1.Clinicopathological analysis of gastric adenocarcinoma with elevated serum alpha-fetoprotein and enteroblastic differentiation
Likun ZAN ; Lulu SHEN ; Xin ZHANG ; Ning GAO ; Baoguo TIAN ; Xiaoxin GENG ; Xiao PENG ; Jiawen LI ; Peng BU ; Guohai ZHAO
Chinese Journal of Oncology 2024;46(7):686-695
Objective:To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED).Methods:The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis.Results:Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177- GNAS, AIM1- FGFR3, and EPHA6- ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis ( P<0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone ( P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone ( P<0.05). Conclusions:Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.
2.Clinicopathological analysis of gastric adenocarcinoma with elevated serum alpha-fetoprotein and enteroblastic differentiation
Likun ZAN ; Lulu SHEN ; Xin ZHANG ; Ning GAO ; Baoguo TIAN ; Xiaoxin GENG ; Xiao PENG ; Jiawen LI ; Peng BU ; Guohai ZHAO
Chinese Journal of Oncology 2024;46(7):686-695
Objective:To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED).Methods:The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis.Results:Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177- GNAS, AIM1- FGFR3, and EPHA6- ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis ( P<0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone ( P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone ( P<0.05). Conclusions:Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.
3.Comparison of the renal function after partial nephrectomy and radical nephrectomy for T1a renal cell carcinoma.
Chengyuan GU ; Hailiang ZHANG ; Bo DAI ; Yao ZHU ; Guohai SHI ; Yijun SHEN ; Yuanyuan QU ; Fangning WAN ; Guiming ZHANG ; Dingwei YE ; Email: DWYE@SHCA.ORG.CN.
Chinese Journal of Oncology 2015;37(6):441-444
OBJECTIVETo evaluate the alterations in renal function after radical nephrectomy (RN) and partial nephrectomy (PN) for renal cell carcinoma (RCC) and to determine the risk factors for the onset of postoperative renal function impairment.
METHODSWe assessed the renal function of 429 T1a RCC patients by investigating the time-dependent changes of the estimated glomerular filtration rate (eGFR) after surgery from August 2003 to August 2010. Univariate and multivariate regression models were used to determine the risk factors for the onset of an eGFR < 60 ml · min⁻¹ · 1.73 m⁻² function, and to evaluate the prognosis for the two groups.
RESULTSThe mean eGFR values (ml · min⁻¹ · 1.73 m⁻²) at postoperative 1, 7 days, 1, 3, 6, 12 and 24 months were 51.4 ± 12.6, 52.1 ± 17.8, 53.2 ± 19.5, 54.6 ± 20.2, 53.8 ± 16.6, 52.7 ± 22.3 and 51.5 ± 18.4 in the RN group and 69.6 ± 18.3, 70.3 ± 19.5, 71.5 ± 21.4, 76.2 ± 22.8, 75.4 ± 19.7, 74.3 ± 16.3 and 73.1 ± 23.2 in the PN group, respectively. The eGFR of the radical nephrectomy group was significantly lower than that of the partial nephrectomy group (P < 0.05). Multivariable analysis revealed that radical nephrectomy and age were risk factors for the onset of postoperative chronic renal dysfunction.
CONCLUSIONSRenal function recovered partially after partial and radical nephrectomy and is maintained constantly after 3 months. Surgical mode and age are risk factors for the onset of postoperative eGFR < 60 ml · min⁻¹ · 1.73 m⁻² impairment. Compared with radical nephrectomy, partial nephrectomy can preserve renal function and reduce the incidence of postoperative chronic renal dysfunction.
Age Factors ; Carcinoma, Renal Cell ; pathology ; physiopathology ; surgery ; Glomerular Filtration Rate ; Humans ; Kidney Neoplasms ; pathology ; physiopathology ; surgery ; Nephrectomy ; adverse effects ; methods ; Postoperative Complications ; physiopathology ; Postoperative Period ; Renal Insufficiency, Chronic ; etiology ; physiopathology ; Risk Factors
4.Laparoscopic retroperitoneal adrenalectomy for adrenal mass:report of 130 cases
Fangning WAN ; Hailiang ZHANG ; Dingwei YE ; Guiming ZHANG ; Chengyuan GU ; Bo DAI ; Shilin ZHANG ; Yijun SHEN ; Yao ZHU ; Guohai SHI ; Yiping ZHU
China Oncology 2015;(10):828-831
Background and purpose:Laparoscopic retroperitoneal adrenalectomy makes access to the adrenal glands easier and less invasive than open surgery. The aim of this study was to evaluate the clinical efifcacy of laparoscopic retroperitoneal adrenalectomy.Methods:A total of 130 patients who underwent retroperitoneal adrenalectomy for adrenal mass from Jan. 2007 to Dec. 2012 in Fudan University Shanghai Cancer Center were retrospectively assessed. Their clinicopathological factors, perioperative complications and short-term prognostic data were retrieved from the medical records.Results:One hundred and twenty-seven of 130 patients underwent retroperitoneal adrenalectomy successfully, and 3 patients were converted to open surgery due to severe bleeding. Among 130 patients, 63 were male and 67 were female, with the mean age 50.0 years. The pathological results of the 130 patients indicated adrenocortical adenoma in 68, pheochromocytoma in 15, medullary lipoma in 13, adrenal cysts in 10 , ganglioneuroma in 7, metastatic cancer in 5, adrenal hyperplasia in 4, schwannoma in 3, lymphangioma in 2, adrenal hematoma in 1, adrenal cortical carcinoma in 1, adrenal angiosarcoma in 1 and the deputy spleen in 1 (one patient suffering from both pheochromocytoma and ganglioneuroma). The maximum diameters were ranging from 0.5 to 9.0 cm, and mean diameter was 3.48 cm. The average blood loss in surgery was 62.73 mL. Mean length of stay in hospital was 7 d. GradeⅠ complications occurred in 5 patients, including 2 of fever, 1 of food allergy, 1 of drug allergy and 1 of hypokalemia.Conclusion: Retroperitoneal adrenalectomy should be considered as the procedure of choice for the resection of most adrenal tumors in skilled centers with the advantages of minimal invasion, increased safety and faster recovery.
5.Comparison of the renal function after partial nephrectomy and radical nephrectomy for T1a renal cell carcinoma
Chengyuan GU ; Hailiang ZHANG ; Bo DAI ; Yao ZHU ; Guohai SHI ; Yijun SHEN ; Yuanyuan QU ; Fangning WAN ; Guiming ZHANG ; Dingwei YE
Chinese Journal of Oncology 2015;(6):441-444
Objective To evaluate the alterations in renal function after radical nephrectomy ( RN) and partial nephrectomy ( PN) for renal cell carcinoma ( RCC) and to determine the risk factors for the onset of postoperative renal function impairment. Methods We assessed the renal function of 429 T1a RCC patients by investigating the time?dependent changes of the estimated glomerular filtration rate ( eGFR) after surgery from August 2003 to August 2010. Univariate and multivariate regression models were used to determine the risk factors for the onset of an eGFR<60 ml·min-1 ·1.73 m-2 function, and to evaluate the prognosis for the two groups. Results The mean eGFR values ( ml·min-1 ·1.73 m-2 ) at postoperative 1, 7 days, 1, 3, 6, 12 and 24 months were 51. 4 ± 12. 6, 52. 1 ± 17. 8, 53. 2 ± 19. 5, 54. 6 ± 20. 2, 53. 8 ± 16. 6, 52.7±22.3 and 51.5±18.4 in the RN group and 69.6±18.3, 70.3±19.5, 71.5±21.4, 76.2±22.8, 75.4± 19.7, 74.3±16.3 and 73.1±23.2 in the PN group, respectively. The eGFR of the radical nephrectomy group was significantly lower than that of the partial nephrectomy group ( P<0.05) . Multivariable analysis revealed that radical nephrectomy and age were risk factors for the onset of postoperative chronic renal dysfunction. Conclusions Renal function recovered partially after partial and radical nephrectomy and is maintained constantly after 3 months. Surgical mode and age are risk factors for the onset of postoperative eGFR<60 ml· min-1 ·1.73 m-2 impairment. Compared with radical nephrectomy, partial nephrectomy can preserve renal function and reduce the incidence of postoperative chronic renal dysfunction.
6.Comparison of the renal function after partial nephrectomy and radical nephrectomy for T1a renal cell carcinoma
Chengyuan GU ; Hailiang ZHANG ; Bo DAI ; Yao ZHU ; Guohai SHI ; Yijun SHEN ; Yuanyuan QU ; Fangning WAN ; Guiming ZHANG ; Dingwei YE
Chinese Journal of Oncology 2015;(6):441-444
Objective To evaluate the alterations in renal function after radical nephrectomy ( RN) and partial nephrectomy ( PN) for renal cell carcinoma ( RCC) and to determine the risk factors for the onset of postoperative renal function impairment. Methods We assessed the renal function of 429 T1a RCC patients by investigating the time?dependent changes of the estimated glomerular filtration rate ( eGFR) after surgery from August 2003 to August 2010. Univariate and multivariate regression models were used to determine the risk factors for the onset of an eGFR<60 ml·min-1 ·1.73 m-2 function, and to evaluate the prognosis for the two groups. Results The mean eGFR values ( ml·min-1 ·1.73 m-2 ) at postoperative 1, 7 days, 1, 3, 6, 12 and 24 months were 51. 4 ± 12. 6, 52. 1 ± 17. 8, 53. 2 ± 19. 5, 54. 6 ± 20. 2, 53. 8 ± 16. 6, 52.7±22.3 and 51.5±18.4 in the RN group and 69.6±18.3, 70.3±19.5, 71.5±21.4, 76.2±22.8, 75.4± 19.7, 74.3±16.3 and 73.1±23.2 in the PN group, respectively. The eGFR of the radical nephrectomy group was significantly lower than that of the partial nephrectomy group ( P<0.05) . Multivariable analysis revealed that radical nephrectomy and age were risk factors for the onset of postoperative chronic renal dysfunction. Conclusions Renal function recovered partially after partial and radical nephrectomy and is maintained constantly after 3 months. Surgical mode and age are risk factors for the onset of postoperative eGFR<60 ml· min-1 ·1.73 m-2 impairment. Compared with radical nephrectomy, partial nephrectomy can preserve renal function and reduce the incidence of postoperative chronic renal dysfunction.
7.The value of preoperative platelet to lymphocyte ratio in predicting of clinical stage and prognosis in upper tract urothelial carcinoma
Jian LI ; Dingwei YE ; Xudong YAO ; Shilin ZHANG ; Bo DAI ; Hailiang ZHANG ; Yijun SHEN ; Yao ZHU ; Guohai SHI ; Yiping ZHU ; Chunguang MA ; Xiaojian QIN ; Guowen LIN ; Wenjun XIAO
China Oncology 2013;(6):457-461
Background and purpose: Platelet to lymphocyte ratio (PLR) is an important factor reflected systematic inflammation. The clinical value of PLR has not been confirmed. The present study was to explore the value of preoperative PLR in predicting clinical stage and prognosis in upper tract urothelial carcinoma. Methods:Patients who underwent surgical therapy with postoperative pathology upper tract urothelial carcinoma without metastasis from Jan. 2007 to Mar. 2012, were collected. Following up was done by telephone and clinic work, 150 vs 1 was taken as the threshold value of PLR, and the association of PLR with tumor stage, whether suffered bladder cancer as comorbidity, recurrent or metastasis, overall survival, tumor lesion, preoperative hematuria, gender and age was analyzed. We further analyzed the association difference of disease free survival (DFS) time and overall survival (OS) time between different PLR groups. Results:Fifty-one cases of UTUC were collected, and the postoperative mean following up time is 21 (9–51) months. Twenty cases recurred or metastasis and 9 cases died. The mean DFS time was 15 (2–51) months,and the mean OS time was 21 (9–51) months. One-factor analysis of variance showed that preoperative PLR was associated with tumor stage, overall survival rate, hematuria and gender, and the P value were 0.028, 0.008, 0.045, 0.036 respectively. High PLR group was intended to be non-organ confined disease, the sensitivity was 57%and the specificity was 74%. Survival analysis by Kaplan-Meier method showed there is no statistical difference in DFS between high and low PLR groups (P=0.155). But OS time in high PLR group was significantly less than that in low PLR group (P=0.006). Cox regression confirmed that only tumor stage is an independent prognostic factor of OS (P=0.029). Conclusion:PLR has potential clinical value in predicting advanced stage disease and Cox regression confirmed that only tumor stage is an independent prognostic factor of OS.
8.Design and clinical application of “exclamation mark” shaped pedicle flaps
Linge LEI ; Meng LI ; Ruxiang HE ; Meihua SHEN ; Guohai LI
Chinese Journal of Trauma 2012;28(9):826-829
Objective To investigate effects of pedicle processing methods on the survival and appearance of the pedicle flaps. Methods The study involved 17 patients with soft tissue defects of extremities treated with the “exclamation mark” shaped pedicle flaps from October 2009 to January 2011.The traditional pedicled rotation flaps was designed to be a tennis racket-like shape,then the rotational pedicle was designed to small round tension reduction flap and pedicled rotation flaps,which contributed to formation of the “exclamation mark” shaped pedicle flaps.The soft tissue defects was located at the upper extremity in three patients and at lower extremity in 14,with defect areas of 4.0 cm× 7.2 cm-5.8 cm × 14.0 cm.There used two superficial radial nerve vasotrophic flaps,one ulnar artery supra-carpal cutaneous flap,eight sural neurocutaneous vasotrophic flaps and six saphenous nerve vasotrophic flaps.Results All flaps survived at Ⅰ stage except that one flap had partial distal necrosis postoperatively,which was cured after dress change.The follow-up ranged from six months to one year,which showed unobvious swelling of the survived flaps and good appearance of the rotation point of the pedicle. Conclusion The “ex(c)lamation mark” shaped pedicle flaps can reduce entrapment of the distal pedicle,promote venous drainage,improve survival and modify the appearance of the flaps.
9.Prognosic analysis of chemotherapy for patients with castration resistant prostate cancer
Guowen LIN ; Dingwei YE ; Xudong YAO ; Shilin ZHANG ; Bo DAI ; Hailiang ZHANG ; Yijun SHEN ; Yao ZHU ; Yiping ZHU ; Guohai SHI ; Chunguang MA ; Wenjun XIAO ; Xiaojian QIN
Chinese Journal of Urology 2012;33(1):63-66
Objective To analyze prognosic factors for patients with hormone refractory prostate cancer (HRPC) after chemotherapy of docetaxel/mitoxantrone plus prednisone and to explore the relationship between prostate specific antigen (PSA) parameters and prognosis. Methods Data from 68 patients with CRPC after chemotherapy were collected and analyzed retrospectively.The median age of these patients were 65 years old with 28 cases of biopsy Gleason score < 8 and 35 cases of ≥ 8.The median serum PSA at diagnosis,nadir and pre-chemotherapy baseline were 142 ng/ml,0.5 ng/ml and 33.0 ng/ml,respectively.There were 38 patients in docetaxel group and 30 in mitoxantrone group.PSA doubling time ( PSADT),progression free survival (PFS) and overall survival (OS) was calculated.Chi square test was used in analysis of chemotherapy effect and Cox proportional hazards regression model was applied to identify the predictors for PFS and OS.The median value of continuous variable as cutoff point was used to divide patients into two groups to compare.Risk ratio and 95% confidence interval (CI) was calculated. Results 38 (55.9%)patients experienced effective chemotherapy. The effective rate were 33% and 74% for PSADT < 1.6 months and ≥ 1.6 months group,85% and 49% for M0 and M1 stage group,and 69% and 40% for docetaxel and mitoxantrone group,(P < 0.05).The median PFS was (3.5 ± 0.5) months for all patients,which were (2.7 ±0.4) months and (5.9 ±0.6) months for patients with PSADT < 1.6 months and ≥ 1.6 months group,(5.0 ± 0.6) months and (2.7 ± 0.5 ) months for patients with docetaxel and mitoxantrone group,and (5.7 ± 0.8) months and ( 3.4 ± 0.6) months for patients with Gleason score < 8 and ≥ 8 group (P <0.05).26 case died in the end and the median OS was (28.3 ± 2.6) months for these patients,which were (15.7 ± 3.4) months and (31.6 ± 1.2) months for patients with PSADT < 1.6 months and ≥1.6 months group,(29 ± 4.1 ) months and (28 ± 3.2) months for patients with docetaxel and mitoxantrone group,and (28.7 ± 2.6) months and (24.3 ± 5.6) months for patients with Gleason score < 8 and ≥ 8 group (P < 0.05). Conclusions The effective rate of chemotherapy was related with PSADT,chemotherapy strategy and M stage.PSADT,chemotherapy strategy and Gleason score may be independent predictors for patients with HRPC taking chemotherapy.Patients with PSADT ≥ 1.6 months,docetaxel chemotherapy and Gleason score < 8 will have longer PFS and OS.
10.Efficacy of Sunitinib in treating metastatic non-clear cell renal cell carcinoma
Guohai SHI ; Xudong YAO ; Shilin ZHANG ; Bo DAI ; Hailiang ZHANG ; Yijun SHEN ; Yao ZHU ; Yiping ZHU ; Chunguang MA ; Wenjun XIAO ; Xiaojian QIN ; Guowen LIN ; Lifeng YANG ; Dingwei YE
Chinese Journal of Urology 2011;32(10):711-713
Objective To investigate the efficacy of Sunitinib in treating metastatic non-clear cell renal cell carcinoma (RCC).Methods Twenty-two metastatic non-clear cell subtype renal cell carcinoma patients with a median age of 46 years (29 -76 years) were treated with Sunitinib.Fourteen cases were found have metastasis post radical nephrectomy,and the remaining eight cases with metastasis received cytoreductive surgery.Pathological diagnosis showed 12 papillary RCCs,one chromophobe RCC,three collecting duct RCCs,and six unclassified RCCs.The metastatic lesions were located in the lung,lymph nodes,adrenal gland,bone,liver,and thyroid gland.The patients were given the treatment of sunitinib 50 mg qd four weeks on and two weeks off.The median time of treatment was 11 months (4.5 - 24 months).Results The objective control rate was 73%.Three papillary RCC and one chromophobe RCC reached partial remission (PR) and 12 cases maintained stable disease (SD) for more than 12 weeks.And the remaining six cases progressed (PD).Conclusions Sunitinib has definitive efficacy in metastatic papillary RCC,chromophobe RCC,collecting duct RCC and unclassified RCC.Metastatic lesions in lungs and lymph nodes might be more sensitive to Sunitinib.

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