Polyphyllin I inhibits gastric cancer cell proliferation by downregulating the expression of fibroblast activation protein alpha (FAP) and hepatocyte growth factor (HGF) in cancer-associated fibroblasts.

The aim of this study was to identify the anti-cancer mechanism of Polyphyllin I (PPI) on gastric cancer cells via its activity on cancer-associated fibroblasts (CAFs). We cultured purified gastric CAFs obtained from fresh human gastric cancer tissue and examined the effect of Polyphyllin I on CAF proliferation using a colorimetric viability assay. In addition, we established a nude mouse xenograft model to examine the effect of Polyphyllin I administration on tumorigenesis. Using Western analysis, we quantified protein expression of the CAF-derived cytokines fibroblast activation protein alpha (FAP), secreted protein acidic and cysteine rich (SPARC), stromal cell-derived factor 1 (SDF-1), hepatocyte growth factor tenascin-C (TNC), and hepatocyte growth factor (HGF) in both in vitro and in vivo models. We found that Polyphyllin I inhibits the proliferation of CAFs in a concentration-dependent manner. Following treatment with 2 µg/ml PPI for 24 h in vitro, the expression of FAP, SDF-1 and HGF protein in CAFs was significantly lower than that in the control group, but there was no significant difference in SPARC and TNC protein expression between the two groups. In the nude mouse xenograft model, the tumor inhibition rate was 45.5% when PPI was administered early and 29.4% with administration in the third week. The expression of FAP and HGF in the xenografts was significantly decreased, while the expression of SPARC, SDF-1, and TNC was largely unaltered. Altogether, these data suggest that Polyphyllin I can inhibit the proliferation of gastric cancer cells by downregulating the expression of FAP and HGF in CAFs in vivo.

Expression of multidrug resistance-associated proteins and their relation to postoperative individualized chemotherapy in gastric cancer.

BACKGROUND: Adjuvant chemotherapy could reduce residual tumor cells and prevent relapse, however, not all patients are suitable for adjuvant chemotherapy. Screening appropriate patients based on molecular markers for individualized adjuvant chemotherapy is necessary. METHODS: Between June 2002 and June 2004, 119 patients who underwent radical gastrectomy were retrospectively analyzed. Some patients had adjuvant chemotherapy based on platinum and 5-FU for four to six cycles. Topoisomerase II (ToPo II) negative, multidrug resistance protein (MRP) positive and glutathione S-transferase π (GST-π) positive were regarded as three risk factors that may be associated with chemotherapy resistance and poor prognosis. Patients were divided into two groups: a high-risk group (≥2 risk factors) and a low-risk group (<2 risk factors), and tumor recurrence and patient survival time of the two groups were analyzed. RESULTS: The average recurrence time of the low-risk group was significantly longer than that of the high-risk group (21.29 ± 11.10 versus 15.16 ± 8.05 months, P < 0.01). The 3-year and 5-year survival rates of the high-risk group were 57.4% and 42.6%, however, it had no significant difference compared to 66.2% and 58.5% of the low-risk group (P >0.05). In the high-risk group, the 3-year survival rates of patients with/without chemotherapy were 62.1% and 52.0% and the 5-year survival rates were 44.8% and 40.0%, respectively, but the difference was not statistically significant (P > 0.05). In the low-risk group, the 3-year survival rates of patients with/without chemotherapy were 81.2% and 51.5%, and the 5-year survival rates were 71.9% and 45.5%, respectively, these differences were statistically significant (P < 0.05). CONCLUSIONS: Combined detection of the multidrug resistance (MDR)-related proteins ToPo II, MRP and GST-π may be prospectively valuable for postoperative individualized chemotherapy and in further predicting the outcomes of gastric cancer patients.

PCF Chemotherapy Combined with Surgical Treatment of Late Gastric Cancer.

BACKGROUND/AIMS: To investigate the efficacy and safety of PCF chemotherapy combined with surgery in the treatment of late-stage gastric cancer. METHODOLOGY: From July 2008 to February 2011, 72 cases of late-stage gastric cancer that could not be treated with R0 resection were treated prospectively. Patients received 2-4 cycles of paclitaxel plus cisplatin and 5-fluorouracil (PCF regimen) chemotherapy followed by cytoreductive surgery for the primary and metastatic tumors and another 2-4 cycles of PCF chemotherapy post-operatively. The treatment completion rate, patient tolerance and overall survival time were analyzed. RESULTS: There was one perioperative death. The overall response rate (complete and partial response) was 72.2%. Fifty patients (69.4%) completed chemotherapy and surgical resection as planned and 42 (58.3%) cases had R0 resection. The median survival time was 23.5 months (95% CI: 15.8-31.2 months). One-year and 2-year survival rates were 67.0% and 47.0%. The survival time of patients with surgical resection was much longer than that of the non-surgery group (30.2 vs. 8.9 months) (P < 0.01). The survival time of local advanced group was 30.3 months, and was significantly longer than 17.6 months of the distant metastasis group (P < 0.01); however, it had no significant difference compared to 28.2 months of the distant metastasis group with R0 resection. CONCLUSIONS: PCF chemotherapy combined with surgical resection were safe and effective, and can make survival benefits for some late-stage gastric cancer patients.

Is surgery necessary for patients with hepatic angiomyolipoma? Retrospective analysis from eight Chinese cases.

BACKGROUND AND AIM: Hepatic angiomyolipoma (AML) is a rare, hepatic mesenchymal neoplasm. Its preoperative diagnosis is very difficult, and the treatment is still controversial. The aim is to summarize experience in diagnosis and management of hepatic AML from a cancer center. METHODS: We retrospectively reviewed the clinical presentation, histopathological, features and treatment of the tumors encountered at our institute from January 2000 to December 2012. RESULTS: The patients included six females and two males, with female preponderance. Six patients are asymptomatic. Laboratory tests lack specificity. Combining imaging modality, only one patient obtained the accurate diagnosis of hepatic AML and was confirmed by fine-needle aspiration biopsy combined with homatropine methylbromide-45 staining. All other patients received hepatic resection. There was no tumor recurrence or increase of tumor size within the follow-up period. CONCLUSION: We suggest fine-needle aspiration combined with homatropine methylbromide-45 staining should be performed in all patients who are asymptomatic and without serological abnormalities. Surgical resection might be considered only if the malignant potential of the lesion cannot be ruled out or the tumor size is increasing during observation.

Laparoscopic-assisted radical gastrectomy for distal gastric cancer.

A 48-year-old female patient was diagnosed with a superficial depressed type early gastric cancer (type IIc) of 1.0 cm at the gastric angle as indicated by gastroscopy. Laparoscopic-assisted greater omentum-preserving D2 radical gastrectomy was performed in combination with Billroth I reconstruction under general anesthesia for the distal gastric cancer on April 5, 2013. The postoperative recovery was satisfying without complications. The patient was discharged seven days after surgery.

D2 plus radical resection combined with perioperative chemotherapy for advanced gastric cancer with pyloric obstruction.

A patient with advanced gastric cancer complicated with pyloric obstruction was treated using D2 + radical resection combined with perioperative chemotherapy, and had satisfying outcomes. The perioperative chemotherapy regimen was Taxol and S1 (tegafur, gimeracil, and oteracil). Three cycles of neoadjuvant chemotherapy were delivered before surgery, and three cycles of adjuvant therapy after surgery. PR was achieved after chemotherapy. D2 + dissection of stations 8p, 12b, 12p, 13 and 14v lymph nodes was performed on September 10, 2012.

Anti-PD-1 Monoclonal Antibody Combined With Anti-VEGF Agent Is Safe and Effective in Patients With Recurrent/Metastatic Head and Neck Squamous Cancer as Second-Line or Beyond Treatment.

Background: Numerous preclinical studies have revealed the complex regulatory mechanisms between anti-angiogenesis and immune inhibition in the tumor immune microenvironment and have proposed the efficacy of combined immunotherapy and anti-angiogenic treatment. Moreover, the combination strategy had been confirmed in a number of clinical trials. In this study, we aimed to evaluate the safety and efficacy of this combination strategy in recurrent/metastatic head and neck squamous cell carcinoma. Methods: In this real-world study, 43 patients who received the combination of programmed cell death protein 1 (PD-1) inhibitors and anti-vascular endothelial growth factor (VEGF) agents in Zhejiang cancer hospitals between March 2019 and December 2020 were reviewed. Clinical characteristics and follow-up data were collected, and the preliminary efficacy and safety of the combination therapy were assessed. Results: The median follow-up time was 12.4 months (range, 3.7-25.3 months), and the follow-up rate was 100%. The median duration of exposure was 9.5 months. Thirty-seven patients (86.0%) reported treatment-related adverse events (TRAEs) of any grade. The most frequently reported events were fatigue, decreased appetite, and hypertension. Grade 3 TRAEs occurred in 8 patients (18.6%), and no grade 4 or 5 TRAEs occurred. Twenty-four patients (55.9%) had an overall response to treatment: 6 (14.0%) had a complete response and 18 (41.9%) had a partial response. In addition, 5 (11.6%) patients had stable disease, and the disease control rate 12 was 67.4%. The median time to response was 1.6 months (range, 1.1-2.8 months). The median progression-free survival (PFS) was not reached, and the 1-year PFS rate was 69.1%. The 1-year overall survival (OS) rate was 87.7%. Patients with primary tumors located in the nasopharynx had better OS than those with tumors outside the nasopharynx. ECOG PS were related to PFS; patients with an ECOG PS of 0 had a slight survival advantage. Conclusion: The combination strategy of anti-PD-1 monoclonal antibodies and anti-VEGF agents was tolerable in patients with recurrent/metastatic head and neck cancer. This treatment exhibited antitumor potential despite the heavily pretreated population.

[Clinical analysis of 168 cases of multiple primary colorectal carcinoma].

OBJECTIVE: To study the incidence rate of multiple primary colorectal carcinomas (MPCC) in colorectal carcinoma and to evaluate its clinical and pathological characteristics. METHODS: One hundred and sixty-eight (4.6%) patients from 3663 cases with colorectal carcinoma were diagnosed with MPCC from January 1985 to December 2003. The clinical data of the patients were collected retrospectively to investigate the diagnosis and treatment of MPCC. RESULTS: Of the 168 patients, 81 were diagnosed as synchronous colorectal carcinoma (SC), 72 with metachronous colorectal carcinoma (MC), 15 with both SC and MC. The median age at time of diagnosis of colorectal carcinoma was 58 years old (range from 20 to 82 years old). Three hundred and ninety-three cancer lesions were detected in these 168 cases (mean, 2.3 lesions/case). The rectum and sigmoid colon were the most involved sites (61.6%). Eighteen cases (10.7%) were verified with hereditary non-polyposis colorectal cancer (HNPCC) while another 9 cases were highly suspected. Fourteen patients (8.3%) were found with other malignancies out of large intestine, 41 patients (24.4%) with colorectal adenomas, 72 (42.9%) with adenoma carcinogenesis. Among the 96 SC patients, 91 were given preoperative colonoscopy and 65 (71.4%) got the diagnosis. All the MC patients were diagnosed by postoperative colonoscopy. The overall 5-year survival rate of the 168 patients was 69.8%. CONCLUSIONS: MPCC should be paid more attention in colorectal cancer management. Colonoscopic surveillance is much more important in diagnosis and follow-up of MPCC for reducing the misdiagnosis of SC and detecting more MC in time. Prompt treatment of adenoma can reduce the occurrence of MPCC, and active and standard surgical treatment should be done for MPCC.

[Surgical treatment and prognosis of Borrmann type IIII( gastric cancer involving the whole stomach].

OBJECTIVE: To explore the surgical treatment and prognosis of Borrmann type IIII( gastric cancer involving the whole stomach. METHODS: Clinicopathological characteristics and survival data of 223 patients with Borrmann type IIII( gastric cancer involving the whole stomach (defined as the tumor infiltrating 3 regions of the stomach) receiving surgical treatment at the Department of Abdominal Surgery of Zhejiang Cancer Hospital between January 2002 and December 2015 were analyzed retrospectively. The survival time of patients with different clinicopathological features and different treatment methods was compared. Cox regression was used to analyze the independent prognostic factors. RESULTS: Two hundred and twenty-three patients with Borrmann type IIII( gastric cancer involving the whole stomach accounted for 24.0% (223/930) of all Borrmann type IIII( gastric cancer cases undergoing surgical resection at the same period. There were 147 males and 76 females with an average age of 57.8 years. All the patients underwent total gastrectomy. Of these patients, radical resection was performed in 149 cases(66.8%) and palliative resection in 74 cases (33.2%). Combined organ resection was performed in 43 patients (19.3%), including 25 splenectomies, 6 pancreatic body and tail plus spleen and transverse colon resections, 2 transverse colon plus spleen resections, 2 right colon resections, 2 transverse colon resections, 2 ovariectomies, 1 partial jejunal resection, 1 pancreatoduodenectomy, 1 pancreatic tail plus transverse colon resection, and 1 partial pancreatectomy. Postoperative complications occurred in 28 patients(12.6%), including 10 patients with combined organ resection. Esophagojejunal fistula was the most frequent complication, accounting for 39.3%(11/28). Perioperative mortality occurred in 3 patients (1.3%). Thirty-nine patients underwent preoperative adjuvant chemotherapy (clinical stage: cT4aN0M0 in 1 patient, cT4bN1-2M0 in 12 patients, cT4aN1-2M0 in 20 patients, and cT4aN3M0 in 6 patients). Among these 39 patients, post-chemotherapeutic degenerative response was detected in 25 postoperative pathological specimens (64.1%), radical resection was performed in 21 patients (53.8%), distant metastasis was observed in 7 patients (17.9%) and peritoneal metastasis was found in 17 patients (43.6%) during operation. The average maximal tumor diameter was 13.2 cm (range from 6 to 22). Histological types included 23 moderate-poorly differentiated adenocarcinomas (10.3%), 146 poorly differentiated adenocarcinomas (65.5%), 41 signet ring cell carcinomas (18.4%), 11 mucinous adenocarcinomas(4.9%), 1 squamous cell carcinoma (0.4%) and 1 undifferentiated carcinoma (0.4%). Tumor-infiltrating duodenum was found in 57 patients (25.6%) and tumor-infiltrating esophagus in 132 patients (59.2%). The positive margin was found in 66 patients (29.6%): upper margin in 35 patients (15.7%), lower margin in 22 patients (9.9%), and both margins in 9 patients(4.0%). Immunohistochemical positive HER2(3+) was detected in 4 patients (1.8%). Tumor infiltrating into serosa(T4a) was found in 197 patients (88.3%) and infiltrating into adjacent organ (T4b) in 26 patients(11.7%). One hundred and forty-three cases (64.1%) had lymphatic or venous invasion, 187 (83.9%) had neural invasion, and 35 (15.7%) had cancer nodules. Of 149 patients undergoing radical resection, 5 patients were stage II(b, 9 patients were III(a, 20 patients were III(b and 115 patients were III(c. Of 145 patients(65.0%) undergoing postoperative chemotherapy, the average cycles of chemotherapy was 3.6 (median 3 cycles) and only 69 patients (47.6%) completed 4 cycles or more. Patients were followed up for 1-102 months (average 17.3 months). The median overall survival time was 13.8 months and the 1-, 3-, and 5-year survival rate was 57.9%, 14.1% and 6.8% respectively. The median survival time of the 149 cases with radical resection was 16.7 months and the 1-, 3- and 5-year survival rate was 67.5%, 16.5% and 8.4% respectively; the median survival time of the 74 cases with palliative resection was 10.3 months and the 1-, 3- and 5-year survival rate was 42.6%, 8.5% and 1.7% respectively, whose differences were statistically significant (all P=0.000). Multivariate analysis showed that tumor staging (P=0.005), radical resection (P=0.009), lymphatic or venous invasion (P=0.017) and postoperative chemotherapy (P=0.001) were independent prognostic factors. CONCLUSIONS: Surgical treatment for Borrmann type IIII( gastric cancer involving the whole stomach is safe. Radical resection can improve the prognosis though the overall survival is poor.

Effects of hepatic blood inflow on liver ultrastructure and regeneration after extensive liver resection in rats with cirrhosis.

The aim of the present study was to investigate the effects of hepatic blood inflow on liver function, liver ultrastructure and the regeneration of future liver remnant (FLR) following major hepatectomy in rats with liver cirrhosis. A rat model of cirrhosis was established through intraperitoneal injection of carbon tetrachloride for 8 consecutive weeks. Extensive liver resection and different blood inflow models by portal vein (PV) and/or hepatic artery (HA) stenosis were conducted on the cirrhosis rats. Animal models were constructed as follows: Control (group A), low-flow PV + high-flow HA (group B), low-flow PV + low-flow HA (group C), high-flow PV + high-flow HA (group D) and high-flow PV + low-flow HA (group E). Hepatic blood inflow was detected by laser speckle contrast analysis, liver function and pathological changes were analyzed, Masson staining was used to identify the fibrosis of the liver and Periodic acid-Schiff staining was used to identify glycogen synthesis and hepatocyte function. The liver cell ultrastructure was evaluated by transmission electron microscopy, and the expression of Ki-67 in hepatocytes and the weight of the FLR were recorded to determine the regeneration of the FLR. Five days after major hepatectomy and liver blood inflow modulation, pathological examination of the livers from groups B and C revealed less congestion and less extensive hepatocellular injury. The serum alanine aminotransferase level of group B at 1, 3 and 5 days after hepatectomy and blood inflow modulation was 460.9±31.7, 331.0±22.0 and 285.6±15.8 U/l, respectively (control group: 676.9±41.7, 574.9±28.0 and 436.1±32.7 U/l, respectively; P<0.05); the total bilirubin of group B at 1, 3 and 5 days was 20.4±1.5, 16.1±1.0 and 13.5±0.6 µmol/l, respectively (control group: 30.3±1.4, 26.5±0.8 and 22.1±1.2 µmol/l, respectively; P<0.05). The size of the endoplasmic reticulum in the low-flow PV groups increased significantly and the mitochondrial swelling was alleviated. The positive rate of Ki-67 in the hepatocytes of groups B, C and D was 23.9±3.6, 15.7±2.3 and 12.9±2.4%, respectively (control group: 10.1±2.1%, P<0.05), and the positive rate of Ki-67 in group E was 6.1±1.4% (compared with that of the control group, P<0.05). The remnant liver weight of group B was 15.4±1.0 g (compared with that of the control group, P<0.05). Therefore, decreased portal blood flow combined with increased hepatic arterial blood flow alleviated the congestion in the liver following major hepatectomy in cirrhotic rats, improved the pathological status and liver function, increased the expression of Ki-67 and promoted liver regeneration.

Prognostic impact and implications of extracapsular lymph node spread in Borrmann type IV gastric cancer.

The purpose of this study was to evaluate the relationship between extracapsular lymph node spread (ECS) and clinicopathology and its influence on the prognosis in patients with Borrmann type IV gastric cancer. Between 2002 and 2014, clinical data were reviewed from 486 patients with Borrmann type IV gastric cancer who underwent curative resection. Of the 486 patients, lymph node metastasis was found in 456. ECS was detected in 213 (46.7%) patients with lymph node metastasis. A positive lymph node with ECS was significantly correlated with the N category, lymphatic/venous invasion, tumor location, and TNM stage. For the whole patients, the mean OS was 34.7 months, and the 5-year OS rate was 15.5%. The 5-year OS rate of node-negative patients was 48%, for node-positive patients without ECS 18.7%, and for node-positive patients with ECS 5.7% (P = 0.000). In a multivariate analysis, adjusted for tumor location, lymphatic/venous invasion, body mass index (BMI), and TNM stages, ECS remained an independent prognostic factor. For patients with the same N category and TNM stage, those with ECS still had a worse survival rate. Recurrent sites were confirmed in 367 patients. The most frequent recurrent site was the peritoneum. There was a significant difference between ECS+ (N = 150) and ECS- (N = 142) patients (P = 0.008). Our results suggested that ECS was an independent prognostic value for Borrmann type IV gastric cancer patients with curative resection and a subgroup indicated a significantly worse long-term survival for patients with the same N or TNM stages. ECS+ was an adverse factor for peritoneal metastasis.

[Discussion for clinical treatment in early stage of colorectal carcinoma with the invasion limited in the layer of muscularis mucosae].

OBJECTIVE: To emphasis the importance of recognizing and treating the early colorectal carcinoma with the invasion limited in the layer of muscularis mucosae, and discuss several questions in using the WHO's new diagnostic standards of the prestage of tumors of digestive system. METHODS: A retrospective review was made of 30 patients with invasive carcinoma limited in the layer of muscularis mucosae. All of the patients were treated between July 1986 and July 1999 in Shanghai Cancer Hospital. RESULTS: Among the 30 cases, there were 19 men and 11 women from 20 to 80 years dd (mean, 57.0). The tumor diameter was ranged from 0.8 cm to 8.0 cm (mean, 2.9 cm). 12 patients were given polypectomy while 18 patients were given radical resection. Among the patients given polypectomy, one got recurrence 3 years later, one had the metastasis of lungs 50 months later and had been dead already. Among the patients given radical resection, one had metastasis of lymph nodes peripheral to the tumor, one also had the metastasis of lungs 68 months later but is still alive now, and one had metastasis of lymph nodes in the right upper part of neck 15 months later and then was lost to follow-up. CONCLUSIONS: The patients with early colorectal carcinoma with the invasion limited in the layer of muscularis mucosae could have metastasis of lymph nodes, get local recurrence after polypectomy and even have blood metastasis. Therefore great attention must be paid. Clinicians should be careful to chosen polypectomy. Meanwhile, in order to provide more information of the correct treatment, it will be better if the pathologists could give the original diagnosis at the same time when they use the WHO's new diagnostic standards of the prestage of tumors of digestive system in diagnosing the early invasive carcinoma limited in the layer of muscularis mucosae, for the concept of high-grade intraepithelial neoplasia will be used instead of it, and whether or not it is a really benign tumor, much more clinical research must be done later.

TAK-242 can be the potential agents for preventing invasion and metastasis of hepatocellular carcinoma.

The long-term prognosis of hepatocellular carcinoma (HCC) remains unsatisfactory even after surgical resection and chemoembolization because of a high recurrence rate. However, fewer agents are currently available to block or postpone HCC progression. Recent studies show that the activation of toll-like receptor 4 (TLR4)-NF-kappaB(NF-κB) signaling pathway can lead to the expression of interleukin (IL)-1, IL-6, IL-10, nitric oxide (NO) and tumor necrosis factor (TNF)-α, and promote chronic liver inflammation and malignant tumor development. A new small molecule TAK-242 (Resatorevid) can selectively inhibit TLR4-mediated signaling pathway and suppress the expression of inflammatory mediators. But the researches have not been reported whether TAK-242 can inhibit liver tumor growth and invasion. So it suggested a new hypothesis that TAK-242 selectively blocks the TLR4-NF-κB pathway and is hoped to be a potential and creative drug for preventing invasion and metastasis of HCC.

Knockdown of long non-coding RNA HOTAIR suppresses tumor invasion and reverses epithelial-mesenchymal transition in gastric cancer.

BACKGROUND: Over-expression of long non-coding RNA HOTAIR has been reported in several types of cancer. Yet its involvement in gastric cancer (GC) has not been well understood. The aim of present study was to examine the expression pattern of HOTAIR in GC patients, then, explore its role in promoting cancer invasion and underlying molecular mechanism. METHODS: The expression level of HOTAIR in the tumor specimens of GC patients was quantified by Realtime RT-PCR. The correlation between HOTAIR level and clinicopathological factors as well as prognosis was then examined. Down-regulation of HOTAIR by RNA interference was applied to investigate its roles in tumor invasiveness via the view of Epithelial-to-mesenchymal transition (EMT). RESULTS: The expression level of HOTAIR in cancer tissues was higher than that in adjacent noncancerous tissues. Expression level of HOTAIR was significantly correlated with lymph node metastasis and TNM stage. Furthermore, high expression level of HOTAIR was a predictor of poor over-all survival in GC patients. In vitro, inhibition of HOTAIR in GC cells could reduce invasiveness, as well as the expression of MMP1 and MMP3. In addition, suppression of HOTAIR could reverse EMT process. CONCLUSIONS: HOTAIR could act as a potential predictor for over-all survival in patients with GC. Inhibition of HOTAIR could reduce invasiveness and reverse EMT process in GC cells, indicating the potential role of HOTAIR in GC diagnostics and therapeutics.

[Synchronous or metachronous primary cancers of other organs in 74 patients with gastric cancer].

OBJECTIVE: To study the incidence, clinicopathological characteristics, diagnosis, treatment, and prognosis of synchronous or metachronous primary cancers in patients with gastric cancer. METHODS: Clinical data of 4426 patients with gastric cancer in our hospital from 1996 to 2007 were reviewed. RESULTS: Seventy-four (1.7%) patients had synchronous or metachronous primary cancer of other organ, of whom 10 were synchronous and 64 were metachronous. Colorectal cancer was the most common type of primary cancer in other organs (43.8%), followed by breast cancer (16.3%). The mean time interval between gastric cancer and metachronous primary cancer was 82.2 (3-354) months. The mean age at the diagnosis of gastric cancer was 61.2 (33-84) years. The 5-year overall survival rate was 42.3%. The 5-year survival rates in patients with synchronous cancer, pre-metachronous cancer or post-metachronous cancer were 15.2%, 42.9% and 51.3%, respectively. Causes of death were primary cancers of other organ in 11 patients, gastric cancer in 24, and renal failure in 1 patient. CONCLUSIONS: Primary cancer of other organ should be considered in the management of gastric cancer. Aggressive treatment should be used for the second primary cancer. Gastric cancer is the main cause of death in these patients.

[Clinicopathological and prognostic analysis of 23 poorly differentiated neuroendocrine carcinomas of the stomach].

OBJECTIVE: To evaluate the clinicopathological characteristics and prognosis of poorly differentiated neuroendocrine carcinoma of the stomach. METHODS: Twenty-three poorly differentiated neuroendocrine carcinomas of the stomach were treated in the Department of Abdominal Surgery at the Cancer Hospital, Fudan University between January 1996 and December 2007. Clinicopathological characteristics and survival data were analyzed. RESULTS: Poorly differentiated neuroendocrine carcinomas of the stomach accounted for 0.52% of all the gastric carcinomas. The tumor occurred more often in males (18 of 23), older patients (mean age of 62 years), upper third of the stomach (16 of 24,one patient had more than one lesion) with large size (mean diameter of 6.8 cm). TNM stages were as follows: stage II in 3 patients, stage III in 12, and stage IIII in 8. Thirteen patients underwent curative resection, while 8 underwent palliative resection and 2 others underwent exploratory laparotomy with biopsy. Of the 21 surgical resection specimens, vascular invasion was found in 18 patients (85.7%), perineural invasion in 16 patients (76.2%), and regional lymph node metastasis in 17 patients (81.0%). Follow up time ranged from 3 to 63 months. Mean overall survival time was 17.7 months. The 1-year, 2-year, and 5-year survival rates were 47.8%, 19.1%, and 4.3%, respectively. Statistically significant differences in survival curves were observed which were related to tumor staging and surgery type, but not related to gender, age, tumor location, or diameter. CONCLUSIONS: Poorly differentiated neuroendocrine carcinomas of the stomach are rare and with poor prognosis. Tumor stage and surgical type have potential impact on survival.

[Surgical treatment for patients with advanced gastrointestinal stromal tumor after targeted therapy].

OBJECTIVE: To explore the role of surgery and its long-term outcome in patients with advanced gastrointestinal stromal tumor(GIST) treated with imatinib preoperatively. METHODS: Thirteen patients receiving imatinib therapy preoperatively, were retrospectively assessed for completeness of surgical resection and for disease-free and overall survival after resection. RESULTS: Thirteen patients, including 3 patients with locally advanced primary GIST and 10 patients with recurrent or metastatic GIST, underwent surgery after preoperative treatment with imatinib. Complete resections were accomplished in 4 of the 5 responsive disease(RD) patients, and in 1 of the 8 progression disease(PD) patients (38.5%). The progression-free survival(PFS) time for patients with RD and PD were 24.8 months and 2.8 months respectively. The difference of PFS between patients with RD and those with PD was significant(P<0.01). Median overall survival(OS) was not reached in both patients with RD and PD. The difference of OS between patients with RD and those with PD was not significant(P>0.05). CONCLUSION: Surgical intervention following imatinib is feasible and can be considered for patients with advanced GIST responsive to imatinib.