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SKP2 High Expression, KIT Exon 11 Deletions, and Gastrointestinal Bleeding as Predictors of Poor Prognosis in Primary Gastrointestinal Stromal Tumors

Background and Aims Considering the indication of adjuvant therapy, the recurrence risk for primary gastrointestinal stromal tumor (GIST) after surgery needs to be accurately estimated. However, current risk stratification schemes may still have room for improvement. This study seeks to analyze prognostic factors for primary GISTs from 3 aspects, including clinicopathological parameters, immunohistochemical biomarkers, and gene mutational status, and attempts to find novel valuable factors predicting the malignancy potential of GISTs. Methods Retrospective data from 114 primary GIST patients after R0 resection were collected. Clinicopathological data was obtained from medical records and re-evaluated. Immunohistochemical analysis was performed using the Tissue Microarray method for Ki67, p16, p27, p53, SKP2, CD133, and actin. KIT gene exons 9, 11, 13, and 17 and PDGFRα gene exons 12 and 18 were tested for mutations using PCR. Results Univariate analysis revealed the following factors as poor prognostic indicators for relapse-free survival with a median follow-up of 50 months: male gender, gastrointestinal bleeding, mitotic index >5/50HPFs, tumor size >5 cm, non-gastric site, necrosis, epithelioid or mixed cell type, surrounding tissue invasion, Ki67>5%, p16>20%, p53 index >10, SKP2>10%, and KIT exon 11 deletion. Besides mitotic index, tumor size and site, SKP2 high expression (RR = 2.91, 95% CI: 1.41–5.99, P = 0.004) and KIT exon 11 deletion (RR = 2.73, 95% CI: 1.04–7.16, P = 0.041) were also independent risk factors in multivariate analysis, with gastrointestinal bleeding also showing a trend towards significance (RR = 1.88, 95% CI: 0.98–3.64, P = 0.059). In addition, gastrointestinal bleeding and SKP2 high expression showed a good ability to stratify high-risk patients further. Conclusion Our results show that gastrointestinal bleeding, SKP2 high expression, and KIT exon 11 deletions may be useful indicators of high recurrence risk for primary GIST patients.

Management of Delayed Post-Pancreaticoduodenectomy Arterial Bleeding: Interventional Radiological Treatment First

Objective: To investigate the diagnosis and treatment of delayed post-pancreaticoduodenectomy arterial bleeding (DPPAB). Methods: Records of 336 patients who underwent pancreaticoduodenectomy (PD) between January 2000 and December 2010 were retrospectively analyzed. Detailed data of patients with DPPAB were assessed by a thorough review of medical records. Results: 14 patients developed DPPAB. The mean time interval between the initial surgery and DPPAB was 33 days (range 7–72). Three patients experienced sentinel bleeding 5–8 days before DPPAB. All DPPAB patients had intra-abdominal septic complications before bleeding. The overall prevalence of success of angiography and transcatheter arterial embolization (TAE) was 85.7% (12/14), including 3 patients who achieved complete hemostasis by TAE after unsuccessful re-laparotomy. The prevalence of mortality of DPPAB was 28.6% (4/14). After hemostasis was achieved, intra-abdominal septic complications were controlled by percutaneous catheter drainage or re-laparotomy with drain replacement. Conclusion: Angiography and TAE are recommended as the first-line diagnostic and treatment choice for DPPAB, respectively. Surgical intervention should be preserved to eliminate the cause of bleeding.

Castleman disease of the mesentery as the great mimic: Incidental finding of one case and the literature review

Castleman disease is an uncommon benign lymphoproliferative disorder characterized by hyperplasia of lymphoid follicles. More commonly described in the mediastinum, its occurrence in the mesentery is exceedingly rare, which is easily to be ignored in differential diagnosis when an abdominal mass is found. We report the case of an asymptomatic 71-year-old woman with a homogenous and hypervascular mass at the inner side of duodenojejunal junction. Based on the clinical suspicion of a gastrointestinal stromal tumor, a surgical resection was performed. Final diagnosis of the mass was hyaline vascular variant of Castleman disease. Here, we summarize the clinicopathological and radiological features of this disease by literature review, which may be helpful to bring awareness of this entity and improve the clinical decision making when similar scenarios are encountered.

Superior mesenteric artery margin in pancreaticoduodenectomy for pancreatic adenocarcinoma

The aim of this study is trying to describe more details of superior mesenteric artery margin in pancreaticoduodenectomy for pancreatic ductal adenocarcinoma, to evaluate biological and prognostic implications of tumor budding in this margin, and to provide more evidence for evaluation of R0 surgery in pancreaticoduodenectomy. 46 patients in 5-years period are included in this study. Immunochemistry and immunofluorescence are used to analyze tumor budding and epithelial–mesenchymal transition. Superior mesenteric artery margin might be described from four aspects including location, gross appearance, microscopic appearance and tumor budding. We find that 1mm rule for R1 surgery is more appropriate to predict prognosis (P = 0.009) than 0mm rule (P = 0.141). Expression of cytokeratin in tumor budding is significantly lower than primary tumor (P = 0.001), and it suggests that tumor budding may participate the procedure of epithelial–mesenchymal transition. High-grade tumor budding and decreasing cytokeratin of tumor budding correlate with distant metastasis and has negative influence on prognosis. So superior mesenteric artery margin might be not only an area that tumor cells may invade, but also a pathway for distant metastasis. It is necessary to evaluate superior mesenteric artery margin in pancreaticoduodenectomy for pancreatic cancer.

A novel scoring system to predict ascites development post hepatectomy for BCLC stage B hepatocellular carcinoma

Background: To develop a novel scoring system to predict the development of post-operative ascites by analyzing clinicopathological characteristics and risk factors of BCLC stage B hepatocellular carcinoma. Methods: Prospective analysis was performed on consecutive patients with BCLC stage B hepatocellular carcinoma, who underwent hepatectomy from January 2005 to December 2014. Results: A total of 181 patients were enrolled, of whom 34.3% (62/181) developed post-operative ascites. Comparing with patients without ascites, patients who developed ascites had longer drain placement, more incidence of pleural effusion, more incidence of intra-abdominal infection and longer inpatient stay. All differences were statistically significant (P Conclusions: The development of post-operative ascites was associated with various clinicopathological factors. The scoring system, which incorporates these factors, provided a valuable means for predicting the development of post-operative ascites. Early identification of these at-risk patients might help to improve their perioperative outcome.

Diagnostic and prognostic value of KRAS mutations in circulating pancreatic ductal adenocarcinoma tumor DNA

Background: Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic tumor and one of the most malignant tumors worldwide. Circulating tumor DNA (ctDNA) has significant diagnostic and prognostic value for cancer patients. Methods: Surgical specimens and plasma samples were obtained from a total of 35 patients with PDAC at the Peking University Cancer Hospital between June 2016 and May 2017. To investigate KRAS mutations (G12R, G12V or G12D) in plasma ctDNA, digital polymerase chain reaction (PCR) was performed on samples obtained from PDAC patients before and after surgical resection. Results: KRAS mutations (G12R, G12V or G12D) between surgical tissue DNA (tDNA) and preoperative plasma ctDNA (pre-ctDNA) were consistent in 27 of 35 samples (77.1%, kappa index =0.397, P=0.003). Moreover, pre-ctDNA and postoperative plasma ctDNA (post-ctDNA) showed statistically significant associations with CA19-9 levels before surgery (P=0.027 and P=0.003, respectively). In addition, the Kaplan-Meier univariate and Cox multivariate analysis revealed that pre-ctDNA (G12V), post-ctDNA (G12V), or pre-post ctDNA (G12V, G12D) might be independent prognostic factors for overall survival (OS) and progression-free survival (PFS). Conclusions: Analysis of pre-ctDNA, post-ctDNA, and pre-post ctDNA showed high PDAC diagnostic and prognostic potential in patients.

Anterior Approach to En Bloc Resection in Left-Sided Retroperitoneal Sarcoma with Adjacent Organ Involvement: A Study of 25 Patients in a Single Center

Background There is no standard surgical approach for the management of retroperitoneal sarcoma. The aim of this clinical study was to describe the experience of an anterior approach to en bloc resection in left-sided retroperitoneal sarcoma with adjacent organ involvement. Material/Methods This retrospective clinical study included 25 patients who were diagnosed with left-sided retroperitoneal sarcoma and underwent tumor resection at a single center between May 2012 and July 2017. All patients had tumors that were adjacent to the left colon, pancreas, left kidney, left adrenal gland, and psoas major; some of the tumors were adjacent to the diaphragm, stomach, and small intestine. An anterior approach was used to remove the left-sided retroperitoneal tumor with the adhesive organs en bloc, an approach that is described in detail. The value of this surgical approach was evaluated based on the histopathological findings, postoperative complications, and patient follow-up. Results The median number of resected organs, in addition to the retroperitoneal tumor, was 8 (range, 6–10). Complete macroscopic tumor resection was achieved in 23 cases (92%). Twenty-four patients (96%) had tumor infiltration of at least one organ or the surrounding fat. Three patients (12%) experienced Grade III and IV postoperative morbidities. The one-year disease-free survival rate was 91.3% among patients with macroscopically complete resections. The one-year overall survival rate was 83.2%. Conclusions In selected patients, left-sided retroperitoneal sarcoma associated with local organ involvement can be surgically managed using an anterior approach with en bloc resection of adjacent organs.

Is Central Pancreatectomy Truly Recommendable? A 9-Year Single-Center Experience

Aims: To compare the short- and long-term outcomes in patients with pancreatic benign or borderline neoplasm who underwent central pancreatectomy (CP) and distal pancreatectomy (DP). Methods: The inclusion criteria were as follows: (1) single benign or low-grade malignant tumor; (2) tumor confined to the pancreatic neck or proximal body; and (3) tumor amenable to either CP or DP. Short and long-term outcomes, including complications, pancreatic exocrine and endocrine function, and quality of life (QoL) were analyzed retrospectively. Results: Sixteen patients who underwent CP and 26 patients who underwent DP were included. The median follow-up period was 53 months (range 21–117 months). Patients undergoing CP were significantly more likely to experience complications (68.7 vs. 23%, p = 0.003) especially grade B/C postoperative pancreatic fistula (62.5 vs. 23%, p = 0.011) than those undergoing DP. During the long-term follow-up, 2 patients in the DP group developed new-onset diabetes mellitus, but no patient in CP group developed this condition (8 vs. 0%, p = 0.382). Evidence of exocrine insufficiency, including severe diarrhea or steatorrhea, was not observed in either group. Both groups were equally satisfied with the overall health status and overall QoL. Conclusion: CP is associated with excellent pancreatic function but a significantly increased postoperative morbidity and risk compared to DP. Therefore, the indication of CP should be chosen strictly.

Infiltration characteristics and influencing factors of retroperitoneal liposarcoma: Novel evidence for extended surgery and a tumor grading system

This study sought to evaluate the infiltration tendency of retroperitoneal liposarcoma (RPLS) from a new pathological angle by exploring the infiltration characteristics, which could provide helpful information to facilitate surgical decision-making and prognosis prediction. Concurrently, we aim to identify significant indicators of infiltration. A total of 61 consecutive patients with RPLS at our institution were retrospectively analyzed. All patients received extended surgery. The tumor infiltration characteristics and influencing factors were studied based on the pathological diagnosis. Univariate and multivariate analyses of organ infiltration (OI) and surrounding fat infiltration (SFI) were performed. OI was found in 95 (28.5%) resected organs from 39 (60.7%) patients, and SFI was found in 119 (35.7%) resected organs from 47 (77%) patients. The tumor infiltrated the serosal layer of 13 organs (13/37, 35.1%), the muscularis layer of 18 organs (18/37, 48.6%) and the submucosa of 6 organs (6/37, 16.2%). The percentage of lipoblasts and the rates of necrosis and mitosis were all significantly higher in high-grade tumors (dedifferentiated, round cell, and pleomorphic). A high lipoblast percentage (≥ 20%) was the only independent risk factor for OI. A recurrent tumor and a high-grade tumor were independent risk factors for SFI. In conclusion, RPLS has a high infiltration tendency, such that it frequently infiltrates organs and surrounding fat tissue. Therefore, extended resection of the tumor and the adjacent organs is recommended. The percentage of lipoblasts was associated with the tumor grade and infiltration characteristics; thus, lipoblast percentage may become a new grading factor for RPLS.

Organ-preserving surgery for locally advanced duodenal gastrointestinal stromal tumor after neoadjuvant treatment

This report aims to investigate the feasibility and outcomes of neoadjuvant imatinib mesylate (IM) administration followed by organ-preserving surgery (OPS) for patients with locally advanced duodenal gastrointestinal stromal tumor (GIST). Between 2012 and 2015, 10 consecutive patients with locally advanced duodenal GISTs were treated in Peking University Cancer Hospital. Multidisciplinary assessment was implemented, and pancreaticoduodenectomy (PD) was initially indicated as the most probable surgical procedure for all 10 patients. To attempt to create opportunities of less-invasive OPS for patients, neoadjuvant IM was administered followed by radical resection. All data were prospectively collected, and the short- and long-term outcomes of the treatment strategy were analyzed. The median treatment duration of neoadjuvant IM administration was 5 mo (range 2-18 mo). Significant tumor shrinkage (from 9.2 to 5.9 cm on average) was observed in all patients, and partial response was achieved in eight patients (80.0%) according to the Response Evaluation Criteria in Solid Tumors 1.1. No tumor perforation occurred, and nine patients (90.0%) underwent successful OPS with four different operation types. Postoperative morbidity rate of OPS was 55.6% (5/9), and no mortality occurred. After a median follow-up of 36 mo, one patient developed multiple distant metastases, but no local recurrence was observed. For long-term follow-up, patients who underwent OPS did not show any degradation in quality of life, whereas the patient who underwent PD suffered weight loss of ~10 kg. In conclusion, in patients with locally advanced duodenal GISTs, neoadjuvant IM administration followed by OPS is a feasible treatment strategy which leads to favorable short- and long-term outcomes.