Thick mesopancreas is a novel predictor of surgical outcomes of patients who undergo pancreaticoduodenectomy.

PURPOSE: Mesopancreas resection is a crucial but difficult procedure when performing pancreaticoduodenectomy. This study evaluated the influence of mesopancreas thickness on surgical outcomes in patients undergoing pancreaticoduodenectomy. METHODS: We measured the thickness of the fat tissue on the right side of the superior mesenteric artery from the dorsal margin of the confluence of the superior mesenteric vein and portal vein to the ventral margin of the left renal vein on preoperative contrast-enhanced computed tomography and defined it as the mesopancreas thickness. We evaluated the correlation between mesopancreas thickness and intraoperative and postoperative variables in 357 patients who underwent pancreaticoduodenectomy. RESULTS: Multivariate analysis revealed that a thick mesopancreas was significantly associated with a long operative time (ß = 10.361; 95% confidence interval, 0.370-20.353, p = 0.042), high estimated blood loss (ß = 36.038; 95% confidence interval, -27.192-99.268, p = 0.013), and a low number of resected lymph nodes (ß = -1.551; 95% confidence interval, -2.662--0.439, p = 0.006). This analysis further revealed that thick mesopancreas was a significant risk factor for overall morbidity (odds ratio 2.170; 95% confidence interval 1.340-3.520, p = 0.002), major morbidity (odds ratio 2.430; 95% confidence interval 1.360-4.340, p = 0.003), and a longer hospital stay (ß = 2.386; 95% confidence interval 0.299-4.474, p = 0.025). CONCLUSION: A thick mesopancreas could predict a longer operation time, higher estimated blood loss, fewer resected lymph nodes, more frequent overall and major morbidities, and a longer hospital stay in patients who underwent pancreaticoduodenectomy more precisely than the body mass index.

Aqueous Povidone-Iodine Versus Normal Saline For Intraoperative Wound Irrigation on The Incidence of Surgical Site Infection in Clean-Contaminated Wounds After Gastroenterological Surgery: A Single-Institute, Prospective, Blinded-Endpoint, Randomized Controlled Trial.

OBJECTIVE: This trial evaluated the superiority of intraoperative wound irrigation (IOWI) with aqueous povidone-iodine (PVP-I) compared with that with saline for reducing the incidence of surgical site infection (SSI). BACKGROUND: IOWI with aqueous PVP-I is recommended for the prevention of SSI by the World Health Organization and the Centers for Disease Control and Prevention, although the evidence level is low. METHODS: This single institute in Japan, prospective, randomized, blinded-endpoint trial was conducted to assess the superiority of IOWI with aqueous PVP-I in comparison with IOWI with saline for reducing the incidence of SSI in clean-contaminated wounds after gastroenterological surgery. Patients 20 years or older were assessed for eligibility, and the eligible participants were randomized at a 1:1 ratio using a computer-generated block randomization. In the study group, IOWI was performed for 1 minute with 40 mL of aqueous 10% PVP-I before skin closure. In the control group, the procedure was performed with 100 mL of saline. Participants, assessors, and analysts were masked to the treatment allocation. The primary outcome was the incidence of incisional SSI in the intention-to-treat set. RESULTS: Between June 2019 and March 2022, 941 patients were randomized to the study group (473 patients) or the control group (468 patients). The incidence of incisional SSI was 7.6% in the study group and 5.1% in the control group (risk difference 0.025, 95% CI -0.006 to 0.056; risk ratio 1.484, 95% CI 0.9 to 2.448; P =0.154). CONCLUSION: The current recommendation of IOWI with aqueous PVP-I should be reconsidered.

Caspase-11 deficiency attenuates neutrophil recruitment into the atherosclerotic lesion in apolipoprotein E-deficient mice.

Caspase-11 is an inflammatory caspase that triggers an inflammatory response by regulating non-canonical NLRP3 inflammasome activation. Although the deficiency of both caspase-11 and caspase-1, another inflammatory caspase that functions as an executor of the inflammasome, prevents the development of atherosclerosis, the effect of caspase-11 deficiency alone on the development of atherosclerosis has not been fully evaluated. In the present study, we found that caspase-11 deficiency prevented the formation of the necrotic core, whereas it did not affect the development of atherosclerosis in Apoe-deficient mice. Notably, the infiltration of neutrophils into atherosclerotic lesions was attenuated by caspase-11 deficiency. RNA-seq analysis of stage-dependent expression of atherosclerotic lesions revealed that both upregulations of caspase-11 and neutrophil migration are common features of advanced atherosclerotic lesions. Furthermore, similar expression profiles were observed in unstable human plaque. These data suggest that caspase-11 regulates neutrophil recruitment and plaque destabilization in advanced atherosclerotic lesions.

Drain output volume after pancreaticoduodenectomy is a useful warning sign for postoperative complications.

INTRODUCTION: The drain output volume (DOV) after pancreaticoduodenectomy (PD) is an easily assessable indicator in clinical settings. We explored the utility of the DOV as a possible warning sign of complications after PD. METHODS: A total of 404 patients undergoing PD were considered for inclusion. The predictability of the DOV for overall morbidity, major complications, intraabdominal infection (IAI), clinically relevant (CR) postoperative pancreatic fistula (POPF), CR delayed gastric emptying (DGE), CR chyle leak (CL), and CR post-pancreatectomy hemorrhaging (PPH) was evaluated. RESULTS: One hundred (24.8%) patients developed major complications, and 131 (32.4%) developed IAI. Regarding CR post-pancreatectomy complications, 75 (18.6%) patients developed CR-POPF, 23 (5.7%) developed CR-DGE, 20 (5.0%) developed CR-CL, and 28 (6.9%) developed CR-PPH. The median DOV on postoperative day (POD) 1 and POD 3 was 266 and 234.5 ml, respectively. A low DOV on POD 1 was an independent predictor of CR-POPF, and a high DOV on POD 3 was an independent predictor of CR-CL. A receiver operating characteristics (ROC) analysis revealed that the DOV on POD 1 had a negative predictive value (area under the curve [AUC] 0.655, sensitivity 65.0%, specificity 65.3%, 95% confidence interval [CI]: 0.587-0.724), with a calculated optimal cut-off value of 227 ml. An ROC analysis also revealed that the DOV on POD 3 had a positive predictive value (AUC 0.753, sensitivity 70.1%, specificity 75.0%, 95% CI: 0.651-0.856), with a calculated optimal cut-off value of 332 ml. CONCLUSION: A low DOV on POD 1 might be a postoperative warning sign for CR-POPF, similar to high drain amylase (DA) on POD 1, high DA on POD 3, and high CRP on POD 3. When the DOV on POD 1 after PD was low, surgeons should evaluate the reasons of a low DOV. A high DOV on POD 3 was a postoperative warning sign CR-CL, and might require an appropriate management of protein loss.

Relationship between surgical R0 resectability and findings of peripancreatic vascular invasion on CT imaging after neoadjuvant S-1 and concurrent radiotherapy in patients with borderline resectable pancreatic cancer.

BACKGROUND: Borderline resectable pancreatic cancer (BRPC) is frequently associated with positive surgical margins and a poor prognosis because the tumor is in contact with major vessels. This study evaluated the relationship between the margin-negative (R0) resection rate and findings indicating peripancreatic vascular invasion on multidetector computed tomography (MDCT) imaging after neoadjuvant chemoradiotherapy (NACRT) in patients with BRPC. METHODS: Twenty-nine BRPC patients who underwent laparotomy after neoadjuvant S-1 with concurrent radiotherapy were studied retrospectively. Peripancreatic major vessel invasion was evaluated based on the length of tumor-vessel contact on MDCT. The R0 resection rates were compared between the progression of vascular invasion (PVI) group and the non-progression of vascular invasion (NVI) group. RESULTS: There were 3 patients with partial responses (10%), 25 with stable disease (86%), and 1 with progressive disease (3%) according to the RECISTv1.1 criteria. Regarding vascular invasion, 9 patients (31%) were classified as having PVI, and 20 patients (69%) were classified as having NVI. Of the 29 patients, 27 (93%) received an R0 resection, and all the PVI patients received an R0 resection (9/9; R0 resection rate = 100%) while 90% (18/20) of the NVI patients underwent an R0 resection. The exact 95% confidence interval of risk difference between those R0 resection rates was - 10.0% [- 31.7-20.4%]. CONCLUSIONS: Patients with BRPC after NACRT achieved high R0 resection rates regardless of the vascular invasion status. BRPC patients can undergo R0 resections unless progressive disease is observed after NACRT. TRIAL REGISTRATION: UMIN-CTR, UMIN000009172 . Registered 23 October 2012.

Bridge of preoperative biliary drainage is a useful management for patients undergoing pancreaticoduodenectomy.

BACKGROUND/OBJECTIVES: The aims of this study were to clarify the effect of preoperative biliary drainage (PBD) on postoperative outcomes and the role of preoperative intentional exchange from endoscopic nasobiliary drainage (ENBD) to endoscopic retrograde biliary drainage (ERBD) for patients waiting to undergo pancreaticoduodenectomy (PD). METHODS: We evaluated the effect of PBD and intentional exchange of PBD on the perioperative variables in 292 patients. RESULTS: A total of 179 (61.3%) of 292 patients received PBD. There was no marked difference in the postoperative outcomes between the patients who did and did not receive PBD. Among the 160 patients who initially received endoscopic PBD, 10 (6.3%) underwent stent exchange for stent dysfunction, 59 (36.9%) who did not develop stent dysfunction underwent intentional stent exchange from ENBD to ERBD (bridge PBD group), and 91 (56.9%) did not receive any stent exchange (unchanged PBD group). The bridge PBD group had a longer duration of PBD (37 days) (p < 0.001) and a shorter preoperative hospital stay after PBD (32 days) (p < 0.001) than the unchanged PBD group (25 and 46 days, respectively); however, there were no significant differences in the postoperative variables. The incidence of stent exchange due to stent dysfunction in the bridge PBD group (11.9%) was lower than that in patients who initially received ERBD (36.0%) (p = 0.015). CONCLUSIONS: Bridge PBD worked well for extending the duration of PBD without worsening the postoperative outcomes after PD.

A lack of postoperative complications after pancreatectomy contributes to the long-term survival of patients with pancreatic cancer.

BACKGROUND: /Objectives: The objectives of this study were to identify the factors affecting patients' survival and the characteristics of five-year survivors of pancreatic ductal adenocarcinoma (PDAC) after pancreatectomy as well as to clarify the correlation between the development of postoperative complications and a five-year survival. METHODS: A total of 104 patients underwent pancreatectomy for PDAC between April 2005 and March 2013 with curative intent. Patients who survived for more than five years after pancreatectomy were classified as long-term survivors. Sixteen demographic and clinical variables and 10 pathological variables were comprehensively assessed for their associations with the patients' survival time and long-term survival. RESULTS: The presence of preoperative comorbidity (OR: 1.65, 95% CI 1.02-2.67, p = 0.042), postoperative overall complications (OR: 1.78, 95% CI 1.03-3.10, p = 0.041), a lymph node positivity ratio of ≥0.2 (OR: 3.04, 95% CI 1.51-6.11, p = 0.002), and portal invasion (OR: 2.58, 95% CI 1.48-4.49, p = 0.001) were identified as independent factors affecting the patients' survival. The absence of postoperative overall complications was identified as an independent factor related to long-term survival in the multivariate analysis (OR: 0.08, 95% CI 0.01-0.82, p = 0.034). CONCLUSIONS: The presence of preoperative comorbidity, postoperative overall complications, LNR ≥0.2, and portal invasion were prognostic factors affecting the patients' survival, and avoiding postoperative complications after pancreatectomy might contribute to the long-term survival of PDAC patients after pancreatectomy. The further improvement of surgical procedures and perioperative care in order to reduce the rate of postoperative complications should be attempted.

Comparison of postoperative early and late complications between pancreas-sparing duodenectomy and pancreatoduodenectomy.

PURPOSE: Pancreas-sparing duodenectomy (PSD) represents an alternative procedure to pancreatoduodenectomy (PD) for patients with duodenal neoplasms. METHODS: The postoperative early and late complications of 21 patients who underwent PSD between 1992 and 2014 were compared with those of 44 patients with soft pancreatic parenchyma who underwent PD between 2009 and 2014. RESULTS: The median operation time and blood loss were less in the PSD group than in the PD group (P < 0.001). The overall incidence of early complications was less in the PSD group than in the PD group (PSD with ampullectomy vs. PSD without ampullectomy vs. PD; 45.5 vs. 20.0 vs. 56.8 %). The incidence of pancreatic fistula formation and overall incidence of late complications were also less in the PSD group than in the PD group (P = 0.031, 0.020). There were no complications related to the pancreatic endocrine or exocrine functions in the PSD group. CONCLUSION: PSD is a less-invasive procedure and has the advantage over PD of preserving the pancreas.

Implementation of intraoperative wound irrigation with aqueous 10% povidone-iodine and triclosan-coated sutures is not effective for reducing the incidence of incisional surgical site infection after major hepato-biliary-pancreatic surgery in patients with preoperative biliary drainage.

BACKGROUND/PURPOSE: Patients who receive preoperative biliary drainage (PBD) and biliary reconstruction are most at risk for incisional surgical site infection (SSI) in major hepatobiliary-pancreatic (HBP) surgery. METHODS: We evaluated 72 patients with PBD who underwent major HBP surgery and received intraoperative wound irrigation (IOWI) with saline and standard sutures between March 2014 and March 2017 (Cohort 1) and 63 patients with PBD who underwent major HBP surgery and received IOWI with aqueous 10% povidone-iodine and antibacterial sutures between June 2019 and February 2022 (Cohort 2). We compared the incidence of incisional SSI between the two cohorts. RESULTS: Twenty-seven (20.0%) of 135 patients developed incisional SSIs. The rate of current smoking was more frequent in patients who developed incisional SSIs than in those who did not (37.0% vs. 14.8%, p = .012). A total of 18 (25%) of 72 patients developed incisional SSI in Cohort 1, and nine (14.3%) of 63 developed incisional SSI in Cohort 2. Cohort 2 had a 10% lower incidence of incisional SSI than Cohort 1, a nonsignificant difference (p = .09). CONCLUSION: The implementation of IOWI with aqueous 10% PVP-I and antibacterial sutures failed to significantly reduce the incidence of incisional SSI in comparison to IOWI with saline and standard sutures in major HBP surgery.

Circulating tumor DNA in molecular assessment feasibly predicts early progression of pancreatic cancer that cannot be identified via initial imaging.

Molecular assessment using circulating tumor DNA (ctDNA) has not been well-defined. We recruited 61 pancreatic cancer (PC) patients who underwent initial computed tomography (CT) imaging study during first-line chemotherapy. Initial molecular assessment was performed using droplet digital PCR and defined as the change in KRAS-mutated ctDNA before and after treatments, which was classified into five categories: mNT, molecular negative; mCR, complete response; mPR, partial response; mSD, stable disease; mPD, progressive disease. Of 61 patients, 14 diagnosed with PD after initial CT imaging showed significantly worse therapeutic outcomes than 47 patients with disease control. In these 47 patients, initial molecular assessment exhibited significant differences in therapeutic outcomes between patients with and without ctDNA (mPD + mSD vs. mCR + mNT; 13.2 M vs. 21.7 M, P = 0.0029) but no difference between those with mPD and mSD + mCR + mNT, suggesting that the presence of ctDNA had more impact on the therapeutic outcomes than change in its number. Multivariate analysis revealed that it was the only independent prognostic factor (P = 0.0405). The presence of ctDNA in initial molecular assessment predicted early tumor progression and identified PC patients more likely to benefit from chemotherapy.

Genome­wide DNA hypomethylation drives a more invasive pancreatic cancer phenotype and has predictive occult distant metastasis and prognosis potential.

Genome­wide DNA hypomethylation is the most common molecular feature in human cancers associated with chromosomal instability (CIN), which is involved in the mechanisms that regulate pancreatic cancer (PC) metastasis. It was investigated whether genome­wide DNA hypomethylation affects the phenotype in PC via CIN in vitro, and its significance on the biological behavior of PC was verified. The relative demethylation level (RDL) of long interspersed nucleotide element­1 (LINE­1) in human PC cell lines was used to characterize DNA hypomethylation using methylation­specific quantitative (q)PCR. CIN was estimated by changes in chromosomal copy number using comparative genomic hybridization analysis. Abnormal segregation of chromosomes was assessed by immunocytochemistry, and the DNA damage response was evaluated using the number of anti­Î³H2AX positive cells. Invasion ability was assessed using a Matrigel invasion assay. Clinical specimens from 49 patients with PC who underwent curative surgery were evaluated for a correlation of DNA hypomethylation with clinical outcome. Successful induction of genome­wide DNA hypomethylation in PC cells led to copy number changes in specific chromosomal regions. The number of cells with abnormal segregation of chromosomes significantly increased with the number of anti­Î³H2AX positive cells. The invasive potential of these cells also significantly increased. The occurrence of occult distant metastasis in the clinical specimens and receiver operating characteristic analysis clearly identified those who were and were not likely to have occult distant metastasis, with high LINE­1 RDL significantly correlated with the presence of occult distant metastasis (P=0.035) and poor prognosis (P=0.048). The significance of genome­wide DNA hypomethylation on the biological behavior of PC, which promotes a more invasive phenotype via CIN in vitro and predicts the susceptibility to occult distant metastasis and poor prognosis in patients with PC was revealed.

A deep pancreas is a novel predictor of pancreatic fistula after pancreaticoduodenectomy in patients with a nondilated main pancreatic duct.

BACKGROUND: We investigated the risk factors for clinically relevant postoperative pancreatic fistula after pancreaticoduodenectomy in patients with a nondilated main pancreatic duct. METHODS: We investigated a total of 354 patients who underwent pancreaticoduodenectomy. The diameter of the main pancreatic duct, the shortest distance from the body surface to the pancreas (the pancreatic depth), and the computed tomography attenuation index (the difference between the pancreatic and splenic computed tomography attenuation) were measured in preoperative computed tomography. RESULTS: One hundred eighty-one (51.1%) patients had a nondilated main pancreatic duct, and 50 (27.6%) of the 181 patients with a nondilated main pancreatic duct developed a clinically relevant postoperative pancreatic fistula. Univariate analyses revealed that the calculated body mass index (≥21.8 kg/m2) (P = .004), deep pancreas (pancreatic depth ≥51.2 mm) (P = .001), and low computed tomography attenuation index (≤-3.8 Hounsfield units) (P = .02) were significant risk factors for clinically relevant postoperative pancreatic fistula. The multivariate logistic regression analysis revealed that deep pancreas (odds ratio 2.370; 95% confidence interval 1.0019-5.590; P = .049) was an independent risk factor for clinically relevant postoperative pancreatic fistula. Among patients with a nondilated main pancreatic duct, deep pancreas (in comparison to patients without deep pancreas) was associated with male sex (72.7% vs 54.9%; P = .016), higher body mass index (22.5 kg/m2 vs 19.6 kg/m2; P < .001), a history of diabetes mellitus (24.5% vs 8.5%; P = .006), a lower computed tomography attenuation index (-9.6 Hounsfield units vs -4.6 Hounsfield units; P = .007), a longer operative time (454 minutes vs 420 minutes; P = .007), and a higher volume of intraoperative blood loss (723 mL vs 500 mL; P < .001), respectively. CONCLUSION: Deep pancreas may be an important parameter associated with significant risk factors for clinically relevant postoperative pancreatic fistula after pancreaticoduodenectomy in patients with a nondilated main pancreatic duct.

Large Brunner's Gland Hyperplasia with Bleeding: A Case Report.

We report a rare case of a large Brunner's gland hyperplasia (BGH) with severe anemia. A 33-year-old woman was transferred to our hospital with anemia and a duodenal mass. She had a 2-week history of melena and mild shortness of breath. Her hemoglobin level was 4.9 g/dl, and she required a blood transfusion. Abdominal computed tomography revealed a 7 cm tumor in the descending duodenum, and duodenoscopy revealed a polyp-like tumor with an ulcer at the duodenal bulb. We decided to perform surgery to prevent further bleeding. Intraoperatively, the tumor stalk was located at the anterior wall of the duodenal bulb; the ampulla was not involved, and we resected the tumor with the wall of the duodenal bulb. The resected tumor measured 7.0 × 4.0 × 2.3 cm, and pathologically, the tumor consisted of proliferated Brunner's glands in a small amount of fibrous stroma. The histological diagnosis was BGH with no malignancy. Most cases of BGH are benign and asymptomatic; however, it is important to be aware that some patients have severe anemia, gastrointestinal obstruction, or malignant potential.

Superiority trial comparing intraoperative wound irrigation with aqueous 10% povidone-iodine to saline for the purpose of reducing surgical site infection after elective gastrointestinal surgery: study protocol for a randomised controlled trial.

INTRODUCTION: Surgical site infection (SSI) is one of the most common complications after gastrointestinal surgery, with a reported incidence of approximately 10%-25%, which is higher than the rates after other types of surgery. Intraoperative wound irrigation (IOWI) is a simple intervention for SSI prevention, and recent studies have reported that IOWI with aqueous povidone-iodine (PVP-I) is significantly more effective at reducing the incidence of SSI than saline. However, the evidence level of previous trials evaluating the efficacy of aqueous PVP-I solution for preventing SSI has been low. METHODS AND ANALYSES: We propose a single-institute, prospective, randomised, blinded-endpoint trial to assess the superiority of IOWI with aqueous 10% PVP-I solution compared with normal saline for reducing SSI in clean-contaminated wounds after elective gastrointestinal surgery. In the study group, IOWI with 40 mL of aqueous 10% PVP-I solution is performed for 1 min before skin suture, and in the control group, IOWI with 100 mL of saline is performed for 1 min before skin suture. We hypothesise that IOWI with aqueous 10% PVP-I solution will achieve a 50% reduction in the incidence of SSIs. The target number of cases is set at 950. The primary outcome is the incidence of incisional SSI up to postoperative day 30 and will be analysed in the modified intention-to-treat set. ETHICS AND DISSEMINATION: This trial was designed and is being conducted by Saitama Medical Center, Jichi Medical University, with approval from the Bioethics Committee for Clinical Research, Saitama Medical Center, Jichi Medical University. Participant recruitment began in June 2019. The final results will be reported in international peer-reviewed journals immediately after trial completion. TRIAL REGISTRATION NUMBER: UMIN000036889.

Preoperative Sarcopenia Strongly Influences the Risk of Postoperative Pancreatic Fistula Formation After Pancreaticoduodenectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is a serious complication of pancreaticoduodenectomy (PD). Sarcopenia is a newly identified marker of frailty. We performed this study to assess whether preoperative sarcopenia has an impact on clinically relevant POPF formation. METHODS: A total of 266 consecutive patients who underwent a PD between 2010 and 2014 were enrolled in this retrospective study. Skeletal muscle mass was measured using preoperative computed tomography images. The impact of preoperative sarcopenia on clinically relevant POPF formation was analyzed using univariate and multivariate analyses. RESULTS: Of the 266 patients, 132 (49.6 %) were classified as having preoperative sarcopenia. The rate of clinically relevant POPF formation was significantly higher in the sarcopenia group (22.0 vs. 10.4 %; P = 0.011). A multivariate logistic regression analysis showed that sarcopenia (odds ratio, 2.869; P = 0.007) was an independent risk factor for the development of clinically relevant POPF, along with a soft pancreas and a parenchymal thickness at the pancreatic resection site of ≥8 mm. CONCLUSIONS: Preoperative sarcopenia was identified as a strong and independent risk factor for clinically relevant POPF formation after PD. Perioperative rehabilitation and nutrition therapy may contribute to the prevention of POPF formation and a safer PD.