Outcomes of colorectal cancer surgery in nonagenarian patients: a multicenter retrospective study.

BACKGROUND: The use of surgery in patients with colorectal cancer (CRC) aged ≥90 years remains controversial. This study aimed to evaluate the short-term postoperative and long-term oncologic outcomes of CRC surgery in patients within this age group. METHODS: A total of 151 consecutive nonagenarian patients who underwent CRC surgery were included from 3 different hospitals. The Comprehensive Complication Index (CCI) was used to grade postoperative complications. Univariate and multivariate analyses were conducted to identify factors associated with CCI and overall survival (OS). RESULTS: The patients had a mean age of 92.8 years (standard deviation ±1.9 years). Forty-six patients (30.5%) underwent emergency surgery, and 105 patients (69.5%) underwent elective surgery. The postoperative complications rate was 66.2% (100/151), and the mean CCI was 26.3 (±30.8). Twenty-three patients (15.2%) died postoperatively, and the perioperative mortality rates for elective surgery and emergency surgery were 7.6% (8/105) and 32.6% (15/46), respectively (P<0.001). The 1-, 3-, and 5-year survival rates were 77.5%, 53.9%, and 38.6%, respectively. Multivariate analysis revealed emergency surgery and American Society of Anesthesiologists (ASA) score to be predictors of postoperative complications. Advanced tumor stage, palliative surgery, ASA score ≥4, and CCI >17 were associated with poor OS. CONCLUSIONS: CRC surgery should not be denied to nonagenarian patients. Surgical treatment can be performed with acceptable morbidity and mortality, and achieves long-term survival in a select group.

Stent as a bridge to surgery versus urgent surgery for malignant right colonic obstruction: A multicenter retrospective study.

BACKGROUND: The impact of self-expandable metal stent (SEMS) for malignant right colonic obstruction remains undefined. The aim of this study was to compare short-term postoperative and long-term oncologic outcomes of colonic stenting as a bridge to surgery (SBTS) and urgent colectomy for patients with malignant right-sided obstruction. METHODS: A total of 98 consecutive patients who underwent SEMS placement during the period 2004-2015 from three hospitals were included. For comparative analyses, patients were matched (1:2) with 196 patients treated with emergency colectomy from our prospective database. RESULTS: The two groups were comparable in terms of demographics and tumor characteristics. The proportion of patients who underwent laparoscopic colectomy was higher in SBTS group than urgent colectomy group (75.5% vs. 37.2%; p < 0.001). Patients treated with SBTS were less likely to have a temporary stoma constructed (3.1% vs. 10.7%; p = 0.024). SBTS was associated with significantly less median estimated blood loss (90 vs. 100 ml; p = 0.029), shorter length of hospital stay (11 vs. 12 days; p < 0.001), lower overall postoperative complication rate (18.4% vs. 31.3%; p = 0.018), and wound-related complication rate (5.1% vs. 14.3%; p = 0.019) compared with urgent surgery. Reoperation rate, 30-day mortality, and lymph nodes harvested were not significantly different between two groups. Disease-free survival rate and overall survival rate were similar between the two groups. CONCLUSIONS: SEMS insertion is safe and feasible for treating malignant right-sided obstruction. SBTS is associated with better short-term outcomes and equivalent long-term oncologic results compared with urgent colectomy.

[Preliminary report on prospective, multicenter, open research of selective surgery after expandable stent combined with neoadjuvant chemotherapy in the treatment of obstructive left hemicolon cancer].

OBJECTIVE: To evaluate the safety and feasibility of neoadjuvant chemotherapy prior elective surgery following self-expanding metallic stents (SEMS) for complete obstructive left hemicolon cancer. METHODS: This prospective, multicenter, open-labelled trial was approved by the Ethics Committee of Beijing Chaoyang Hospital, Capital Medical University(2016-ke-161-1) and registered in Clinicaltrials.gov (NCT02972541). INCLUSION CRITERIA: (1)age between 18 and 75 years old;(2) adenocarcinoma confirmed by pathology;(3) left hemicolon cancer confirmed by clinical manifestations and imaging examinations with the distance to anal verge > 15 cm; (4) resectable cancer evaluated by imaging examination without distant metastasis; (5) Eastern Cooperative Oncology Group (ECOG) score ≤ 1 or Karnofsky Performance Scale (KPS) > 70, indicating tolerance of neoadjuvant chemotherapy and operation; (6) absence of chemotherapy or radiotherapy within past six months; (7) bone marrow system and hepatorenal function: hemoglobin ≥ 90 g/L, neutrophil ≥ 1.5×109/L, platelet ≥ 80×109/L, total bilirubin ≤ 1.5×ULN(upper limits of normal), serum transaminase ≤ 2.5×ULN, serum creatinine ≤ 1.0×ULN, endogenous creatinine clearance rate > 50 ml/min; (8) sign for informed consent. EXCLUSION CRITERIA: (1) multiple primary colorectal cancer; (2) rejection of operation;(3) presenting peritonitis or bowel perforation before SEMS; (4) unqualified conditions proved by inspector from registration data. According to inclusion criteria, 62 consecutive patients receiving neoadjuvant chemotherapy prior to elective surgery following SEMS for complete obstructive left hemicolon cancer from Beijing Chaoyang Hospital of Capital Medical University (n=31), Qilu Hospital of Shandong University (n=14), the Third Xiangya Hospital of Central South University (n=13), Zhongnan Hospital of Wuhan University (n=2), the Fourth Hospital of Hebei Medical University (n=2) between December 2015 and December 2017 were prospectively enrolled in this study. Patients were divided into neoadjuvant chemotherapy group and elective surgery group according to the investigator's clinical experience and patient's preference. Patients in the elective surgery group received surgery within one to two weeks after SEMS placement without neoadjuvant chemotherapy. Those in the neoadjuvant chemotherapy group received 2 cycles of CapeOX or 3 cycles of mFOLFOX6 neoadjuvant chemotherapy within one to two weeks after SEMS placement, and then underwent surgery within 3 weeks after finishing neoadjuvant chemotherapy. Data between groups were compared using Student t-test, chi-square analysis or Fisher exact test analysis, including basic clinical informations, operational conditions and postoperative complications. The adverse reactions during the neoadjuvant chemotherapy were recorded. Surgical difficulty was assessed using visual analog scales ranging from 1 to 10, where 1 represented the lowest and 10 the highest degree of surgical difficulty, as judged by the surgeon. RESULTS: The study included 38 males and 24 females with mean age of (64.8±8.8) years. The clinical baseline data between 2 groups were not significantly different (all P>0.05) except the average time interval between SEMS and surgery was significantly longer in neoadjuvant chemotherapy group [(61.6±13.5) days vs. (10.4±5.2) days, t=16.679, P<0.001]. There was no stent migration in either group. Three patients had perforation in the elective surgery group; one patient had perforation and one had obstruction in the neoadjuvant chemotherapy group; and all these patients received emergent surgery. Adverse reactions of neodajuvant chemotherapy were mainly degree 1 and 2 except one patient with degree 3 diarrhea. Patients in neoadjuvant chemotherapy group had significantly lower rate of stoma [4.8%(1/21) vs. 34.1%(14/41), χ²=6.538, P=0.011], higher rate of laparoscopic surgery [71.4%(15/21) vs. 36.6%(15/41), χ²=6.751, P=0.009], shorter mean operative time (147 minutes vs. 178 minutes, t=-3.255, P=0.002), less mean intraoperative blood loss (47 ml vs. 127 ml, t=-4.129, P<0.001), lower degree of surgical difficulty(3.3 vs. 5.6, t=-5.091, P<0.001), shorter mean postoperative exhausting time (56.2 hours vs. 69.0 hours, t=-2.891, P=0.006), and shorter mean postoperative hospital stay (8.5 days vs. 13.5 days, t=-2.246, P=0.028) as compared with patients in the elective surgery group. Surgical site infection rate and anastomotic leakage rate did not differ significantly between two groups(all P>0.05). CONCLUSION: Neoadjuvant chemotherapy prior elective surgery following SEMS is a relatively safe and feasible approach in the treatment for obstructive left hemicolon cancer, and is associated with less stoma, more laparoscopic surgery, shorter operative time, less blood loss, lower surgical difficulty, and faster postoperative recovery as compared with conventional elective surgery.

A Distal Resection Margin of ≤1 mm and Rectal Cancer Recurrence After Sphincter-Preserving Surgery: The Role of a Positive Distal Margin in Rectal Cancer Surgery.

BACKGROUND: There is little information about the prognostic value of a microscopically positive distal margin in patients who have rectal cancer. OBJECTIVE: We aimed to investigate the influence of a distal margin of ≤1 mm on oncologic outcomes after sphincter-preserving resection for rectal cancer. DESIGN: This is a retrospective cohort study. SETTINGS: The study was conducted at 2 hospitals. PATIENTS: A total of 6574 patients underwent anterior resection for rectal cancer from January 1999 to December 2014; 97 (1.5%) patients with a distal margin of ≤1 mm were included in this study. For comparative analyses, patients were matched with 194 patients with a negative distal margin (>1 mm) according to sex, age, BMI, ASA score, neoadjuvant treatment, tumor location, and stage. MAIN OUTCOME MEASURES: The oncologic outcomes of the 2 groups were compared. RESULTS: Perineural and lymphovascular invasion rates were significantly higher in patients with a positive distal margin (54.6% vs 28.9%; 67.0% vs 42.8%; both p < 0.001) compared with to patients with negative distal margin. Comparison between microscopically positive and negative distal margin showed worse oncologic outcomes in patients with a microscopically positive distal margin, including 5-year local recurrence rate (24.1% vs 12.0%, p = 0.005); 5-year distant recurrence rate (35.5% vs 20.2%, p = 0.011); 5-year disease-free survival (45.5% vs 69.5%, p < 0.001); and 5-year OS (69.2% vs 79.7%, p = 0.004). Among the 97 patients with a microscopically positive distal margin, the 5-year disease-free survival rate was higher in patients who received adjuvant therapy (52.0% vs 30.7%, p = 0.089). LIMITATIONS: This is a retrospective study; bias may exist. CONCLUSIONS: A distal margin of 1 mm is associated with worse oncologic results. Our data indicate the importance of achieving a clear distal margin in the surgical treatment of rectal cancer. Adjuvant therapy should be used in these patients to reduce recurrence. See Video Abstract at http://links.lww.com/DCR/A408.

Integrated transcriptomic analysis of distance-related field cancerization in rectal cancer patients.

Field cancerization (FC) occurs in various epithelial carcinomas, including colorectal cancer, which indicates that the molecular events in carcinogenesis might occur in normal tissues extending from tumors. However, the transcriptomic characteristics of FC in colorectal cancer (CRC) remain largely unexplored. To investigate the changes in gene expression associated with proximity to the tumor, we analyzed the global gene expression profiles of cancer tissues and histologically normal tissues taken at various distances from the tumor (1 cm, 5 cm and the proximal end of the resected sample) from 32 rectal cancer patients. Significantly differentially expressed genes related to the distance from the tumor were screened by linear mixed effects analysis using the lme4 package in R. The distance-related differentially expressed genes that were gradually up-regulated (n=302) or gradually down-regulated (n=568) from normal tissues to the tumor were used to construct protein-protein interaction (PPI) networks. Three subnetworks among the gradually up-regulated genes and four subnetworks among the gradually down-regulated genes were identified using the MCODE plugin in the Cytoscape software program. The most significantly enriched Gene Ontology (GO) biological process terms were "ribosome biogenesis", "mRNA splicing via spliceosome", and "positive regulation of leukocyte migration" for the gradually up-regulated subnetworks and "cellular calcium ion homeostasis", "cell separation after cytokinesis", "cell junction assembly", and "fatty acid metabolic process" for the gradually down-regulated subnetworks. Combined with the previously constructed multistep carcinogenesis model used for the analysis, 50.59% of the genes in the subnetworks (43/85) displayed identical changes in expression from normal colon tissues to adenoma and colon cancer. We focused on the 7 genes associated with fatty acid metabolic processes in the distance-related down-regulated subnetwork. Survival analysis of patients in the CRC dataset from The Cancer Genome Atlas (TCGA) revealed that higher expression of these 7 genes, especially CPT2, ACAA2 and ACADM, was associated with better prognosis (p = 0.034, p = 0.00058, p = 0.039, p = 0.04). Cox proportional hazards regression analysis revealed that CPT2 was an independent prognostic factor (p = 0.004131). Our results demonstrate that field cancerization occurs in CRC and affects gene expression in normal tissues extending from the tumor, which may provide new insights into CRC oncogenesis and patient progression.

[Analysis of clinicopathologic and survival characteristics in patients with right-or left-sided colon cancer].

OBJECTIVE: This study aimed to clarify the clinical and histological parameters, and survival difference between right- and left-sided colon cancer. METHODS: We retrospectively analyzed the medical records (2006.1-2009.12) of 1 088 consecutive colon cancer patients who received surgery at our hospital. Right- and left-sided colon cancers were compared regarding the clinical and histological parameters. The survival analysis was performed by the Kaplan-Meier method, and the log-rank test was used to determine the statistical significance of differences. RESULTS: Right-sided colon cancer was associated with older age, a more advanced state, and poorly differentiated and undifferentiated adenocarcinoma (25.2% vs 13.2%), mucinous adenocarcinoma (33.5% vs 17.3%) and vascular invasion (9.9% vs 3.9%) were more commonly seen in right-sided colon cancer compared with right-sided colon cancer, and all these differences were statistically significant. Median overall survival was right, 67 months; and left, 68 months. The five-years overall survival of right- and left-sided colon cancer was I/II stage, 91.4% vs 88.6% (P = 0.819); III stage, 66.1% vs 75.4% (P = 0.010); and IV stage, 27.8% vs 38.5% (P = 0.020) respectively. CONCLUSION: Right- and left-sided colon cancers are significantly different regarding clinical and histological parameters. Right-sided colon cancers in stage III and IV have a worse prognosis.

Clinical parameters predicting pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer.

INTRODUCTION: Preoperative chemoradiotherapy (CRT), followed by total mesorectal excision, has become the standard of care for patients with clinical stages II and III rectal cancer. Patients with pathologic complete response (pCR) to preoperative CRT have been reported to have better outcomes than those without pCR. However, the factors that predict the response to neoadjuvant CRT have not been well defined. In this study, we aimed to investigate the impact of clinical parameters on the development of pCR after neoadjuvant chemoradiation for rectal cancer. METHODS: A total of 323 consecutive patients from a single institution who had clinical stage II or III rectal cancer and underwent a long-course neoadjuvant CRT, followed by curative surgery, between 2005 and 2013 were included. Patients were divided into two groups according to their responses to neoadjuvant therapy: the pCR and non-pCR groups. The clinical parameters were analyzed by univariate and multivariate analyses, with pCR as the dependent variable. RESULTS: Of the 323 patients, 75 (23.2%) achieved pCR. The two groups were comparable in terms of age, sex, body mass index, tumor stage, tumor location, tumor differentiation, radiation dose, and chemotherapy regimen. On multivariate analysis, a pretreatment carcinoembryonic antigen (CEA) level of ≤ 5 ng/mL [odds ratio (OR) = 2.170, 95% confidence interval (CI) = 1.195-3.939, P = 0.011] and an interval of >7 weeks between the completion of chemoradiation and surgical resection (OR = 2.588, 95% CI = 1.484-4.512, P = 0.001) were significantly associated with an increased rate of pCR. CONCLUSIONS: The pretreatment CEA level and neoadjuvant chemoradiotherapy-surgery interval were independent clinical predictors for achieving pCR. These results may help clinicians predict the prognosis of patients and develop adaptive treatment strategies.

Outcome of Laparoscopic Versus Open Resection for Transverse Colon Cancer.

BACKGROUND: Laparoscopic resection for transverse colon cancer remains controversial. The aim of this study is to investigate the short- and long-term outcomes of laparoscopic surgery for transverse colon cancer. METHODS: A total of 278 patients with transverse colon cancer from a single institution were included. All patients underwent curative surgery, 156 patients underwent laparoscopic resection (LR), and 122 patients underwent open resection (OR). The short- and long-term results were compared between two groups. RESULTS: Baseline demographic and clinical characteristics were comparable between two groups. Conversions were required in eight (5.1 %) patients. LR group was associated with significantly longer median operating time (180 vs. 140 min; P < 0.001). Median estimated blood loss was significantly less in LR group (90 vs. 100 ml; P = 0.001). Time to first flatus and oral intake was significantly earlier in LR group. Perioperative mortality and morbidity rate were not significantly different between two groups. Tumor size, number of lymph nodes harvested, length of proximal, and distal resection margin were comparable between two groups. Postoperative hospital stay was significantly shorter in LR group (9 vs. 10d; P < 0.001). Five-year disease-free survival and overall survival rate were similar between two groups. CONCLUSIONS: Laparoscopic resection for transverse colon cancer is associated with better short-term outcomes and equivalent long-term oncologic outcomes.

Impact of previous abdominal surgery on the outcome of laparoscopic resection for colorectal cancer: a case-control study in 756 patients.

BACKGROUND: A history of previous abdominal surgery (PAS) may increase the complexity of laparoscopic colorectal surgery. The aim of this study was to investigate the impact of PAS on the outcomes of laparoscopic colorectal resection for colorectal cancer. METHODS: A total of 378 colorectal cancer patients (group A) with a history of PAS were 1:1 matched to 378 controls (group B) without PAS from our prospective laparoscopic colorectal surgery database. The two groups were matched for age, gender, body mass index, American Society of Anesthesiology score, tumor location, type of surgical procedure, and tumor stage. RESULTS: Patients in the two groups were well balanced with respect to baseline demographic and clinical characteristics. Group A was associated with significantly longer median operating time (220 versus 200 min; P = 0.002). Conversion rate in group A (63/378, 16.67%) was almost twice as high as that in group B (36/378, 9.55%; P = 0.004). Conversions caused by adhesion were more common in patients with a history of PAS (55.56% [35/63] versus 27.78% [10/36], P = 0.008). Postoperative recovery time, length of postoperative hospital stay, perioperative mortality and morbidity rate, lymph nodes harvested, circumferential resection margin positive rate, 3-y disease-free survival, and overall survival rate were not significantly different between the two groups. CONCLUSIONS: Laparoscopic colorectal surgery for colorectal cancer patients with PAS is time consuming, but the incidence of a successfully completed laparoscopic colorectal resection remains high, and the short- and long-term outcomes are not affected by PAS.

[Short-term outcomes of incisionless laparoscopic low anterior resection using prolapsing technique for rectal cancer].

OBJECTIVE: Laparoscopic-assisted surgery for colorectal cancer has been widely spread worldwide. To avoid the invasiveness of abdominal wound and get better good-looking, incisionless laparoscopic low anterior resection with transanal natural orifice specimen extraction using prolapsing technique for rectal cancer has been developed in our center. The aim of this study was to evaluate the feasibility, safety and short-term outcomes of this technique. METHODS: From January 2013 to October 2013, twenty-seven patients with rectal carcinoma were treated by incisionless laparoscopic low anterior resection, and the data of these patients were collected and retrospectively analyzed to assess the value of this technique. RESULTS: All operations were successfully accomplished without conversion to open surgery or laparoscopic-assisted surgery. The mean operation time was 135 minutes. The mean blood loss was 50 ml. The mean first bowel movement was 48 hours. The post-operative hospital stay was 9 days. All patients had clean distal margin and the mean number of dissected lymph nodes was 18. One patient had anastomotic leakage. CONCLUSIONS: Incisionless laparoscopic low anterior resection with transanal natural orifice specimen extraction using prolapsing technique for rectal cancer appears to be feasible, safe and oncologically acceptable with a satisfactory short-term outcome for selected cases.

Treatment of human thyroid carcinoma cells with the g47delta oncolytic herpes simplex virus.

BACKGROUND: Thyroid carcinoma is the most common malignancy of the endocrine organs. Although the majority of thyroid cancer patients experience positive outcomes, anaplastic thyroid carcinoma is considered one of the most aggressive malignancies. Current therapeutic regimens do not confer a significant survival benefit, and new therapies are urgently needed. Oncolytic herpes simplex virus (oHSV) may represent a promising therapy for cancer. In the present study, we investigated the therapeutic effects of a third-generation HSV vector, G47Δ, on various human thyroid carcinoma cell lines in vitro. Two subcutaneous (s.c.) models of anaplastic thyroid carcinoma were also established to evaluate the in vivo anti-tumor efficacy of G47Δ. MATERIALS AND METHODS: The human thyroid carcinoma cell line ARO, FRO, WRO, and KAT-5, were infected with G47Δat different multiplicities of infection (MOIs) in vitro. The survival rates of infected cells were calculated each day. Two s.c. tumor models were established using ARO and FRO cells in Balb/c nude mice, which were intratumorally (i.t.) treated with either G47Δor mock. Tumor volumes and mouse survival times were documented. RESULTS: G47Δ was highly cytotoxic to different types of thyroid carcinomas. For ARO, FRO, and KAT-5, greater than 30% and 80% of cells were killed at MOI=0.01 and MOI=0.1, respectively on day 5. WRO cells displayed modest sensitivity to G47Δ, with only 21% and 38% of cells killed. In the s.c. tumor model, both of the anaplastic thyroid carcinoma cell lines (ARO and FRO) were highly sensitive to G47Δ G47Δ significantly inhibited tumor growth and prolonged the survival of mice bearing s.c. ARO and FRO tumors. CONCLUSIONS: The oHSV G47Δ can effectively kill different types of human thyroid carcinomas in vitro. G47Δ significantly inhibited growth of anaplastic thyroid carcinoma in vivo and prolonged animal survival. Therefore, G47Δ may hold great promise for thyroid cancer patients.

Short-term outcomes for laparoscopy-assisted distal gastrectomy for body mass index ≥30 patients with gastric cancer.

BACKGROUND: Obesity is known to be a preoperative risk factor for gastric cancer surgery. This study aimed to investigate the influence of obesity on the surgical outcomes of laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer. METHODS: The clinical data of 131 patients with gastric cancer from January 2010-December 2013 were analyzed retrospectively. Perioperative outcomes were compared between 43 patients with a body mass index (BMI) ≥30 kg/m(2) (obese group) and 88 patients with a BMI <30 kg/m(2) (nonobese group) who underwent LADG. RESULTS: Operation times were significantly longer for the obese group than for the nonobese group (234.1 ± 57.2 min versus 212.2 ± 43.5 min, P = 0.026). There were no statistically significant differences between two groups in terms of intraoperative blood loss, the number of retrieved lymph nodes, postoperative recovery, and postoperative complications (P > 0.05). During the follow-up period of 5 mo-49 mo (average, 36 mo), the overall survival rates were not significantly different between the two groups (80.0% [32/40] versus 81.9% [68/83], P > 0.05). The differences in recurrence and metastasis between the two groups were not statistically significant. CONCLUSIONS: Our analysis revealed that LADG can be safely performed in patients with BMI ≥30. The procedure was considered to be difficult but sufficiently feasible.

Outcome of laparoscopic versus open resection for rectal cancer in elderly patients.

BACKGROUND: Laparoscopic colorectal resection has been gaining popularity over the past two decades. However, studies about laparoscopic rectal surgery in elderly patients with long-term oncologic outcomes are limited. In this study, we evaluated the short-term and long-term outcomes of laparoscopic and open resection in patients with rectal cancer aged ≥ 70 y. METHODS: From 2007-2012, a total of 294 consecutive patients with rectal cancer from a single institution were included, 112 patients undergoing laparoscopic rectal resection were compared with 182 patients undergoing open rectal resection. RESULTS: Seven (6.3%) patients in the laparoscopic group required conversion to open surgery. The two groups were well balanced in terms of age, gender, body mass index, American society of anesthesiologists scores, site, and stage of the tumors. Laparoscopic surgery was associated with significantly longer median operating time (220 versus 200 min; P = 0.005), less estimated blood loss (100 versus 150 mL; P < 0.001), a shorter postoperative hospital stay (8 versus 11 d), lower overall postoperative complication rate (15.2% versus 26.4%; P = 0.025), wound-related complication rate (7.14% versus 17.03%; P = 0.015), less need of blood transfusion (8.04% versus 16.5%; P = 0.038), and surgical intensive care unit after surgery (12.5% versus 22.0%; P = 0.042) when compared with open surgery. Mortality, quality of surgical specimen, lymph nodes harvested, positive distal, and circumferential margin rate were not significantly different between two groups. The estimated 3-y survival rates were similar between two groups. CONCLUSIONS: Laparoscopic rectal surgery is safe and feasible in patients >70 y and is associated with better short-term outcomes when compared with open surgery.

Treatment of human hepatocellular carcinoma by the oncolytic herpes simplex virus G47delta.

BACKGROUND: Oncolytic herpes simplex virus (HSV) can replicate in and kill cancer cells while sparing the adjacent normal tissue. Hepatocellular carcinoma (HCC) is amongst the most common and lethal cancers, especially in Third World countries. In this study, the cytotoxicity of a third-generation oncolytic HSV, G47Δ, was investigated in different human HCC cell lines and in an immortalized human hepatic cell line. Additionally, subcutaneous models of HCC were established to evaluate the in vivo anti-tumor efficacy of G47Δ. METHODS: The HepG2, HepB, SMMC-7721, BEL-7404, and BEL-7405 human HCC cell lines and the HL-7702 human hepatic immortalized cell lines were infected with G47Δ at different multiplicities of infection (MOIs). The viability of infected cells was determined, and the G47Δ replication was identified by X-gal staining for LacZ expression. Two subcutaneous (s.c.) HCC tumor models of HCC were also established in Balb/c nude mice, which were intratumorally(i.t.) treated with either G47Δ or mock virus. Tumor volume and mouse survival times were documented. RESULTS: More than 95% of the HepG2, Hep3B,and SMMC-7721 HCC cells were killed on by day 5 after infection with a MOI's of 0.01. For the HL-7702 human hepatic immortalized cells, 100% of the cells were killed on by day 5 after infection with a MOI's of 0.01. The BEL-7404 HCC cell line was less susceptible with about 70% cells were killed by day 5 after infection with a MOI's of 0.01. Whereas the BEL-7405 HCC cells were the least susceptible, with only 30% of the cells were killed. Both the SMMC-7721 and BEL-7404 cells form aggressive sc tumor models. G47Δ replicates in the tumors, such that most of the tumors regressed after the G47Δ-treatment, and treated tumor-bearing mice survived much longer than the control animals. CONCLUSIONS: G47Δ effectively kills human HCC cells and an immortalized hepatic cell line at low MOI. Intra-tumor injection of G47Δ can induce a therapeutic effect and prolong the survival of treated mice bearing SMMC-7721 and BEL-7404 subcutaneously (s.c.) tumors. Thus, G47Δ may be useful as a novel therapeutic agent for HCC.

Lymph node ratio is an independent prognostic factor in node positive rectal cancer patients treated with preoperative chemoradiotherapy followed by curative resection.

BACKGROUND: The lymph node ratio (LNR) has been shown to be an important prognostic factor for colorectal cancer. However, studies focusing on the prognostic impact of LNR in rectal cancer patients who received neoadjuvant chemoradiotherapy (CRT) followed by curative resection have been limited. The aim of this study was to investigate LNR in rectal cancer patients who received neoadjuvant chemoradiotherapy (CRT) followed by curative resection. MATERIALS AND METHODS: A total of 131 consecutive rectal cancer patients who underwent neoadjuvant CRT and total mesorectal excision were included in this study. Patients were divided into two groups according to the LNR (≤ 0.2 [n=86], >0.2 [n=45]) to evaluate the prognostic effect on overall survival (OS) and disease-free survival (DFS). RESULTS: The median number of retrieved and metastatic lymph node (LN) was 14 (range 1-48) and 2 (range 1-10), respectively. The median LNR was 0.154 (range 0.04-1.0). In multivariate analysis, LNR was shown to be an independent prognostic factor for both overall survival (hazard ratio[HR]= 3.778; 95% confidence interval [CI] 1.741-8.198; p=0.001) and disease-free survival (HR=3.637; 95%CI 1.838- 7.195; p<0.001). Increased LNR was significantly associated with worse OS and DFS in patients with <12 harvested LNs, and as well as in those ≥ 12 harvested LNs (p<0.05). In addition, LNR had a prognostic impact on both OS and DFS in patients with N1 staging (p<0.001). CONCLUSIONS: LNR is an independent prognostic factor in ypN-positive rectal cancer patients, both in patients with <12 harvested LNs, and as well as in those ≥ 12 harvested LNs. LNR provides better prognostic value than pN staging. Therefore, it should be used as an additional prognostic indicator in ypN-positive rectal cancer patients.

Impact of interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer on surgical and oncologic outcome.

BACKGROUND: The aim of this study was to evaluate the effect of a longer interval between long-course neoadjuvant chemoradiotherapy and surgery on surgical and oncologic outcome. METHODS: A total of 233 consecutive patients with clinical stage II and III rectal cancer were divided into 2 groups according to the neoadjuvant-surgery interval: short-interval group (≤ 7 weeks, n = 111), and long-interval group (>7 weeks, n = 122). Data on neoadjuvant-surgery interval, operative time, perioperative complications, final pathology, disease recurrence, and mortality were prospectively collected and analyzed. RESULTS: The two groups were comparable in terms of demographics, tumor, and treatment characteristics. Operative time and perioperative complications were not influenced by a longer interval. Patients in the long-interval group had a significantly higher pathologic complete response (pCR) rate (27.1% vs. 15.3%, P = 0.029), and a decreased rate of circumferential resection margin involvement (1.6% vs. 8.1%, P = 0.020). After a median follow-up of 42 months (range 6-90 months), the 3-year local recurrence rate was 12.9% in the short-interval group versus 4.8% in the long-interval group (P = 0.025). CONCLUSIONS: A neoadjuvant-surgery interval >7 weeks is safe and is associated with a higher rate of pCR and R0 resection, and decreased local recurrence.

Prognostic factors for desmoid tumor: a surgical series of 233 patients at a single institution.

Desmoid tumors are rare soft tissue tumors with limited data on their management and prognosis. We sought to determine the rates of recurrence after surgery for desmoid tumors and analyze factors predictive of recurrence-free survival (RFS). From February 1976 to October 2011, 233 consecutive patients with desmoid tumors who underwent macroscopically complete resection were included in this study. Clinicopathologic and treatment characteristics were evaluated to determine predictors of recurrence. Patterns of presentation included primary (n = 156, 67.0 %) and locally recurrent (n = 77, 33.0 %) disease initially treated elsewhere. Most patients had a R0 resection (n = 169, 72.5 %). In addition to surgery, 43 (18.5 %) patients received radiotherapy and 10 (4.3 %) patients received systemic therapy. Median follow-up was 54 months; recurrence disease was observed in 62 (26.6 %) patients. The estimated 5- and 10-year RFS was 74.2 % (95 % confidence interval (CI), 68.3-80.1) and 70.7 % (95 % CI, 64.2-77.2), respectively. Factors associated with worse RFS were tumor size larger than 5 cm (hazard ratio (HR) = 3.757; 95 % CI, 1.945-7.259; p < 0.001), extra-abdominal tumor location (abdominal wall referent; HR = 3.373; 95 % CI, 1.425-7.984; p = 0.006), and R1 resection status (HR = 1.901; 95 % CI, 1.140-3.171; p = 0.014). Patients were grouped according to the number of unfavorable prognostic factors; the 10-year RFS rates of patients with zero, one, two, and three prognostic factors were 100, 86.9, 48.5, and 34.4 %, respectively (p < 0.001). Regardless of primary or recurrent disease, surgical resection remains central to the management of patients with desmoid tumors. However, there are clearly different prognostic subgroups that could benefit from different therapeutic strategies, and a wait-and-see policy is a possible option for a subset of patients.

Predictive factors for lymph node metastasis in early gastric cancer with signet ring cell histology and their impact on the surgical strategy: analysis of single institutional experience.

BACKGROUND: The prognosis of early gastric cancer (EGC) with signet ring cell histology is more favorable than other undifferentiated gastric adenocarcinomas. An accurate assessment of potential lymph node metastasis is important for the appropriate treatment of EGC with signet ring cell histology. Therefore, this study analyzed the predictive factors associated with lymph node metastasis in patients with this type of EGC. METHODS: A total of 136 EGC with signet ring cell histology patients who underwent D2 radical gastrectomy were reviewed in this study. The clinicopathologic features were analyzed to identify predictive factors for lymph node metastasis. RESULTS: The overall rate of lymph node metastasis in EGC with signet ring cell histology was 10.3%. Using a univariate analysis, the risk factors for lymph node metastasis were identified as the tumor size, depth of tumor invasion, and lymphovascular invasion. The multivariate analysis revealed that tumor size >2 cm, submucosal invasion, and lymphovascular invasion were independent risk factors of lymph node metastasis (P < 0.05). CONCLUSIONS: The risk of lymph node metastasis of EGC with signet ring cell histology was high in those with tumor sizes ≥2 cm, submucosal tumors, and lymphovascular invasion. A minimally invasive treatment, such as endoscopic resection, might be possible in highly selective cases of EGC with signet ring cell histology with intramucosal invasion, tumor size <2 cm, and no lymphovascular invasion.

Mini-invasive surgery for colorectal cancer.

Laparoscopic techniques have been extensively used for the surgical management of colorectal cancer during the last two decades. Accumulating data have demonstrated that laparoscopic colectomy is associated with better short-term outcomes and equivalent oncologic outcomes when compared with open surgery. However, some controversies regarding the oncologic quality of mini-invasive surgery for rectal cancer exist. Meanwhile, some progresses in colorectal surgery, such as robotic technology, single-incision laparoscopic surgery, natural orifice specimen extraction, and natural orifice transluminal endoscopic surgery, have been made in recent years. In this article, we review the published data and mainly focus on the current status and latest advances of mini-invasive surgery for colorectal cancer.

Evaluation of short-term outcomes after laparoscopically assisted abdominoperineal resection for low rectal cancer.

BACKGROUND: To investigate the feasibility, safety and short-term efficacy of laparoscopic techniques applied in the abdominoperineal resection (APR) for low rectal cancer. METHODS: The clinical data of 236 patients with APR from January 2010 to January 2012 were analysed retrospectively, including 100 patients underwent laparoscopically assisted APR (LAAPR group), 136 cases of open APR (OAPR group). The demographics, tumor and procedure-related parameters, perioperative results and short-term oncological outcomes were evaluated using t-test or χ(2) -test. RESULTS: The demographic data of the two groups were comparable. Perioperative results were better after laparoscopic surgery, with less intraoperative blood loss (P = 0.017), earlier return of bowel function (P < 0.05) and lower complication rates (P = 0.015). No significant differences were detected between the two groups in operation time, tumor size, specimen length, the distance of tumor from the anal verge, lymph nodes removed and the status of circumferential resection margin (P > 0.05). During the follow-up period of 17-38 months (average, 26 months), the overall survival rates were not significantly different between the two groups [82.5% (80/97) versus 82.7% (110/133), P > 0.05]. The differences in recurrence and metastasis between the two groups were not statistically significant. CONCLUSION: Laparoscopically assisted APR for low rectal cancer is safe and effective. It has the advantages of less bleeding, rapid postoperative recovery and fewer complications, without affecting the radical degree of the surgery. Further studies are needed to fully assess oncological outcomes in the future.