such as infection or nerve injury occurred. In terms of selection of future anesthesia, 22 patients chose a nerve blockade of the lower extremity under ultrasound guidance, and one chose general anesthesia. CONCLUSIONS: Overall, ultrasound-guided nerve block of the lower extremity for patellar fracture surgery showed satisfactory results. Therefore, it could be a useful method to prevent complications associated with general or spinal anesthesia.

Quinacrine for extremity melanoma in a mouse model of isolated limb perfusion (ILP).

PURPOSE: Quinacrine is a relatively non-toxic drug, once given almost exclusively for malaria. However, recent studies show that quinacrine can suppress nuclear factor-κB (NF-κB), and activate p53 signaling. We investigated the anti-cancer effect of quinacrine, using a novel mouse model of isolated limb perfusion (ILP) for extremity melanoma. METHOD: Female C57BL/6 mice (22-25 g) were injected with B16 melanoma cells (1 × 10(5)) subcutaneously in the distal thigh. After 7 days of tumor establishment, mice were perfused with either PBS, melphalan (90 µg), or quinacrine (3.5 and 4.5 mg) through the superficial femoral artery for 30 min at either 37 or 42 °C in a non-oxygenated circuit. We analyzed morbidity, toxicity, tumor apoptosis, and responses. RESULTS: Melanoma cell death following in vitro exposure to quinacrine was dose and time dependent. A significant decrease in mean tumor volume was observed after perfusion with low-dose and high-dose quinacrine (both P = 0.002) at 37 °C as well as after perfusion with low-dose quinacrine (P = 0.0008) at 42 °C. CONCLUSION: Quinacrine has demonstrable efficacy against melanoma cells in vitro and in a clinically relevant model of ILP. Further studies to evaluate the optimal conditions for quinacrine usage are warranted.

Metastatic Brain Neuroendocrine Tumor Originating from the Liver.

A 67-year-old male presented with left temporal hemianopsia and left hemiparesis. A contrast-enhanced magnetic resonance image revealed a 4.5×3.5×5.0 cm rim-enhancing mass with central necrosis and associated edema located in the left occipital lobe. Of positron emission tomography and abdominal computed tomography, a 9-cm mass with poor enhancement was found in the right hepatic lobe. Craniotomy and right hemihepatectomy was performed. The resected specimen showed histological features and immunochemical staining consistent with a metastatic neuroendocrine tumor (NET). Four months later, the tumors recurred in the brain, liverand spinal cord. Palliative chemotherapy with etoposide and cisplatin led to complete remission of recurred lesions, but the patient died for pneumonia. This is the first case of a metastatic brain NET originating from the liver. If the metastatic NET of brain is suspicious, investigation for primary lesion should be considered including liver.

MicroRNA expression profiling of diagnostic needle aspirates from surgical pancreatic cancer specimens.

PURPOSE: MicroRNAs (miRNAs) have been widely investigated as potential biomarkers for several malignancies. To establish the feasibility of miRNA expression profiling of small biopsy samples of pancreatic cancers, we assessed expression profiles in freshly collected aspirates obtained immediately after surgical resection of the pancreas. METHODS: We used separate fine needles (20-23 gauge) to aspirate the pancreatic cancer and adjacent normal pancreatic tissue. miRNAs that were differentially expressed in pancreatic cancers and matched paraneoplastic normal pancreatic tissues were identified using an miRNA microarray. RESULTS: We identified 158 aberrantly expressed miRNAs in pancreatic cancers; 51 were overexpressed and 107 underexpressed compared with normal pancreatic tissue. To confirm the microarray findings, quantitative RT-PCR was performed on individual samples. We chose eight miRNAs for further analysis; of which five were overexpressed (miR-21, miR-27a, miR-146a, miR-200a, and miR-196a) and three underexpressed (miR-217, miR-20a, and miR-96) in pancreatic cancer samples compared to benign pancreatic tissue. Expression of miR-21, miR-27a, miR-146a, miR-200a, and miR-196a was significantly increased in cancer fine-needle aspirates relative to matched controls in all samples. Expression of miR-217, miR-20a, and miR-96 was significantly downregulated in almost all pancreatic cancer tissues. CONCLUSION: We demonstrate the feasibility of performing miRNA profiling on very small specimens obtained using fine-needle aspiration of pancreatic cancers.

[Recurrence of multiple focal nodular hyperplasia in a young male patient].

Focal nodular hyperplasia (FNH) is the second most common benign hepatic tumor that is usually found in women. Diagnosis of FNH mainly depends on imaging studies such as color Doppler flow imaging, computed tomography, and magnetic resonance imaging. It is characterized by the presence of stellate central scar and is nowadays incidentally diagnosed with increasing frequency due to advances in radiologic imaging technique. FNH typically presents as a single lesion in 70% of cases and generally does not progress to malignancy or recur after resection. Herein, we report a case of a young male patient with recurrent multiple FNH who underwent surgical resection for presumed hepatic adenoma on computed tomography.