Publications by authors named "Ai-Wen Wu"

44 Publications

Correlation Between the Distance to Mesorectal Fascia and Prognosis of Ct3 Rectal Cancer: A Multicenter Study Results of China.

Dis Colon Rectum 2021 Aug 17. Epub 2021 Aug 17.

Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiology, Peking University Cancer Hospital & Institute, Hai Dian District, Beijing 100142, China Department of Radiology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, China Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Beijing 100021, China Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Hai Dian District, Beijing 100142, China Department of Medical Imaging, Cancer Hospital of China Medical University, No.44 Xiaoheyan Road, Dadong District, Shenyang 110042, Liaoning Province, China Department of Medical Imaging, Liaoning Cancer Hospital & Institute, No.44 Xiaoheyan Road, Dadong District, Shenyang 110042, Liaoning Province, China.

Background: cT3 substage criteria based on extramural depth of tumor invasion in rectal cancer has several limitations.

Objective: This study proposed the distance between the deepest tumor invasion and mesorectal fascia on pre-therapy magnetic resonance imaging can distinguish cT3 patients' prognosis.

Design: Cohort study.

Setting: The study included a prospective, single-center, observational cohort and a retrospective, multicenter, independent validation cohort.

Patient: cT3 rectal cancer patients with negative mesorectal fascia undergoing neoadjuvant chemoradiotherapy followed by radical surgery were included in four centers of China from January 2013 to September 2014.

Intervention: Baseline magnetic resonance imaging with the distance between the deepest tumor invasion and mesorectal fascia, extramural depth of tumor invasion and mesorectum thickness were measured.

Main Outcome Measures: The cutoff of the distance between the deepest tumor invasion and mesorectal fascia was determined by time-dependent receiver operative characteristic curves and supported by 5-year progression rate from prospective cohort, and was then validated in retrospective cohort.

Results: There were 124 and 274 patients included in the prospective and independent validation cohort, respectively. The distance between the deepest tumor invasion mesorectal fascia was the only predictor for cancer-specific death (Hazard ratio: 0.1, 95% CI, 0.0-0.7); and was also a significant predictor for distant recurrence (Hazard ratio: 0.4, 95% CI, 0.2-0.9). No statistically significant difference was observed in prognosis between patient classified as T3a/b and T3c/d.

Limitations: The sample size is relatively small and the study focused on cT3 rectal cancers with a negative mesorectal fascia.

Conclusions: A cutoff of 7 mm of the distance between the deepest tumor invasion and mesorectal fascia on baseline magnetic resonance imaging can distinguish cT3 rectal cancer from different prognosis. We recommended the distance between the deepest tumor invasion and mesorectal fascia on baseline magnetic resonance imaging for local and systemic risk assessment, providing tailored schedule of neoadjuvant treatment. See Video Abstract at http://links.lww.com/DCR/B682 .
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http://dx.doi.org/10.1097/DCR.0000000000002167DOI Listing
August 2021

Preliminary results of simultaneous integrated boost intensity-modulated radiation therapy based neoadjuvant chemoradiotherapy on locally advanced rectal cancer with clinically suspected positive lateral pelvic lymph nodes.

Ann Transl Med 2021 Feb;9(3):217

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, China.

Background: Lateral pelvic lymph node (LPLN) is approximately 11-14% and always associated with poorer prognosis. This study investigated the efficacy and safety of simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) based on neoadjuvant chemoradiotherapy (NCRT) on locally advanced rectal cancer (LARC) patients with clinically suspected positive LPLNs.

Methods: We retrospectively screened distal LARC patients with NCRT in our center from May 2016 and June 2019. The diagnostic criteria of positive LPLN were nodes of over 7 mm in short axis and irregular border or mixed-signal intensity. All patients with clinically suspected positive LPLN received 56-60 Gy SIB-IMRT in the LPLN area. Concurrent chemotherapy regimens were capecitabine as monotherapy treatment or in combination with oxaliplatin. The toxicities, local-regional recurrence (LRR), and disease-free survival (DFS) were investigated.

Results: Fifty-two eligible patients with clinically suspected positive LPLN were screened and analyzed. The median distance from the distal tumor to the anal verge was 4 cm (range, 0-8 cm), while magnetic resonance imaging (MRI) analysis revealed the median short diameter of the pelvic LPLN to be 8 mm (range, 7-20 mm). There were 28 (53.8%) mesorectal fascia (MRF) positive and 22 (42.3%) extramural venous invasion (EMVI) positive patients. A radiotherapy dose of 41.8 Gy was administered to the pelvic area, while the LPLN received a median SIB dose of 60.0 Gy (range, 56-60 Gy) across 22 fractions. Synchronous capecitabine with or without oxaliplatin was administered during radiotherapy. In summary, 15 (28.8%) patients displayed grade 2-3 radiation-related toxicity, 8 (15.4%) patients underwent additional LPLN dissection, and positive nodes (26 nodes in total) were not observed. One patient suffered a LLR in the presacral region. The median follow-up duration was 21.2 months (range, 4.7-45.0 months), while the duration of 1- and 2-year DFS were 89.9% and 74.6%, respectively. Patients did not display LPLN recurrence.

Conclusions: The safety and efficacy of SIB-IMRT on clinically suspected positive LPLN of LARC patients were deemed acceptable. Patients did not exhibit in-field LPLN recurrence after NCRT combined with single total mesorectal excision (TME).
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http://dx.doi.org/10.21037/atm-20-4040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940951PMC
February 2021

Laparoscopy-assisted transanal total mesorectal excision for lower rectal cancer: A feasible and innovative technique.

World J Gastrointest Oncol 2021 Jan;13(1):12-23

Gastrointestinal Cancer Center Unit III, Beijing Cancer Hospital and Beijing Institute for Cancer Research, Beijing 100142, China.

Background: Transanal total mesorectal excision (taTME) is a new technique with many potential technical advantages. Laparoscopy-assisted taTME is a combination of transabdominal taTME and transluminal endoscopic surgery taTME. Laparoscopy-assisted taTME is a combination of techniques such as minimally invasive surgery, intersphincter-assisted resection, natural orifice extraction, ta minimally invasive surgery, and ultralow-level preservation of the anus.

Aim: To verify the feasibility and safety of an innovative technique of taTME for treatment of cancer located in the lower rectum.

Methods: From January 2016 to March 2018, we attempted to perform laparoscopy-assisted taTME surgery in 24 patients with lower rectal cancer.

Results: The new technique of laparoscopy-assisted taTME was successfully performed in all 24 patients. Mean operating time was 310.0 min and mean intraoperative blood loss was 69.1 mL. The mean time to passing of first flatus was 3.1 d, and mean postoperative hospital stay was 9.2 d. Two patients were given postoperative analgesics due to anal pain. Twenty-three patients were able to walk in first 2 d, and five patients had postoperative complications.

Conclusion: Laparoscopy-assisted taTME is suitable for selected patients with lower rectal cancer, and this technique is worthy of further recommendation.
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http://dx.doi.org/10.4251/wjgo.v13.i1.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805274PMC
January 2021

Clinical Decision Support for High-Risk Stage II Colon Cancer: A Real-World Study of Treatment Concordance and Survival.

Dis Colon Rectum 2020 10;63(10):1383-1392

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Cancer Center, Unit III, Peking University Cancer, Beijing, China.

Background: Prognostic and pathologic risk factors typically guide clinicians and patients in their choice of surveillance or adjuvant chemotherapy when managing high-risk stage II colon cancer. However, variations in treatment and outcomes in patients with stage II colon cancer remain.

Objective: This study aimed to assess the survival benefits of treatments concordant with suggested therapeutic options from Watson for Oncology, a clinical decision support system.

Design: This is a retrospective observational study of concordance between actual treatment and Watson for Oncology therapeutic options.

Setting: This study was conducted at a top-tier cancer center in China.

Patients: Postoperative treatment data were retrieved from the electronic health records of 306 patients with high-risk stage II colon adenocarcinoma.

Main Outcome Measures: The primary outcomes measured were the treatment patterns plus 3- and 5-year overall and disease-free survival for concordant and nonconcordant cases.

Results: Overall concordance was 90%. Most nonconcordant care resulted from adjuvant chemotherapy use (rather than surveillance) in patients with high-level microsatellite instability and ≥70 years old. No difference in overall survival (p = 0.56) or disease-free survival (p = 0.19) was observed between concordance groups. Patients receiving adjuvant chemotherapy had significantly higher 5-year overall survival than those undergoing surveillance (94% vs 84%, p = 0.01).

Limitations: This study was limited by the use of retrospective cases drawn from patients presenting for surgery, the lack of complete follow-up data for 58% of patients who could not be included in the analysis, and a survival analysis that assumes no unmeasured correlation between survival and censoring.

Conclusions: Watson for Oncology produced therapeutic options highly concordant with human decisions at a top-tier cancer center in China. Treatment patterns suggest that Watson for Oncology may be able to guide clinicians to minimize overtreatment of patients with high-risk stage II colon cancer with chemotherapy. Survival analyses suggest the need for further investigation to specifically assess the association between surveillance, single-agent and multiagent chemotherapy, and survival outcomes in this population. See Video Abstract at http://links.lww.com/DCR/B291. APOYO A LA DECISIÓN CLÍNICA DEL CÁNCER DE COLON EN ESTADIO II DE ALTO RIESGO: UN ESTUDIO DEL MUNDO REAL SOBRE LA CONCORDANCIA DEL TRATAMIENTO Y LA SUPERVIVENCIA: Los factores de riesgo pronósticos y patológicos generalmente guían a los médicos y pacientes en su elección de vigilancia o quimioterapia adyuvante cuando se trata el cáncer de colon en estadio II de alto riesgo. Sin embargo, las variaciones en el tratamiento y los resultados en pacientes con cáncer de colon en estadio II permanecen.Evaluar los beneficios de supervivencia de los tratamientos concordantes con las opciones terapéuticas sugeridas por "Watson for Oncology" (Watson para la oncología), un sistema de apoyo a la decisión clínica.Estudio observacional retrospectivo de concordancia entre el tratamiento real y las opciones terapéuticas de Watson para oncología.Un centro oncológico de primer nivel en China.Datos de tratamiento postoperatorio de registros de salud electrónicos de 306 pacientes con adenocarcinoma de colon en estadio II de alto riesgo.Patrones de tratamiento más supervivencia global y libre de enfermedad a 3 y 5 años para casos concordantes y no concordantes.La concordancia general fue del 90%. La mayoría de la atención no concordante resultó del uso de quimioterapia adyuvante (en lugar de vigilancia) en pacientes de alto nivel con inestabilidad de microsatélites y pacientes ≥70 años. No se observaron diferencias en la supervivencia global (p = 0,56) o la supervivencia libre de enfermedad (p = 0,19) entre los grupos de concordancia. Los pacientes que recibieron quimioterapia adyuvante tuvieron una supervivencia global a los 5 años significativamente más alta que los que fueron sometidos a vigilancia (94% frente a 84%, p = 0,01).Uso de casos retrospectivos extraídos de pacientes que se presentan para cirugía, falta de datos de seguimiento completos para el 58% de los pacientes que no pudieron ser incluidos en el análisis, y análisis de supervivencia que asume que no exite una correlación no medida entre supervivencia y censura.Watson para Oncología produjo opciones terapéuticas altamente concordantes con las decisiones humanas en un centro oncológico de primer nivel en China. Los patrones de tratamiento sugieren que Watson para Oncología puede guiar a los médicos para minimizar el sobretratamiento de pacientes con cáncer de colon en estadio II de alto riesgo con quimioterapia. Los análisis de supervivencia sugieren la necesidad de realizar mas investigaciónes para evaluar específicamente la asociación entre la vigilancia, la quimioterapia con uno solo o múltiples agentes y los resultados de supervivencia en esta población. Consulte Video Resumen en http://links.lww.com/DCR/B291. (Traducción-Dr. Gonzalo Hagerman).
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http://dx.doi.org/10.1097/DCR.0000000000001690DOI Listing
October 2020

Organoid in colorectal cancer: progress and challenges.

Chin Med J (Engl) 2020 Aug;133(16):1971-1977

Department of Gastrointestinal Surgery III, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital & Institute, Beijing 100142, China.

Patient-derived tumor organoids (PDOs) currently represent important modeling tools in pre-clinical investigation of malignancies. Organoid cultures conserve the genetic and phenotypic characteristics of the original tumor and maintain its heterogeneity, allowing their application in many research fields. PDOs derived from colorectal cancer (CRC) have been used for genetic modeling to investigate the function of driver genes. Some researchers have been exploring the value of CRC PDOs in chemotherapy, targeted therapy, and radiotherapy response prediction. The successful generation of PDOs derived from CRC could deepen our understanding of CRC biology and provide novel tools for cancer modeling, for realizing precision medicine by assessing specimens from individual patients ex vivo. The present review discusses recently reported advances in CRC PDOs and the challenges they face as pre-clinical models in CRC research.
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http://dx.doi.org/10.1097/CM9.0000000000000882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462208PMC
August 2020

Surgical intervention for malignant bowel obstruction caused by gastrointestinal malignancies.

World J Gastrointest Oncol 2020 Mar;12(3):323-331

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital and Institute, Beijing 100142, China.

Background: Malignant bowel obstruction (MBO) is a common event for end-stage gastrointestinal cancer patients. Previous studies had demonstrated manifestations and clinical management of MBO with mixed malignancies. There still lack reports of the surgical treatment of MBO.

Aim: To analyze the short-term outcomes and prognosis of palliative surgery for MBO caused by gastrointestinal cancer.

Methods: A retrospective chart review of 61 patients received palliative surgery between January 2016 to October 2018 was performed, of which 31 patients underwent massive debulking surgery (MDS) and 30 underwent ostomy/by-pass surgery (OBS). The 60-d symptom palliation rate, 30-d morbidity and mortality, and overall survival rates were compared between the two groups.

Results: The overall symptom palliation rate was 75.4% (46/61); patients in the MDS group had significantly higher symptom palliation rate than OBS group (90% 61.2%, = 0.016). Patients with colorectal cancer who were in the MDS group showed significantly higher symptom improvement rates compared to the OBS group (overall, 76.4%; MDS, 61.5%; OBS, 92%; = 0.019). However, patients with gastric cancer did not show a significant difference in symptom palliation rate between the MDS and OBS groups (OBS, 60%; MDS, 80%; = 1.0). The median survival time in the MDS group was significantly longer than in the OBS group (10.9 mo 5.3 mo, = 0.05).

Conclusion: For patients with MBO caused by peritoneal metastatic colorectal cancer, MDS can improve symptom palliation rates and prolong survival, without increasing mortality and morbidity rates.
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http://dx.doi.org/10.4251/wjgo.v12.i3.323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081110PMC
March 2020

Fat clearance and conventional fixation identified ypN0 rectal cancers following intermediate neoadjuvant radiotherapy have similar long-term outcomes.

World J Gastrointest Oncol 2019 Oct;11(10):877-886

Department of Gastrointestinal Surgery, Peking University Cancer Hospital, Beijing 100142, China.

Background: As a prognostic factor for colorectal cancer, lymph node (LN) status, particularly the number of LN harvested, has been demonstrated to be essential in the evaluation of quality control in terms of surgical specimen. Neoadjuvant chemoradiation, however, decreases the LN harvest. Therefore, certain approaches (such as fat clearance or methylene blue) has drawn significant attention in order to raise LN yield.

Aim: To compare the long-term oncologic outcome of ypN0 rectal cancer identified using fat clearance (FC) or conventional fixation (CF) following 30 Gy in 10 fractions (30 Gy/10f) of neoadjuvant radiotherapy (nRT).

Methods: Three hundred and eighty-two patients with resectable and locally advanced rectal cancer were treated by 30 Gy/10f intermediate nRT (biologically equivalent dose of 36 Gy) plus total mesorectal excision. Two specimen fixation methods (FC or CF) were non-randomly used. The ypN0 status was identified in 124 and 101 patients in the FL and CF groups, respectively. Primary endpoints were local recurrence-free survival (LRFS) and cancer-specific survival (CSS).

Results: The median follow-up of patients was 5.1 years. The median numbers of retrieved LNs in the FC and CF groups were 19.5 (range, 4-47) and 12 (range, 0-44), respectively, with a significant difference ( = 0.000). The percentages of patients with 12 or more retrieved nodes were 82.3% and 50.5% (101/159) in the FC and CF groups, respectively, with a significant difference ( = 0.000). The LRFS at 5 years were 95.7% and 94.6% in the FC and CF groups, respectively, without statistical difference ( = 0.819). The CSS at 5 years were 92.0% and 87.2% in the FC and CF groups, respectively, without statistical difference ( = 0.482).

Conclusion: For patients with ypN0 rectal cancer who underwent 30 Gy/10f preoperative radiotherapy, the increased retrieval of LNs using fat clearance is not associated with survival benefit. This time-consuming fixation method has a low efficacy as a routine practice.
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http://dx.doi.org/10.4251/wjgo.v11.i10.877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815923PMC
October 2019

Significance of HER2 protein expression and gene amplification in colorectal adenocarcinomas.

World J Gastrointest Oncol 2019 Apr;11(4):335-347

Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing 100142, China.

Background: Human epidermal growth factor receptor 2 (HER2) is an oncogenic driver, and a well-established therapeutic target in breast and gastric cancers. While the role of HER2 as a prognostic biomarker in colorectal adenocarcinomas (CRCs) remains uncertain, its relevance as a therapeutic target has been established. We undertook the present study to evaluate the frequency of HER2 expression in CRC and to correlate it with various clinicopathological variables.

Aim: To correlate HER2 protein expression and gene amplification with clinicopathological features and survival in surgically resected CRC.

Methods: About 1195 consecutive surgically resected CRCs were analyzed by immunohistochemical staining (IHC) to assess HER2 protein expression, and 141 selected tumors were further evaluated by fluorescence hybridization (FISH) to assess gene amplification. Follow-up information was available for 1058 patients, and using this information we investigated the prevalence of HER2 protein overexpression and gene amplification in a large series of surgically resected CRCs, and evaluated the relationship between overexpression and clinicopathological parameters and prognosis.

Results: HER2 IHC scores of 3+, 2+, 1+, and 0 were seen in 31 (2.6%), 105 (8.8%), 475 (39.7%), and 584 (48.9%) tumors, respectively. gene amplification was seen in 24/29 tumors with an IHC score of 3+ (82.8%; unreadable in 2/31), 12/102 tumors with an IHC score of 2+ (11.8%; unreadable in 2/104), and 0 tumors with IHC score of 1+ (0/10). gene amplification was seen in 36/1191 tumors (3.0%; unreadable in 4/1195). Among the tumors with HER2 IHC scores of 3+ and 2+, the mean percentage of tumor cells with positive IHC staining was 90% (median 100%, range 40%-100%) and 67% (median 75%, range 5%-95%), respectively ( < 0.05). Among tumors with IHC scores of 2+, those with gene amplification had a higher number of tumors cells with positive IHC staining ( = 12, mean 93%, median 95%, range 90%-95%) than those without ( = 90, mean 70%, median 50%, range 5%-95%) ( < 0.05). gene status was significantly associated with distant tumor metastasis and stage ( = 0.028 and 0.025). HER2 protein overexpression as measured by IHC or gene amplification as measured by FISH was not associated with overall survival (OS) or disease-specific survival for the overall group of 1058 patients. However, further stratification revealed that among patients with tubular adenocarcinomas who were 65 years old or younger ( = 601), those exhibiting gene amplification had a shorter OS than those without (mean: 47.9 mo 65.1 mo, = 0.04). Among those patients with moderately to poorly differentiated tubular adenocarcinomas, those with positive HER2 tumor IHC scores (2+, 3+) had a shorter mean OS than those with negative HER2 IHC scores (0, 1+) (47.2 mo 64.8 mo, = 0.033). Moreover, among patients with T2 to T4 stage tumors, those with positive HER2 IHC scores also had a shorter mean OS than those with negative HER2 IHC scores (47.1 mo 64.8 mo, = 0.031).

Conclusion: HER2 protein levels are correlated with clinical outcomes, and positive HER2 expression as measured by IHC confers a worse prognosis in those patients 65 years old or younger with tubular adenocarcinomas.
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http://dx.doi.org/10.4251/wjgo.v11.i4.335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6475672PMC
April 2019

MRI of Extramural Venous Invasion in Locally Advanced Rectal Cancer: Relationship to Tumor Recurrence and Overall Survival.

Radiology 2018 12 28;289(3):677-685. Epub 2018 Aug 28.

From the Departments of Radiology (X.Y.Z., S.W., X.T.L., Y.P.W., Y.J.S., Y.S.S.) and Gastrointestinal Surgery (L.W., A.W.W.), Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, No. 52 Fu Cheng Road, Hai Dian District, Beijing 100142, China.

Purpose To study the relationship between MRI-defined extramural venous invasion (EMVI) prior to treatment and prognosis in patients with locally advanced rectal cancer treated with neoadjuvant chemotherapy-radiation therapy followed by surgery. Materials and Methods This retrospective study included 517 patients with locally advanced rectal cancer evaluated from August 2008 to December 2014. Baseline and posttherapy MRI and follow-up data were retrieved for all patients. After training by using 328 cases with pathologic evaluation of EMVI after therapy, radiologists evaluated baseline MRI for EMVI status in addition to tumor size and characteristics, nodal status, and invasion of the mesorectal fascia. Reader reproducibility was determined by using κ coefficient. Kaplan-Meier curves and adjusted Cox models were used to determine the relationship of baseline MRI parameters to overall survival, metastasis-free survival, and local relapse-free survival. Results Among 517 patients, 335 (64.8%) were men; the mean age was 55.6 years ± 11.5 (standard deviation). At baseline, radiologists identified 259 of 517 (50%) patients with EMVI by using MRI. In adjusted analysis, EMVI and mesorectal fascial invasion at baseline MRI were predictors of metastasis-free survival (hazard ratio, 0.3 and 0.6; P ˂ .01 and P ˂ .02, respectively) and overall survival (hazard ratio, 0.5 and 0.5; P = .01 and P = .02, respectively). EMVI was the only factor associated with local relapse-free survival (hazard ratio, 0.3; P ˂ .01). The κ coefficient for determination of EMVI was 0.80. Conclusion Extramural venous invasion (EMVI) can be reliably evaluated with MRI. The presence of EMVI was associated with greater risk of local and distant tumor recurrence and overall death in patients with locally advanced rectal cancer treated with neoadjuvant chemotherapy-radiation therapy. © RSNA, 2018 Online supplemental material is available for this article.
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http://dx.doi.org/10.1148/radiol.2018172889DOI Listing
December 2018

Pattern and Management of Recurrence of Mid-Low Rectal Cancer After Neoadjuvant Intensity-Modulated Radiotherapy: Single-Center Results of 687 Cases.

Clin Colorectal Cancer 2018 06 7;17(2):e307-e313. Epub 2018 Mar 7.

Department of Gastrointestinal Surgery, Peking University Cancer Hospital, Beijing, PR China.

Background: The purpose of this study was to retrospectively analyze the pattern and the management of recurrence of rectal cancer treated with 22-fraction intensity-modulated radiation therapy (IMRT).

Patients And Methods: This study included patients who underwent IMRT with gross tumor volume of 50.6 Gy in 22 fractions with concurrent capecitabine treatment over a period of 30 days, after which the patients underwent total mesorectal excision at Peking University Cancer Hospital (2007-2015). Study end points were local recurrence-free survival (LRFS), local disease-free survival (LDFS), disease-free survival (DFS), and cancer-specific survival (CSS).

Results: A total of 687 patients were included in our analysis. The median age was 57 years (range, 21-87 years), and 66.4% of the patients were male. The estimated 5-year LRFS and 5-year LDFS rates were 94.4% (95% confidence interval [CI], 92.1%-96.7%) and 96.1% (95% CI, 94.1%-98.1%), respectively. The estimated 3-year DFS and 5-year CSS rates were 77.5% (95% CI, 74.1%-80.9%) and 84.7% (95% CI, 80.9%-88.4%), respectively. Overall, 33.3% of patients (9 of 27) who developed local recurrence, 35.8% of patients (19 of 53) who developed lung metastasis, and 60% of patients (15 of 25) who developed liver metastasis received curative treatment after recurrence. The estimated 3-year survival after recurrence rates of patients who received curative versus palliative treatment were significantly different (87.8% vs. 15.3%, P = .000).

Conclusion: Rectal cancer treated with the 22-fraction IMRT regimen provides good local control. More than one-fourth of patients who develop recurrence have the chance to receive curative treatment with the incorporation of a multidisciplinary team and achieves excellent survival after recurrence.
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http://dx.doi.org/10.1016/j.clcc.2018.01.006DOI Listing
June 2018

The 8th edition of the American Joint Committee on Cancer tumor-node-metastasis staging system for gastric cancer is superior to the 7th edition: results from a Chinese mono-institutional study of 1663 patients.

Gastric Cancer 2018 07 22;21(4):643-652. Epub 2017 Nov 22.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing, China.

Background: We investigated the superiority of the 8th edition of the tumor-node-metastasis (TNM) system for patients in China with gastric cancer.

Methods: The survival outcomes of 1663 patients with gastric cancer undergoing radical resection were analyzed.

Results: In the 8th edition system, homogeneous 5-year survival rates among different pathological TNM (pTNM) categories belonging to the same stage were observed. However, in the 7th edition system, the differences of 5-year survival rate among pTNM categories belonging to the same stage were observed in stages IIB (P = 0.010), IIIB (P = 0.004), and IIIC (P < 0.001). For patients in the pT1-3 (P < 0.001) and pT4a (P < 0.001) categories, there were significant differences in survival between patients in the pN3a and pN3b categories. Furthermore, partial cases (pT4bN0M0/T4aN2M0) of stage IIIB were downstaged to stage IIIA in the 8th edition system, and the 5-year survival rate of these patients was significantly better than that of patients in stage IIIB in the 8th edition system. Similarly, the 5-year survival rate of patients in p4bN2M0/T4aN3aM0 downstaged from stage IIIC to IIIB was significantly better than that of patients in stage IIIC. Compared with the 7th edition system, the 8th edition system had a higher likelihood ratio and linear trend chi-squared score and a smaller Akaike information criteria value.

Conclusions: The 8th edition system is superior to the 7th edition system in terms of homogeneity, discriminatory ability, and monotonicity of gradients for Chinese patients with gastric cancer.
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http://dx.doi.org/10.1007/s10120-017-0779-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002446PMC
July 2018

Prognostic significance of the total number of harvested lymph nodes for lymph node-negative gastric cancer patients.

BMC Cancer 2017 Aug 22;17(1):558. Epub 2017 Aug 22.

Department of Gastrointestinal SurgeryKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China.

Background: The relationship between the number of harvested lymph nodes (HLNs) and prognosis of gastric cancer patients without an involvement of lymph nodes has not been well-evaluated. The objective of this study is to further explore this issue.

Methods: We collected data from 399 gastric cancer patients between November 2006 and October 2011. All of them were without metastatic lymph nodes.

Results: Survival analyses showed that statistically significant differences existed in the survival outcomes between the two groups allocated by the total number of HLNs ranging from 16 to 22. Therefore, we adopted 22 as the cut-off value of the total number of HLNs for grouping (group A: HLNs <22; group B: HLNs≥22). The intraoperative and postoperative characteristics, including operative blood loss (P=0.096), operation time (P=0.430), postoperative hospital stay (P=0.142), complications (P=0.552), rate of reoperation (P=0.966) and postoperative mortality (P=1.000), were comparable between the two groups. T-stage-stratified Kaplan-Meier analyses revealed that the 5-year survival rate of patients at the T4 stage was better in group B than in group A (76.9% vs. 58.5%; P=0.004). An analysis of multiple factors elucidated that the total number of HLNs, T stage, operation time and age were independently correlated factors of prognosis.

Conclusions: Regarding gastric cancer patients without the involvement of lymph nodes, an HLN number ≥22 would be helpful in prolonging their overall survival, especially for those at T4 stage. The total number of HLNs was an independent prognostic factor for this population of patients.
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http://dx.doi.org/10.1186/s12885-017-3544-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5567479PMC
August 2017

The optimal extent of gastrectomy for middle-third gastric cancer: distal subtotal gastrectomy is superior to total gastrectomy in short-term effect without sacrificing long-term survival.

BMC Cancer 2017 05 19;17(1):345. Epub 2017 May 19.

Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China.

Background: The optimal extent of gastrectomy for middle-third gastric cancer remains controversial. In our study, the short-term effects and longer-term survival outcomes of distal subtotal gastrectomy and total gastrectomy are analysed to determine the optimal extent of gastrectomy for middle-third gastric cancer.

Methods: We retrospectively collect and analyse clinicopathologic data and follow-up outcomes from a prospectively collected database at the Peking University Cancer Hospital. Patients with middle-third gastric adenocarcinoma who underwent curative resection are enrolled in our study.

Results: We collect data of 339 patients between January 2005 and October 2011. A total of 144 patients underwent distal subtotal gastrectomy, and 195 patients underwent total gastrectomy. Patients in the total gastrectomy group have longer operative duration (P < 0.001) and postoperative hospital stay (P = 0.001) than those in the distal subtotal gastrectomy group. In the total gastrectomy group, more lymph nodes are harvested (P < 0.001). Meanwhile, the rate of postoperative complications is lower in the distal subtotal gastrectomy group than in the total gastrectomy group (8% vs 15%, P = 0.047). Further analysis demonstrates that the rate of anastomosis leakage is lower in the distal subtotal gastrectomy group than in the total gastrectomy group (0% vs 4%, P = 0.023). Kaplan-Meier (log rank test) analysis shows a significant difference in overall survival between the two groups. The 5-year overall survival rates in the distal subtotal gastrectomy and total gastrectomy groups are 65% and 47%, respectively (P < 0.001). Further stage-stratified analysis reveals that no statistical significance exists in 5-year survival rate between the distal subtotal gastrectomy and total gastrectomy groups at the same stage. Multivariate analysis shows that age (P = 0.046), operation duration (P < 0.001), complications (P = 0.037), usage of neoadjuvant chemotherapy (P < 0.001), tumor size (P = 0.012), presence of lymphovascular invasion (P = 0.043) and N stage (P < 0.001) are independent prognostic factors for survival.

Conclusions: For patients with middle-third gastric cancer, distal subtotal gastrectomy shortens the operation duration and postoperative hospital stay and reduces postoperative complications. Meanwhile, the long-term survival of patients with distal subtotal gastrectomy is similar to that of those with total gastrectomy at the same stage. The extent of gastrectomy for middle-third gastric cancer is not an independent prognostic factor for survival.
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http://dx.doi.org/10.1186/s12885-017-3343-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437661PMC
May 2017

Organoid Culture of Isolated Cells from Patient-derived Tissues with Colorectal Cancer.

Chin Med J (Engl) 2016 10;129(20):2469-2475

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing100142, China.

Background: Colorectal cancer (CRC) is a heterogeneous disease; current research relies on cancer cell lines and animal cancer models, which may not precisely imitate inner human tumors and guide clinical medicine. The purpose of our study was to explore and further improve the process of producing three-dimensional (3D) organoid model and impel the development of personalized therapy.

Methods: We subcutaneously injected surgically resected CRC tissues from a patient into BALB/c-nu mice to build patient-derived xenografts (PDXs). Isolated cells from PDXs at appropriate tumor size were mingled with Matrigel, and then seeded in ultra-low attachment 96-well plates at four cell densities (500, 1000, 2000, and 4000 single cells/well). Cells were cultured with advanced Dulbecco's Modified Eagle Medium/F12 medium additional with various factors added to maintain tumor's biological traits and growth activity. The growth curves of the four cell densities were measured after 24 h of culture until 25 days. We evaluated the effects of four chemotherapeutic agents on organoid model by the CellTiter-Glo ® Luminescent Cell Viability Assay. Hematoxylin and eosin (H and E) staining of 3D organoids was performed and compared with patient and CRC PDX tissues. Furthermore, immunohistochemistry was performed, in which the organoids were stained with the proliferation marker, Ki-67. During the experimental process, a phase-contrast microscope was used.

Results: Phenotype experimental results showed that 3D organoids were tightly packed together and grew robustly over time. All four densities of cells formed organoids while that composed of 2000 cells/well provided an adequate cultivation system and grew approximately 8-fold at the 25 th day. The chemosensitivity of the four conventional drugs was [s]-10-hydroxycamptothecin > mitomycin C > adriamycin > paclitaxel, which can guide clinical treatment. Histological features of CRC patient's tumor tissues and mice tumor xenograft tissues were highly similar, with high-column-like epithelium and extracellular matrix. H and E-stained sections showed heterogeneous cell populations harbored in cancer organoids and were histologically similar to tumor tissues. The proliferation index was only 8.33% within spheroids, which exhibited confined proliferative cells that might be cancer stem cells.

Conclusions: We successfully constructed a CRC organoid model that grew robustly over 25 days and demonstrated that 2000 cells/well in 96-well plate was a prime seeding density for cells to form organoids. The results confirmed that organoid model can be used for agent screening and personalized medicine.
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http://dx.doi.org/10.4103/0366-6999.191782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072260PMC
October 2016

Capecitabine plus paclitaxel induction treatment in gastric cancer patients with liver metastasis: a prospective, uncontrolled, open-label Phase II clinical study.

Future Oncol 2016 Sep 3;12(18):2107-16. Epub 2016 Jun 3.

Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis & Translational Research (Ministry of Education), Peking University Cancer Hospital, Beijing Cancer Hospital & Institute, Beijing 100142, China.

Aim: To determine the overall survival rate, radical resection rate, objective response rate and safety of capecitabine plus paclitaxel induction chemotherapy in gastric cancer patients with liver metastases.

Patients & Methods: A total of 30 patients (median age: 59.5 years) diagnosed as gastric adenocarcinoma with liver metastasis received ≥3 cycles of capecitabine and paclitaxel therapy followed by radical resection 4-6 weeks after termination of chemotherapy.

Results: The median survival time was 11.4 months, and the objective response rate was 53.3%. The radical resection rate was 23.3% (95% CI: 9.9-42.3). Major toxicities included grade 3 neutropenia (10.0%) and grade 3 diarrhea (3.3%).

Conclusion: Capecitabine plus paclitaxel chemotherapy may be effective and safe to improve overall survival and the resection rate of gastric cancer patients with liver metastases. ClinicalTrials.gov identifier: NCT0116704.
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http://dx.doi.org/10.2217/fon-2016-0145DOI Listing
September 2016

Differences in gastric cancer survival between the U.S. and China.

J Surg Oncol 2015 Jul 14;112(1):31-7. Epub 2015 Jul 14.

Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York.

Background: Previous comparisons of gastric cancer between the West and the East have focused predominantly on Japan and Korea, where early gastric cancer is prevalent, and have not included the Chinese experience, which accounts for approximately half the world's gastric cancer.

Methods: Patient characteristics, surgical procedures, pathologic information, and survival were compared among gastric cancer patients who underwent curative intent gastrectomy at two large volume cancer centers in China and the US between 1995 and 2005.

Results: Median age and body mass index were significantly higher in US patients. The proportion of proximal gastric cancer was comparable. Gastric cancer patients in China had larger tumors and a later stage at presentation. The median number of positive lymph nodes was higher (5 vs 4, P < 0.02) despite a lower lymph node retrieval (16 vs 22, P < 0.001) in Chinese patients. The probability of death due to gastric cancer in Chinese patients was 1.7 fold of that in the US (P < 0.0001) after adjusting for important prognostic factors.

Conclusions: Even after adjusting for important prognostic factors Chinese gastric cancer patients have a worse outcome than US gastric cancer patients. The differences between Chinese and US gastric cancer are a potential resource for understanding the disease.
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http://dx.doi.org/10.1002/jso.23940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667726PMC
July 2015

Neoadjuvant chemoradiation therapy for resectable esophago-gastric adenocarcinoma: a meta-analysis of randomized clinical trials.

BMC Cancer 2015 Apr 28;15:322. Epub 2015 Apr 28.

Department of gastrointestinal surgery, Peking University Cancer Hospital & Institute, Haidian District Fuchengmen Road No. 52, Beijing, 100142, China.

Background: The efficacy and safety of preoperative chemoradiation therapy (CRT) for advanced esophago-gastric adenocarcinoma are still in question, and the prognosis of these patients is poor.

Methods: We systematically searched electronic databases from January 1990 to July 2014. The primary outcome was overall survival. The secondary outcomes were a R0 resection rate, positive rate of lymph node metastasis, postoperative recurrence rate, pathological complete response (pCR) rate and perioperative mortality. Overall survival was measured with a hazard ratio (HR), while other secondary outcomes were measured with an odds ratio (OR).

Results: Seven randomized controlled trials (RCTs) including 1085 patients were searched and, of these, 869 had adenocarcinoma. Patients receiving preoperative CRT had a longer overall survival (HR 0.74; 95% confidence interval (CI) 0.63-0.88), higher likelihood of R0 resection and greater chance of pCR, while they had a lower likelihood of lymph node metastasis and postoperative recurrence. The difference of perioperative mortality was non-significant. In addition, the result of the comparison between preoperative CRT and preoperative chemotherapy (CT) in two RCTs was non-significant.

Conclusion: Patients with resectable esophago-gastric adenocarcinoma can gain a survival advantage from preoperative CRT. However, limited to the number of RCTs, the effect of adding radiotherapy to preoperative CT separately is still uncertain and more high-quality prospective trials are needed.
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http://dx.doi.org/10.1186/s12885-015-1341-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4415228PMC
April 2015

Towards personalized perioperative treatment for advanced gastric cancer.

World J Gastroenterol 2014 Sep;20(33):11586-94

Ru-Lin Miao, Ai-Wen Wu, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Gastrointestinal Surgery, Peking University Cancer Hospital, Beijing Cancer Hospital and Institute, Beijing 100142, China.

Gastric cancer is one of the most frequently diagnosed cancers worldwide. Although the rate of gastric cancer has declined dramatically over the past decades in most developed Western countries, it has not declined in East Asia. Currently, a radical gastrectomy is still the only curative treatment for gastric cancer. Over the last twenty years, however, surgery alone has been replaced by a multimodal perioperative approach. To achieve the maximum benefit from the perioperative treatment, a thorough evaluation of the tumor must first be performed. A complete assessment of gastric cancer is divided into two parts: staging and histology. According to the stage and histology of the cancer, perioperative chemotherapy or radiochemotherapy can be implemented, and perioperative targeted therapies such as trastuzumab may also play a role in this field. However, perioperative treatment approaches have not been widely accepted until a series of clinical trials were performed to evaluate the value of perioperative treatment. Although multimodal perioperative treatment has been widely applied in clinical practice, personalization of perioperative treatment represents the next stage in the treatment of gastric cancer. Genomic-guided treatment and efficacy prediction using molecular biomarkers in perioperative treatment are of great importance in the evolution of treatment and may become an ideal treatment method.
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http://dx.doi.org/10.3748/wjg.v20.i33.11586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155352PMC
September 2014

Intestinal stem cell marker LGR5 expression during gastric carcinogenesis.

World J Gastroenterol 2013 Dec;19(46):8714-21

Zhi-Xue Zheng, Zhao-De Bu, Lian-Hai Zhang, Zi-Yu Li, Ai-Wen Wu, Xiao-Jiang Wu, Jia-Fu Ji, Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, China.

Aim: To investigate the differential expression of leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) in gastric cancer tissues and its significance related to tumor growth and spread.

Methods: Formalin-fixed biopsy specimens of intestinal metaplasia (n = 90), dysplasia (n = 53), gastric adenocarcinoma (n = 180), metastases in lymph nodes and the liver (n = 15), and lesion-adjacent normal gastric mucosa (controls; n = 145) were obtained for analysis from the Peking University Cancer Hospital's Department of Pathology and Gastrointestinal Surgery tissue archives (January 2003 to December 2011). The biopsied patients' demographic and clinicopathologic data were retrieved from the hospital's medical records database. Each specimen was subjected to histopathological typing to classify the tumor node metastasis (TNM) stage and to immunohistochemistry staining to detect the expression of the cancer stem cell marker LGR5. The intergroup differences in LGR5 expression were assessed by Spearman's rank correlation analysis, and the relationship between LGR5 expression level and the patients' clinicopathological characteristics was evaluated by the χ(2) test or Fisher's exact test.

Results: Significantly more gastric cancer tissues showed LGR5(+) staining than normal control tissues (all P < 0.01), with immunoreactivity detected in 72.2% (65/90) and 50.9% (27/53) of intestinal metaplasia and dysplasia specimens, respectively, 52.8% (95/180) of gastric adenocarcinoma specimens, and 73.3%% (11/15) of metastasis specimens, but 26.9% (39/145) of lesion-adjacent normal gastric mucosa specimens. Comparison of the intensity of LGR5(+) staining showed an increasing trend that generally followed increasing dedifferentiation and tumor spread (normal tissue < dysplasia, < gastric adenocarcinoma
Conclusion: Enhanced LGR5 is related to progressive dedifferentiation and metastasis of gastric cancer, indicating the potential of this receptor as an early diagnostic and prognostic biomarker.
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http://dx.doi.org/10.3748/wjg.v19.i46.8714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870519PMC
December 2013

[Regulation mechanism study of S100A6 on invasion and metastasis in gastric cancer].

Zhonghua Wei Chang Wai Ke Za Zhi 2013 Nov;16(11):1096-101

Department of Gastrointestinal Cancer Surgery, Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, China.

Objective: To detect the expression of S100A6 in gastric cancer, and to investigate the regulation mechanism of S100A6 in invasion and metastasis of gastric cancer.

Methods: Expression of S100A6 protein in gastric cancer specimens, tissue adjacent to cancer, liver and lymph node metastasis tissue specimens was detected by immunohistochemical staining in 166 patients with gastric cancer from January 1995 to December 2001. Their association with clinicopathological factors was analyzed. Chromatin Immunoprecipitation-chip was used to detect the downstream factors potentially regulated by S100A6 in gastric cancer cell lines KATO3. S100A6 gene was transfected into gastric cancer cell line AGS, and cell invasion experiment and real time Q-polymerase chain reaction(RT Q-PCR) were used to detect the cell invasive ability and the mRNA expression of invasion-related factors (CDK5 and FLJ12438) in transfection group, negative control group and blank control group, respectively.

Results: Low expression of S100A6 protein was found in cytoplasm of peritumoral tissues. In gastric cancer, liver and lymph node metastasis tissues, S100A6 protein expression was up-regulated in cytoplasm and (or) nuclei, especially in the tumor cells of invasive edge. The expression rates of gastric cancer, liver and lymph node metastasis tissues were 67.5%(112/166), 92.9%(26/28) and 100% (30/30) respectively. The high expression of S100A6 was associated with tumor local invasion, lymph node metastasis, cancer embolus, distant metastasis and TNM stages(all P<0.05). The transmembrane cell number was 31.3±5.5 in the S100A6 transfection group, significantly higher than that in negative control group (7.7±1.5) and blank control group (9.3±2.1)(both P<0.05), indicating an increase of cell invasion after S100A6 transfection. In transfection group, CDK5 mRNA expression was significantly higher than that in negative control group and blank control group(P<0.05). While FLJ1243 mRNA expression was similar among the three groups(P<0.05).

Conclusion: S100A6 may affect the malignant biological behavior of gastric cancer cells by regulating the expressions of down-stream invasion-associated factors, such as CDK5.
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November 2013

[Analysis of risk factors for pulmonary metastasis after curative resection of colorectal cancer].

Zhonghua Wei Chang Wai Ke Za Zhi 2013 May;16(5):463-6

Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education), Department of Minimally Invasive Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100142, China.

Objective: To explore the risk factors for pulmonary metastasis after curative resection of colorectal cancer in order to improve the effectiveness of follow-up and the rate of early diagnosis for the high-risk patients.

Methods: The clinicopathological and follow-up data of 268 patients with colorectal cancer undergoing radical resection from January 2004 to December 2006 in the Beijing Cancer Hospital were analyzed retrospectively. Patients were divided into study group including 16(6.0%) patients who developed lung metastasis and control group without lung metastasis. The high-risk variables associated with lung metastasis were reviewed by univariate analysis and multivariate analysis.

Results: Lung metastasis developed in 16 patients, including 10 cases with unilateral lung metastasis and 6 with bilateral. The median duration from colorectal surgery to identification of lung metastasis was 13.9 months. The diagnosis rate of pulmonary metastasis by enhanced chest CT was 81.3%(13/16). Univariate analysis identified the following associated with significant factors associated with pulmonary metastasis: primary tumor location(P=0.003), adjuvant chemotherapy(P=0.034), TNM stage(P=0.005) and preoperative serum carcinoembryonic antigen(CEA) level (P=0.001). Multivariate analysis revealed that primary tumor location(rectum) and preoperative serum CEA level(≥5 μg/L) were independent risk factors for pulmonary metastasis(both P<0.05).

Conclusions: Primary tumor location and elevated preoperative CEA level are independent risk factors for pulmonary metastasis. Strict postoperative follow-up and routine chest enhanced CT examination is necessary for this particular patient population.
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May 2013

[Application of perioperative imatinib mesylate therapy in initial resectable primary local advanced gastrointestinal stromal tumor at intermediate or high risk].

Zhonghua Wei Chang Wai Ke Za Zhi 2013 Mar;16(3):226-9

Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education), Beijing Cancer Hospital and Institute, Peking University School of Oncology, Beijing 100142, China.

Objective: To evaluate the effect of perioperative imatinib mesylate (IM) therapy for patients with initial resectable primary local advanced gastrointestinal stromal tumor (GIST) at intermediate or high risk on R0 resection rate and the prognosis.

Methods: Forty-eight above GIST patients between December 2001 and February 2012 were divided into 2 groups: neoadjuvant group (15 cases, pre- and post-operation IM therapy) and adjuvant group (33 cases, post-operative IM therapy). R0 resection rate, complication rate, disease-free survival (DFS) and overall survival (OS) were analyzed and compared between the two groups.

Results: The maximal tumor diameter and average tumor diameter were larger in neoadjuvant group as compared to adjuvant group (11.2 cm vs. 7.7 cm, P=0.005; 9.1 cm vs. 6.2 cm, P=0.014). The response rate of preoperative IM therapy was 93.3% (14/15). The R0 resection rate was 86.7% and 84.8% (P=1.000), and the complication rate was 13.3% and 9.1% (P=0.642) in neoadjuvant and adjuvant group respectively. The 3-year DFS was 55% and 41% (P=0.935), and 5-year OS was 83% and 75% (P=0.766) in neoadjuvant and adjuvant group respectively.

Conclusions: Resectable primary local advanced GIST at intermediate or high risk with larger tumor diameter receiving perioperative IM therapy can achieve the same R0 resection rate, complication rate, DFS and OS as the GIST with smaller diameter receiving operation first. Perioperative IM therapy has potential advantage.
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March 2013

[Diagnosis and minimally invasive treatment of gastric remnant cancer].

Authors:
Ai-wen Wu Jia-fu Ji

Zhonghua Wei Chang Wai Ke Za Zhi 2013 Feb;16(2):132-4

Department of Gastrointestinal Cancer Surgery, Beijing Cancer Hospital and Institute, Peking University Cancer Hospital, Peking University School of Oncology, China.

Gastric remnant cancer (GRC) is defined as cancer in the remnant stomach after partial gastrectomy. The incidence of GRC is rising in recent years. The carcinogenesis, development, and metastasis of GRC are different from primary gastric cancer. The early detection of GRC should be based on rational surveillance of patients following gastrectomy. For early stage GRC, endoscopic resection is one of the safe and effective methods. For advanced GRC, the primary treatment alternative is surgical resection. Minimally invasive procedures such as laparoscopic exploration, laparoscopic-assisted resection of GRC are still safe choices for experienced surgeons.
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February 2013

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves the survival of gastric cancer patients with ovarian metastasis and peritoneal dissemination.

Tumour Biol 2013 Feb 30;34(1):463-9. Epub 2012 Oct 30.

Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital, Beijing Cancer Hospital & Institute, 52 Fu-Cheng Road, Hai-Dian District, 100142, Beijing, China.

The prognosis for ovarian metastasis of gastric cancer is poor. There is no currently available treatment for this disease. The purpose of this study was to evaluate the efficacy and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) in female gastric cancer patients with metachronous ovarian metastasis. From January 2000 to December 2010, 62 patients developed ovarian metastasis after undergoing gastrectomy with D2 lymphadenectomy. Thirty-two patients underwent CRS plus HIPEC, and 30 patients underwent CRS alone. The median age of all 62 patients was 44 years (range 19-71 years). Metastatic carcinoma involving bilateral ovaries was observed in 50 patients (80.6 %). The median survival time in the CRS + HIPEC group was 15.5 months (95 % confidence interval [CI] 12.1-18.9 months) but was only 10.4 months (95 % CI 8.5-12.2 months) in the CRS group (P = 0.018). Among the 32 patients with pelvic peritoneal metastasis, a stratified analysis revealed that the median survival period for the 15 patients treated with CRS + HIPEC was significantly higher than that for the patients treated with CRS alone (P = 0.046). Among the 30 patients who suffered from ovarian metastasis alone, the median survival times were similar in both groups (P = 0.141). A multivariate analysis revealed that CRS + HIPEC and a low Peritoneal Cancer Index (PCI) were independent predictors for improved survival. In conclusion, our study indicates that employing the HIPEC procedure after CRS could improve the survival time of patients with ovarian metastasis with few complications; however, we do not recommend HIPEC treatment for ovarian metastasis alone.
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http://dx.doi.org/10.1007/s13277-012-0571-4DOI Listing
February 2013

Myofibrillogenesis regulator-1 overexpression is associated with poor prognosis of gastric cancer patients.

World J Gastroenterol 2012 Oct;18(38):5434-41

Key Laboratory of Carcinogenesis and Translational Research-Ministry of Education, Department of Gastrointestinal Surgery, Peking University Cancer Hospital, Beijing Cancer Hospital and Institute, Beijing 100142, China.

Aim: To investigate the expression of myofibrillogenesis regulator-1 (MR-1) in relation to clinicopathological parameters and postoperative survival in a group of Chinese patients with gastric cancer.

Methods: In our previous study of human whole-genome gene expression profiling, the differentially expressed genes were detected in the gastric cancer and its adjacent noncancerous mucosa. We found that MR-1 was associated with the location and differentiation of tumors. In this study, MR-1 protein expression was determined by immunohistochemistry in specimens of primary cancer and the adjacent noncancerous tissues from gastric cancer patients. A set of real-time quantitative polymerase chain reaction assays based on the Universal ProbeLibrary-a collection of 165 presynthesized, fluorescence-labeled locked nucleic acid hydrolysis probes-was designed specifically to detect the expression of MR-1 mRNA. The correlation was analyzed between the expression of MR-1 and other tumor characteristics which may influence the prognosis of gastric cancer patients. A retrospective cohort study on the prognosis was carried out and clinical data were collected from medical records.

Results: MR-1 mRNA and protein could be detected in gastric cancer tissues as well as in matched noncancerous tissues. MR-1 was up-regulated at both mRNA (5.459 ± 0.639 vs 1.233 ± 0.238, P < 0.001) and protein levels (34.2% vs 13.2%, P = 0.003) in gastric cancer tissues. Correlation analysis demonstrated that high expression of MR-1 in gastric cancer was significantly correlated with clinical stage (P = 0.034). Kaplan-Meier analysis showed that the postoperative survival of the MR-1 positive group tended to be poorer than that of the MR-1 negative group, and the difference was statistically significant (P = 0.002). Among all the patients with stage I-IV carcinoma, the 5-year survival rates of MR-1 positive and negative groups were 50.40% and 12.70%, respectively, with respective median survival times of 64.27 mo (95%CI: 13.41-115.13) and 16.77 mo (95%CI: 8.80-24.74). Univariate and multivariate analyses were performed to compare the impact of MR-1 expression and other clinicopathological parameters on prognosis. In a univariate analysis on all 70 specimens, 6 factors were found to be significantly associated with the overall survival statistically: including MR-1 expression, depth of invasion, distant metastasis, lymph node metastasis, vascular invasion and the tumor node metastasis (TNM) stage based on the 7th edition of the International Union against Cancer TNM classification. To avoid the influence caused by univariate analysis, the expressions of MR-1 as well as other parameters were examined in multivariate Cox analysis. Clinicopathological variables that might affect the prognosis of gastric cancer patients were analyzed by Cox regression analysis, which showed that MR-1 expression and TNM stage were independent predictors of postoperative survival. The best mathematical multivariate Cox regression model consisted of two factors: MR-1 expression and TNM stage. Our results indicated that MR-1 protein could act as an independent marker for patient overall survival [Hazard ratio (HR): 2.215, P = 0.043].

Conclusion: MR-1 is an important variable that can be used to evaluate the outcome, prognosis and targeted therapy of gastric cancer patients.
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http://dx.doi.org/10.3748/wjg.v18.i38.5434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471113PMC
October 2012

Neoadjuvant chemotherapy for locally advanced gastric cancer: With or without radiation.

Authors:
Ai-Wen Wu Jia-Fu Ji

World J Gastrointest Surg 2012 Feb;4(2):27-31

Ai-Wen Wu, Jia-Fu Ji, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital, Beijing Cancer Hospital and Institute, Beijing 100142, China.

The role of perioperative chemotherapy for gastric cancer has been established for gastric cancers in their advanced stage. In most parts of the world, even in Japan and Korea, local recurrence of gastric cancer following curative resection remains a problem. Should radiation be added to chemotherapy to achieve better local and regional control? What is the current evidence? What are the concerns regarding neoadjuvant chemoradiation in terms of safety, efficacy and survival benefit? After a serious review of the literature, the authors conclude that it is still too early to get a definitive answer but radiation seems promising. It may bring a higher pathological response rate. Rationally, more high level clinical trials are needed to confirm the role of radiotherapy in the neoadjuvant setting or to ascertain subsets of patients who may benefit from it. It is of note that surgeons should pay attention to possible complicated circumstances following radiotherapy, maintain proper nutrition status and minimize the occurrence of postoperative complications. As few data are available in Japan and Korea, interpretation and implementation of neoadjuvant radiation or chemoradiation should be done with caution.
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http://dx.doi.org/10.4240/wjgs.v4.i2.27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3297664PMC
February 2012

Neoadjuvant chemotherapy with FOLFOX: improved outcomes in Chinese patients with locally advanced gastric cancer.

J Surg Oncol 2012 Jun 20;105(8):793-9. Epub 2011 Dec 20.

Department of Gastrointestinal Surgery, Beijing Cancer Hospital and Institute, Peking University School of Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, China.

Background: Although the role of peri-operative chemotherapy is established in the treatment of locally advanced gastric cancer, the optimal regime remains to be determined. FOLFOX has been used in palliative setting with good response rates but its role in a neoadjuvant setting is not well established.

Methods: This is a prospective non-randomized study comparing peri-operative FOLFOX versus adjuvant FOLFOX in patients with resectable locally advanced gastric cancer. Response to chemotherapy was assessed according to WHO criteria and pathological changes. Kaplan-Meier log rank test was used to calculate and compare survival differences.

Results: There were 73 patients (neoadjuvant = 36). Complete and partial response was observed in 2 (6%) and 21 (64%) patients, respectively. Four-year overall survival (OS) in the neoadjuvant arm was 78% versus 51% in the adjuvant arm (P = 0.031). Subgroup analysis found R0 resection (86% vs. 55%, P = 0.011) and patients with proximal cancers (87% vs. 14%, P < 0.001) to have improved OS. The most common side effect was grade 1-2 leukopenia. There were no grade 3 neuropathies, grade 4 cytopaenias, or treatment related deaths.

Conclusion: Peri-operative treatment with FOLFOX shows promise in patients with resectable locally advanced gastric cancer. It warrants further evaluation and should be considered an alternative to peri-operative ECF.
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http://dx.doi.org/10.1002/jso.23009DOI Listing
June 2012

Complications after radical gastrectomy following FOLFOX7 neoadjuvant chemotherapy for gastric cancer.

World J Surg Oncol 2011 Sep 26;9:110. Epub 2011 Sep 26.

Department of Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing 100142, China.

Background: This study assessed the postoperative morbidity and mortality occurring in the first 30 days after radical gastrectomy by comparing gastric cancer patients who did or did not receive the FOLFOX7 regimen of neoadjuvant chemotherapy.

Methods: We completed a retrospective analysis of 377 patients after their radical gastrectomies were performed in our department between 2005 and 2009. Two groups of patients were studied: the SURG group received surgical treatment immediately after diagnosis; the NACT underwent surgery after 2-6 cycles of neoadjuvant chemotherapy.

Results: There were 267 patients in the SURG group and 110 patients in the NACT group. The NACT group had more proximal tumours (P = 0.000), more total/proximal gastrectomies (P = 0.000) and longer operative time (P = 0.005) than the SURG group. Morbidity was 10.0% in the NACT patients and 17.2% in the SURG patients (P = 0.075). There were two cases of postoperative death, both in the SURG group (P = 1.000). No changes in complications or mortality rate were observed between the SURG and NACT groups.

Conclusion: The FOLFOX7 neoadjuvant chemotherapy is not associated with increased postoperative morbidity, indicating that the FOLFOX7 neoadjuvant chemotherapy is a safe choice for the treatment of local advanced gastric cancer.
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http://dx.doi.org/10.1186/1477-7819-9-110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3204253PMC
September 2011

Preoperative concomitant boost intensity-modulated radiotherapy with oral capecitabine in locally advanced mid-low rectal cancer: a phase II trial.

Radiother Oncol 2012 Jan 6;102(1):4-9. Epub 2011 Sep 6.

Department of Radiation Oncology, Beijing Cancer Hospital and Institute, People's Republic of China.

Purpose: We aimed to assess the safety and efficacy of preoperative intensity-modulated radiotherapy (IMRT) with oral capecitabine in patients with locally advanced mid-low rectal cancer using a concomitant boost technique.

Materials And Methods: Patients with resectable locally advanced mid-low rectal cancer (node-negative ≥T3 or any node-positive tumor) were eligible. The eligible patients received IMRT to 2 dose levels simultaneously (50.6 and 41.8 Gy in 22 fractions) with concurrent capecitabine 825 mg/m(2) twice daily 5 days/week. The primary end point included toxicity, postoperative complication, and pathological complete response rate (ypCR). The secondary endpoints included local recurrence rate, progression-free survival (PFS), and overall survival (OS).

Results: Sixty-three eligible patients were enrolled; five patients did not undergo surgery. Of the 58 patients evaluable for pathologic response, the ypCR rate was 31.0% (95% CI 19.1-42.9). Grade 3 toxicities included diarrhea (9.5%), radiation dermatitis (3.2%), and neutropenia (1.6%). There was no Grade 4 toxicity reported. Four (6.9%) patients developed postoperative complications. Two-year local recurrence rate, PFS, and OS were 5.7%, 90.5%, and 96.0%, respectively.

Conclusions: The design of preoperative concurrent boost IMRT with oral capecitabine could achieve high rate of ypCR with an acceptable toxicity profile.
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http://dx.doi.org/10.1016/j.radonc.2011.07.030DOI Listing
January 2012
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