Risk stratification of clinically relevant delayed gastric emptying after pancreaticoduodenectomy.

BACKGROUND: Delayed gastric emptying (DGE) remains one of the major complications after pancreaticoduodenectomy (PD), with discrepant reports of its contributing factors. This study aimed to develop a nomogram to identify potential predictors and predict the probability of DGE after PD. METHODS: This retrospective study enrolled 422 consecutive patients who underwent PD from January 2019 to December 2021 at our institution. The LASSO algorithm and multivariate logistic regression were performed to identify independent risk and protective factors associated with clinically relevant delayed gastric emptying (CR-DGE). A nomogram was established based on the selected variables. Then, the calibration curve, ROC curve, decision curve analysis (DCA), and clinical impact curve (CIC) were applied to evaluate the predictive performance of our model. Finally, an independent cohort of 45 consecutive patients from January 2022 to March 2022 was enrolled to further validate the nomogram. RESULTS: Among 422 patients, CR-DGE occurred in 94 patients (22.2%). A previous history of chronic gastropathy, intraoperative plasma transfusion ≥ 400 ml, end-to-side gastrointestinal anastomosis, intra-abdominal infection, incisional infection, and clinically relevant postoperative pancreatic fistula (CR-POPF) were identified as risk predictors. Minimally invasive pancreaticoduodenectomy (MIPD) was demonstrated to be a protective predictor of CR-DGE. The areas under the curve (AUCs) were 0.768 (95% CI, 0.706-0.830) in the development cohort, 0.766 (95% CI, 0.671-0.861) in the validation cohort, and 0.787 (95% CI, 0.633-0.940) in the independent cohort. Then, we built a simplified scale based on our nomogram for risk stratification. CONCLUSIONS: Our study identified seven predictors and constructed a validated nomogram that effectively predicted CR-DGE for patients who underwent PD.

Pancreatic ductal adenocarcinoma with synchronous and metachronous hepatic metastasis predicted by contrast-enhanced ultrasound.

Background: Contrast-enhanced ultrasound (CEUS) has proven valuable in diagnosing benign and malignant pancreatic diseases, but its value in evaluating hepatic metastasis remains to be further explored. This study investigated the relationship between CEUS features of pancreatic ductal adenocarcinoma (PDAC) and concomitant or recurrent liver metastases after treatment. Methods: This retrospective study included 133 participants with PDAC who were diagnosed with pancreatic lesions with CEUS at Peking Union Medical College Hospital from January 2017 to November 2020. According to the CEUS classification methods in our center, all the pancreatic lesions were classified as either with rich or poor blood supply. Additionally, quantitative ultrasonographic parameters were measured in the center and periphery of all pancreatic lesions. CEUS modes and parameters of the different hepatic metastasis groups were compared. The diagnostic performance of CEUS was calculated for diagnosing synchronous and metachronous hepatic metastasis. Results: The proportions of rich blood supply and poor blood supply were 46% (32/69) and 54% (37/69), respectively, in the no hepatic metastasis group; 42% (14/33) and 58% (19/33), respectively, in the metachronous hepatic metastasis (MHM) group; and 19% (6/31) and 81% (25/31), respectively, in the synchronous hepatic metastasis (SHM) group. The wash-in slope ratio (WIS ratio) between the center of the lesion and around the lesion and peak intensity ratio (PI ratio) between the center of the lesion and around the lesion had higher values in the negative hepatic metastasis group (P<0.05). In predicting synchronous and metachronous hepatic metastasis, the WIS ratio had the best diagnostic performance. The sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) were 81.8%, 95.7%, 91.2%, 90.0%, and 91.7%, respectively, for MHM; and 87.1%, 95.7%, 93.0%, 90.0%, and 94.3%, respectively, for SHM. Conclusions: CEUS would be helpful in image surveillance for synchronous or metachronous hepatic metastasis of PDAC.

Staple line lockstitch reinforcement decreases clinically relevant pancreatic fistula following distal pancreatectomy: Results of a propensity score matched retrospective analysis.

Background: Postoperative pancreatic fistula (POPF) remains the primary complication of distal pancreatectomies. We aimed to review whether staple line reinforcement with continuous lockstitches would lead to decreased grade B and C pancreatic fistula in patients undergoing distal pancreatectomy. Methods: This retrospective study enrolled consecutive patients scheduled to undergo distal pancreatectomy at a large tertiary hospital. A comparison was conducted between lockstitch reinforcement and non-reinforcement for remnant closure during distal pancreatectomies from August 2016 to February 2021. Propensity score matching was applied to balance the two groups with covariates including abdominal and back pain, diabetes mellitus, and estimated blood loss. The primary outcome was POPF rate. Results: A total of 153 patients were enrolled in the study (89 lockstitch reinforcements, 64 non-reinforcements), of whom 128 patients (64 per group) were analyzed after propensity score matching (1:1). The total POPF rate was 21.9%. POPF was identified in 12.5% (8/64) of the patients who underwent resection with lockstitch reinforcement and 31.2% (20/64) of the patients without reinforcement (odds ratio 0.314, 95% confidence interval 0.130-0.760, P=0.010). No deaths occurred in either group. Neither the major complication rate nor the length of hospital stay after surgery differed between the groups. Conclusions: Compared with the use of stapler alone, staple line lockstitch reinforcement for remnant closure during distal pancreatectomy could reduce the POPF rate. Further multicenter randomized clinical trials are required to confirm these results.

FGFR3 Nuclear Translocation Contributes to Proliferative Potential and Poor Prognosis in Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: Fibroblast growth factor receptor 3 (FGFR3) was revealed to have divergent, even opposite roles in different neoplasms. In pancreatic ductal adenocarcinoma (PDAC), its impact on biological behavior and prognosis was not well elucidated. METHODS: Fibroblast growth factor receptor 3 was downregulated by RNA interference to explore its impact on cell proliferative proclivity in PDAC cells. Furthermore, tissue microarray-based immunohistochemistry for FGFR3 was performed in 326 patients with PDAC who underwent radical resection, and its clinicopathologic and prognostic implications were then evaluated. RESULTS: First, successful FGFR3 knockdown remarkably decreased its expression, cell proliferation, and S-phase ratio in the cell cycle in 2 PDAC cell lines, BxPC-3 and AsPC-1. Meanwhile, alterations in p-Akt, cyclin D1, cyclin B1, and p21 were also observed. Subsequently, high nuclear FGFR3 expression, but not cytoplasmic, was significantly common in tumor tissues and positively associated with N stage and dismal overall survival in the entire cohort. In addition, nuclear FGFR3 expression was also prognostic in 10 of 14 subsets. Univariate and multivariate Cox regression analyses identified nuclear expression of FGFR3 as an independent prognosticator in the entire cohort. CONCLUSIONS: Our data showed that FGFR3 nuclear translocation contributes to cell proliferative potential and predicts poor long-term prognosis in PDAC after surgical resection.

Evaluation of the diagnostic performance of the EFSUMB CEUS Pancreatic Applications guidelines (2017 version): a retrospective single-center analysis of 455 solid pancreatic masses.

OBJECTIVES: To explore the diagnostic performance of EFSUMB CEUS Pancreatic Applications guidelines (version 2017) before and after the addition of iso-enhancement and very fast/fast washout as supplementary diagnostic criteria for PDAC. METHODS: In this retrospective study, patients diagnosed with solid pancreatic lesions from January 2017 to December 2020 were evaluated. Pancreatic ductal adenocarcinoma (PDAC) is reported to show hypo-enhancement in all phases according to the EFSUMB guidelines. First, based on this definition, all lesions were categorized as PDAC and non-PDAC. Then, iso-enhancement and very fast/fast washout were added as supplementary diagnostic criteria, and all lesions were recategorized. The diagnostic performance was assessed in terms of the accuracy (ACC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV). The reference standard consisted of histologic evaluation or composite imaging and clinical follow-up findings. RESULTS: A total of 455 nodules in 450 patients (median age, 58.37 years; 250 men) were included. The diagnostic performance using the EFSUMB CEUS guidelines for PDAC had an ACC of 69.5%, SEN of 65.4%, SPE of 84%, PPV of 93.5%, NPV of 40.6%, and ROC of 0.747. After recategorization according to the supplementary diagnostic criteria, the diagnostic performance for PDAC had an ACC of 95.8%, SEN of 99.2%, SPE of 84%, PPV of 95.7%, NPV of 96.6%, and ROC of 0.916. CONCLUSION: The EFSUMB guidelines and recommendations for pancreatic lesions can effectively identify PDAC via hypo-enhancement on CEUS. However, the diagnostic performance may be further improved by the reclassification of PDAC lesions after adding iso-enhancement and very fast/fast washout mode. KEY POINTS: • In the EFSUMB guidelines, the only diagnostic criterion for PDAC is hypo-enhancement, to which iso-enhancement and very fast/fast washout mode were added in our research. • Using hypo-enhancement/iso-enhancement with very fast/fast washout patterns as the diagnostic criteria for PDAC for solid pancreatic masses on CEUS has high diagnostic accuracy. • The blood supply pattern of PDAC can provide important information, and CEUS has unique advantages in this respect due to its real-time dynamic attenuation ability.

Expression and Prognostic Value of Small Mothers Against Decapentaplegic 7, Matrix Metalloproteinase 2, and Matrix Metalloproteinase 9 in Resectable Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: Thus far, expression, clinicopathologic, and prognostic implication of small mothers against decapentaplegic 7 (Smad7), matrix metalloproteinase 2 (MMP2), and matrix metalloproteinase 9 (MMP9) in pancreatic ductal adenocarcinoma (PDAC) were rarely investigated or controversial. METHODS: Expression of Smad7, MMP2, and MMP9 was detected using immunohistochemistry in tissue microarrays based on 322 patients with curatively resected PDAC. Their expression pattern, clinicopathologic, and prognostic relevance were further evaluated. RESULTS: Smad7 expression was found to be lower in tumor than in adjacent nontumor tissues, whereas tumoral MMP2 and MMP9 staining scores were much higher than in adjacent nontumor ones. Furthermore, Smad7 was negatively associated with serum carbohydrate antigen 19-9 level. Univariate survival analyses showed that patients with high Smad7 tumors had significantly better disease-specific survival (P = 0.0007), whereas MMP2 and MMP9 predicted poor disease-specific survival (P = 0.0211 and 0.0404). In multivariate Cox regression test, Smad7 was an independent prognostic indicator (P = 0.021). In addition, these 3 proteins were also prognostic in many subgroups. CONCLUSIONS: Smad7 and MMP2/9 significantly predict good or poor prognosis in resectable PDAC, respectively. Therefore, the genes might serve as a tool or targets for molecular therapy in PDAC.

Retrograde artery first approach for "shoulder" pancreatic cancers in minimally invasive distal pancreatectomy.

BACKGROUND: "Shoulder" pancreatic cancer, defined as tumor located at the confluence where the splenic vein meets the portal vein, has specific adjacent anatomies. It's difficult to resect this type of tumor with adequate regional lymphadenectomy. METHODS: We described a new concept of "shoulder" pancreatic cancer, and retrospectively analyzed eleven consecutive cases from September 2019 to April 2020, to assess the safety and efficacy of the retrograde artery first approach in minimally invasive distal pancreatectomy. The primary outcome was set as radical (R0) resection rate. RESULTS: All of the 11 cases achieved R0 resection, with a median of 8 (range 5-32) lymph nodes harvested, given the ratio of embraced splenic vein in 72.7% of the cases, splenic artery embracement in 45.5%, and SMV-PV wall invasion in 27.3%. The maximum tumor size on pathology was 35 (range 20-65) mm. The median operative time was 260 (range 155-470) min, and the median estimated blood loss was 200 (range 50-1000) ml. One case needed intraoperative transfusion. One grade B postoperative pancreatic fistula occurred accompanied with abdominal infection, while the rest of cases recovered uneventful. The median postoperative length of stay was 9 (range 6-20) days. CONCLUSIONS: "Shoulder" pancreatic cancers are clinically significant. Retrograde artery first approach is a potentially safe and effective alternative to achieve a radical resection margin for shoulder pancreatic cancers in minimally invasive era. More evidences are needed in the future.

Dynamic hematological changes in patients undergoing distal pancreatectomy with or without splenectomy: a population-based cohort study.

BACKGROUND: The clinical outcomes of patients who received distal pancreatectomy with splenectomy (DPS) and spleen-preserving distal pancreatectomy (SPDP) have been generally investigated. However, postoperative hematological changes after distal pancreatectomy with or without splenectomy are poorly understood. METHODS: Information from patients undergoing distal pancreatectomy (DP) between January 2014 and June 2019 at a single institution was reviewed. A linear mixed-effects model was used to compare dynamic hematological changes between different groups. RESULTS: A total of 302 patients who underwent DP were enrolled. In the long term, most postoperative hematological parameters remained significantly higher than preoperative levels in the DPS group, while postoperative lymphocyte, monocyte, basophil, and platelet levels returned to preoperative levels in the SPDP group. All postoperative hematological parameters except for red blood cell count and serum hemoglobulin level were significantly higher in the DPS group than in the SPDP group. There were no significant differences in hematological changes between the splenic vessel preservation (SVP) and Warshaw technique (WT) groups. CONCLUSIONS: Postoperative hematological changes were significantly different between the DPS and SPDP groups. Compared to DPS, SPDP reduced abnormal hematological changes caused by splenectomy. SVP and WT were comparable in terms of postoperative hematological changes.

Prognostic and predictive value of a five-molecule panel in resected pancreatic ductal adenocarcinoma: A multicentre study.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a devastating prognosis. The performance of clinicopathologic parameters and molecules as prognostic factors remains limited and inconsistent. The present study aimed to construct a multi-molecule biomarker panel to more accurately predict post-resectional prognosis of PDAC patients. METHODS: Firstly, a novel computational strategy integrating prognostic evidence from omics and literature on the basis of bioinformatics prediction (CIPHER) to generate the network, was designed to systematically identify potential high-confidence PDAC-related prognostic candidates. After specimens from 605 resected PDAC patients were retrospectively collected, 23 candidates were detected immunohistochemically in tissue-microarrays for the development cohort to construct a multi-molecule panel. Lastly, the panel was validated in two independent cohorts. FINDINGS: According to the constructed five-molecule panel, disease-specific survival (DSS) was significantly poorer in high-risk patients than in low-risk ones in development cohort (HR 2.15, 95%CI 1.51-3.05, P<0.0001; AUC 0.67). In two validation cohorts, similar significant differences between the two groups were also observed (HR 3.18 and 3.31, 95%CI 1.89-5.37 and 1.78-6.16, All P<0.0001; AUC 0.72 and 0.73). In multivariate analyses, this panel was the sole prognosticator that was significant in each cohort. Furthermore, its predictive power for long-term survival, higher than its individual constituents, could be largely enhanced by combination with traditional clinicopathological variables. Finally, adjuvant chemotherapy (ACT) correlated with better DSS only in high-risk patients, uni- and multi-variately, in all the cohorts. INTERPRETATION: The novel prognostic panel developed by a systematically network-based strategy presents strong ability in prediction of post-resectional survival of PDAC patients. Furthermore, panel-defined high-risk patients might benefit more from ACT.

Laparoscopic assisted pancreaticoduodenectomy: an important link in the process of transition from open to total laparoscopic pancreaticoduodenectomy.

BACKGROUND: The safety of total laparoscopic pancreaticoduodenectomy still remains controversial. Laparoscopic assisted pancreaticoduodenectomy (LAPD) may be an alternative selection. The purpose of the present study is to compare a consecutive cohort of LAPD and open pancreaticoduodenectomy (OPD) from a single surgeon. METHODS: A comparison was conducted between LAPD and OPD from January 2013 to December 2018. Perioperative outcomes and short-term oncological results were compared. Univariate and multivariable analyses were performed to determine associations among variables. RESULTS: 133 patients were enrolled, 36 patients (27.1%) underwent LAPD and 97 (72.9%) underwent OPD. No 30-day and 90-day mortality occurred. LAPD was associated with decreased intraoperative estimated blood loss (300 versus 500 ml; P = 0.002), longer operative time (372 versus 305 min; P < 0.001) compared with OPD. LAPD had a conversion rate of 16.7%, and wasn't associated with an increased grade B/C pancreatic fistula rate, major surgical complications, intraoperative blood transfusion, reoperation rate or length of hospital stay after surgery. In the subset of 58 pancreatic ductal adenocarcinomas, R0 resection rate, median total harvested lymph node or lymph nodes ≥12 did not differ between the two groups. CONCLUSION: LAPD could be performed with non-inferior short-term perioperative and oncologic outcomes achieved by OPD in selected patients.

The Biomechanical Relationship between Hallux Valgus Deformity and Metatarsal Pain.

Metatarsal pain is a common pathological outcome in patients with a hallux valgus (HV) deformity. However, the relationship between the degree of HV deformity and metatarsal pain has not been systematically examined. The purpose of the present study was to investigate the correlation between metatarsal pain and the degree of HV deformity. Between October 2017 and September 2018, 512 HV patients (944 feet) participated in an evaluation of their HV angle (HVA) using X-ray images. The participants were divided into four groups corresponding to their HVA (<15°, 15° to 20°, 21° to 40°, or >40°). Load rate, impulse, contact duration, and contact area were measured and recorded as dynamic gait parameters using the RsScan system. Data were evaluated using SPSS statistical software. The visual analog scale (VAS) was used to assess metatarsal pain. For the four HV deformity groups, the peak value of impulse and contact duration was concentrated on the second and third metatarsals (Meta2 and Meta3) (P < 0.05); contact area was also shown on metatarsals 1, 2, and 5 (P < 0.05). Metatarsal pain on Meta2 had the highest VAS score (VAS: 6.57), followed by Meta3 (Mean VAS: 5.72). In the HV > 40° group, the load location on Meta2 was transferred to Meta1. The percent of pain attributed to Meta2 and Meta3 was also increased in this group. These findings illustrated that metatarsal pain was primarily located on Meta2 and Meta3 in the different degrees of HV deformity. This information can provide the location to target for pain relief and help guide further rehabilitation.

Air in the biliary duct as an indicator of Type V Mirizzi syndrome: a case report.

Mirizzi syndrome, known as extrinsic bile compression syndrome (EBCS), is difficult to diagnose without surgery. To the best of our knowledge, our case shows that air in the biliary duct may indicate Type V Mirizzi syndrome. A 48-year-old Chinese male, complaining of anorexia with weight loss and jaundice, showed decreased bilirubin for two months after being diagnosed with gallbladder stones. Upon re-examination of the CT, evidence of air in the biliary duct was discovered. Type V EBCS was finally diagnosed during surgery. The patient underwent cholecystectomy, cholecystocolic fistula excision, and Roux-en-Y choledochojejunostomy. The postoperative course was uneventful. Mirizzi's syndrome is a condition which is difficult to diagnose and treat. Air in the biliary duct can be a sign of Type V Mirizzi syndrome, which aids in diagnosis of Type V EBCS before surgery. Cholecystectomy, fistula excision and biliary-enteric anastomosis with Roux-en-Y loop appear to be the most appropriate surgical interventions for the condition.

Intraductal oncocytic papillary neoplasm of the pancreas: A systematic review.

BACKGROUND: Intraductal oncocytic papillary neoplasm of the pancreas (IOPN-P) is a rare subtype of intraductal papillary mucinous neoplasm (IPMN). This study was performed to summarize the clinicopathological features and management of IOPN-P. METHODS: English-language articles were searched from MEDLINE and EMBASE from the first report of IOPN-P in 1996 until 1 May 2019 following the methodology in the PRISMA guidelines. RESULTS: In total, 66 patients from 24 full articles were included in the final data analysis. The patients' average age was 61 years, and the male/female ratio was 1. Most lesions were large (average size, 5.50 cm), located in the pancreatic head, and found either incidentally or by uncharacteristic abdominal symptoms. IOPN-P was usually a cystic and solid lesion with or without mural nodules on radiological examination. A definitive diagnosis was often acquired from fine needle aspiration biopsy or postoperative pathology. All tumors were diagnosed as carcinoma in situ or minimally invasive carcinoma, necessitating surgical resection. The prognosis of IOPN-P was better than that of other IPMN subtypes, even when metastasis occurred. Recurrence after surgical resection of IOPN-P was rare. CONCLUSIONS: IOPN-P is rare among IPMN subtypes with unique pathological characteristics. Because of the nontypical symptoms and radiological findings, a definitive preoperative diagnosis usually depends on multimodal examinations. Management and surveillance of IOPN-P after surgical resection should be differentiated from those of other pancreatic benign cystic lesions because of its relative malignancy, but IOPN-P should also be differentiated from other IPMN subtypes and malignant cystic tumors because of its favorable prognosis.

Research progress on circularRNAs in pancreatic cancer: emerging but promising.

There is currently no diagnostic modality for early-stage pancreatic cancer. Given that adjuvant therapies require further development, the overall survival of pancreatic cancer remains unsatisfactory. Circular RNAs (circRNAs) are a class of noncoding RNAs that play an important role in the progression of many diseases including cancer. CircRNAs mainly bind to microRNAs as microRNA sponges to restore the expression of targeted genes and regulate tumor invasion, metastasis, proliferation, and apoptosis. CircRNAs also play roles in the diagnosis and targeted therapy of tumors. Studies on the mechanisms of action of circRNAs in pancreatic cancer are still in their infancy, but it is anticipated that this field will gradually advance. In this review, we provide a brief introduction to circRNAs from four perspectives: biogenesis, functions, and mechanisms of action, tumor therapy with circRNAs, and circRNAs' roles in pancreatic cancer.

WT1 associated protein promotes metastasis and chemo-resistance to gemcitabine by stabilizing Fak mRNA in pancreatic cancer.

WT1 associated protein (WTAP), playing an important role in several malignancies owing to its complex function in transcriptional and post-transcriptional regulation, is an independent prognostic indicator for pancreatic cancer (PC). However, its specific role and underlying mechanism in PC remain unclear. In the present study, we found that WTAP could promote migration/invasion and suppress chemo-sensitivity to gemcitabine in PC. Further mechanical investigation revealed that WTAP could bind to and stabilize Fak mRNA which in turn activated the Fak-PI3K-AKT and Fak-Src-GRB2-Erk1/2 signaling pathways. In addition, GSK2256098, a specific Fak inhibitor, could reverse WTAP-mediated chemo-resistance to gemcitabine and metastasis in PC. Taken together, Fak inhibitor might be a promising therapeutic option for PC patients with WTAP overexpression.

A rare intrahepatic subcapsular hematoma (ISH) after laparoscopic cholecystectomy: a case report and literature review.

BACKGROUND: Intrahepatic subcapsular hematoma (ISH) is an extremely rare, life-threatening complication after laparoscopic cholecystectomy (LC). Only few cases have been reported. Herein, we reported a rare giant ISH after LC and summarized all of the reported cases. CASE PRESENTATION: A 32-year old woman with recurrent acute cholecystitis for one year, underwent elective LC without intra-operative complications and was discharged 2 days after operation. On the next day after discharge, she developed severe right upper abdominal pain and was sent to our emergency department. The computed tomography scan showed a 10.9 × 12.5 × 6.6 cm ISH in the right liver without free fluid and the hemoglobin dropped to 86 g/l from 127 g/l. Postoperative hemorrhagic shock and a giant ISH after LC were diagnosed. After fluid resuscitation, the hemodynamic was still unstable and the hemoglobin kept dropping. An emergency laparoscopic exploration was performed and the ISH was confirmed, however no active bleeding point was found. A drainage tube was placed under liver for early warning of rupture. Patient was discharged home 10 days after readmission. CONCLUSIONS: Giant ISH is an extremely rare, life-threatening complication after LC. This case showed that the need to consider this rare complication in patients suffering abdominal pain after LC and timely and correct diagnosis and treatment were crucial to saving the lives of the patients.

Preservation or Ligation of Splenic Vessels During Spleen-Preserving Distal Pancreatectomy: A Meta-Analysis.

Purpose/aim: Spleen preservation distal pancreatectomy (SPDP) can be achieved by either splenic vessel preservation distal pancreatectomy (SVP-DP) or Warshaw technique (WT). Although studies comparing SVP-DP with WT have been reported, controversies exist. The aim of our study is to assess and compare the safety and feasibility of SVP-DP and WT. Materials and methods: Two authors searched the online database independently till April 30, 2017. Data extraction and quality assessment were performed independently by two authors. Short- and long-term outcomes of WT and SVP-DP were evaluated. Subgroup analysis was performed on laparoscopic surgery. Odds ratios (OR) with 95% confidence interval (CI) and mean difference (MD) with 95% CI were estimated. Results: A total of 664 patients from 11 retrospective cohort studies were included. Meta-analysis showed the WT group had a significantly higher incidence of splenic infarction (OR = 0.12; 95% CI: 0.07-0.20; p < 0.00001) and gastric/epigastric varices (OR = 0.11; 95% CI: 0.05-0.24; p < 0.00001). And more patients suffering from splenic infarction from WT group needed further splenectomy (OR = 0.13; 95% CI: 0.02-0.84; p = 0.03). While there was no difference between the two procedures in terms of pancreatic fistula (OR = 0.55; 95% CI: 0.25-1.19; p = 0.13), overall morbidity (OR = 0.87; 95% CI: 0.59-1.30; p = 0.50) and hospital stay (MD = -0.45; 95% CI: -1.73-0.82; p = 0.49). Conclusions: Due to relatively higher risk of postoperative splenic infarction, gastric/epigastric varices and Clavien-Dindo III-V complications, WT is not as safe as SVP-DP. However, well-conducted randomized clinical trials are still needed due to the limitations of current studies.

Clinicopathological and prognostic significance of MKK4 and MKK7 in resectable pancreatic ductal adenocarcinoma.

Mitogen-activated protein kinase kinase 4 (MKK4) and mitogen-activated protein kinase kinase 7 (MKK7) were shown to regulate biological behavior in many malignancies. In pancreatic ductal adenocarcinoma (PDAC), it remains controversial whether MKK4 and MKK7 have pro-oncogenic or tumor-suppressive activities. Furthermore, their clinicopathological and prognostic implications are unknown. In the present study, we detected MKK4 and MKK7 expressions in the nucleus and cytoplasm of resected PDAC tissues from 321 patients by tissue microarray-based immunohistochemistry. Cytoplasmic MKK4 and MKK7 expressions were significantly downregulated, whereas nuclear MKK4 expression was significantly upregulated in tumor tissues compared with nontumor tissues. Tumor cytoplasmic MKK4 and MKK7 expressions were significantly negatively associated with histologic grade. Cytoplasmic MKK4 expression was also negatively correlated with CA19-9 level. By univariate analysis, high cytoplasmic MKK4 expression was significantly associated with longer cancer-specific survival (hazard ratio [HR], 0.705; 95% confidence interval, 0.510-0.974), with a similar trend observed for MKK7 expression. High MKK4 and MKK7 messenger RNA expressions were significantly associated with longer overall survival in The Cancer Genome Atlas database. Although MKK4 expression was not significant in a multivariate Cox regression analysis, combination of MKK4/MKK7 and pN stage was identified as an independent prognostic indicator and had the lowest HR (HR, 0.308; 95% confidence interval, 0.126-0.752). Furthermore, combined analysis of MKK4 and MKK7 greatly increased the prognostic predictive power. In addition, downregulation of MKK4 or MKK7 increased proliferation of pancreatic cancer cells in vitro. In conclusion, high MKK4 expression and its combination with high MKK7 expression both predicted favorable prognosis in resectable PDAC.

Epidermoid cyst in intrapancreatic accessory spleen: A systematic review.

BACKGROUND/OBJECTIVES: Due to its rarity, epidermoid cyst in intrapancreatic accessory spleen (ECIPAS) is still a diagnostic dilemma during clinical practice. The aim of this review was to summarize the epidemiologic features and management of ECIPAS. METHODS: MEDLINE and EMBASE were searched for English articles reporting on ECIPAS up to April 30th, 2018 following the methodology suggested by the PRISMA guidelines. Categorical variables were reported as frequency and percentage. Continuous variables were reported as median (range). RESULTS: A total of 56 patients from 47 full articles were included for the final data synthesis. More than half of the ECIPASs (59%) were found incidentally. The female/male ratio was 1.33. ECIPAS is typically a single mono-/multi-lobular cystic lesions in the pancreatic tail with thickened cystic wall or various amount of solid component which had identical density/signal to the spleen on imaging examinations. The cyst is filled with serous or non-serous fluid. Recognition of the surrounding ectopic splenic tissue is the key point to diagnose ECIPAS. However, no preoperative examination was able to make a definite diagnosis. Almost all the patients (96%) received surgical treatment, due to the suspicion of pancreatic malignant or potentially malignant cystic tumor, especially mucinous cystic neoplasm (MCN). CONCLUSIONS: Although seldom encountered, ECIPAS should be considered as a differential diagnosis for pancreatic cystic lesions, especially when solid component was detected. As a benign disease, unnecessary surgery should be avoided. Because it is difficult to make a definite diagnosis preoperatively by one single examination, multiple modalities may be required.

High nuclear Survivin expression as a poor prognostic marker in pancreatic ductal adenocarcinoma.

BACKGROUND: Survivin, one of the key regulators of mitosis and apoptosis, has long been well recognized to play important biological roles in many neoplasms, including pancreatic ductal adenocarcinoma (PDAC). However, its prognostic value in PDAC remains controversial. PATIENTS AND METHODS: Nuclear expression of Survivin was detected, using tissue microarray-based immunohistochemistry, in paired-tumor and nontumor samples from 306 patients with radically resected PDAC. The staining H scores were further correlated with clinicopathologic features and disease-specific survival (DSS). RESULTS: Nuclear Survivin expression was much higher in tumor than in nontumor tissues (P < 0.001). No significant association between tumoral Survivin expression and clinicopathologic variables was found. For prognosis, high Survivin expression was associated with shortened DSS in all eligible patients and four subgroups, that is, male and nondiabetic patients as well as those with head-located and G1-2 tumors, shown by univariate analyses. In addition, a statistically marginal significance was revealed in eight subgroups. For the entire cohort and two subgroups, nuclear Survivin expression was also multivariate identified as an independent predictor for DSS. For patients with G1-2 tumors, it was the single prognostic marker. CONCLUSION: Our data suggest an association between high nuclear Survivin expression and poor prognosis in PDAC. However, further confirmation might be necessary.