Should Positive Cytology Revealed by Intraoperative Lavage Preclude Radical Resection in Resectable Pancreatic Cancer?: A Systemic Review and Meta-analysis.

OBJECTIVES: The aims of this review were to determine whether positive peritoneal lavage cytology (CY+) precludes radical resection in pancreatic cancer and to propose prospections for future studies. METHODS: MEDLINE, Embase, and Cochrane Central were searched for related articles. Dichotomous variables and survival outcomes were analyzed with the estimation of odds ratio and hazards ratio (HR), respectively. RESULTS: A total of 4905 patients were included, of which 7.8% were CY+. Positive peritoneal lavage cytology was correlated with poor overall survival (univariate survival analysis [HR, 2.35; P < 0.00001]; multivariate analysis [HR, 1.62; P < 0.00001]), poor recurrence-free survival (univariate survival analysis [HR, 2.50; P < 0.00001]; multivariate analysis [HR, 1.84; P < 0.00001]), and higher initial peritoneal recurrence rate (odds ratio, 5.49; P < 0.00001). CONCLUSIONS: Although CY+ predicts poor prognosis and a higher risk of peritoneal metastasis after curative resection, it is not sufficient to preclude curative resection based on the current evidence, and high-quality trials should be conducted to assess the prognostic impact of operation among resectable CY+ patients. In addition, more sensitive and accurate methods to detect peritoneal exfoliated tumor cells and more effective comprehensive treatment for resectable CY+ pancreatic cancer patients are clearly warranted.

The eighth version of American Joint Committee on Cancer nodal classification for high grade pancreatic neuroendocrine tumor should be generalized for the whole population with this disease.

Several indexes evaluating the lymph node metastasis of pancreatic neuroendocrine tumor (pNET) have been raised. We aimed to compare the prognostic value of the indexes via the analysis of Surveillance, Epidemiology, and End Results (SEER) database.We identified pNETs patients from SEER database (2004-2015). The prognostic value of N classification which adopted the 8th American Joint Committee on Cancer (AJCC) N classification for well differentiated pNET, revised N classification (rN) which adopted the AJCC 8th N classification for exocrine pancreatic cancer (EPC) and high grade pNET, lymph node ratio and log odds of positive nodes were analyzed.A total of 1791 eligible patients in the SEER cohort were included in this study. The indexes N, rN, lymph node ratio, and log odds of positive nodes were all significant independent prognostic factors for the overall survival. Specifically, the rN had the lowest akaike information criterion of 4050.19, the highest likelihood ratio test (χ) of 48.87, and the highest C-index of 0.6094. The rN was significantly associated with age, tumor location, tumor differentiation, T classification and M classification (P < .05 for all).The 8th version of AJCC N classification for high grade pNET could be generalized for the pNET population.

Preoperative neutrophil-to-lymphocyte ratio and tumor-related factors to predict lymph node metastasis in patients with pancreatic ductal adenocarcinoma (PDAC).

As a poor prognosis indicator in patients with pancreatic ductal adenocarcinoma (PDCA), lymph node (LN) metastasis is of great importance in treatment. Present study was performed to evaluate the predictive value of preoperative neutrophil-to-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR) and possible clinical parameters on the LN metastasis in PDCA patients. A total of 159 operable patients with PDCA were enrolled in our study. The clinical utility of NLR and other clinical parameters was evaluated by receiver operating characteristic (ROC) curves. Overall survival analysis indicated that LN metastasis is an independent prognostic factor. The logistic analysis was used to determine the independent parameters associated with LN metastasis. Ideal cutoff values for predicting LN metastasis are 2.12 for NLR and 130.96 for PLR according to the ROC curve. Multivariate analyses indicate that NLR (HR 2.588; 95% CI 1.246-5.376; P = 0.011), CA125 (HR 6.348; 95% CI 2.056-19.594; P = 0.001) and CA19-9 (HR 2.738; 95% CI 1.151-6.515; P = 0.023) are associated significantly with LN metastasis independently. Preoperative NLR, CA125 and CA19-9 are useful biomarkers for the prediction of LN metastasis in PDCA patients.

Postoperative pancreatic fistula in distal pancreatectomy: experience from 1 institution.

OBJECTIVE: Postoperative pancreatic fistula (POPF) and readmission remain the significant sources of morbidity after distal pancreatectomy (DP). We describe a technique of drainage and postoperation management to prevent severe POPF and readmission. METHODS: A retrospective analysis of 57 patients who underwent DP from January 2009 to November 2011 was conducted. The drain was placed just abutting the pancreatic stump by suturing the tissue near the stump. Each patient was discharged carrying an intraabdominal drain, and a strict follow-up was made in the outpatient clinic. Postoperative pancreatic fistula was defined using the international study group classification for pancreatic fistula definition. RESULTS: Thirty-two patients accepted laparoscopic DP (LDP), and 25 patients accepted open DP (ODP). There was no significant difference in the rate of POPF between the 2 groups (12/32 vs 11/25, P = 0.786). All the POPF cases were grades A and B, but no case was grade C. No case needed a specific intervention. There was no reoperation, readmission, intraabdominal abscess, or surgical site infection. CONCLUSIONS: We conclude that our technique of drainage and postoperation management is associated with a low incidence of severe POPF and readmission. Continued investigation of this technique is warranted.

[Outcomes evaluation of laparoscopic radical coloproctectomy and hepatectomy for resectable colorectal cancer with liver metastases].

OBJECTIVE: To explore the feasibility and safety of laparoscopic radical coloproctectomy and hepatectomy for resectalble colorectal cancer with liver metastases (CRCLM), and evaluate the survival outcomes of short-middle term for these patients. METHODS: Totally 36 cases of CRCLM which were evaluated to undergo laparoscopic coloproctectomy and hepatectomy preoperatively, were enrolled from January 2009 to January 2014, including 28 synchronous and 8 metachronous CLM respectively. Laparoscopic colorectal resection and hepatectomies were performed in 35 cases, including 24 male and 11 female patients, with a mean age of (64 ± 12) years and a median age of 67 years (ranging from 35 to 80 years). Management strategies were made by a board of multi-disciplinary team. Intra-operative ultrasonography was used to detect the metastases in all cases. Overall survival and disease free survival were calculated by Kaplan-Meier curve. RESULTS: Radical total colectomy, right hemicolectomy, left hemicolectomy, sigmoidectomy, and proctectomy and were performed in 1 case of familial adenomatous polyposis with transverse colon cancer, 5 cases of cecal or asending colon cancer, 1 case of descending colon cancer, 14 cases of sigmoid colon cancer, and 14 cases of rectal cancer respectively. Metastasectomy only, anatomic hepatectomy only, and metastasectomy plus anatomic hepatectomy were done in 21, 10 and 4 cases respectively. Totally 35 colorectal tumors and 62 liver lesions were removed. The mean blood loss of colorectal and liver surgery were (80 ± 32) and (212 ± 153) ml, the median blood loss was 70 ml and 150 ml respectively. Colorectal and hepatic specific complications were not observed in all cases except a case of biliary leakage following right hemihepatectomy. Relapses were observed in 15 cases during a mean follow-up of (26 ± 16) months (median follow-up of 22 months). Four cases died of late-stage cachexia. The 1- and 3-year cumulative overall survival rates were 92.9% and 79.4% respectively. The 1- and 3-year cumulative disease free survival rates were 61.1% and 49.4% respectively. CONCLUSIONS: Laparoscopic coloproctectomy and hepatectomy for resectable CRCLM in carefully selected cases is safe and feasible, which makes simultaneous surgery possible. The oncologic outcome of short-middle term is acceptable, and long-term survival is expected.

Oncogenic function of DACT1 in colon cancer through the regulation of ß-catenin.

The Wnt/ß-catenin signaling pathway plays important roles in the progression of colon cancer. DACT1 has been identified as a modulator of Wnt signaling through its interaction with Dishevelled (Dvl), a central mediator of both the canonical and noncanonical Wnt pathways. However, the functions of DACT1 in the WNT/ß-catenin signaling pathway remain unclear. Here, we present evidence that DACT1 is an important positive regulator in colon cancer through regulating the stability and sublocation of ß-catenin. We have shown that DACT1 promotes cancer cell proliferation in vitro and tumor growth in vivo and enhances the migratory and invasive potential of colon cancer cells. Furthermore, the higher expression of DACT1 not only increases the nuclear and cytoplasmic fractions of ß-catenin, but also increases its membrane-associated fraction. The overexpression of DACT1 leads to the increased accumulation of nonphosphorylated ß-catenin in the cytoplasm and particularly in the nuclei. We have demonstrated that DACT1 interacts with GSK-3ß and ß-catenin. DACT1 stabilizes ß-catenin via DACT1-induced effects on GSK-3ß and directly interacts with ß-catenin proteins. The level of phosphorylated GSK-3ß at Ser9 is significantly increased following the elevated expression of DACT1. DACT1 mediates the subcellular localization of ß-catenin via increasing the level of phosphorylated GSK-3ß at Ser9 to inhibit the activity of GSK-3ß. Taken together, our study identifies DACT1 as an important positive regulator in colon cancer and suggests a potential strategy for the therapeutic control of the ß-catenin-dependent pathway.

[A clinical study on multi-disciplinary team and surgery for resectable colorectal cancer with liver metastases].

OBJECTIVES: To analyze the survival outcomes of the surgery for colorectal cancer with liver metastases (CRCLM), and study the mode of multi-disciplinary team (MDT) for CRCLM. METHODS: The retrospective analysis was conducted for 38 patients with CRCLM received MDT management and surgical treatment from January 2009 to August 2011. The peri-operative and survival outcomes of MDT and surgery were evaluated. RESULTS: All the cases met the present criteria of resetability for CRCLM, but only 4 cases (10.5%) met the previous one. Coloproctectomy and hepatectomy were performed in all cases, with 39 colorectal neoplasms and 155 liver lesions removed. One case died of postoperative septic shock. Colorectal and hepatic specific complications were absent in the others patients except one case of biliary leak which was treated with conservative management. Neoadjuvant chemotherapy was arranged in 13 cases. Adjuvant chemotherapy was administered for every patient. After a mean follow-up of (22 ± 10) months according to the finding time of liver metastases, recurrence and metastases were observed in 16 cases and 6 cases died of late-stage cachexia. The 1-, 2- and 3-overall survival rate were 94.4%, 85.3% and 75.8% respectively, and the 1-, 2- and 3-disease-free survival rate were 70.1%, 54.2% and 54.2% respectively. CONCLUSIONS: MDT mode for resectable CRCLM is recommendable. Surgical resection of CRCLM is feasible and safe, which seems to achieve favourable short-middle oncologic outcomes. And long-term survival is expected.