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This phase I/II study evaluated the safety and efficacy of a new histone deacetylase (HDAC) inhibitor, ivaltinostat, in combination with gemcitabine and erlotinib for advanced pancreatic ductal adenocarcinoma (PDAC). Patients diagnosed with unresectable, histologically confirmed PDAC who had not undergone previous therapy were eligible. Phase I had a 3 + 3 dose escalation design to determine the maximum tolerable dose (MTD) of ivaltinostat (intravenously on days 1, 8 and 15) with gemcitabine (1000 mg/m 2 intravenously on days 1, 8 and 15) and erlotinib (100 mg/day, orally) for a 28-day cycle. In phase II, patients received a six-cycle treatment with the MTD of ivaltinostat determined in phase I. The primary endpoint was the objective response rate (ORR). Secondary endpoints included overall survival (OS), disease control rate (DCR) and progression-free survival (PFS). The MTD of ivaltinostat for the phase II trial was determined to be 250 mg/m 2 . In phase II, 24 patients were enrolled. The median OS and PFS were 8.6 (95% confidence interval [CI]: 5.3-11.2) and 5.3 months (95% CI: 3.7-5.8). Of the 16 patients evaluated for response, ORR and DCR were 25.0% and 93.8% with a median OS/PFS of 10.8 (95% CI: 8.3-16.7)/5.8 (95% CI: 4.6-6.7) months. Correlative studies showed that mutation burden detected by cfDNA and specific blood markers such as TIMP1, pro-MMP10, PECAM1, proMMP-2 and IGFBP1 were associated with clinical outcomes. Although the result of a small study, a combination of ivaltinostat, gemcitabine and erlotinib appeared to be a potential treatment option for advanced PDAC., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background and Aim: The aim of this study is to identify the predictive factors for futile surgery in patients with radiologically resectable or borderline resectable pancreatic cancer and to develop a prediction model., Methods: This retrospective study included patients who underwent pancreatic surgery for pancreatic cancer between 2006 and 2017. To identify independent risk factors for futile surgery, logistic regression and random forest analyses were performed in the training cohort, based on which a nomogram was established. The predictive accuracy and discriminative ability of the nomogram were validated in the validation cohort., Results: Of 389 patients who underwent pancreatic surgery, the laparotomy was futile in 40 patients (10.3%). In the training cohort, the univariate and multivariate logistic regression analyses revealed that serum carbohydrate antigen 19-9 level of ≥ 150 U/mL (P = 0.003), the presence of suspicious lymph node (P = 0.013), and more extensive peripancreatic tumor infiltration (P < 0.001) were independent predictive factors for futile surgery. The bootstrap-corrected concordance index of the nomogram was high in the training cohort, 0.826 with a 95% confidence interval of 0.745-0.907. This model also showed a good discriminative performance in the validation cohort, with a concordance index of 0.831., Conclusions: We established and validated a novel nomogram that predicts the risk of futile surgery due to occult distant metastasis in patients with radiologically resectable or borderline resectable pancreatic cancer., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Lung cancer is a common comorbidity of idiopathic pulmonary fibrosis (IPF) and has poor outcomes. The incidence and clinical factors related to development of lung cancer in idiopathic pulmonary fibrosis (IPF) are unclear. The aim of this study was to elucidate the cumulative incidence, risk factors, and clinical characteristics of lung cancer in IPF., Methods: In this retrospective study, we analyzed clinical data for 938 patients who were diagnosed with IPF without lung cancer between 1998 and 2013. Demographic, physiologic, radiographic, and histologic characteristics were reviewed. Cumulative incidence of lung cancer and survival were estimated by the Kaplan-Meier method. Risk factors of lung cancer development were determined by Cox proportional hazard analysis., Results: Among 938 IPF patients without lung cancer at initial diagnosis, lung cancer developed in 135 (14.5%) during the follow-up period. The cumulative incidences of lung cancer were 1.1% at 1 year, 8.7% at 3, 15.9% at 5, and 31.1% at 10 years. Risk factors of lung cancer were male gender, current smoking at IPF diagnosis, and rapid annual decline of 10% or more in forced vital capacity (FVC). Patients who developed lung cancer were mostly elderly men with smoking history. Squamous cell carcinoma followed by adenocarcinoma was the most common histologic type. Lung cancer was frequently located in areas abutting or within fibrosis. Survival was significantly worse in patients with lung cancer compared to patients with IPF alone., Conclusion: Lung cancer frequently developed in patients with IPF and was common in current-smoking men with rapid decline of FVC.

Objective: To determine the toxicity and oncologic outcome of neoadjuvant chemoradiotherapy (CRT) followed by curative total mesorectal excision (TME) in the elderly (≥70 yrs) and younger (<70 yrs) rectal cancer patients., Background: Sufficient data for elderly rectal cancer patients who received definitive trimodality have not been accumulated yet., Patients and Methods: A total of 1232 rectal cancer patients who received neoadjuvant CRT and TME were enrolled in this study. After propensity-score matching, 310 younger patients and 310 elderly patients were matched with 1:1 manner. Treatment response, toxicity, surgical outcome, recurrence, and survival were assessed and compared between the 2 groups of patients., Results: The median age was 58 years for the younger patient group and 74 years for the elderly group. Pathologic complete response rates were not significantly different between the 2 groups (younger and elderly: 17.1% vs 14.8%, P = 0.443). The 5-year recurrence-free survival (younger and elderly: 67.7% vs 65.5%, P = 0.483) and overall survival (younger and elderly: 82.9% vs. 79.5%, P = 0.271) rates were not significantly different between the 2 groups either. Adjuvant chemotherapy after surgery was less frequently delivered to the elderly than that to younger patients (83.9% vs 69.0%). Grade 3 or higher acute hematologic toxicity was observed more frequently in the elderly than that in the younger group (9.0% vs 16.1%, P = 0.008). Late complication rate was higher in the elderly group compared with that in the younger group without statistical significance (2.6% vs 4.5%, P = 0.193)., Conclusions: Although acute hematologic toxicity was observed more frequently in the elderly patients than that in the younger patients, elderly rectal cancer patients with good performance status who received preoperative CRT and TME showed favorable tumor response and recurrence-free survival similar to younger patients.

Pancreatic cancer has poor prognosis because of its rapid progression and treatment resistance. Based on the results of the Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT), a combination regimen of gemcitabine with nab-paclitaxel is currently used as standard therapy for the treatment of metastatic pancreatic cancer. However, because studies in Asian populations are lacking, we investigated the treatment efficacy and safety of this combination therapy in Korean population. Patients with metastatic pancreatic cancer (n=81) treated with gemcitabine and nab-paclitaxel (1,000 and 125 mg/m 2 , respectively) as the first-line chemotherapy from January 2016 were identified using the Severance Hospital Pancreatic Cancer Cohort Registry. Treatment efficacy and treatment-related adverse events (AEs) were analyzed. The median follow-up period was 10.7 months (range, 1.5-23.3 months). Median overall survival, progression-free survival, and objective response rates were 12.1 months (95% confidence interval [CI], 10.7-not estimable), 8.4 months (95% CI, 5.0-11.8), and 46.9%, respectively. The incidence of grade ≥3 neurotoxicity and neutropenia were 18.5% and 46.9%, respectively. Febrile neutropenia and grade ≥3 gastrointestinal AEs occurred in 13 (16.0%) and 16 (19.8%) patients, respectively. Dose reductions because of AEs were required in 60.5% of patients. The combination of gemcitabine with nab-paclitaxel is an effective anti-cancer regimen in Korean population of patients with metastatic pancreatic adenocarcinoma. However, careful monitoring and management are required because of occurrence of treatment-related AEs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: The documented incidence of multiple primary lung cancer has increased as a result of the widespread use of early detection tools. We report the successful surgical treatment of a case who had consecutive metachronous adenocarcinoma and squamous cell carcinoma of the lung after successful treatment for small cell carcinoma of the lung.A 73-year-old man underwent a routine health check-up. Computed tomography showed ground-glass opacity in the upper lobe of the right lung, which was diagnosed as small cell carcinoma. Twenty-nine months after concurrent chemoradiotherapy for the carcinoma, which was in complete remission, a nodule was detected in the apical segment of the right upper lobe. Histopathologically, the tumor was diagnosed as poorly differentiated adenocarcinoma. The second metachronous adenocarcinoma was completely removed by right upper lobectomy with lymph node dissection. Seventeen months later, the patient underwent left upper lobectomy with lymph node dissection and received 4 cycles of adjuvant chemotherapy for another moderately differentiated squamous cell carcinoma., Conclusion: This case highlights the need for continuous screening for metachronous lung cancer following the successful treatment of primary lung cancer, even small cell carcinoma, to identify patients who could benefit from curative surgery.

Epithelial-mesenchymal transition (EMT) is known to be associated with cancer progression, metastatic spread, and therapeutic resistance and to occur at the invasive front. Cancer stem cells (CSCs) display stemness features and might be implicated in tumor initiation, local recurrence and metastasis. The present study was conducted to examine the expression status and relationships between EMT- and CSC-related proteins in the different tumor areas of primary colorectal cancer (CRC), along with their clinicopathological significance. We performed immunohistochemical staining for 4 EMT-related proteins, namely E-cadherin, β-catenin, snail and vimentin, and two CSC-related proteins, namely CD44 and CD133, in two different tumor areas (the representative tumor center and the deepest invasive front) in 286 cases of primary CRC using tissue microarrays. Altered expression of all EMT-related proteins was more frequently observed in the invasive front than in the tumor center. Altered expression of E-cadherin, β-catenin and vimentin significantly associated with aggressive tumor characteristics. In particular, loss of E-cadherin expression in the invasive front significantly associated with shorter disease-free survival (DFS, P=0.002) and overall survival (OS, P=0.007). Overexpression of vimentin in the invasive front significantly correlated with poor OS (P=0.028). Loss of CD44 expression both in the tumor center and in the invasive front significantly associated with unfavorable clinicopathological characteristics. In the invasive front, but not in the tumor center, combination of the altered protein expression patterns of E-cadherin, β-catenin, vimentin, snail and CD133 significantly associated with aggressive clinicopathological factors and shorter DFS (P=0.003) and OS (P=0.005). The present data suggest that cancer cells expressing a combination of altered EMT- and CSC-related proteins may represent a potential biomarker for aggressive tumor behavior and may be a possible future candidate for molecular targeted treatments for CRC.

Background: This phase III trial compared the efficacy and safety of gemcitabine plus capecitabine (GemCap) versus single-agent gemcitabine (Gem) in advanced pancreatic cancer as first-line chemotherapy., Methods: A total of 214 advanced pancreatic cancer patients were enrolled from 16 hospitals in South Korea between 2007 and 2011. Patients were randomly assigned to receive GemCap (oral capecitabine 1660 mg/m plus Gem 1000 mg/m by 30-minute intravenous infusion weekly for 3 weeks followed by a 1-week break every 4 weeks) or Gem (by 30-minute intravenous infusion weekly for 3 weeks every 4 weeks)., Results: Median overall survival (OS) time, the primary end point, was 10.3 and 7.5 months in the GemCap and Gem arms, respectively (P = 0.06). Progression-free survival was 6.2 and 5.3 months in the GemCap and Gem arms, respectively (P = 0.08). GemCap significantly improved overall response rate compared with Gem alone (43.7% vs 17.6%; P = 0.001). Overall frequency of grade 3 or 4 toxicities was similar in each group. Neutropenia was the most frequent grade 3 or 4 toxicity in both groups., Conclusion: GemCap failed to improve OS at a statistically significant level compared to Gem treatment. This study showed a trend toward improved OS compared to Gem alone. GemCap and Gem both exhibited similar safety profiles., Competing Interests: The authors have no conflicts of interest to disclose.

Purpose: Erlotinib-gemcitabine combined chemotherapy is considered as the standard treatment for unresectable pancreatic cancer. This study aimed to determine the clinical factors associated with response to this treatment., Materials and Methods: This retrospective study included 180 patients with unresectable pancreatic cancer who received ≥2 cycles of gemcitabine-erlotinib combination therapy as first-line palliative chemotherapy between 2006 and 2014. "Long-term response" was defined as tumor stabilization after >6 chemotherapy cycles., Results: The median progression-free survival (PFS) and overall survival (OS) were 3.9 and 8.1 months, respectively. On univariate analysis, liver metastasis (p=0.023) was negatively correlated with long-term response. Locally advanced stage (p=0.017), a history of statin treatment (p=0.01), and carcinoembryonic antigen levels <4.5 (p=0.029) had a favorable effect on long-term response. On multivariate analysis, a history of statin treatment was the only independent favorable factor for long-term response (p=0.017). Prognostic factors for OS and PFS were significantly correlated with liver metastasis (p=0.031 and 0.013, respectively). A history of statin treatment was also significantly associated with OS after adjusting for all potential confounders (hazard ratio, 0.48; 95% confidence interval, 0.26-0.92; p=0.026)., Conclusion: These results suggest that statins have a favorable effect on "long-term response" to gemcitabine-erlotinib chemotherapy in unresectable pancreatic cancer patients. Statins may have a chemoadjuvant role in stabilizing long-term tumor growth.

Statins are cholesterol-lowering medications that are associated with a number of signaling pathways involved in carcinogenesis. Recent observational studies raised the possibility that the use of statins may reduce overall mortality in various types of cancer. We investigated whether statins used after pancreatic cancer diagnosis are associated with longer survival in pancreatic cancer patients.We retrospectively analyzed data from 1761 patients newly diagnosed with pancreatic adenocarcinoma between January 1, 2006, and December 31, 2014. We used the time-dependent Cox proportional hazards regression model to estimate mortality among pancreatic cancer patients according to statin use.Among the 1761 pancreatic cancer patients, 118 patients had used statins. During the study period, 1176 patients (66.7%) died. After adjusting for age, sex, location of cancer, cancer stage, diabetes mellitus, hypertension, dyslipidemia, smoking, alcohol use, body mass index, and CA 19-9, statin use was associated with a lower risk of cancer death (hazard ratio [HR], 0.780; 95% confidence interval [CI], 0.617-0.986), especially among simvastatin users (HR, 0.554; 95% CI, 0.312-0.982) and atorvastatin users (HR, 0.636; 95% CI, 0.437-0.927). Subgroup analysis showed that overall survival was statistically significantly longer in patients with nonmetastatic pancreatic cancer (log-rank P = 0.024).We found that the use of simvastatin and atorvastatin after cancer diagnosis is associated with longer survival in patients with nonmetastatic pancreatic adenocarcinoma.

An association between obesity and unfavorable outcomes for various types of malignancy has been established. Nevertheless, the impact of visceral obesity (VO) on outcomes in pancreatic cancer is still unknown and controversial. The aim of this study was to uncover an association between VO and pancreatic cancer outcomes. We retrospectively reviewed 499 patients with pancreatic cancer who were diagnosed and treated in Severance Hospital from January 2006 to December 2011. Compared to the low-VO group (n = 260), the high-VO group (n = 239) was mostly male (68.2% vs. 31.8%, P < 0.001) and was more likely to have current smoking status (29.7% vs. 17.7%, P < 0.001), current alcohol intake status (52.3% vs. 26.4%, P < 0.001) and diabetes mellitus (54.4% vs. 31.9%, P = 0.028). The progression free survival (PFS) and overall survival (OS) were found to be significantly shorter by the Kaplan-Meier method in the high-VO group than in the low-VO group (PFS; P = 0.044, OS: P = 0.013). In addition, the higher percentage of visceral fat was correlated with more lymph node metastasis and shorter OS (P = 0.011 and P = 0.017, respectively). In patients with pancreatic cancer, VO at the time of diagnosis is associated with negative outcomes, such as shorter PFS and OS.

We evaluated the tumor response and survival according to the KRAS oncogene status in locally advanced rectal cancer. One hundred patients with locally advanced rectal cancer (cT3-4N0-2M0) received preoperative radiation of 50.4 Gy in 28 fractions with 5-fluorouracil and total mesorectal excision. Tumor DNA from each patient was obtained from pretreatment biopsy tissues. A Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation was found in 26 (26%) of the 100 patients. Downstaging (ypT0-2N0M0) rates after preoperative chemoradiotheray were not statistically different between the wild-type and mutant-type KRAS groups (30.8% vs 27.0%, P = 0.715, respectively). After a median follow-up time of 34 months, there was no statistically significant difference in the 3-year relapse-free survival (82.2% vs 82.6%, P = 0.512) and overall survival (94.7% vs 92.3%, P = 0.249) rates between wild-type and mutant-type KRAS groups, respectively. The KRAS mutation status does not influence the tumor response to the radiotherapy and survival in locally advanced rectal cancer patients who received preoperative chemoradiotherapy and curative surgery.

CK2α has diverse effects on the tumorigenesis owing to its kinase activity, which phosphorylates various proteins involved in tumorigenesis. We, therefore, investigated the expression and role of CK2α in the phosphorylation of deleted in breast cancer 1 (DBC1) in gastric carcinomas. We used 187 gastric carcinomas and human gastric cancer cells to investigate the roles and relationship between CK2α and DBC1 in gastric carcinomas. Positive expression of CK2α and phospho-DBC1 predicted shorter overall survival and relapse-free survival by univariate analysis. Especially, CK2α expression was an independent prognostic indicator for gastric carcinoma patients. In gastric carcinoma cells, CK2α was bound to DBC1 and phosphorylated DBC1. The phosphorylation of DBC1 by CK2α was evidenced by co-immunoprecipitation of CK2α and DBC1 in a GST pull-down assay, an in vitro kinase assay, and immunofluorescence staining. Inhibition of both CK2α and DBC1 decreased proliferation and invasive activity of cancer cells. Decreased migration and invasive activity was associated with a downregulation of MMP2, MMP9 and the epithelial-mesenchymal transition. A mutation at the phosphorylation site of DBC1 also downregulated the signals related with the epithelial-mesenchymal transition. Our study demonstrated that CK2α is an independent prognostic indicator for gastric carcinoma patients and is involved in tumorigenesis by regulating the phosphorylation of DBC1. In addition, the blocking of CK2α and DBC1 inhibited the proliferation and invasive potential of gastric cancer cells. Therefore, our study suggests that CK2α-DBC1 pathway might be a new therapeutic target for the treatment of gastric carcinoma., (© 2014 UICC.)

Background and Objective: Subcentimeter nodules without change in size during long-term follow-up period (for minimum 2 years) are assumed as benign lesions. However, the 2-year stability rule has not been fully verified so far and is still questionable. Thus, we aimed to retrospectively investigate long-term follow-up results for 2-year stable subcentimeter nodules at screening low-dose computed tomography (LDCT)., Methods: A total of 635 subjects having had follow-up LDCTs for the initial 2-year screening period and additional 3 years thereafter and having had non-calcified subcentimeter nodules were included. By using computed tomography (CT) nodule volumetry software, we measured interval changes in nodule volume., Results: A total of 1107 subcentimeter nodules (1037 solid, 70 ground-glass opacity nodules (GGNs)) were detected at baseline CT. Of 1037 solid nodules, 1032 showed no growth during the initial 2-year and 5-year follow-up period. Fifty-nine GGNs were stable for initial 2 years, but two (3.4%) were later proved as adenocarcinomas. Among five solid nodules that showed growth during the initial 2-year follow-up period, one (20%) proved to be an adenocarcinoma, whereas four (36.4%) of 11 GGNs that demonstrated growth were diagnosed as lung cancers., Conclusions: All solid subcentimeter nodules having initial 2-year stability at screening LDCT can be considered benign because none shows growth at further follow-up CT. On the other hand, subcentimeter GGNs have more chance of growth than solid nodules and need further follow-up CT for more than 2 years., (© 2014 Asian Pacific Society of Respirology.)

Primary duodenal adenocarcinoma is a rare malignant neoplasm accounting for 0.3% of all gastrointestinal tract carcinomas. We herein present one case of duodenal adenocarcinoma after duodenal neuroendocrine carcinoma. Poorly differentiated duodenal neuroendocrine carcinoma with liver metastasis (TxNxM1) was confirmed, and eight cycles of palliative chemotherapy (5-fluorouracil/etoposide/cisplatin) were administered. The patient was then in a clinically complete response status. About 1 year later, newly developed adenocarcinoma was detected at the same site. It was completely surgically resected, and the patient was cured.

Cortactin is an F-actin binding protein involved in cell migration and tumor metastasis. Recent reports suggest that silent mating-type information regulation 2 homologue 1 (sirtuin1; SIRT1) enhances the function of cortactin and promotes cell migration. We investigated SIRT1 and cortactin expression in 144 invasive non-small cell lung cancers (NSCLC) and 19 adenocarcinomas in situ (AIS) by immunohistochemistry and evaluated their clinicopathological significance in NSCLC. Positive SIRT1 and cortactin expression was observed in 67% (96 of 144) and 58% (84 of 144) of patients with invasive NSCLC, respectively. SIRT1 and cortactin expression was significantly associated with unfavorable clinicopathological factors, including high pathological T stage, lymph node metastasis, and advanced tumor invasion (AIS vs. invasive adenocarcinoma). Cortactin was significantly associated with high pathological T stage and lymph node metastasis in SIRT1-positive tumors. Cytoplasmic SIRT1 was significantly associated with high pathological T stage and large tumor size compared to that of nuclear SIRT1. Large tumor size, high pathological T stage, lymph node metastasis, and cytoplasmic SIRT1 expression were significantly associated with shorter overall survival in a univariate analysis. Our findings suggest that SIRT1 and cortactin may play a role in the progression of NSCLC and may cooperate during tumor progression in NSCLC., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

Purpose: To investigate the use of pretreatment carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) as prognostic factors to determine survival in pancreatic adenocarcinoma., Materials and Methods: A retrospective review of the medical records of patients who were diagnosed with pancreatic adenocarcinoma and received surgery, chemoradiotherapy or chemotherapy was performed. Factors, including CA 19-9 and CEA, associated with the survival of pancreatic cancer patients were analyzed., Results: Patients with the median age of 65 years were included (n=187). Elevated serum CA 19-9 levels and CEA levels were observed in 75.4% and 39% of patients at diagnosis, respectively. CEA was correlated with tumor stages (p=0.005), but CA 19-9 was not. CA 19-9 and CEA were elevated in 69.0% and 33.3% of patients with resectable pancreatic cancer, and elevated in 72.9% and 47.2% of patients with advanced pancreatic cancer, respectively. The median overall survival of the normal serum CEA group was longer than that of the elevated serum CEA group (16.3 months vs. 10.2 months, p=0.004). However, the median overall survival of the normal serum CA 19-9 group was not different from that of the elevated serum CA 19-9 group (12.4 months vs. 13.5 months, p=0.969). The independent factors associated with overall survival were advanced pancreatic cancer [harzard ratio (HR) 4.33, p=0.001] and elevated serum CEA level (HR 1.52, p=0.032)., Conclusion: Patients with elevated serum CEA level at diagnosis demonstrated poor overall survival. Pretreatment CEA level may predict the prognosis of patients with pancreatic adenocarcinoma.

Myoid angioendothelioma of the spleen is an uncommon, benign vascular tumor that is morphologically characterized by a composite of vascular spaces and stromal cells with myoid feature. Herein, we report a case of the myoid angioendothelioma of the spleen, concurrent with rectal adenocarcinoma. A 41-year-old woman presented with hematochezia for several weeks. Grossly, the rectal mass was a 2.5 × 2-cm ulcerative fungating lesion. The splenic mass was a 2.2 × 2-cm well-circumscribed lesion. Microscopically, the rectal mass was a well-differentiated adenocarcinoma that invaded into the pericolic adipose tissue. The splenic mass was composed of slit-like vascular spaces and fascicles of elongated stromal cells. Vascular endothelial cells were immunopositive for CD31, factor VIII-related antigen, and CD34 but negative for CD8. Stromal cells were immunopositive for smooth muscle actin but negative for desmin., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Paclitaxel (taxol) has been used for the treatment of various human tumors and is an exceedingly efficient chemotherapy agent against esophageal cancer. However, the precise molecular mechanisms of paclitaxel effects on human esophageal adenocarcinoma cells are not well understood. MTT assay and cell cycle analysis were performed to examine the mechanism of antiproliferative and cell viability effects of paclitaxel in human esophageal adenocarcinoma cancer cells. Western blotting was also used to examine the cell cycle- and apoptosis-related proteins. Paclitaxel inhibited the proliferation of SKGT4 cells in a dose- and time-dependent manner with G2/M arrest. In addition, paclitaxel induced apoptosis through the activation of caspase-3 followed by PARP degradation. In conclusion, our results suggest that paclitaxel leads to mitotic cell cycle arrest following G2/M arrest and induces apoptosis via a caspase-3 pathway in SKGT4 cells.

Background: Recently, endoscopic submucosal dissection has been carefully applied in early gastric cancer (EGC) with undifferentiated type. However, there are no individual guidelines for endoscopic treatment of EGCs with poorly differentiated tubular adenocarcinoma or signet ring cell carcinoma. The aim of this study was to investigate and compare the clinicopathologic features of these two types of EGC to guide the application of endoscopic treatment., Methods: Patients to undergo radical gastrectomy for the treatment of EGC were selected for inclusion in this study. Histology was classified according to the Japanese Gastric Cancer Association. Between January 2005 and December 2008, 288 patients with poorly differentiated EGC and 419 patients with signet ring cell EGC were enrolled. Their medical records were reviewed retrospectively., Results: Compared with signet ring cell EGC, poorly differentiated EGC had higher rates of male gender, old age (≥45 years), large tumor length (>20 mm), ulcer, submucosal invasion, lymphovascular invasion, and lymph node metastasis. In the multivariate analyses, poorly differentiated EGC was significantly associated with ulcer (odds ratio [OR]: 2.4, 95% confidence interval [CI]: 1.5-3.8), submucosal invasion (OR: 3.6, 95% CI: 2.6-5.1) and lymphovascular invasion (OR: 2.0, 95% CI: 1.1-3.6) with a reference of signet ring cell EGC. The independent risk factors for lymph node metastasis were large tumor length, submucosal invasion, and lymphovascular invasion in both types of EGC. Young age was an independent risk factor of lymph node metastasis only in poorly differentiated EGC., Conclusions: Poorly differentiated EGC has clinicopathologic features that are less favorable to endoscopic treatment than are those of signet ring cell EGC. Therefore, these two types of EGC should be approached separately, not as a united type of undifferentiated histology, during the planning of endoscopic treatment.

D2-40 is a recently developed monoclonal antibody that reacts with a 40 kDa O-linked sialoglycoprotein and has been used for the assessment of lymphatic invasion in tumor specimens. We have evaluated the diagnostic usefulness of D2-40 and association of its immunopositivity with clinicopathological parameters in adenocarcinoma and squamous cell carcinoma of the lung. We investigated 97 cases of surgically resected adenocarcinoma or squamous cell carcinoma of the lung for the determination of D2-40 positivity in tumor cells and peritumoral lymphatic vessel density (LVD) using an immunostaining method. D2-40 immunoreactivity in tumor cells was invariably negative in adenocarcinoma but 47% of squamous cell carcinomas were positive. D2-40 positivity in the tumor was significantly associated with high LVD in squamous cell carcinoma (P < 0.006). There was no significant association between peritumoral LVD and clinicopathologic parameters, including lymphatic vessel invasion, lymph node metastasis, and survival in adenocarcinoma and squamous cell carcinoma. These results suggest that D2-40 immunoreactivity in tumor cells can be used for distinguishing between adenocarcinoma and squamous cell carcinoma and that the reactivity of tumor cells with D2-40 is positively correlated with LVD in squamous cell carcinoma but not with lymph node metastasis in adenocarcinoma and squamous cell carcinoma.

We aimed to evaluate prospectively the efficacy of positron emission tomography (PET)/computed tomography (CT) plus brain magnetic resonance imaging (MRI) for detecting extrathoracic metastases in lung adenocarcinoma. Metastatic evaluations were feasible for 442 consecutive patients (M:F=238:204; mean age, 54 yr) with a lung adenocarcinoma who underwent PET/CT (CT, without IV contrast medium injection) plus contrast-enhanced brain MRI. The presence of metastases in the brain was evaluated by assessing brain MRI or PET/CT, and in other organs by PET/CT. Diagnostic efficacies for metastasis detection with PET/CT plus brain MRI and with PET/CT only were calculated on a per-patient basis and compared from each other. Of 442 patients, 88 (20%, including 50 [11.3%] with brain metastasis) had metastasis. Regarding sensitivity of overall extrathoracic metastasis detection, a significant difference was found between PET/CT and PET/CT plus brain MRI (68% vs. 84%; P=0.03). As for brain metastasis detection sensitivity, brain MRI was significantly higher than PET/CT (88% vs. 24%; P<0.001). By adding MRI to PET/CT, brain metastases were detected in additional 32 (7% of 442 patients) patients. In lung adenocarcinoma patients, significant increase in sensitivity can be achieved for detecting extrathoracic metastases by adding dedicated brain MRI to PET/CT and thus enhancing brain metastasis detection.

Objective: The aim of this study was to describe retrospectively the CT findings of dry pleural dissemination of peripheral lung adenocarcinoma, and to compare the mutual roles of PET and CT components of integrated PET/CT in the diagnosis of the disease., Methods: The authors analyzed retrospectively the CT findings of pathologically proved dry pleural dissemination in 8 of 172 patients with peripheral adenocarcinoma of the lung. Subsequently, one radiologist and one nuclear medicine physician (unaware of the CT and pathologic results) evaluated together in a random order the integrated PET/CT of 172 adenocarcinoma patients (8 with dry pleural dissemination and 164 without). They recorded the presence of pleural dissemination using PET images only and using both PET and CT images. The diagnostic accuracies with respect to the presence of pleural dissemination were evaluated., Results: The CT findings of dry pleural dissemination were pleural small nodules (n=8, 100%) (>or=6 in number in all patients; 198/204 nodules were <5 mm in diameter and 6/204 were 5-10 mm) and uneven (n=4, 50%) or band-like (n=3, 38%) fissural thickening. By PET only, the sensitivity, specificity, and accuracy of dry pleural dissemination were 25% (2/8), 90% (147/164), and 87% (149/172), respectively; by PET plus CT these were 100% (8/8), 100% (164/164), and 100% (172/172), respectively., Conclusions: The CT findings of dry pleural dissemination are multiple small pleural nodules and uneven pleural thickening. Dry pleural dissemination should be diagnosed using CT findings at integrated PET/CT because lesions causing pleural dissemination without pleural effusion are usually beyond PET resolution.

Objective: To estimate the utility of thyroid transcription factor-1 (TTF-1) and the combined cytokeratin 7 (CK7) and 20 (CK20) immunoprofile as a marker for identifying the primary site of metastatic adenocarcinoma in effusions of the serous cavity., Study Design: Formalin-fixed, paraffin-embedded cell block specimens of pleural and peritonealfluid diagnosed as metastatic adenocarcinomas with known sites of origin were used for TTF-1, CK7 and CK20 immunohistochemistry. The primary sites of these cases were lung (16 cases), ovary (15), stomach (9), colon (8) and breast (8) and were confirmed by radiologic and/or histologic evaluation., Results: The lung adenocarcinomas showed TTF-1 positivity in 81% (13/16) of cases. All nonpulmonary adenocarcinomas lacked TTF-1 staining. The CK7-/CK20+ immunophenotype was seen in 63% of colonic adenocarcinomas and not seen in lung, ovary, stomach or breast adenocarcinomas. The CK7+/CK20- immunophenotype was seen in 100%, 88% and 87% of cases that originated in the lung, breast and ovary, respectively., Conclusion: TTF-7 immunostaining is useful in the differentiation between pulmonary and nonpulmonary origin of adenocarcinomas in malignant effusions. The combination of CK7-/CK20+ immunostaining is useful in identifying colon adenocarcinomas.

Background: Spiral computed tomography (CT) allows the pancreas to be imaged during peak contrast levels owing to the capability of fast data acquisition. The objective of this study was to evaluate the relative value of the arterial and late phases of spiral CT for detecting pancreatic adenocarcinomas., Methods: Twenty-two patients with pathologically proved pancreatic adenocarcinomas underwent two-phase spiral CT. The CT scans were performed with 5 mm collimation and 5 mm/s table speed. Images during the arterial and late phases were obtained at 30- and 180-second delays, respectively. The images of the arterial phase were compared with those of the late phase in terms of tumor conspicuity from surrounding pancreatic parenchyma and tumor detectability by means of a 3-point grading system: 1 (poor), 2 (fair), and 3 (good)., Results: In terms of tumor conspicuity from surrounding pancreatic parenchyma, 16 lesions (73%) were good, 5 lesions (23%) were fair, and 1 lesion (4%) was poor during the arterial phase, whereas 6 lesions (27%) were good, 9 lesions (41%) were fair, and 7 lesions (32%) were poor during the late phase (p = 0.0007). The arterial phase was superior to the late phase in 16 patients (73%) and equal in 6 patients (27%). For tumor detectability, 18 lesions (82%) were good, 3 lesions (14%) were fair, and 1 lesion (4%) was poor during the arterial phase, whereas 10 lesions (45%) were good, 7 lesions (32%) were fair, and 5 lesions (23%) were poor during the late phase (p = 0.0033). For detectability, the arterial phase was superior to the late phase in 14 patients (64%) and equal in 8 patients (36%)., Conclusion: The arterial phase of spiral CT is superior to the late phase, which is equivalent to conventional CT for detecting pancreatic adenocarcinoma.