Comparison Between Plastic and Metallic Biliary Stent Placement for Preoperative Patients with Pancreatic Head Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Optimal preoperative biliary drainage for patients with pancreatic cancer before pancreatoduodenectomy remains unclear. This study aimed to investigate the comparison of efficacy and safety between a metallic stent (MS) and a plastic stent (PS). METHODS: Comparative studies on the use of MS and PS for pancreatic cancer before pancreatoduodenectomy were systematically searched using the MEDLINE and Web of Science databases. Pre- and postoperative data also were extracted. Random-effects meta-analyses were performed to compare post-endoscopic retrograde cholangiopancreatography (ERCP) complications as well as intra- and postoperative outcomes between the two arms of the study, and pooled odds ratios (ORs) or mean differences (MDs) were calculated with 95 percent confidence intervals (CIs). RESULTS: The study analyzed 12 studies involving 683 patients. Insertion of MS was associated with a lower incidence of re-intervention (OR, 0.06; 95% CI 0.03-0.15; P < 0.001), increased post-ERCP adverse events (OR, 2.22; 95% CI 1.13-4.36; P = 0.02), and similar operation time (MD, 18.0 min; 95% CI -29.1 to 65.6 min; P = 0.46), amount of blood loss (MD, 43.0 ml; 95% CI -207.1 to 288.2 ml; P = 0.73), and surgical complication rate (OR, 0.78; 95% CI 0.53-1.15; P = 0.21). The cumulative stent patency rate after 3 months was higher in the MS group than in the PS group (70-100 % vs 30.0-45.0 %). CONCLUSION: For biliary drainage in patients with pancreatic cancer during this era of multidisciplinary treatment, MS use might be the first choice because MS provides a more durable biliary drainage and a similar risk of postoperative outcomes compared with PS.

Impact of the COVID-19 pandemic on the number and short-term outcomes in hepatectomy for hepatocellular carcinoma: Results from the Japanese National Clinical Database, 2018-2021.

AIM: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the allocation of medical resources, including cancer screening, diagnosis, and treatment. We aimed to investigate the effects of the pandemic on morbidity and mortality following hepatectomy for hepatocellular carcinoma (HCC). METHODS: We identified patients who underwent hepatectomy for HCC between 2018 and 2021 from the Japanese National Clinical Database (NCD). The number of surgical cases, the use of intensive care units, and the incidence of morbidity were assessed. The standardized morbidity / mortality ratio (SMR) was used to evaluate the rates of morbidity (bile leakage and pneumonia) and mortality in each month, which compares the observed incidence to the expected incidence calculated by the NCD's risk calculator. RESULTS: The study included a total of 10 647 cases. The number of patients undergoing hepatectomy for HCC gradually decreased. The proportion of patients aged 80 years or older increased and that of cases with T1 stage decreased. The proportion of patients who were admitted to the intensive care unit did not change between the pre- and postpandemic period. The mean actual incidence rates of bile leakage, pneumonia, 30-day mortality, and surgical mortality were 9.2%, 2.3%, 1.4%, and 2.1%, respectively. The SMR for the mortalities and morbidities in each month did not increase mostly throughout the COVID-19 pandemic. CONCLUSIONS: The present study showed the decreasing number of resected cases for HCC, while the surgical safety for hepatectomy was enough to be maintained by managing medical resources in Japan.

Preoperative predictive factors for positive peritoneal cytology results in patients with pancreatic ductal adenocarcinomas: a retrospective study.

BACKGROUND: The clinical importance of positive peritoneal cytology results in patients with pancreatic ductal adenocarcinomas remains controversial. We evaluated the prognosis of these patients and the predictive preoperative risk factors for positive peritoneal cytology results. METHODS: We retrospectively reviewed patients who underwent curative-intent surgery at our institution between May 2010 and June 2020. Preoperative risk factors for positive peritoneal cytology results were identified using logistic regression analysis. A scoring model was constructed using the total number of significant independent predictors for positive peritoneal cytology results. RESULTS: Of 233 patients, 18 (7.7%) had positive peritoneal cytology results. The recurrence-free survival and cancer-specific survival were markedly worse in patients with positive peritoneal cytology results than in those with negative peritoneal cytology results (recurrence-free survival: 6.0 months vs. 16.6 months, p = 0.050; cancer-specific survival: 19.4 months vs. 47.5 months, p = 0.034). Tumor location (odds ratio: 3.760, 95% confidence interval: 1.099-11.818, p = 0.023), tumor size > 25 mm (odds ratio: 3.410, 95% confidence interval: 1.031-11.277, p = 0.046), preoperative serosal invasion (odds ratio: 5.193, 95% confidence interval: 1.099-24.531, p = 0.038), and preoperative carcinoembryonic antigen level > 5.6 ng/mL (odds ratio: 3.816, 95% confidence interval: 1.248-10.667, p = 0.019) were identified as significant independent predictive factors. Our predictive model's optimal cutoff and positive predictive values for positive peritoneal cytology results were 3 and 27.9%, respectively. CONCLUSIONS: The indications for curative-intent surgery should be considered carefully in patients with high-risk factors for positive peritoneal cytology results.

Standardized upfront Glissonean approach and liver hanging maneuver reduces bile leakage from the hepatic hilum in living donors.

Biliary complications after hepatectomy in living donors have yet to be eradicated. We hypothesized that a standardized upfront Glissonean approach and liver hanging maneuver (GH) would prevent mechanical and thermal injuries to the hilar plate of the remnant liver by determining the point of bile duct division and the final destination of hepatectomy preceding liver parenchymal transection (safety) and facilitate liver transection deep within the parenchyma and allow maximum length of hilar structures (rationality). GH was implemented in 2016 and its incidence of bile leakage was retrospectively compared against the conventional technique. GH comprises six steps: (1) development of the retrohepatic avascular plane between the right hepatic vein (RHV) and the middle hepatic vein (MHV) and isolation of the hepatic vein(s); (2) isolation of the right or left Glissonean pedicle with the corresponding Glissonean pedicles of the caudate lobe; (3) for right liver grafts and left liver grafts with the caudate lobe, passage of the tape for the liver hanging maneuver along the retrohepatic avascular plane and above the hilar plate, and for left liver grafts without the caudate lobe and for left lateral section grafts, passage of the tape from between the RHV and the MHV, along the Arantius ligament, and to the right of the umbilical portion; (4) liver transection; (5) isolation of hilar structures; and (6) graft procurement. Until 2020, 62 consecutive living donors underwent GH (success rate, 100%). The incidence of bile leakage from the hepatic hilum (0%) was significantly lower than that among 59 donors who underwent the conventional technique in 2011-2015 (9%; p = 0.01). In conclusion, GH is highly effective in reducing bile leakage from the hepatic hilum in living donors.

Clinical characteristics and predictive factors of postoperative intra-abdominal abscess after distal pancreatectomy.

PURPOSE: The postoperative mortality rate of distal pancreatectomy is lower than that of pancreaticoduodenectomy, although persistent complications may occur after distal pancreatectomy. Fluid collection (FC) is frequently observed after distal pancreatectomy; however, FC may occasionally progress to postoperative intra-abdominal abscess (PIAA), which requires conservative or progressive interventional treatment. This study aimed to compare the status between patients with or without PIAA, identify predictive factors for PIAA and clinically relevant postoperative pancreatic fistula, and investigate the clinical characteristics of patients with PIAA with interventional drainage. METHODS: We retrospectively reviewed data of patients who underwent distal pancreatectomy between January 2012 and December 2019 at two high-volume centers, where hepatobiliary-pancreatic surgeries were performed by expert specialist surgeons. Logistic regression analysis was performed to determine the predictive factors for PIAA. RESULTS: Overall, 242 patients were analyzed, among whom 49 (20.2%) had PIAA. The median postoperative period of PIAA formation was 9 (range: 3-49) days. Among the 49 patients with PIAA, 25 (51.0%) underwent percutaneous ultrasound, computed tomography, or endoscopic ultrasound-guided interventions for PIAA. In the univariate analysis, preoperative indices representing abdominal fat mass (i.e., body mass index, subcutaneous fat area, and visceral fat area) were identified as predictive factors for PIAA; in the multivariate analysis, C-reactive protein (CRP) level (continuous variable) on postoperative day (POD) 3 (odds ratio: 1.189, 95.0% confidence interval: 1.111 - 1.274; P < 0.001) was the only independent and significant predictive factor for PIAA. CONCLUSIONS: CRP level on POD 3 was an independent and significant predictive factor for PIAA after distal pancreatectomy.

Analysis of the short-term outcomes after esophagectomy for esophageal cancer during the COVID-19 pandemic using data from a nationwide Japanese database.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic had adversely impacted cancer screening, diagnosis, and treatment. We investigated the change in medical resource, such as the intensive care unit use, and short-term outcomes after esophagectomy during the pandemic. METHODS: Data of patients who underwent esophagectomy for esophageal cancer registered in the National Clinical Database (NCD) in Japan from January 2018 to December 2021 were analyzed. The time series change in the number of surgical cases; usage of intensive care unit; incidence of morbidity and mortality; standardized mortality and morbidity ratio (SMR) for 30-days mortality; surgical mortality; and morbidities for pneumonia, sepsis, unplanned intubation, and anastomotic leakage were evaluated. RESULTS: The annual number of patients undergoing esophagectomy remained similar from 2018 to 2021. The negative impact of the pandemic on medical resources was strongly identified in the patients from an epidemic area where there is a higher cumulative number of infections per population as compared to all prefectures. The proportions of patients admitted to the intensive care unit were 91.4%, 93.0%, 91.6%, and 90.5% in 2018, 2019, 2020, and 2021, respectively. Moreover, 93.3%, 94.0%, 92.0%, and 90.9% patients who underwent surgery in an epidemic area were admitted to the intensive care unit in 2018, 2019, 2020, and 2021, respectively. However, the morbidity and mortality rates during the pandemic did not worsen according to the SMR values. CONCLUSIONS: Esophagectomy was performed during the pandemic despite limited medical resources by a systematic endeavor of the entire surgical department in Japan, without increasing the incidence rate of worse outcome.

Genomic analysis of familial pancreatic cancers and intraductal papillary mucinous neoplasms: A cross-sectional study.

Environmental and genetic factors play a critical role in the pathogenesis of pancreatic cancer, which is likely to follow a multistep process that includes intraductal papillary mucinous neoplasm. The pathogenesis of familial pancreatic cancer has been reported; however, epidemiological characteristics and causative genes remain unclear. This study aimed to determine the relationship between the family history of pancreatic cancer and tumor malignancy and identify novel susceptible germline variants of pancreatic cancer. We performed an epidemiologic study at our institute on a cohort of 668 patients with intraductal papillary mucinous neoplasm and 242 with pancreatic cancer but without associated intraductal papillary mucinous neoplasm stratified by family history of pancreatic cancer. Whole-exome sequencing was conducted for 10 patients from seven families with familial pancreatic cancer and intraductal papillary mucinous neoplasm. We found that patients who had intraductal papillary mucinous neoplasm with positive family history of pancreatic cancer within first-degree relatives were more likely to develop malignancy in a shorter period than those without family history. Duplicate frameshift variants in TET2 c.3180dupG (p.Pro1061fs) and ASXL1 c.1934dupG (p.Gly646fs) in one family and POLN c.1194dupT (p.Glu399fs) in another were identified as pathogenic truncating germline variants which were previously recognised susceptibility genes. Moreover, PDIA2 c.1403C>T (p.Pro468Leu) and DPYSL4 c.926C>A (p.Pro309Gln) were shared in four and two patients, respectively. In particular, PDIA2 was identified as a novel candidate for one of the deleterious variants of familial pancreatic cancer.

KRAS variant allele frequency, but not mutation positivity, associates with survival of patients with pancreatic cancer.

KRAS mutation is a major driver of pancreatic carcinogenesis and will likely be a therapeutic target. Due to lack of sensitive assays for clinical samples of pancreatic cancer with low cellularity, KRAS mutations and their prognostic association have not been fully examined in large populations. In a multi-institutional cohort of 1162 pancreatic cancer patients with formalin-fixed paraffin-embedded tumor samples, we undertook droplet digital PCR (ddPCR) for KRAS codons 12/13/61. We examined detection rates of KRAS mutations by clinicopathological parameters and survival associations of KRAS mutation status. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were computed using the Cox regression model with adjustment for potential confounders. KRAS mutations were detected in 1139 (98%) patients. The detection rate did not differ by age of tissue blocks, tumor cellularity, or receipt of neoadjuvant chemotherapy. KRAS mutations were not associated with DFS or OS (multivariable HR comparing KRAS-mutant to KRAS-wild-type tumors, 1.04 [95% CI, 0.62-1.75] and 1.05 [95% CI, 0.60-1.84], respectively). Among KRAS-mutant tumors, KRAS variant allele frequency (VAF) was inversely associated with DFS and OS with HRs per 20% VAF increase of 1.27 (95% CI, 1.13-1.42; ptrend <0.001) and 1.31 (95% CI, 1.16-1.48; ptrend <0.001), respectively. In summary, ddPCR detected KRAS mutations in clinical specimens of pancreatic cancer with high sensitivity irrespective of parameters potentially affecting mutation detections. KRAS VAF, but not mutation positivity, was associated with survival of pancreatic cancer patients.

Reappraisal of liver transplantation for erythropoietic protoporphyria: A deadly combination of disease recurrence and biliary complication.

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare inherited disorder that causes the accumulation of protoporphyrin in the erythrocytes, skin, and liver. Severe protoporphyric hepatopathy results in liver failure, requiring both liver and bone marrow transplantation as a life-saving procedure and to correct the underlying enzymatic defect, respectively. CASE PRESENTATION: We report a 20-year-old man who underwent split liver transplantation using a right trisegment and caudate lobe graft for EPP-induced liver failure, but succumbed to a deadly combination of early relapse of EPP and subsequent, intractable, late-onset bile leakage from the cut surface of segment 4. EPP recurrence most likely created a high-risk situation for bile leakage from the non-communicating bile ducts of segment 4; therefore, this case shed light on the potential relationship between EPP recurrence and biliary complications. CONCLUSION: Physicians should recognize the potentially rapid and life-threatening progression of protoporphyric hepatopathy that leads to liver failure. For young patients with EPP, LT and sequential BMT should thoroughly be considered by a multidisciplinary team as soon as hepatic reserve deterioration becomes evident. Split liver transplantation should preferably be avoided and appropriate post-transplant management is critical before protoporphyrin depositions to the bile duct and hepatocyte causes irreversible damage to the liver graft.

Reconsideration of operative indications in pancreatic neuroendocrine neoplasms.

BACKGROUND: The incidence of pancreatic neuroendocrine neoplasm (PNEN) has been increasing. Resection is typically indicated for PNEN, regardless of its size; however, the indications for its resection are controversial. This study aimed to evaluate the treatment results of surgical resection of PNEN at our institute. METHODS: In this single-center, retrospective, case-control study, 87 patients who underwent PNEN resection and 17 patients with PNEN who did not undergo surgical resection between 1993 and 2020 were included in this study. Clinical characteristics and outcomes were reviewed and statistically compared. Survival was also estimated for the patients in each cohort. RESULTS: Seventeen patients who underwent resection (20%) had lymph node metastasis. Tumors measuring ≥ 2.0 cm and multiple lesions were identified as independent predictors for lymph node metastasis (odds ratio [OR] 17.3, 95% confidence interval [CI] 3.0-100.0, p = 0.001 and OR 8.7, 95% CI 1.5-52.0, p = 0.018, respectively). There was a significant difference in the survival curves depending on the presence or absence of lymph node metastasis (5-year overall survival 74.7% vs. 94.3%, p < 0.001; 5-year recurrence-free survival: 66.3% vs. 93.6%, p < 0.001). All 17 PNEN cases under observation with a median 8 mm (range 5-23) tumor size for a median of 34 (range 2.4-114) months showed slight morphological change with a median tumor growth rate of 0.15 mm (range 0-3.33) per year. CONCLUSION: Patients with tumors measuring ≥ 2.0 cm have a high probability of lymph node metastasis or recurrence, thereby requiring resection. PNEN measuring < 1.0 cm may be acceptable for observation.

Indication for resection and possibility of observation for intraductal papillary mucinous neoplasm with high-risk stigmata.

BACKGROUND/OBJECTIVES: According to the revised international intraductal papillary mucinous neoplasm (IPMN) guidelines (2017), the indication for surgery is based on risk classification. However, some IPMNs with high-risk stigmata (HRS) can be observed for long periods without resection. Hence, we need to reconsider the risk stratification, and this study aimed to propose a novel risk stratification for HRS-IPMNs. METHODS: We enrolled 328 patients diagnosed with IPMN using endoscopic ultrasound between 2012 and 2019. We compared clinicopathological features between HRS and worrisome features (WF) and evaluated outcomes of HRS-IPMN. RESULTS: Fifty-three patients (HRS 38, WF 15) underwent resection at initial diagnosis and 275 patients were observed. Following observation for 30 months, 22 patients (17 HRS, 5 WF) underwent resection. Analysis of resected IPMNs (n = 75) revealed that HRS had dominantly pancreatobiliary mucin subtype. Pancreatobiliary-type IPMN had larger nodule sizes and lymphatic invasion and high recurrence with poor prognosis. Seventy-four patients were diagnosed with HRS, 55 underwent resection, and 19 continue to be observed. The resected group had larger nodule sizes (median 8 mm vs. 5 mm; P = 0.060), whereas the observed group had more main pancreatic duct (MPD) dilation (median 10 mm vs. 5 mm; P = 0.005). In the resected HRS group, only patients with MPD dilation ≥10 mm (n = 10) had no recurrence but had a favorable prognosis compared with those nodule size ≥5 mm (n = 45). CONCLUSIONS: Large nodule size may be associated with pancreatobiliary subtype and poor prognosis; however, patients with MPD dilation ≥10 mm with nodule size <5 mm did not require resection.

Combination of KRAS and SMAD4 mutations in formalin-fixed paraffin-embedded tissues as a biomarker for pancreatic cancer.

Formalin-fixed paraffin-embedded (FFPE) tissues used for routine pathological diagnosis are valuable for cancer genomic analysis; however, the association between mutation status derived from these specimens and prognosis in pancreatic ductal adenocarcinoma (PDAC) remains unclear. We analyzed 50 cancer-related gene mutations including driver genes in PDAC, using next-generation sequencing (NGS) to clarify the association between gene mutations and prognosis. DNA was extracted from FFPE tissues obtained from 74 patients with untreated resectable PDAC who underwent surgery at our institution between 2013 and 2018. Fifty of the 74 patients with DNA extracts from FFPE samples suitable for NGS were analyzed. The prevalence of driver gene mutations was as follows: 84% for KRAS, 62% for TP53, 32% for SMAD4, and 18% for CDKN2A. There were no cases of single SMAD4 mutations; its rate of coincidence with KRAS or TP53 mutations was 30% and 2%, respectively. The combination of KRAS and SMAD4 mutations resulted in significantly shorter relapse-free survival (RFS; median survival time [MST], 12.3 vs. 28.9 months, P = .014) and overall survival (OS; MST, 22.3 months vs. not reached, P = .048). On multivariate analysis, the combination of KRAS and SMAD4 mutations was an independent prognostic factor for RFS (hazard ratio [HR] 4.218; 95% confidence interval [CI], 1.77-10.08; P = .001) and OS (HR 6.730; 95% CI, 1.93-23.43; P = .003). The combination of KRAS and SMAD4 mutations in DNA obtained from FFPE tissues is an independent poor prognostic factor in PDAC.

Frailty is a useful predictive marker of postoperative complications after pancreaticoduodenectomy.

BACKGROUND: Frailty results in a high risk for disability, hospitalization, and mortality. This study aimed to investigate perioperative details of frail patients who underwent pancreatectomy and whether frailty can be a predictive factor of postoperative complications, especially of clinically relevant postoperative pancreatic fistula (CR-POPF). METHODS: This retrospective study included patients who underwent pancreatectomy in our hospital between August 2016 and March 2019. The patients were divided into frail and pre-/non-frail groups. The diagnostic criteria were based on the Japanese version of the Cardiovascular Health Study. RESULTS: Of 93 patients, 11 (11.8%) and 82 (88.2%) were frail and pre-/non-frail patients, with median ages of 82 and 72 years, respectively (p = 0.041). Postoperative complications (Clavien-Dindo ≧ IIIa) were found in 8 and 32 patients (p = 0.034), CR-POPF in 3 and 13 patients (p = 0.346), and postoperative hospital stays were 21 and 17 days (p = 0.041), respectively. On multivariate analysis, frailty was an independent predictive factor (odds ratio [OR] 5.604, 95.0% confidence interval [CI] 1.002-30.734; p = 0.047) of postoperative complications (Clavien-Dindo ≧ IIIa) after pancreaticoduodenectomy. On multivariate analysis, a soft pancreas (OR 5.696, 95.0% CI 1.142-28.149; p = 0.034) was an independent and significant predictive factor of CR-POPF after pancreaticoduodenectomy. CONCLUSIONS: Frailty may be a useful predictive factor of postoperative complications in patients undergoing pancreaticoduodenectomy.

Predictive factors for liver volume and function recovery after resection using three-dimensional analysis.

BACKGROUND: Clinical and biological factors that predict liver volume recovery rate (LVRR) after liver resection of different resected volume (RV) have not been studied extensively. Moreover, it remains uncertain whether remnant liver volume influences the liver function recovery rate (LFRR). This study examined the predictive factors for LVRR after liver resections of different RV and investigated LFRR by focusing on LVRR improvements after hepatectomy. METHODS: Patients who underwent hepatectomy between January 2013 and August 2015 were reviewed retrospectively. LVRR and LFRR were assessed at postoperative months (POMs) 3, 6, and 12. LVRR was evaluated on the basis of RV (0%-15%, 15%-30%, 30%-45%, and >45%). LFRR was evaluated using total bilirubin, prothrombin time, and platelet count. RESULTS: LVRR was lower with more extensive liver resections. Significant independent predictors of LVRR were type IV collagen 7s domain levels and resection magnitude. Platelet count correlated positively with LVRR at all POMs. CONCLUSIONS: Resected livers regenerated after surgery but did not reach preoperative volumes. Preserving the liver as much as possible during resection can result in greater LFRR after hepatectomy. Therefore, decisions regarding liver resection volume should be made very carefully, particularly in patients with higher type IV collagen 7s domain levels.

[A Case of DIC Following Mixed Acidosis during Laparoscopic Hepatectomy].

The patient was an 81-year-old man. Laparoscopic sigmoidectomy was performed for a sigmoid colon cancer(S, type 2, pT3[SS], INF a, Ly0, V0, BD1, Pn0, pPM0, pDM0, RM0, pN0, pM0, pStage Ⅲa, R0, Cur A). One year after the surgery, a blood test showed CEA as high as 68.9 ng/mL, and an abdominal enhanced computed tomography revealed a hepatic tumor showing marginal contrast in the 4th liver segment. Positron emission tomography showed an accumulation of SUVmax 19.0 at the same site, and a metastatic liver tumor was diagnosed. A laparoscopic medial hepatectomy was performed. Bleeding from the hepatectomy site increased significantly after completion. Subcutaneous emphysema spreading from the face to the trunk and thigh was observed, and blood tests revealed a pH of 7.172, PaCO2 of 71.0 mmHg, lactate of 67 mg/dL, mixed acidosis, D-dimer of 118 µg/mL, and a disseminated intravascular coagulation(DIC)syndrome was diagnosed. Following the difficulty of hemostasis, the surgery was changed to laparotomy and terminated by gauze packing. We encountered a case of acidosis exacerbated by hypercapnia that progressed to DIC during laparoscopic medial hepatectomy.

The impact of epidural catheter insertion level on pain control after esophagectomy for esophageal cancer.

BACKGROUND: Although the effectiveness of epidural anesthesia on pain control after esophagectomy has been reported, the appropriate insertion level of the epidural catheter remains unclear for adequate postoperative pain control. We investigated the relationship between the epidural catheter insertion level and postoperative pain control after esophagectomy for esophageal cancer. METHODS: We analyzed retrospectively 63 patients who underwent McKeown esophagectomy for esophageal cancer between October 2014 and November 2018. The epidural catheter was inserted at the T4-T10 level before general anesthesia induction, and epidural anesthesia was started during the operation. In the analysis, the epidural catheter insertion level was divided into three groups (over T6/T7, T7/T8, and under T8/T9) and determined. Postoperative pain was evaluated a numeric rating scale (NRS) for at least 7 postoperative days, and the first NRS after extubation was used to evaluate the impact of the epidural catheter insertion level on pain control. RESULTS: Ten patients (15.9%) failed pain control. The χ2 test and a forward stepwise logistic regression analysis revealed that only the epidural catheter insertion level affected pain control (P < 0.05). The T7/T8 insertion level significantly decreased postoperative pain after esophagectomy. In the subgroup analysis, epidural catheter insertion under T8/T9 significantly increased postoperative pain after esophagectomy when thoracoscopy/laparoscopy was assisted. No significant differences were observed in the incidence of postoperative complications among the epidural catheter insertion levels. CONCLUSIONS: The T7/T8 epidural catheter insertion level contributed to postoperative pain relief and could lead to enhanced recovery after esophagectomy for esophageal cancer.

Efficacy and safety of preoperative 5-fluorouracil, cisplatin, and mitomycin C in combination with radiotherapy in patients with resectable and borderline resectable pancreatic cancer: a long-term follow-up study.

BACKGROUND: We aimed to evaluate the efficacy and safety of 5-fluorouracil-based neoadjuvant chemoradiotherapy (NACRT) in patients with resectable/borderline resectable pancreatic ductal adenocarcinoma (PDAC). METHODS: This retrospective study investigated the clinicopathological features and > 5-year survival of patients with T3/T4 PDAC who underwent NACRT at our institute between 2003 and 2012. RESULTS: Seventeen resectable and eight borderline resectable patients were included. The protocol treatment completion and resection rates were 92.0% and 68.0%, respectively. Two patients failed to complete chemotherapy owing to cholangitis or anorexia. Common grade 3 toxicities included anorexia (12%), neutropenia (4%), thrombocytopenia (4%), anemia (4%), and leukopenia (12%). Pathologically negative margins were achieved in 94.1% of patients who underwent pancreatectomy. Pathological response according to Evans' classification was grade IIA in 10 patients (58.8%), IIB in 5 patients (29.4%), and IV in 2 patients (11.8%). Postoperative pancreatic fistulas were observed in four patients (23.5%), delayed gastric emptying in one patient (5.9%), and other operative morbidities in four patients (23.5%). The 1-, 2-, 5-, and 10-year overall survival rates were 73.9%, 60.9%, 60.9%, and 39.1%, respectively (median follow-up period, 80.3 months). CONCLUSIONS: NACRT is tolerable and beneficial for resectable/borderline resectable PDAC, even in the long-term.

[A Case of Giant Hematogenous Left Quadricep Muscle Metastasis of Hepatocellular Carcinoma].

The patient was a 62-year-old man with no specific medical history. Lateral segmentectomy was performed for hepatocellular carcinoma with a tumor size of approximately 14×13 cm. The histopathological diagnosis was moderately differentiated hepatocellular carcinoma: Fc(-), Fc-Inf(-), Sf(-), S0, N0, Vp2, Vv1, Va0, B0, P0, SM(-), CH. Five years after the first surgery, computed tomography(CT)revealed a left lung tumor in segment 9/10 and left lymph nodes; thus, left pneumonectomy was performed, and these tumors were identified to have metastasized from the primary tumor. Six years after the first surgery, his serum alpha-fetoprotein level was remarkably elevated from 254.9 ng/mL to 3,143.0 ng/mL for three months, and at the same time, he developed left meralgia and swelling of the left femur. Magnetic resonance imaging showed a high-density mass(30×14 cm)in the left quadriceps, and positron emission tomography-CT revealed high uptake in the left quadriceps with a maximum standardized uptake value of 12.3. A needle biopsy of the left femur tumor confirmed metastasis from the primary tumor. Radiotherapy was administered because general anesthesia can prove to be hazardous due to the patient having undergone left pneumonectomy.

KRAS mutations in cell-free DNA from preoperative and postoperative sera as a pancreatic cancer marker: a retrospective study.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has very poor prognosis despite existing multimodal therapies. This study aimed to investigate whether KRAS mutations at codons 12/13 in cell-free DNA (cfDNA) from preoperative and postoperative sera from patients with PDAC can serve as a predictive biomarker for treatment response and outcomes after surgery. METHODS: Preoperative and postoperative serum samples obtained from 45 patients with PDAC whom underwent curative pancreatectomy at our institution between January 2013 and July 2016 were retrospectively analysed. Peptide nucleic acid-directed PCR clamping was used to identify KRAS mutations in cfDNA. RESULTS: Among the 45 patients enrolled, 11 (24.4%) and 20 (44.4%) had KRAS mutations in cfDNA from preoperative and postoperative sera, respectively. Multivariate analysis revealed that KRAS mutations in postoperative serum (hazard ratio (HR)=2.919; 95% confidence interval (CI)=1.109-5.621; P=0.027) are an independent prognostic factor for disease-free survival. Furthermore, the shift from wild-type KRAS in preoperative to mutant KRAS in postoperative cfDNA (HR=9.419; 95% Cl=2.015-44.036; P=0.004) was an independent prognostic factor for overall survival. CONCLUSIONS: Changes in KRAS mutation status between preoperative and postoperative cfDNA may be a useful predictive biomarker for survival and treatment response.

Next­generation sequencing to identify genetic mutations in pancreatic cancer using intraoperative peritoneal washing fluid.

The efficacy of next-generation sequencing (NGS) of tumor-derived DNA from intraoperative peritoneal washing fluid (IPWF) of patients with pancreatic ductal adenocarcinoma (PDAC) who intend to undergo curative resection remains unclear. The aim of the present study was to evaluate whether genomic mutations in tumor-derived DNA from IPWF samples of patients with PDAC who intend to undergo curative resection could be detected using NGS. A total of 12 such patients were included in this study. Cytology of IPWF (CY) was assessed and NGS of genomic tumor-derived DNA from the IPWF was performed to determine whether genomic mutations could be detected in these patient samples. A total of 2 patients (16.7%) had a CY(+) status and 1 patient (8.3%) showed intraoperative macro-peritoneal dissemination; 11 patients underwent radical surgery. Actionable gene alterations were detected in 8 (80.0%) out of the 10 patients with CY(-) status based on NGS of IPWF samples, and 3 (37.5%) patients among those with actionable gene mutations identified from IPWF samples underwent peritoneal dissemination after surgery within ~12 months. The most common genomic mutation was in KRAS (9 patients, 75.0%), followed by TP53 (3 patients, 25.0%), SMAD4 (1 patient, 8.3%) and CDKN2A (1 patient, 8.3%). These findings indicated that the genomic mutations identified in tumor-derived DNA from IPWF samples of patients with PDAC with a CY(-) status who intend to undergo curative resection are potential biomarkers for predicting the recurrence of early peritoneal dissemination.