Clinical impact of skeletal muscle mass change during the neoadjuvant chemotherapy period in patients with gastric cancer: An ancillary study of JCOG1002.

BACKGROUND: Recent studies have revealed that sarcopenia is associated with postoperative complications and poor prognosis. Although neoadjuvant chemotherapy is a promising treatment for gastric cancer, its toxicity may lead to the loss of skeletal muscle mass. This study investigates the changes in skeletal muscle mass during neoadjuvant chemotherapy and its clinical impact on patients with locally advanced gastric cancer. METHODS: Fifty patients who completed two courses of neoadjuvant chemotherapy followed by surgery were included. Skeletal muscle mass was measured using computed tomography images before and after chemotherapy. The proportion of skeletal muscle mass change (%SMC) during neoadjuvant chemotherapy and its cutoff value was explored using the receiver operating characteristic for the overall survival of patients undergoing R0 resection. Risk factors of skeletal muscle mass loss were also evaluated. RESULTS: Overall, 64% of patients had skeletal muscle mass loss during neoadjuvant chemotherapy (median %SMC -3.4%; range: -18.9% to 10.3%). Multivariable analysis identified older age (≥70 years) as an independent predictor of skeletal muscle mass loss (mean [95% confidence interval]: -4.70% [-8.83 to -0.58], p = 0.026). Among 43 patients undergoing R0 resection, %SMC <-6.9% was an independent poor prognostic factor for overall survival (hazard ratio, 11.53; 95% confidence interval, 2.78-47.80) and relapse-free survival (hazard ratio 4.54, 95% confidence interval 1.50-13.81). CONCLUSIONS: Skeletal muscle mass loss occurs frequently during neoadjuvant chemotherapy for locally advanced gastric cancer and could adversely affect survival outcomes.

Treatment of hepatocellular carcinoma with a portal vein tumor thrombus and pulmonary metastases of rectal cancer with microsatellite stability using atezolizumab plus bevacizumab.

Herein, we report the successful treatment using atezolizumab plus bevacizumab of a patient with hepatocellular carcinoma (HCC) with a portal vein tumor thrombus and multiple pulmonary metastases from rectal cancer with microsatellite stability. This patient developed rectal cancer with synchronous pulmonary metastases and HCC. After resecting the primary lesion of the rectal cancer, transcatheter arterial chemoembolization was performed for the HCC. Drug therapy was planned for multiple pulmonary metastases of rectal cancer; however, the early development of recurrent HCC with portal vein tumor thrombus had to be highly prioritized, and atezolizumab plus bevacizumab was introduced. Following the disappearance of the recurrent HCC lesion, the metastatic pulmonary nodules shrunk into scar-like spots. The treatment for both HCC and pulmonary metastases of rectal cancer were considered to result in clinical complete response.

Difficult removal of totally implantable venous access devices in adult patients: Incidence, risk factors, and management.

BACKGROUND: Totally implantable venous access devices (TIVADs) have played an important role of medical oncology practice. However, operators sometimes encounter considerable difficulty when removing TIVADs. This study aimed to investigate the incidence of difficult TIVAD removal, determine associated risk factors, and investigate interventional radiology (IR) approaches to difficult removal. METHODS: A total of 514 TIVAD removal procedures performed in a single-center between January 2014 and May 2021 were retrospectively analyzed to determine incidence of difficult removal and associated risk factors. IR approaches applied in difficult removal cases were also reviewed. RESULTS: The incidence of difficult removal was 7.4% (38/514). In univariable analysis, indwelling duration, silicone catheter, and subcutaneous leakage of fluid were identified as significant risk factors for difficult removal. Multivariable analysis showed that indwelling duration per year (odds ratio (OR), 1.46; 95% confidence interval (CI), 1.28-1.67; p < 0.01) and subcutaneous leakage of fluid (OR, 6.04; 95% CI, 2.45-14.91; p < 0.01) were significantly associated with difficult removal. In the 38 difficult removal cases, 32 TIVADs could be removed using more dissection and traction than the standard removal method. In the other 6, TIVADs were successfully removed by using several IR techniques, including insertion of a guide wire (n = 1), dissection using an introducer sheath (n = 2), pushing with a dilator (n = 1), and pulling with a snare (n = 2). CONCLUSION: Difficult TIVAD removal is uncommon. However, operators should expect it when removing long indwelling TIVADs and those with subcutaneous leakage. IR approaches to difficult removal are minimally invasive and can be useful.

Clinical usefulness of Somatostatin Receptor Scintigraphy in the Diagnosis of Neuroendocrine Neoplasms.

OBJECTIVES: We investigated the detectability of somatostatin receptor scintigraphy (SRS) for neuroendocrine neoplasms (NEN). METHODS: From January 2016 to October 2020, 125 SRS examinations using indium-111 pentetreotide performed for patients with NEN lesions were retrospectively evaluated. The detection rate of NEN lesions was determined according to histopathological classification by primary site and by organ. RESULTS: At least one NEN lesion was detected in 73% (91/125) with a positive Krenning score of ≥2 in SRS. The detection of abdominal NENs (gastrointestinal tract, 38; pancreas, 62; and others, 14) was 89% (49/55) for neuroendocrine tumor (NET)-grade (G) 1, 78% (32/41) for NET-G2, 66% (2/3) for NET-G3, 31% (4/13) for neuroendocrine carcinoma (NEC), 100% (1/1) for mixed neuroendocrine-non-neuroendocrine neoplasm, and 0% (0/1) for non-classified NEN. That of thoracic NENs was 33% (2/6) for typical carcinoid tumor and 40% (2/5) for atypical carcinoid tumor. For a total of 226 organ lesions, hepatic lesions were 76% (58/76); pancreatic lesions, 61% (31/51); lymph node lesions, 77% (27/35); bone lesions, 83% (20/24); duodenal lesions, 82% (9/11); and other lesions, 41% (11/27). CONCLUSION: The detectability of SRS for NEN in Japan was verified at a center, and its usefulness was confirmed.

A phase III randomized controlled trial comparing surgery plus adjuvant chemotherapy with preoperative chemoradiotherapy followed by surgery plus adjuvant chemotherapy for locally recurrent rectal cancer: Japan Clinical Oncology Group study JCOG1801 (RC-SURVIVE study).

A randomized phase III trial was initiated in Japan in August 2019 to confirm the superiority of preoperative chemoradiotherapy followed by surgery plus adjuvant chemotherapy compared to the standard treatment, i.e. surgery plus adjuvant chemotherapy, for locally recurrent rectal cancer in local relapse-free survival. In all, 110 patients from 43 Japanese institutions will be recruited over a period of 6 years. Eligible patients would be registered and randomly assigned to each group with an allocation ratio of 1:1. The primary endpoint is local relapse-free survival. The secondary endpoints are overall survival, relapse-free survival, proportion of local relapse, proportion of distant relapse, proportion of patients with pathological R0 resection, response rate of preoperative chemoradiotherapy (preoperative chemoradiotherapy arm), pathological complete response rate (preoperative chemoradiotherapy arm), proportion of patients who completed the protocol treatment, incidence of adverse events (adverse reactions) and quality of life after surgery. This trial has been registered at the Japan Registry of Clinical Trial: jRCTs031190076 [https://jrct.niph.go.jp/latest-detail/jRCTs031190076] and ClinicalTrials.gov: NCT04288999 [https://clinicaltrials.gov/ct2/show/NCT04288999].

Clinical Outcomes and Techniques for Radiofrequency Ablation of Lung Tumors Smaller than 1 cm.

Purpose: To evaluate the outcomes of radiofrequency ablation (RFA) on lung tumors < 1 cm in maximum diameter. Materials and Methods: Twenty-eight patients (12 male, 16 female; median age, 59 years; mean age, 58 ± 16 years; range, 16-78 years) who underwent RFA for lung tumors < 1 cm in diameter between November 2009 and September 2018 were included in this study. Thirty-five tumors (median size, 8.4 mm; mean size, 7.7 ± 1.9 mm; range, 3.6-9.9 mm) were treated with 33 sessions of RFA. Technique efficacy and safety were subsequently evaluated. Initial and secondary technique efficacy were defined as complete ablation without residual tumor or local tumor progression after initial and repeat RFA, respectively. Safety was evaluated according to the Common Terminology Criteria for Adverse Events, version 5.0. Results: Residual tumor remained for 1 tumor (3%, 1/35) and local tumor progression was found in 2 tumors (6%, 2/35). Initial technique efficacy rate was therefore 91% (32/35). The remaining 3 tumors were treated by repeat RFA (secondary technique efficacy rate: 100%, 35/35). Initial technique efficacy rate was significantly lower for tumors treated with starting energy ≥ 20 W (P = 0.02) and showing a quick increase in tissue impedance (P = 0.01). There were 4 grade 2 adverse events (12%, 4/33) comprising pneumothorax requiring chest tube placement, and 14 grade 1 adverse events comprising self-limiting pneumothorax (36%, 12/33) and pulmonary parenchymal hemorrhage (6%, 2/33). Conclusion: To achieve good outcomes for lung tumors < 1 cm, radiofrequency energy should be started at < 20 W. Application of manual mode ablation might be considered when delivery of power cannot be continued due to a quick increase in tissue impedance.

Adenocarcinoma and neuroendocrine tumor arising within presacral teratoma associated with Currarino syndrome: A case report.

We present a case of a 59-year-old woman with a malignant tumor arising within presacral teratoma associated with Currarino syndrome (CS). A characteristic crescent-shaped sacrum was detected on preoperative image examination and the presacral mass was pathologically diagnosed as a malignant tumor associated with CS. To our knowledge, this is the first case report of presacral teratoma associated with CS coexisting with both adenocarcinoma and a neuroendocrine tumor.

A phase II study of preoperative chemotherapy with docetaxel, cisplatin, and S-1 followed by gastrectomy with D2 plus para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis: JCOG1002.

BACKGROUND: Gastric cancer with extensive lymph node metastasis is commonly considered unresectable, with a poor prognosis. We previously reported the results of the use of cisplatin and S-1 as preoperative chemotherapy for gastric cancer with extensive lymph node metastasis; docetaxel, cisplatin, and S-1 (DCS) have now been investigated for the same purpose. METHODS: Patients received two or three 28-day cycles of DCS therapy (docetaxel at 40 mg/m2 and cisplatin at 60 mg/m2 on day 1, S-1 at 40 mg/m2 twice daily for 2 weeks) followed by gastrectomy with D2 plus para-aortic nodal dissection. After R0 resection, S-1 chemotherapy was given for 1 year. The primary end point was the response rate (RR) to preoperative chemotherapy determined by central peer review according to the Response Evaluation Criteria in Solid Tumors version 1.0. The planned sample size was 50, with one-sided alpha of 10 %, power of 80 %, expected RR of 80 %, and threshold of 65 %. RESULTS: Between July 2011 and May 2013, 53 patients were enrolled, of whom 52 were eligible. The clinical RR was 57.7 % [30/52, 80 % confidence interval 47.9-67.1 %, p = 0.89], and R0 resection was achieved in 84.6 % of patients (44/52). Common grade 3 or grade 4 adverse events during DCS therapy were leukocytopenia (18.9 %), neutropenia (39.6 %), and hyponatremia (15.1 %). The common grade 3 or grade 4 surgical morbidity was abdominal infection (10.2 %). The pathological RR was 50.0 % (26/52). CONCLUSIONS: Preoperative DCS therapy was feasible but did not show a sufficient RR. Preoperative cisplatin and S-1 therapy is still considered the tentative standard treatment for this population until survival results are known.

Evaluation of the degree of pancreatic fatty infiltration by area-based assessment of CT images: comparison with histopathology-based and CT attenuation index-based assessments.

PURPOSE: The purpose of this study was to evaluate the degree of fatty infiltration (FI) of the pancreas using area-based assessment on computed tomography (CT) (CT area-based assessment) in its correlation and agreement/concordance with histopathology-based assessment. Furthermore, we examined whether CT area-based assessment was better than CT attenuation index-based assessment. MATERIALS AND METHODS: We retrospectively evaluated the degree of FI of the pancreas in 37 pancreatic cancer patients who had undergone preoperative CT and pancreaticoduodenectomy. The degree of FI of the pancreas was examined by histopathology-based assessment using surgical resection samples, and CT area-based and CT attenuation index-based assessments. RESULTS: Mean values of pancreatic FI measured by area-based assessment on unenhanced CT and by histopathology-based assessments were 14.4 ± 23.2 % (range 0-77.7 %) and 16.2 ± 17.4 % (range 0.2-60.2 %), respectively. Area-based assessment on unenhanced CT showed higher correlation and concordance with histopathology-based assessment, demonstrating a Spearman correlation coefficient of 0.78 (P < 0.0001) and a Kendall's tau-b coefficient of 0.69 (P < 0.0001). For CT attenuation index-based assessment, the corresponding values were -0.66 (P < 0.0001) and -0.39 (P = 0.008), respectively. CONCLUSIONS: To order/categorize subjects according to the degree of FI of the pancreas, CT area-based assessment is suggested to be better than CT attenuation index-based assessment.

Evaluation of 64-Channel Contrast-Enhanced Multi-detector Row Computed Tomography for Preoperative N Staging in cT2-4 Gastric Carcinoma.

BACKGROUND: Preoperative N staging is essential for the best treatment planning in patients with gastric carcinoma. The aim of this study was to evaluate the accuracy of preoperative N staging using contrast-enhanced multi-detector row computed tomography (CE-MDCT) in patients with resectable cT2-4 gastric carcinoma. METHODS: A total of 218 patients who underwent a gastrectomy with D2 lymphadenectomy for previously untreated cT2-4 primary gastric carcinoma were studied. Preoperative N staging was performed according to the 7th (UICC) TNM Staging System using pre-specified criteria on a 64-channel CE-MDCT and was compared with postoperative pathologic N staging. RESULTS: In all 218 patients, a distal or total gastrectomy was performed. The overall accuracy of the preoperative N staging was 46.3% (101/218), with the proportion of over- and under-staging being 26.6% (58/218) and 27.1% (59/218), respectively. The sensitivity, specificity, and accuracy for lymph node metastasis (≥pN1) were 79.1% (106/134), 50.0% (42/84), and 67.9% (148/218), respectively. The sensitivity, specificity, and accuracy for multiple lymph node metastases (≥pN2) were 80.2% (73/91), 68.5% (87/127), and 73.4% (160/218), respectively. Multivariate analyses showed that macroscopic type 2 and ≥6 cm-sized tumors were associated with preoperative over-N staging, while macroscopic type 1/3 tumors were associated with under-N staging. CONCLUSION: Preoperative N staging with pinpoint accuracy is difficult. However, CE-MDCT offers a reasonably high sensitivity and specificity for ≥pN2 and may be useful for selecting candidates for neoadjuvant therapies. The macroscopic type and size of the primary tumor may affect the accuracy of preoperative N staging.

Multiple Intraglandular Metastases in a Patient with Invasive Ductal Carcinoma of the Pancreas.

A 56-year-old man was admitted to our hospital for an evaluation of pancreatic lesions. Computed tomography revealed a hypoattenuating tumor in the head of the pancreas, with three other tumors detected in the body and tail. Magnetic resonance imaging showed similar enhancement patterns and signal intensities in all four lesions. The patient underwent total pancreatectomy based on a preoperative diagnosis of multiple invasive ductal carcinomas. Histopathologically, the lesion in the pancreatic head was considered to be the primary lesion, while the others were diagnosed as metastases. This is a rare case of pancreatic cancer with intraglandular metastases. The possibility of this differential diagnosis should thus be considered when imaging shows multiple hypovascular lesions in the pancreas.

Primary staging of laryngeal and hypopharyngeal cancer: CT, MR imaging and dual-energy CT.

Laryngeal and hypopharyngeal cancer, in particular T4a disease associated with cartilage invasion and extralaryngeal spread, needs to be evaluated accurately because treatment can impact heavily on a patient's quality of life. Reliable imaging tools are therefore indispensible. CT offers high spatial and temporal resolution and remains the preferred imaging modality. Although cartilage invasion can be diagnosed with acceptable accuracy by applying defined criteria for combinations of erosion, lysis and transmural extralaryngeal spread, iodine-enhanced tumors and non-ossified cartilage are sometimes difficult to distinguish. MR offers high contrast resolution for images without motion artifacts, although inflammatory changes in cartilage sometimes resemble cartilage invasion. With dual-energy CT, combined iodine overlay images and weighted average images can be used for evaluation of cartilage invasion, since iodine enhancement is evident in tumor tissue but not in cartilage. Extralaryngeal spread can be evaluated from CT, MR or dual-energy CT images and the routes of tumor spread into the extralaryngeal soft tissue must be considered; (1) via the thyrohyoid membrane along the superior laryngeal neurovascular bundle, (2) via the inferior pharyngeal constrictor muscle, and (3) via the cricothyroid membrane. Radiologists need to understand the advantages and limitations of each imaging modality for staging of laryngeal and hypopharyngeal cancer.

Early venous return in hepatic angiomyolipoma due to an intratumoral structure resembling an arteriovenous fistula.

Early venous return (EVR) is an important radiological feature of hepatic angiomyolipoma (HAML) that can aid in differential diagnosis, but the pathogenic mechanisms of EVR have yet to be elucidated. We present the first HAML case for which a probable mechanism for EVR is described. The patient was a 46-year-old woman, who had a growing 6-cm tumor with EVR in segment 3 of the liver as revealed by dynamic contrast-enhanced computed tomography. Left hepatic lobectomy was performed to prevent tumor rupture. Histopathological and immunohistochemical analyses of the excised tumor indicated HAML. Successive microsections of the tumor were stained with hematoxylin-eosin and Victoria blue to visualize the vascular structure within and around the tumor. These analyses led to three major findings. First, many well-defined thick-walled vessels, such as arteries, were found entering the tumor. Second, many thick-walled vessels within the tumor were connected directly to thin-walled vessels, resembling arteriovenous fistulae. Finally, thin-walled intratumoral vessels were connected directly to the hepatic vein. These histological findings suggested that the rich arterial flow into the tumor was being rapidly drained into the hepatic vein through intratumoral arteriovenous connections. We also detected these same anomalous circulatory pathways in tissue sections from three of four additional HAML cases with EVR. Aberrant arteriovenous fistulae within the tumor may account for many cases of EVR in HAML patients.

Histopathological characteristics of hypervascular cholangiocellular carcinoma as an early stage of cholangiocellular carcinoma.

AIM: Prognosis of hypervascular cholangiocellular carcinoma (h-CCC) is reportedly better than that of ordinary hypovascular CCC (o-CCC). The aim of this study is to clarify the histopathological characteristics of h-CCC. METHODS: On the basis of the findings in the arterial phase of contrast-enhanced computed tomography, 16 cases of mass-forming-type CCC were divided into two groups (h-CCC, n = 8; o-CCC, n = 8). Areas of high (Area H-a) and low (Area H-b) attenuation in h-CCC cases and areas of low attenuation in o-CCC cases (Area O) were delineated. These areas were then evaluated histopathologically to determine the proportion of tumor cells, fibrous stroma, arterial vessel density, and immunohistochemical expression of Vascular endothelial growth factor; angiopoietin-2; cytokeratin 7, CK19, SOX9 and SOX17 genes; epithelial cell adhesion molecule; and the Bmi-1, Ki-67, epithelial membrane antigen and polyclonal carcinoembryonic antigen. RESULTS: The areal ratio of tumor cells decreased and that of fibrous stroma increased in the following order: Area H-a, Area H-b and Area O. Values for AVD and neural cell adhesion molecule positivity rate were significantly higher in Area H-a than in Areas H-b or O. Expressions of vascular endothelial growth factor and angiopoietin-2 were significantly higher in Areas H-a and H-b than in Area O. The Ki-67 labeling index increased in the following order: Area H-a, Area H-b and Area O. CONCLUSION: A high areal ratio of tumor cells and AVD as well as a high expression of stem cells and angiogenic markers were observed in cases of h-CCC, whereas the areal ratio of fibrous stroma and malignant potential were low. These results suggest that h-CCC may represent the early stage of CCC.

Tumor response evaluation criteria for HCC (hepatocellular carcinoma) treated using TACE (transcatheter arterial chemoembolization): RECIST (response evaluation criteria in solid tumors) version 1.1 and mRECIST (modified RECIST): JIVROSG-0602.

BACKGROUND: Two standard sets of criteria are used to evaluate the tumor response of hepatocellular carcinoma (HCC): RECIST (Response Evaluation Criteria in Solid Tumors) and modified RECIST (mRECIST). The purpose was to compare two tumor response evaluation criteria, RECIST version 1.1 and mRECIST, for HCC treated using transcatheter arterial chemoembolization (TACE). METHODS: The radiological findings of patients who underwent TACE for HCCs in a multicenter clinical trial were examined. Sixty-five lesions in 21 patients treated with TACE without mixing iodized-oil were evaluated. The tumor size was evaluated by measuring the entire lesion, including the necrotic part, using RECIST version 1.1, whereas only the contrast-enhanced part observed during the arterial phase was measured using mRECIST. Five radiologists independently measured each lesion twice. To evaluate the inter-criteria reproducibility, the complete response (CR) rate, the response rate, the kappa statistics, and the proportion of agreement (PA) for response categories were calculated. The same analyses were conducted for inter- and intra-observer reproducibility. RESULTS: In the inter-criteria reproducibility study, the CR rate and the response rate obtained using mRECIST (56.9% and 79.7%) were higher than those obtained using RECIST version 1.1 (9.2% and 43.1%). In the inter- and intra-observer reproducibility study, mRECIST exhibited an 'almost perfect agreement', while RECIST version 1.1 exhibited a 'substantial agreement'. CONCLUSIONS: Considerable differences in the CR rate and the response rate were observed. From the viewpoint of the high inter- and intra-observer reproducibility, mRECIST may be more suitable for tumor response criteria in clinical trials of TACE for HCC.

Evaluation of cartilage invasion by laryngeal and hypopharyngeal squamous cell carcinoma with dual-energy CT.

PURPOSE: To evaluate the clinical usefulness of dual-energy computed tomography (CT) with weighted-average (WA) images and iodine overlay (IO) images in the evaluation of laryngeal cartilage invasion in patients with laryngeal and hypopharyngeal squamous cell carcinoma (SCC). MATERIALS AND METHODS: The institutional review board approved this retrospective study, and written comprehensive consent was obtained from all patients. Seventy-two consecutive patients underwent 128-section dual-source dual-energy CT to stage laryngeal (n=27) or hypopharyngeal (n=45) cancer. Three observers who were blinded to the patients' clinical histories and histopathologic findings evaluated cartilage invasion on WA images alone or in combination with IO images (nonossified cartilages were selectively evaluated on IO images) by using a five-point scale. Thirty of the 72 patients (42%) underwent surgery, and findings from histopathologic examination in those patients were used as the standard of reference for the evaluation of diagnostic performance with receiver operating characteristic (ROC) curve analysis and in terms of sensitivity and specificity. Interobserver reproducibility was calculated with κ statistics. RESULTS: For thyroid cartilage, the area under the ROC curve (AUC) of the WA plus IO images was marginally larger than that for WA images alone (AUC=0.957 vs 0.870, respectively; P=.075). The specificity of WA plus IO images was significantly superior to that of WA images alone (96% vs 70%, respectively; P=.031), with no compromise to the sensitivity (86% for both). For thyroid and cricoid cartilages, the interobserver reproducibility was higher for diagnoses made with WA plus IO images (κ=0.68-0.72 and 0.64-0.79, respectively) than for those made with WA images alone (κ=0.29-0.56 and 0.20-0.64, respectively). CONCLUSION: Combined analysis of WA and IO images obtained with dual-energy CT improves the diagnostic performance and interobserver reproducibility of evaluations of laryngeal cartilage invasion by SCC.

Mucin-producing carcinoma of the gallbladder: evaluation by magnetic resonance cholangiopancreatography in three cases.

We report three cases of mucin-producing carcinoma of the gallbladder, along with the magnetic resonance (MR) findings, especially the findings on a MR cholangiopancreatography. In our cases, linear or curvilinear streaks were detected running along the long axis of an enlarged gallbladder (mucus thread sign). When such findings were seen, a mucin-producing carcinoma of the gallbladder should be included as a differential diagnosis. Thus, gadolinium-enhanced MR imaging is mandatory for the precise diagnosis of the mucin-producing carcinoma of the gallbladder.

Macrophage-capping protein as a tissue biomarker for prediction of response to gemcitabine treatment and prognosis in cholangiocarcinoma.

Cholangiocarcinoma is one of the deadliest malignancies worldwide. Recent studies reported that treatment with gemcitabine was effective in prolonging survival. However, as the treatment only benefited a limited subset of patients, selection of patients before treatment is required. To discover biomarkers predictive of the response to gemcitabine treatment in cholangiocarcinoma, we examined the proteome of three types of material resource; ten cell lines, nine xenografts and nine surgically resected primary tumors from patients who exhibited different response to gemcitabine treatment. Two-dimensional difference gel electrophoresis generated quantitative protein expression profiles including 3571 protein spots. We detected 172 protein spots with significant correlation with response to gemcitabine treatment. All proteins corresponding to these 172 protein spots were identified by mass spectrometry. We found that the macrophage-capping protein (CapG) was associated with response to gemcitabin treatment in all three types of material source. Immunohistochemical validation in an additional set of 196 cholangiocarcinoma cases revealed that CapG expression was associated with lymphatic invasion status and overall survival. Multivariate analysis showed that CapG protein expression was an independent prognostic factor for overall survival. In conclusion, CapG was identified as a novel candidate biomarker to predict response to gemcitabine treatment and survival in cholangiocarcinoma.