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.

A postoperative body weight increase is a novel risk factor for incisional hernia of midline abdominal incision after elective gastroenterological surgery.

PURPOSE: Midline abdominal incisions (MAIs) are widely used in both open and minimally invasive surgery. Incisional hernia (IH) accounts for most long-term postoperative wound complications. This study explored the risk factors for IH due to MAI in patients with clean-contaminated wounds after elective gastroenterological surgery. METHODS: The present study targeted patients enrolled in 2 randomized controlled trials to evaluate the efficacy of intraoperative interventions for incisional SSI prevention after gastroenterological surgery for clean-contaminated wounds. The patients were reassessed, and pre- and intraoperative variables and postoperative outcomes were collected. IH was defined as any abdominal wall gap, regardless of bulge, in the area of a postoperative scar that was perceptible or palpable on clinical examination or computed tomography according to the European Hernia Society guidelines. The risk factors for IH were identified using univariate and multivariate analyses. RESULTS: The study population included 1,281 patients, of whom 273 (21.3%) developed IH. Seventy-four (5.8%) patients developed incisional SSI. Multivariate logistic regression analysis revealed that female sex (odds ratio [OR], 1.39; 95% confidence interval [CI] 1.03-1.86, p = 0.031), high preoperative body mass index (OR, 1.81; 95% CI 1.19-2.77, p = 0.006), incisional SSI (OR, 2.29; 95% CI 1.34-3.93, p = 0.003), and postoperative body weight increase (OR, 1.49; 95% CI 1.09-2.04, p = 0.012) were independent risk factors for IH due to MAI in patients who underwent elective gastroenterological surgery. CONCLUSION: We identified postoperative body weight increase at one year as a novel risk factor for IH in patients with MAI after elective gastroenterological surgery.

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.

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.

Efficacy of ramucirumab and subsequent nivolumab therapy in patients with advanced gastric cancer: A retrospective study.

Nivolumab monotherapy is a standard treatment of metastatic gastric cancer, and this type of cancer involves vascular endothelial growth factor (VEGF) signaling in the tumor immunological environment. The subgroup analysis of the ATTRACTION-2 trial revealed that prior treatment with ramucirumab (RAM), a VEGF inhibitor, affected the therapeutic effect of nivolumab. The present retrospective study aimed to review patients with metastatic gastric cancer who were treated with paclitaxel (PTX) and RAM followed by nivolumab. A total of 29 patients with metastatic gastric cancer were treated with PTX + RAM as second-line treatment, followed by nivolumab monotherapy as third-line treatment. The therapeutic efficacy of nivolumab was compared in 13 patients with progression-free survival (PFS) of <5 months and 16 patients with PFS ≥5 months after PTX + RAM therapy. The present study included 22 male and seven female patients, with a median age of 68 years (range, 45-82 years). Human epidermal growth factor receptor 2 positivity was observed in six patients. The disease control rate was 62.1%. The PFS and overall survival (OS) were 4.4 and 11.9 months, respectively. Patients with PFS ≥5 months after PTX + RAM therapy showed better outcome in both PFS (5.3 months vs. 2.8 months, P=0.039) and OS (6.9 months vs. 15.2 months, P=0.066) after nivolumab treatment than patients with PFS of <5 months after PTX + RAM therapy. However, no significant relationship was observed between the outcome of first-line treatment and nivolumab. The therapeutic effect of nivolumab was associated with prior PTX + RAM treatment in advanced gastric cancer.

Contrasting seasonality of the incidence of incisional surgical site infection after general and gastroenterological surgery: An analysis of 8,436 patients in a single institute.

BACKGROUND: While seasonality of hospital-acquired infections, including incisional SSI after orthopaedic surgery, is recognized, the seasonality of incisional SSI after general and gastroenterological surgeries remains unclear. STUDY DESIGN: This retrospective single-institute observational study analysed the seasonality and risk factors of incisional SSI after general and gastroenterological surgeries using univariate and multivariable analyses. The evaluated variables included age, sex, surgical approach, surgical urgency, operation time, wound classification, and the American Society of Anesthesiologists physical status (ASA-PS). RESULTS: 8,436 patients were enrolled. General surgeries (n=2,241) showed a pronounced SSI incidence in summer (3.9%; odds ratio [OR] 1.87; 95% confidence interval [CI] 1.05-3.27; p=0.025) compared to other seasons (2.1%). Conversely, gastroenterological surgeries (n=6,195) showed a higher incidence in winter (8.3%; OR 1.38; 95% CI 1.10-1.73; p=0.005) than in other seasons (6.1%). Summer for general surgery (OR 1.90; 95% CI 1.12-3.24; p=0.018) and winter for gastroenterological surgery (OR 1.46; 95% CI 1.17-1.82; p=0.001) emerged as independent risk factors for incisional SSI. Open surgery (OR, 2.72; 95% CI 1.73-4.29, p<0.001) and an ASA-PS score ≥3 (OR, 1.64; 95% CI 1.08-2.50, p=0.021) were independent risk factors for incisional SSI in patients undergoing gastroenterological surgery during winter. CONCLUSION: Seasonality exists in the incisional SSI incidence following general and gastroenterological surgeries. Recognizing these trends may help enhance preventive strategies, highlighting the elevated risk in summer for general surgery and in winter for gastroenterological surgery.

Superiority trial for the development of an ideal method for the closure of midline abdominal wall incisions to reduce the incidence of wound complications after elective gastroenterological surgery: study protocol for a randomized controlled trial.

BACKGROUND: The recent guidelines from the European and American Hernia Societies recommend a continuous small-bite suturing technique with slowly absorbable sutures for fascial closure of midline abdominal wall incisions to reduce the incidence of wound complications, especially for incisional hernia. However, this is based on low-certainty evidence. We could not find any recommendations for skin closure. The wound closure technique is an important determinant of the risk of wound complications, and a comprehensive approach to prevent wound complications should be developed. METHODS: We propose a single-institute, prospective, randomized, blinded-endpoint trial to assess the superiority of the combination of continuous suturing of the fascia without peritoneal closure and continuous suturing of the subcuticular tissue (study group) over that of interrupted suturing of the fascia together with the peritoneum and interrupted suturing of the subcuticular tissue (control group) for reducing the incidence of midline abdominal wall incision wound complications after elective gastroenterological surgery with a clean-contaminated wound. Permuted-block randomization with an allocation ratio of 1:1 and blocking will be used. We hypothesize that the study group will show a 50% reduction in the incidence of wound complications. The target number of cases is set at 284. The primary outcome is the incidence of wound complications, including incisional surgical site infection, hemorrhage, seroma, wound dehiscence within 30 days after surgery, and incisional hernia at approximately 1 year after surgery. DISCUSSION: This trial will provide initial evidence on the ideal combination of fascial and skin closure for midline abdominal wall incision to reduce the incidence of overall postoperative wound complications after gastroenterological surgery with a clean-contaminated wound. This trial is expected to generate high-quality evidence that supports the current guidelines for the closure of abdominal wall incisions from the European and American Hernia Societies and to contribute to their next updates. TRIAL REGISTRATION: UMIN-CTR UMIN000048442. Registered on 1 August 2022. https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000055205.

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.

Update of risk factors for surgical site infection in clean-contaminated wounds after gastroenterological surgery: An analysis of 1,878 participants enrolled in 2 recent randomized control trials for the prevention of surgical site infection.

BACKGROUND: Clean-contaminated wounds should be the main target for reducing the burden of harm caused by surgical site infection after gastroenterological surgery. METHODS: The present study targeted 1,973 patients enrolled in 2 randomized controlled trials to evaluate the efficacy of intraoperative interventions for incisional surgical site infection prevention after gastroenterological surgery with clean-contaminated wounds. Patients were reassessed, and preoperative and postoperative variables were collected. Risk factors for surgical site infection were identified by univariate and multivariate analyses. RESULTS: The study population included 1,878 patients, among whom 213 (11.3%) developed overall surgical site infection and 119 (6.3%) developed incisional surgical site infection. A multivariate analysis revealed that steroid or immunosuppressant use (odds ratio 3.03; 95% confidence interval 1.37-6.73, P = .0064), open surgery (odds ratio 1.77; 95% confidence interval 1.11-2.83, P = .0167), and long operative time (odds ratio 2.31; 95% confidence interval 1.5-3.56, P < .001) were independent risk factors for incisional surgical site infection. Steroid or immunosuppressant use (odds ratio 2.62; 95% confidence interval 1.29-5.33, P = .0078), open surgery (odds ratio 2.13; 95% confidence interval 1.44-3.16, P < .001), and long operative time (odds ratio 2.92; 95% confidence interval 2.08-4.10, P < .001) were also independent risk factors for overall surgical site infection in the multivariate analysis. Furthermore, a multivariate analysis revealed that a long operative time (odds ratio 3.21; 95% confidence interval 1.69-6.1, P = .00378) was an independent risk factor for incisional surgical site infection in patients who underwent laparoscopic surgery. CONCLUSION: Even under current measures for surgical site infection prevention, surgeons should continue to make efforts to appropriately expand the indication of laparoscopic surgery and to reduce operative times even when performing laparoscopic surgery.

Enhancement of DNA hypomethylation alterations by gastric and bile acids promotes chromosomal instability in Barrett's epithelial cell line.

Gastric and bile acid reflux leads to chronic inflammation, resulting in methylation alterations in Barrett's esophagus (BE) together with chromosomal instability (CIN). We investigated DNA hypomethylation following acid exposure and confirmed its significance in BE-related carcinogenesis by inducing CIN in vitro. OACP4C, an esophageal cancer cell line, and CP-A, a non-dysplastic cell line originating from BE, were exposed to acidic conditions using deoxycholic acid. CP-A exhibited substantially increased DNA hypomethylation of alpha satellite sequences in the centromere region, as well as increased levels of alpha satellite transcripts, but no changes were observed in the long interspersed nucleotide element-1 sequences distributed throughout the entire genome. These changes were not clearly found in OACP4C. Copy number changes at specific chromosomes were identified in CP-A, along with an increased number of cells exhibiting abnormal segregations, whereas these changes were rarely observed in OACP4C. The changes were maintained after several cell divisions. These findings suggest that alpha satellites are likely targets of DNA hypomethylation induced by acid exposure. CP-A was more sensitive to acid exposure than OACP4C, indicating that acid-induced DNA hypomethylation is involved in cancer development rather than progression, which could be involved in the underlying mechanism of esophagogastric junction carcinoma development.

Prophylactic use of pegfilgrastim enables the management of severe neutropenia without dose delays in patients with metastatic colorectal cancer treated with TAS-102 plus bevacizumab.

Combined treatment with bevacizumab and trifluridine/tipiracil (TAS-102) leads to an increased chance of survival in patients with refractory metastatic colorectal cancer (mCRC); however, this treatment is associated with an increased frequency of severe neutropenia (number of neutrophils <1,000), which should ideally be managed without dose delays. The present study provided a retrospective review of 35 patients with mCRC, and aimed to elucidate the benefits of prophylactic pegfilgrastim for the treatment of severe neutropenia. Patients received TAS-102 (35 mg/m2) orally twice daily on days 1-5 and 8-12 of each 28-day treatment cycle, along with intravenous bevacizumab (5 mg/kg) on days 1 and 15. Moreover, the patients received 3.6 mg pegfilgrastim on day 15 of each cycle. The incidence of adverse events (AEs), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were assessed. In the first and subsequent cycles, 23 and 12 patients, respectively, received pegfilgrastim. The most common AE experienced was grade 3/4 neutropenia (8 patients; 22.9%). Among these 8 patients, 6 (17.1%) and 3 (8.6%) exhibited neutropenia prior to receiving pegfilgrastim or following discontinuation of pegfilgrastim administration, respectively. Moreover, 1 individual among these 8 patients (2.9%) demonstrated grade 3 neutropenia both prior to receiving pegfilgrastim and following discontinuation of pegfilgrastim. A total of 2 patients (5.7%) exhibited grade 3 bone pain, which prevented sustainable administration of pegfilgrastim and resulted in grade 3 neutropenia. Dose delays and dose reduction of TAS-102 due to neutropenia were required in 5 (14.3%) and 2 (5.7%) patients, respectively, during the treatment period. None of the patients exhibited severe neutropenia during chemotherapy after pegfilgrastim administration, thereby preventing dose delays and dose reduction of TAS-102. The relative dose intensity was 96.8% (65.0-100.0%), and the DCR was 54.3%. The median PFS and median OS were 4.4 and 14.9 months, respectively. In conclusion, prophylactic pegfilgrastim may facilitate the management of severe neutropenia without dose delays in patients with mCRC treated with TAS-102 plus bevacizumab.

Overexpression of satellite RNAs in heterochromatin induces chromosomal instability and reflects drug sensitivity in mouse cancer cells.

Overexpression of satellite RNAs in heterochromatin induces chromosomal instability (CIN) through the DNA damage response and cell cycle checkpoint activation. Although satellite RNAs may be therapeutic targets, the associated mechanisms underlying drug sensitivity are unknown. Here, we determined whether satellite RNAs reflect drug sensitivity to the topoisomerase I inhibitor camptothecin (CPT) via CIN induction. We constructed retroviral vectors expressing major satellite and control viruses, infected microsatellite stable mouse colon cancer cells (CT26) and MC38 cells harboring microsatellite instability, and assessed drug sensitivity after 48 h. Cells overexpressing satellite RNAs showed clear features of abnormal segregation, including micronuclei and anaphase bridging, and elevated levels of the DNA damage marker γH2AX relative to controls. Additionally, overexpression of satellite RNAs enhanced MC38 cell susceptibility to CPT [half-maximal inhibitory concentration: 0.814 µM (control) vs. 0.332 µM (MC38 cells with a major satellite), p = 0.003] but not that of CT26. These findings imply that MC38 cells, which are unlikely to harbor CIN, are more susceptible to CIN-induced CPT sensitivity than CT26 cells, which are characterized by CIN. Furthermore, CPT administration upregulated p53 levels but not those of p21, indicating that overexpression of major satellite transcripts likely induces CPT-responsive cell death rather than cellular senescence.

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.

Optimal value of CA19-9 determined by KRAS-mutated circulating tumor DNA contributes to the prediction of prognosis in pancreatic cancer patients.

Despite the acceptance of carbohydrate antigen 19-9 (CA19-9) as a valuable predictor for the prognosis of pancreatic ductal adenocarcinoma (PDAC), its cutoff value remains controversial. Our previous study showed a significant correlation between CA19-9 levels and the presence of KRAS-mutated ctDNA in the blood of patients with PDAC. Based on this correlation, we investigated the optimal cutoff value of CA19-9 before surgery. Continuous CA19-9 values and KRAS-mutated ctDNAs were monitored in 22 patients with unresectable PDAC who underwent chemotherapy between 2015 and 2017. Receiver operating characteristic curve analysis identified 949.7 U/mL of CA19-9 as the cutoff value corresponding to the presence of KRAS-mutated ctDNA. The median value of CA19-9 was 221.1 U/mL. Subsequently, these values were verified for their prognostic values of recurrence-free survival (RFS) and overall survival (OS) in 60 patients who underwent surgery between 2005 and 2013. Multivariate analysis revealed that 949.7 U/mL of CA19-9 was an independent risk factor for OS and RFS in these patients (P = 0.001 and P = 0.010, respectively), along with lymph node metastasis (P = 0.008 and P = 0.017), unlike the median CA19-9 level (P = 0.150 and P = 0.210). The optimal CA19-9 level contributes to the prediction of prognosis in patients with PDAC before surgery.

A Retrospective Analysis of Preoperative Evaluation and Surgical Resection for Metastatic Tumors of the Pancreas.

Pancreatectomy might confer a survival benefit in patients with metastatic tumors of the pancreas (MTPs); however, the optimal treatment for MTP has not been established. We reviewed six patients with MTP undergoing pancreatectomy and discussed the clinical features, surgical treatment, and survival. The sites of primary cancer included renal cell carcinoma (RCC) (n = 5; 83.3%) and rectal cancer (n = 1; 16.7%). The median interval between the resection of the primary site and the development of MTP was 157 months (range, 16-180 months). Three (60.0%) of the five cases of MTP-originating RCC and a MTP-originating rectal cancer, biopsy was performed under endoscopic ultrasonography guidance and MTP was pathologically diagnosed. All patients with MTP originating from RCC have remained alive for 3, 13, 18, 18, and 113 months without recurrence after pancreatectomy. In contrast, the patient with MTP originating from rectal cancer developed multiple liver metastases at 7 months after pancreatectomy, and then underwent chemotherapy. A preoperative pathological diagnosis using biopsy under endoscopic ultrasonography guidance was indispensable for the treatment of MTP. Pancreatectomy for MTP conferred a survival benefit in patients with metastatic RCC, whereas a combination of pancreatectomy and chemotherapy might be necessary to improve the prognosis of patients with metastatic colorectal cancer.

Temporary loss of consciousness during cetuximab treatment of a patient with metastatic colon cancer: a case report.

BACKGROUND: Anti-epidermal growth factor receptor (EGFR) antibody is widely used for the treatment of patients with metastatic colorectal cancer. Hypomagnesemia is a comparatively frequent adverse event of this drug, which is likely overlooked because it occurs later in treatment without symptoms. Furthermore, hypomagnesemia and hypomagnesemia-induced corrected QT (QTc) prolongation may lead to loss of consciousness (LOC), the onset of which is not generally considered associated with the treatment of anti-EGFR antibody because of its rare occurrence. Here, we present a colorectal cancer patient treated with anti-EGFR antibody, who suffered LOC during treatment while severe hypomagnesemia or QTc prolongation was not observed. CASE PRESENTATION: A 69-year-old man with metastatic colon cancer was treated with cetuximab (anti-EGFR antibody) plus irinotecan as third-line chemotherapy. His serum magnesium level gradually decreased, and grade 2 hypomagnesemia (a serum magnesium level of 0.9 mg/dL) was observed at the 12th administration of cetuximab. In light of this development, intravenous supplementation of 20 mEq magnesium sulfate began with careful blood monitoring despite the lack of clinical symptoms. Electrocardiogram (ECG) showed prolonged QT or corrected QT (QTc) intervals (grade 1). His serum magnesium level remained at 0.9 mg/dL, and no hypomagnesemia symptoms were observed by the 17th administration of cetuximab. After the treatment, however, he suddenly lost consciousness without symptoms related to infusion or allergic reactions. Circulatory collapse following dermatological reactions and respiratory events were not evident. Intravenous supplementation of magnesium sulfate was administered again. He awakened 2 min after the onset of temporary LOC without any other symptoms related to hypomagnesemia, such as lethargy, tremor, tetany, and seizures. No other etiology outside of the low level of serum magnesium was confirmed in further examinations. Cetuximab was discontinued, and his serum magnesium level returned to a level within the normal range after 6 weeks. Because of tumor progression, regorafenib and TAS-102 (trifluridine tipiracil hydrochloride) were introduced sequentially for 6 months. Five months after the final treatment of TAS-102, he died of his primary disease, which reflected a survival period of 4 years and 6 months since the beginning of treatment. CONCLUSIONS: This case report reminds clinicians that LOC can be induced without severe hypomagnesemia or QTc prolongation, during anti-EGFR antibody treatment for metastatic colorectal cancer even while under carefully monitored magnesium supplementation.