Prognostic significance of regional lymphadenectomy in T1b gallbladder cancer: Results from 24 hospitals in China.

BACKGROUND: Whether regional lymphadenectomy (RL) should be routinely performed in patients with T1b gallbladder cancer (GBC) remains a subject of debate. AIM: To investigate whether RL can improve the prognosis of patients with T1b GBC. METHODS: We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in China. The log-rank test and Cox proportional hazards model were used to compare the overall survival (OS) of patients who underwent cholecystectomy (Ch) + RL and those who underwent Ch only. To investigate whether combined hepatectomy (Hep) improved OS in T1b patients, we studied patients who underwent Ch + RL to compare the OS of patients who underwent combined Hep and patients who did not. RESULTS: Of the 121 patients (aged 61.9 ± 10.1 years), 77 (63.6%) underwent Ch + RL, and 44 (36.4%) underwent Ch only. Seven (9.1%) patients in the Ch + RL group had lymph node metastasis. The 5-year OS rate was significantly higher in the Ch + RL group than in the Ch group (76.3% vs 56.8%, P = 0.036). Multivariate analysis showed that Ch + RL was significantly associated with improved OS (hazard ratio: 0.51; 95% confidence interval: 0.26-0.99). Among the 77 patients who underwent Ch + RL, no survival improvement was found in patients who underwent combined Hep (5-year OS rate: 79.5% for combined Hep and 76.1% for no Hep; P = 0.50). CONCLUSION: T1b GBC patients who underwent Ch + RL had a better prognosis than those who underwent Ch. Hep + Ch showed no improvement in prognosis in T1b GBC patients. Although recommended by both the National Comprehensive Cancer Network and Chinese Medical Association guidelines, RL was only performed in 63.6% of T1b GBC patients. Routine Ch + RL should be advised in T1b GBC.

[Reconstruction of the March-April average maximum air temperature over 165 years based on Pinus tabuliformis tree-rings of Zhen'an County, Shaanxi Province, China]. / åŸºäºŽæ²¹æ¾æ ‘è½®é‡å»ºé™•è¥¿çœé•‡å®‰åŽ¿165年以来3­4月平均最高气温.

We used tree rings of Pinus tabuliformis sampled in the Muwang National Forest Park to establish a standardized chronology (STD) and calculated the correlation coefficients between the standardized chronology and climatic factors of Zhen'an meteorological station. With linear regression analysis, we reconstructed the March-April mean maximum temperature of Zhen'an over 165 years from 1853 to 2017. The highest correlation coefficient was observed between the standardized chronology and the March-April mean maximum temperature (r=0.596, n=60, P＜0.01). The variance interpretation of the March-April mean maximum temperature reconstruction function was 33.2%, and the reconstruction function and results were credible and reliable. Warm years occurred 25 times and cold years occurred 29 times in the reconstruction sequence. The warm years were more accompanied by flood events, while the cold years were accompanied by more drought events. Temperature fluctuated obviously in the reconstruction sequence, with two cold periods (1902-1917 and 1953-2000) and four warm periods (1868-1892, 1917-1937, 1941-1953 and 2001-2012). The obvious periodic variations of 2-7, 8-15, 18-28, 75-96, and 100-125 years were found in the reconstruction sequence, in which the quasi-113, 88 and 22 years were the first, second and third main periods, respectively. These variations might potentially be the fingerprints of some climate change forces such as solar activity, monsoon and EI Niño-Southern Oscillation (ENSO) activity.

Clinical evaluation of cetuximab combined with an S-1 and oxaliplatin regimen for Chinese patients with advanced gastric cancer.

BACKGROUND: The prognosis of patients with advanced gastric cancer is poor. The goal of this study was to evaluate the efficacy and safety of combination therapy of cetuximab and S-1 combined with oxaliplatin (SOX) in Chinese patients with advanced gastric cancer. METHODS: For patients in the experimental group (cetuximab in combination with SOX (Ce-SOX), 30 patients), once-weekly cetuximab (400 mg/m2 at the first infusion then 250 mg/m2 every week) was administered. For patients in both the control (SOX alone, 26 patients) and experimental groups, oxaliplatin (100 mg/m2) was administered intravenously on day 1, while S-1 (80 mg/m2/day) was given orally twice daily for 14 days. The endpoints of this study included progression-free survival, response rate, and disease-control rate. RESULTS: There was no statistically significant difference in response rate between the Ce-SOX and SOX groups (54.8% versus 44%, P=0.225). The difference in disease-control rate was also statistically insignificant between the two groups (87.1% versus 76%, P=0.162). Median progression-free survival in the Ce-SOX group was significantly higher than that in the SOX group (12.8 versus 10.1 months, P=0.007). The median overall survival of the Ce-SOX group and SOX group was 14.0 and 12.2 months, respectively (P=0.043). The one-year survival rate for the Ce-SOX group was 57% compared to 40% in the SOX group. There was no statistical difference in the grade 3 or 4 adverse effects between the two groups. CONCLUSIONS: These findings suggest that the cetuximab combined with SOX regimen is feasible and shows promising efficacy with tolerable adverse effects in Chinese patients with advanced gastric cancer.

[Comparison study of three methods of digestive tract reconstruction after radical gastrectomy in gastric cancer patients].

OBJECTIVE: To investigate the ideal digestive tract reconstruction methods among three different surgical methods after radical gastrectomy of gastric cancer patients. METHODS: A total of 123 patients who received elective radical gastrectomy for gastric cancer from February 2010 to August 2011 were prospectively enrolled and randomly divided into radical proximal gastrectomy and jejunal interposition group, radical proximal gastrectomy and esophageal with the posterior of residual-stomach group, and radical total gastrectomy and Roux-en-Y esophagojejunostomy group. Patients were followed up for 12 months. Symptoms of reflux esophagitis were observed, gastric emptying tests were done, liver and kidney function was also monitored. The quality of life was documented before operation, and one and twelve months after operation. RESULTS: No significant differences were found among these three groups in the pH value of lower part of esophagus, the blood regular test results and the functional parameters of kidney and liver before and after operation(all P>0.05). Symptoms of reflux esophagitis was reported in 1(2.4%) patients in the jejunal interposition group, 10(24.4%) in esophageal with the posterial of residual-stomach group, and 7(17.1%) in the Roux-en-Y esophagojejunostomy group(P=0.017). There was 1(2.4%), 10(17.1%), and 8(19.5%) patients presented reflux of barium meal in these three groups, respectively (P=0.046). There were no statistically significant difference in PH at the distal esophagus(6.9±0.2 vs. 6.8±0.1 vs. 6.9±0.1, P=0.196). The quality of life was significantly improved one year after surgery in terms of general status, physical function, emotional function, fatigue, nausea/vomiting, pain, constipation, and diarrhea (all P<0.05), with the jejunal interposition superior than the other two methods. CONCLUSION: Three methods of digestive tract reconstruction in radical gastrectomy of gastric cancer patients can improve the health status and the quality of life in gastric cancer patients. Radical proximal gastrectomy and jejunal interposition is the preferred method.

[Application of jejunal interposition after radical proximal gastrectomy].

OBJECTIVE: To explore an ideal method of digestive tract reconstruction and tolerance to adjuvant chemotherapy after radical proximal gastrectomy. METHODS: Thirty patients in the reconstruction group were treated by jejunal interposition, and other 30 patients received gastroesophagostomy (control group). The operation time, operation risk, occurrence of reflux esophagitis and postoperative 1-, 3-, 6-month nutrition statuses were evaluated. Forty-three patients received postoperative adjuvant chemotherapy with mFOLFOX-6 and tolerance to the chemotherapy was assessed. RESULTS: The operation time of the reconstructional group was (162.2 ± 14.0)min and that of the control group was (137.6 ± 18.9)mi, with a statistically significant difference. (t = -5.7, P<0.01). There were no significant differences of operation risk, postoperative 2-, 4-, and 6-day C-reactive protein, 2-, 4- and 6-day systemic inflammatory response syndrome between the two groups. The differences of the occurrence of postoperative 1-, 3- and 6-month reflux esophagitis and 3- and 6-month nutritional status between the two groups were statistically significant. 18 of 19 (94.7%) patients in the reconstruction group completed all six cycles of chemotherapy, 24 patients in the control group received chemotherapy, and 12 (50.0%) of them completed 6 cycles of chemotherapy. There was a significant difference in the completion rate of chemotherapy of the two groups (P<0.05). CONCLUSIONS: The postoperative complications of jejunal interposition are not inceased, the symptoms of reflux esophagitis are alleviated, the quality of life can be improved, and there is a better tolerance to adjuvant chemotherapy. Therefore, jejunal interposition after radical proximal gastrectomy is a rational method of digestive tract reconstruction.

Safe temperature range for intraoperative and early postoperative continuous hyperthermic intraperitoneal perfusion in a swine model of experimental distal gastrectomy with Billroth II reconstruction.

BACKGROUND: The current study sought to investigate the safety of intraoperative and early postoperative continuous hyperthermic intraperitoneal perfusion (IEPCHIP) at different temperatures in a swine model of experimental distal gastrectomy with Billroth II reconstruction. METHODS: Thirty pigs were randomly divided into 5 groups. Two groups were used as the control groups (groups A1 and A2), and 3 groups were used as the perfusion groups (groups B, C and D). Pigs in group A1 received distal gastrectomy with Billroth II reconstruction only. Pigs in groups A2, B, C and D received the same surgery as group A1, followed by IEPCHIP at 37 ± 0.5°C, 42.5 ± 0.5°C, 43.5 ± 0.5°C or 44.5 ± 0.5°C, respectively. The perfusion time was assessed for each pig in group A2 as well as in the perfusion groups, and the perfusions were performed twice for each group. The first perfusion was conducted intraoperatively, and the second perfusion was initiated 1 day after surgery. Data concerning vital signs and hepatic and renal function were collected. Parameters concerning anastomotic healing, the pathology of the anastomotic tissue and abdominal adhesion were compared. RESULTS: The vital signs and hepatic and renal functions of the pigs in groups A1, A2, B and C were not significantly affected by this procedure. In contrast, the vital signs and hepatic and renal functions of the pigs in group D were significantly affected. Compared to the pigs in groups A1, A2 or B, the anastomotic bursting pressure, breaking strength and hydroxyproline content in group C and D pigs were significantly lower. No significant differences were observed in these parameters between groups A1, A2 and B. Abdominal adhesion was more severe in group D pigs. Collagen deposition in group A1, A2 and B pigs was dense in the anastomosis, and inflammatory cell infiltration was observed in group D. CONCLUSIONS: IEPCHIP at 42.5 ± 0.5°C was safe and caused minimal impairments. However, anastomotic healing was affected by perfusion at 43.5 ± 0.5°C and 44.5 ± 0.5°C, and abdominal adhesion was most severe in the group D animals, which were perfused at 44.5 ± 0.5°C.

Use of serum circulating CCNB2 in cancer surveillance.

Cyclin B2 (CCNB2), a member of the cyclin protein family, has been found to be up-regulated in human cancers. To evaluate the potential use of circulating CCNB2 in serum in cancer surveillance, we examined relative expression levels of serum circulating CCNB2 mRNA in 103 cancer patients, 19 normal controls, and 40 benign disease patients using real-time quantitative reverse transcriptase polymerase chain reaction. We found that the relative expression level of circulating CCNB2 mRNA in cancer patients was significantly higher (p<0.0001) than that in normal controls and benign diseases group. Circulating CCNB2 mRNA level was significantly (p<0.001) correlated with cancer stage and metastasis status. Receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.87 and 0.83 (p<0.05) in identifying cancer patients' metastasis status in lung and digestive tract cancer, respectively. Moreover, we observed that expression levels of circulating CCNB2 mRNA in cancer patients significantly decreased (p=0.0084) after their therapeutic treatments. These data suggest that detection of serum circulating CCNB2 mRNA may have potential clinical applications in screening and monitoring of metastasis and therapeutic treatments.

Use of serum circulating CCNB2 in cancer surveillance.

Cyclin B2 (CCNB2), a member of the cyclin protein family, has been found to be up-regulated in human cancers. To evaluate the potential use of circulating CCNB2 in serum in cancer surveillance, we examined relative expression levels of serum circulating CCNB2 mRNA in 103 cancer patients, 19 normal controls, and 40 benign disease patients using real-time quantitative reverse transcriptase polymerase chain reaction. We found that the relative expression level of circulating CCNB2 mRNA in cancer patients was significantly higher (p<0.0001) than that in normal controls and benign diseases group. Circulating CCNB2 mRNA level was significantly (p<0.001) correlated with cancer stage and metastasis status. Receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.87 and 0.83 (p<0.05) in identifying cancer patients' metastasis status in lung and digestive tract cancer, respectively. Moreover, we observed that expression levels of circulating CCNB2 mRNA in cancer patients significantly decreased (p=0.0084) after their therapeutic treatments. These data suggest that detection of serum circulating CCNB2 mRNA may have potential clinical applications in screening and monitoring of metastasis and therapeutic treatments.

[Analysis of the treatment of unexpected gallbladder cancer].

OBJECTIVE: To investigate the secondary operation methods and the effects on the prognosis of unexpected gallbladder cancer (UGC). METHODS: A retrospective analysis on the clinical data was made for 41 patients who underwent extended radical excision from June 1995 to December 2002. Among the patients, 12 were male, 29 were female. The average age was 51 years old. The 41 patients had undergone gallbladder excision because of cholecystitis complicated lithiasis of gallbladder (32 cases), polypi of gallbladder or adenoma (9 cases). Postoperative pathology showed that 32 cases were adenocarcinoma of gallbladder, 6 cases were squamous carcinoma, 3 cases were squamous adenocarcinoma. Six cases were on the stage of Nevin I, 16 on Nevin II, 17 on Nevin III, 2 on Nevin IV. The second operation was performed after 6-30 d of the first operation. The second operation chose the improved method of Glenn excision of carcinoma of gallbladder. RESULTS: On the second operation, 14 cases were with lymphatic metastasis, 14 with gallbladder metastasis, 6 with bile duct metastasis, 2 with pancreas metastasis. Fourteen cases were on the stage of Nevin IV, 9 on Nevin V, none on Nevin I, II and III. After the second operation, 1 year survival rate was 100% (41 cases); The three-year survival rate was 53.8% (22 cases); The five-year survival rate was 17.5% (7 cases). CONCLUSION: Extended radical excision is one of the most important methods for the treatment of UGC.

Metastatic pattern of lymph node and surgery for gastric stump cancer.

BACKGROUND AND OBJECTIVES: Metastatic pattern of lymph node (LN) and surgery options for gastric stump cancer (GSC) remain controversial. The aim of this study was to investigate LN metastasis and lymphadenectomy for GSC for curative purposes. METHODS: Sixty-seven patients with GSC were analyzed retrospectively. RESULTS: The metastatic rates of LN were as follows: 63.3% in right cardia (No. 1), 33.3% in left cardia (No. 2), 75.0% in lesser curvature (No. 3), 53.3% in greater curvature (No. 4), 40.0% in celiac artery (No. 9), 60.0% in splenic hilus (No. 10), 72.7% in splenic artery (No. 11), 36.1% in hepatoduodenal ligament (No. 12), 8.3% in retropancreatic (No. 13), 21.4% in para-aortic (No. 16), 50% in supra-diaphragm (No. 111), 16.7% in LN within jejunal mesentery, respectively. All nine patients who only received simple laparotomy died within 1 year. The overall 5-year survival rate of GSC was 17.9% (12/67), including 100% for stage I, 80.0% for stage II, 12.1% for stage III, and 0% for stage IV. Moreover, the 5-year survival rate (36.7%, 11/30) for curative patients was significantly better than that (3.6%, 1/28) of non-curative patients (chi(2) = 7.76, P < 0.01). CONCLUSIONS: Our results imply that GSC has a wide range of LN metastases, including LN within jejunal mesentery in B-II reconstruction cases, and curable resection may obtain better results. Therefore, we suggest that radical operation for B-I patients needs removal of gastroduodenectomy anastomosis and the above LNs, and that B-II patients need removal of 10 cm of jejunum besides gastrojejunostomy anastomosis, and clearance of LN within its mesentery, in addition to B-I GSC.

[Significance of COX-2, p53, proliferating cell nuclear antigen and nm23 expressions in gastric cancer and its behavior].

BACKGROUND & OBJECTIVE: Molecular biological studies indicated that abnormal expression of cyclooxygenase-2(COX-2), p53, proliferating cell nuclear antigen(PCNA), and nm23 correlate with the development of gastric cancer, but the relationship between abnormal expression of above gene proteins and the biological behavior of gastric cancer was not yet clear. This study was designed to investigate the relationship between expressions of COX-2, p53, PCNA, and nm23 and the clinicopathological behavior in gastric cancer. METHODS: The expressions of COX-2, p53, PCNA, and nm23 were detected by using immunohistochemical(SP) method. RESULTS: (1) The overexpression rate of COX-2 in gastric cancer was 70.4% (50/71), and the overexpression of COX-2 was correlated to tumor size, gross morphology, histological type, lymph node metastases, and clinicopathological stage of gastric cancer (P < 0.05, or P < 0.01). (2) The overexpression rates of p53 and PCNA in 71 surgically removed specimens from the patients with gastric cancer were 74.6% and 78.9%, respectively. And the expressions of p53 (86.7%) and PCNA (88.8%) in gastric cancer patients with lymph node metastasis were significantly higher than those in patients without lymph node metastasis (53.8% and 61.5%) (both, P < 0.05), respectively. Moreover, expressions of p53(52.2%) and PCNA(60.9%) in stage I + II patients were lower than those(85.4% and 87.5%) in stage III + IV (both, P < 0.05). (3) The low-expression of nm23 in gastric cancer was 71.8%, and its low-expression rate of nm23 in patients without lymph node metastasis(88.5%) and in stage I + II (91.3%) were much higher than those in the patients with lymph node metastasis (62.2%) and in stage III + IV (62.5%) (respectively, P < 0.05). (4) The differences of histological types, depth of invasion, lymph node metastasis and clinical stage were significantly different(P < 0.05 or P < 0.001), between the patients with two or more genes expression of COX-2, p53, PCNA, and nm23 and those with less one gene expression. CONCLUSION: Our results suggest that abnormal expressions of COX-2, p53, PCNA, and nm23 associate with malignant potential, lymph node metastasis and clinical stage, and they might therefore play a role in development of gastric cancer.