A COMPARATIVE STUDY OF MEDIUM-SIZED MACULAR HOLE SURGERY WITH INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE VERSUS CONVENTIONAL PEELING.

PURPOSE: To investigate surgical results for medium-sized (251-400 µ m) macular holes (MHs). METHODS: This retrospective observational study involved 266 eyes of 262 consecutive patients who underwent internal limiting membrane (ILM) peeling (147 eyes in the ILM peeling group) or inverted ILM flap cover technique (119 eyes in the inverted flap group) for primary medium-sized full-thickness MHs. Macular hole associated with retinal detachment, recurrent MH, and traumatic MH were excluded. RESULTS: The primary closure rate for overall medium-sized MHs was 100% (119 of 119 eyes) in the inverted flap group, which was significantly higher than that (94.6% [139/147 eyes]; P = 0.010) in the ILM peeling group. Notably, even after adjusting for the minimum MH diameter, presence of high myopia, or preexisting posterior vitreous detachment, the primary closure rate was significantly better in the inverted flap group than in the ILM peeling group (Cochran-Mantel-Haenszel test, overall adjusted P = 0.006, 0.009, 0.005, respectively). The preoperative and postoperative restoration of the outer retinal layers and visual acuity were comparable between the inverted ILM flap and ILM peeling techniques. CONCLUSION: Primary closure for medium-sized MHs was significantly superior in the inverted flap group than in the ILM peeling group.

Different post-pancreatectomy glucagon responses to a meal test between surgical approaches.

Residual pancreatic endocrine function is important for maintaining metabolic status after pancreatectomy and is closely related to patient nutritional status and prognosis. In contrast to insulin secretion, the significance of glucagon secretion following pancreatectomy remains unclear. In this study, we assessed the changes in pancreatic glucagon secretion during pancreatectomy to determine their pathophysiological significance. We evaluated glucagon and insulin secretion using a liquid meal tolerance test before and after pancreatectomy in patients scheduled to undergo pancreaticoduodenectomy (PD) or distal pancreatectomy (DP). After pancreatectomy, fasting plasma glucagon levels were significantly decreased in both the PD (n = 10) and DP (n = 5) groups (PD: from 18.4 to 10.5 pg/mL, p = 0.037; DP: from 21.0 to 12.1 pg/mL, p = 0.043), whereas postprandial plasma glucagon levels were not changed. In the liquid meal tolerance test after pancreatectomy, 60-min plasma glucagon levels and the area under the curve (AUC) for 0-120 min of PD were significantly higher than those for DP (60-min plasma glucagon: PD 49.0 vs. DP 21.7 pg/mL, p = 0.040; AUC0-120min: PD 4,749 vs. DP 3,564 µg min/mL, p = 0.028). Postoperative plasma glucose, serum insulin, and serum C-peptide levels during the liquid meal tolerance test were not significantly different between the two groups. Although fasting plasma glucagon levels decreased, postprandial glucagon responses were maintained after both PD and DP. The difference in residual meal-stimulated glucagon response between PD and DP suggests that a relative excess of postprandial glucagon is involved in the postoperative nutritional status after PD through its impact on systemic metabolic status.

Inhibitory Effect of Zinc on Colorectal Cancer by Granzyme B Transcriptional Regulation in Cytotoxic T Cells.

Zinc is one of the essential trace elements and is involved in various functions in the body. Zinc deficiency is known to cause immune abnormalities, but the mechanism is not fully understood. Therefore, we focused our research on tumor immunity to elucidate the effect of zinc on colorectal cancer and its mechanisms. Mice were treated with azoxymethane (AOM) and dextran sodium sulfate (DSS) to develop colorectal cancer, and the relationship between zinc content in the diet and the number and area of tumors in the colon was observed. The number of tumors in the colon was significantly higher in the no-zinc-added group than in the normal zinc intake group, and about half as many in the high-zinc-intake group as in the normal-zinc-intake group. In T-cell-deficient mice, the number of tumors in the high-zinc-intake group was similar to that in the normal-zinc-intake group, suggesting that the inhibitory effect of zinc was dependent on T cells. Furthermore, we found that the amount of granzyme B transcript released by cytotoxic T cells upon antigen stimulation was significantly increased by the addition of zinc. We also showed that granzyme B transcriptional activation by zinc addition was dependent on calcineurin activity. In this study, we have shown that zinc exerts its tumor-suppressive effect by acting on cytotoxic T cells, the center of cellular immunity, and increases the transcription of granzyme B, one of the key molecules in tumor immunity.

[A Case of Advanced Esophageal Cancer with Esophago-Bronchial Fistula Closed by Pembrolizumab plus Chemotherapy Therapy].

We report a case of unresectable advanced esophageal cancer with an esophageal fistula that was treated with pembrolizumab plus CDDP plus 5-FU therapy and the fistula was closed. A 73-year-old male was diagnosed with cervical-upper thoracic esophageal cancer and esophago-bronchial fistula on CT and esophagogastroduodenoscopy. He underwent chemotherapy containing pembrolizumab. The fistula was closed after 4 cycles and oral intake became possible. Six months have passed since the first visit and chemotherapy is ongoing. The prognosis of esophago-bronchial fistula is extremely poor, and there is no established treatment, including fistula closure. Chemotherapy containing immune checkpoint inhibitors could considered to be expected not only for local control but also for long-term survival.

Clinical Implications of Pre- and Postoperative Circulating Tumor DNA in Patients with Resected Pancreatic Ductal Adenocarcinoma.

BACKGROUND: The clinical implications of pre- and postoperative KRAS-mutated circulating tumor DNA (ctDNA) present in patients with pancreatic ductal adenocarcinoma (PDAC) have remained an unresolved issue. This study sought to investigate the clinical significance of pre- and postoperative ctDNA analyses and their impact on the prognosis of PDAC patients. METHODS: Digital droplet polymerase chain reaction detected ctDNA in pre- and postoperative plasma samples prospectively obtained from patients with resectable and borderline-resectable PDAC. Its associations with recurrence-free survival (RFS) and overall survival (OS) were analyzed. The patients were sorted according to the presence of pre- and postoperative ctDNA, and its ability to stratify prognosis was evaluated. RESULTS: The study analyzed 97 patients. Both pre- and postoperative ctDNA were detected in 9 patients, and neither was detected in 55 patients. Whereas 15 patients harbored only preoperative ctDNA, 18 patients had only postoperative ctDNA. The multivariate analysis showed that the presence of preoperative ctDNA was associated with poorer OS (P = 0.008) and that postoperative ctDNA was not associated with either RFS or OS. Survival did not differ significantly between the patients with a positive shift in ctDNA status and those without detectable pre- or postoperative ctDNA. CONCLUSIONS: For the patients with PDAC, the presence of preoperative ctDNA was significantly associated poor OS, whereas postoperative ctDNA was not associated with poor survival. A positive change in ctDNA did not affect patients' survival.

Survival impact of distal pancreatectomy with en bloc celiac axis resection combined with neoadjuvant chemotherapy for borderline resectable or locally advanced pancreatic body carcinoma.

BACKGROUND: The survival benefit associated with distal pancreatectomy with en bloc celiac axis resection (DP-CAR) for patients with borderline resectable or locally advanced pancreatic body carcinoma is controversial. The aim of this study was to evaluate the impact of DP-CAR following neoadjuvant chemotherapy on survival in patients with borderline resectable or locally advanced pancreatic body carcinoma. METHODS: Medical records of patients with pancreatic ductal adenocarcinoma who underwent distal pancreatectomy (DP, n = 102) and DP-CAR following neoadjuvant chemotherapy (n = 32) between 2008 and 2019 were analyzed retrospectively. Short- and long-term outcomes were compared between the two groups. RESULTS: All patients who underwent DP-CAR had tumor contact with the celiac axis. Of these, 30 patients underwent preoperative embolization of the common hepatic artery. The pretreatment tumor size of patients who underwent DP-CAR was larger (P < 0.001), and rates of blood transfusion (P = 0.003) and postoperative complications (P = 0.016) were higher in patients who underwent DP-CAR compared with patients who underwent DP. The 5-year survival rate of patients who underwent DP and DP-CAR were 50.6% and 41.1%, respectively (median survival time, 65.9 vs 37.0 months). For all 134 patients, pretreatment serum CA19-9 levels (P < 0.001), adjuvant chemotherapy (P < 0.001), and lymph node status (P = 0.035) were independent prognostic factors of overall survival by multivariate analysis. CONCLUSIONS: DP-CAR following neoadjuvant chemotherapy for patients with borderline resectable or locally advanced pancreatic body carcinoma may bring the same survival impact as DP, despite increased morbidity.

Prognostic significance of dissecting the nerve plexus around the common hepatic artery in pancreatic cancer.

PURPOSE: This study aims to investigate the positivity rate of the nerve plexus (NPL) around the common hepatic artery (CHA), as well as the impact of dissecting the NPL-CHA, during surgical resection of pancreatic cancer. METHODS: Clinicopathological factors, including hematoxylin and eosin (H&E) staining and immunohistochemistry, were compared between the resectable pancreatic cancer (RPC) and borderline resectable PC (BRPC) groups. Moreover, the relationship between the NPL-CHA status and overall survival (OS) was investigated. RESULTS: In this study, 136 eligible patients were divided into the RPC (72) and BRPC (64) groups. In the RPC group, all patients were negative for H&E staining and microinvasion, whereas 13 (20%) and five patients (8%) were positive for H&E staining and microinvasion, respectively, in the BRPC group. The median OS times in the NPL-CHA-positive and -negative groups were 29.8 and 60.2 months, respectively (p = 0.088). The multivariate analysis of OS indicated an elevated initial carbohydrate antigen 19-9, lymph node (LN) metastasis, and lack of adjuvant chemotherapy (AC), which independently predicted poor outcomes. In the BRPC subgroup, contact with the CHA on preoperative computed tomography (CT) was a high-risk factor for NPL-CHA positivity. CONCLUSION: NPL-CHA positivity was only present in the BRPC group. In the absence of CT evidence of CHA contact, NPL-CHA dissection may not have survival benefits.

Incidence of anastomotic stricture after hepaticojejunostomy with continuous sutures in patients who underwent laparoscopic pancreaticoduodenectomy.

PURPOSE: Laparoscopic hepatojejunostomy (HJ) with continuous sutures is commonly performed in laparoscopic pancreaticoduodenectomy (LPD). This study aimed to investigate the long-term surgical outcomes of HJ in LPD. METHODS: We retrospectively evaluated 103 consecutive patients who underwent pancreaticoduodenectomy via laparoscopic HJ with continuous suturing using multifilament (n = 48) or monofilament-absorbable sutures (n = 47). RESULTS: During follow-up, anastomotic stricture of HJ was identified in 8 (7.8%) patients via balloon enteroscopy-assisted cholangiography. The median time from surgery to confirmation of stricture formation was 7.6 months (range 3.6-19.4). The incidence of HJ stricture was significantly higher in patients with a thin bile duct (diameter < 6.0 mm) than in those with a thick bile duct (diameter ≥ 6.0 mm) [7/27 (25.9%) vs. 1/76 (1.3%), respectively, p < 0.01]. Similarly, it was significantly higher in the monofilament group than in the multifilament group [7/54 (13.0%) vs. 1/49 (2.0%), respectively, p = 0.04]. In the monofilament suture group, 37.5% of patients with thin bile ducts developed stricture after HJ. A multivariate analysis revealed that a thin bile duct was an independent risk factor for HJ stricture (hazard ratio: 25.3, p < 0.01). CONCLUSIONS: Stricture after laparoscopic HJ using continuous sutures frequently occurs in patients with thin bile ducts, particularly when monofilament-absorbable suture is used.

Causative bacteria associated with a clinically relevant postoperative pancreatic fistula infection after distal pancreatectomy.

PURPOSE: Clinically relevant postoperative pancreatic fistulas (CR-POPF) occurring after distal pancreatectomy often cause intra-abdominal infections. We monitored the presence of bacterial contamination in the ascitic fluid after distal pancreatectomy to clarify the bacterial origin of intra-abdominal infections associated with CR-POPF. METHODS: In 176 patients who underwent distal pancreatectomy, ascitic fluid bacterial cultures were performed on postoperative days (POD) 1-4 and when the drainage fluid became turbid. The association between postoperative ascitic bacterial contamination and CR-POPF incidence was investigated. RESULTS: CR-POPF occurred in 18 cases (10.2%). Among the patients with CR-POPF, bacterial contamination was detected in 0% on POD 1, in 38.9% on POD 4, and in 72.2% on the day (median, day 9.5) when the drainage fluid became turbid. A univariate analysis revealed a significant difference in ascitic bacterial contamination on POD 4 (p < 0.001) and amylase level on POD 3-4 (p < 0.001). A multivariate analysis revealed the amylase level and ascitic bacterial contamination on POD 4 to be independent risk factors. CONCLUSIONS: In the CR-POPF group, ascitic bacterial contamination was not observed in the early postoperative stage, but the bacterial contamination rate increased after pancreatic juice leakage occurred. Therefore, CR-POPF-related infections in distal pancreatectomy may be caused by a retrograde infection of pancreatic juice.

Clinical characteristics of initial recurrence in lung after surgical resection for pancreatic ductal adenocarcinoma.

BACKGROUND: The clinical characteristic differences at the initial recurrence site after resection for pancreatic ductal adenocarcinoma (PDAC) remain unknown. We investigated the clinical characteristics in patients with lung recurrence after surgical resection and evaluated the outcome of resection for isolated lung recurrence. METHODS: Of 442 consecutive PDAC patients who underwent surgical resection between 2002 and 2018, 229 had recurrence on imaging. Initial recurrence sites were the liver, lung, local, peritoneal, multiple organs, and others. We analyzed the clinicopathologic factors and outcomes, comparing by initial recurrence site, and investigated the outcomes of resection for isolated lung recurrence. RESULTS: Liver recurrences were the most frequent (n = 60, 26%), followed by lung recurrence (n = 48, 21%). The interval from surgery to recurrence was significantly longer in lung recurrence (P = 0.0001). Patients with lung recurrence had significantly longer overall survival after diagnosis (P < 0.0001). Patients who underwent surgical resection of lung recurrence had a significantly prolonged overall survival rate after recurrence diagnosis (P = 0.004). CONCLUSIONS: Patients with lung recurrence had significantly prolonged survival than those with other recurrence patterns. Resection for isolated lung recurrence represented relatively good prognosis, and possibly may be beneficial in highly-selected patients.

Flooring the Major Vessels with Falciform Ligament to Prevent Post-Pancreatectomy Hemorrhage.

BACKGROUND: One of the most severe pancreatic surgery complications is post-pancreatectomy hemorrhage (PPH). This study's aim was to evaluate the efficacy of flooring the major vessels with falciform ligament in preventing PPH after pancreatoduodenectomy (PD). METHODS: This study was a retrospective review of 500 consecutive patients who underwent PD between Jan 2010 and Dec 2019 at Hiroshima University. Morbidities, including postoperative pancreatic fistula (POPF) or PPH and 90-day mortality, were analyzed. The study cohort was divided into two groups based on the time of surgery (2010-2016 and 2017-2019), i.e., before and after implementation of falciform ligament flooring method. The patient characteristics, operative parameters, clinicopathological factors, morbidity, and mortality were compared between the two periods. RESULTS: Morbidity and mortality rates in the entire cohort were 21% and 1.4%, respectively. The incidence of Grade B/C POPF and PPH was 9.0% and 3.8%, respectively. There was no significant difference between the two periods with respect to Grade B/C POPF, morbidity rate, and mortality rate; however, the rate of Grade B/C PPH significantly decreased from 5.2 to 1.6% p = .027. On multivariate analysis, the absence of the falciform ligament flooring method was an independent PPH risk factor p = .003. CONCLUSIONS: Falciform ligament flooring method may help decrease the incidence of PPH after PD.

Neoadjuvant therapy for pancreatic cancer: an intention-to-treat analysis.

PURPOSE: This study aimed to reassess the duration of neoadjuvant therapy (NAT) for patients with borderline resectable pancreatic cancer (BRPC). METHODS: The medical records of patients with BRPC who received NAT before intended curative resection were retrospectively reviewed. Patient demographics, clinicopathological factors, and prognostic factors for overall survival were analyzed. The serum carbohydrate antigen (CA) 19-9 level was examined monthly during NAT. RESULTS: A total of 118 patients with BRPC were enrolled. The median survival time and 5-year overall survival were 28.0 months and 31%, respectively. Three months after NAT, the CA19-9 levels were normal in 57% of the patients, and 92% underwent resection. Multivariate analysis showed that radiological partial response (hazard ratio (HR), 0.53; 95% confidence interval (CI), 0.26-0.99; p = 0.047); a normal CA19-9 level after NAT (HR, 0.30; 95% CI, 0.22-0.66; p = 0.006); and tumor resection (HR, 0.29; 95% CI, 0.13-0.67; p = 0.005) were independent predictors of better survival. The median CA19-9 level and the rate of normal CA19-9 levels before and after NAT were 256 (interquartile range (IQR), 23-1197) U/mL and 33%, and 27 (IQR, 7-176) U/mL and 57%, respectively. CONCLUSION: A normal CA19-9 level after NAT was an independent predictor of better survival in patients with BRPC. A longer NAT duration might contribute to improved prognosis of patients with elevated CA19-9 levels.

Safe exposure of the left renal vein during laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma: anatomical variations and pitfalls.

PURPOSE: The left renal vein is technically difficult to expose during laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma despite being an important landmark for posterior dissection. We hereby propose a novel technique to safely expose the left renal vein while avoiding the associated anatomical pitfalls. METHODS: The anatomy of the left renal artery and vein was analyzed using multidetector computed tomography. We initially exposed the left renal vein on the left posterior side of the superior mesenteric artery followed by exposure toward the left kidney. We retrospectively examined the perioperative results of this technique in 33 patients who underwent laparoscopic distal pancreatectomy. RESULTS: 15.7% of the patients had an accessory left renal artery coursing cranial to the vein. In 43.1%, the left renal arterial branch ventrally traversed the vein at the renal hilum, thereby posing a risk for arterial injury. The location of the left renal vein varies cranial (17.6%) or caudal (82.4%) to the pancreas. The left renal vein was exposed without any vascular injury using this technique. The median operative time was 259 min, blood loss was 18 mL, and R0 resection rate was 97.0%. CONCLUSIONS: The initial exposure of the left renal vein should, therefore, be on the left posterior side of the superior mesenteric artery.

A Multicenter, Randomized, Controlled Trial Comparing Reinforced Staplers with Bare Staplers During Distal Pancreatectomy (HiSCO-07 Trial).

BACKGROUND: Although distal pancreatectomy (DP) using a reinforced stapler is expected to reduce PF, no multicenter RCT has been performed. To investigate whether reinforced staplers reduce the incidence of clinically relevant pancreatic fistula (PF) after DP compared with staplers without reinforcement. METHODS: Between July 2016 and December 2017, patients scheduled for DP were enrolled in a multicenter, randomized, controlled trial (RCT) at nine hospitals in Hiroshima Japan. Patients were randomized either to reinforced stapler or bare stapler. The primary endpoint was incidence of clinically relevant PF. This RCT was registered with UMIN Clinical Trial Registry (UMIN000022341). RESULTS: A total of 122 patients were assigned to reinforced stapler (n = 61) or bare stapler (n = 61), and 119 patients (61 reinforced stapler and 59 bare stapler) were analyzed. There was no significant difference in the incidence of clinically relevant PF between the reinforced stapler and bare stapler groups (16.3% vs. 27.1%, p = 0.15). Furthermore, the rates of major complication (16.3% vs. 18.6%, p = 0.74), postpancreatectomy hemorrhage (0% vs. 3.4%, p = 0.08), and median postoperative in-hospital days (19 days vs. 20 days, p = 0.78) did not differ between the two groups. Within a subset of 82 patients in whom the thickness of pancreatic transection line was less than 14 mm, a significant difference was found in the incidence of clinically relevant PF (4.5% vs. 21.0% in the reinforced stapler vs. bare stapler groups, respectively, p = 0.01). CONCLUSIONS: Reinforced stapler for pancreatic transection during DP does not reduce the incidence of clinically relevant PF compared to stapler without reinforcement.

Cytoplasmic Hu-Antigen R (HuR) Expression is Associated with Poor Survival in Patients with Surgically Resected Cholangiocarcinoma Treated with Adjuvant Gemcitabine-Based Chemotherapy.

BACKGROUND: Hu-antigen R (HuR) is an RNA-binding protein that regulates the stability, translation, and nucleus-to-cytoplasm translocation of messenger RNAs (mRNAs). OBJECTIVE: The aim of this study was to investigate the prognostic significance of HuR in cholangiocarcinoma patients who received adjuvant gemcitabine-based chemotherapy (AGC) after surgical resection. METHODS: Nuclear and cytoplasmic HuR expression was investigated immunohistochemically in 131 patients with resected cholangiocarcinoma, including 91 patients administered AGC and 40 patients who did not receive adjuvant chemotherapy. The correlation between HuR expression and survival was evaluated by statistical analysis. RESULTS: High nuclear and cytoplasmic HuR expression was observed in 67 (51%) and 45 (34%) patients, respectively. Cytoplasmic HuR expression was significantly associated with lymph node metastasis (p < 0.01), while high cytoplasmic HuR expression was significantly associated with poor disease-free survival [DFS] (p = 0.03) and overall survival [OS] (p = 0.001) in the 91 patients who received AGC, but not in the 40 patients who did not receive AGC (DFS p = 0.17; OS p = 0.07). In the multivariate analysis of patients who received AGC, high cytoplasmic HuR expression was an independent predictor of poor DFS (hazard ratio [HR] 1.77; p = 0.04) and OS (HR 2.09; p = 0.02). Nuclear HuR expression did not affect the survival of enrolled patients. CONCLUSIONS: High cytoplasmic HuR expression was closely associated with the efficacy of AGC in patients with cholangiocarcinoma. The current findings warrant further investigations to optimize adjuvant chemotherapy regimens for resectable cholangiocarcinoma.

The high stromal SPARC expression is independently associated with poor survival of patients with resected pancreatic ductal adenocarcinoma treated with adjuvant gemcitabine in combination with S-1 or adjuvant gemcitabine alone.

BACKGROUND: Although postoperative adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDAC) improves survival, its efficacy varies among individuals. Identification of biomarkers that can predict the efficacy of adjuvant chemotherapy for PDAC is essential. OBJECTIVES: To investigate the predictive value of secreted protein acidic and rich in cysteine (SPARC) expression in patients with PDAC treated with adjuvant gemcitabine in combination with S-1 (adjuvant GS) or adjuvant gemcitabine alone (adjuvant G alone). METHODS: Stromal SPARC and cytoplasmic SPARC were examined immunohistochemically in 211 PDAC patients treated with adjuvant GS or G alone after resection. The association of SPARC expression with clinicopathological factors, disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: In multivariate analysis, borderline resectable with arterial contact (BR-A) (P = .002), higher preoperative CA 19-9 level (≥91 U/ml) (P = .005), moderately or poorly (P = .003), presence of lymph node metastasis (P = .012) and high stromal SPARC expression (P = .013) were independent predictors of poor DFS. Moreover, BR-A (P = .003), higher preoperative CA 19-9 level (≥91 U/ml) (P = .007) and high stromal SPARC expression (P < .001) were identified as independent predictors of poor OS. In contrast, cytoplasmic SPARC expression did not affect DFS and OS. CONCLUSIONS: High stromal SPARC expression was an independent predictor of poor DFS and OS in patients treated with adjuvant GS or G alone. Stromal SPARC expression could be a relevant biomarker for prediction of prognosis in PDAC patients after resection treated with adjuvant GS or G alone.

Prognostic impact of postoperative complication after pancreatoduodenectomy for pancreatic adenocarcinoma stratified by the resectability status.

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the prognostic impact of postoperative complications after pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) stratified by resectability status. METHODS: Medical records of 226 patients with pancreatic head carcinoma who underwent PD, including 115 with resectable (R) and 111 with borderline resectable/unresectable (BR/UR) PDAC, were reviewed retrospectively. Major complications were defined as grade III or IV based on the Clavien-Dindo classification system. The prognostic impact of major complications on overall survival (OS) was analyzed using univariate and multivariate analyses with stratification by resectability status. RESULTS: A multivariate analysis in the BR/UR group identified R1 resection (P = 0.03), T 3/4 stage (P = 0.03), and incidence of major complications (P = 0.03) as independent risk factors for poor survival, whereas major complications did not affect survival in the R group. Initiation of adjuvant gemcitabine plus S-1 chemotherapy occurred significantly less frequently for patients with major complications than for those without major complications in the BR/UR group (P = 0.02). CONCLUSION: A negative prognostic impact of postoperative major complications after PD was observed in patients with BR/UR PDAC, whereas the prognostic impact was unclear in patients with R PDAC.

Comparison of the prognostic impact of pre- and post-operative CA19-9, SPan-1, and DUPAN-II levels in patients with pancreatic carcinoma.

BACKGROUND: Although serum carbohydrate antigen 19-9 (CA19-9), s-pancreas antigen-1 (SPan-1), and duke pancreatic monoclonal antigen type 2 (DUPAN-II) are commonly utilized tumor markers in pancreatic ductal adenocarcinoma (PDAC), it is still unclear which is the most useful for predicting prognosis after surgical resection. Here, we aimed to compare the prognostic impact of pre- and post-operative serum CA19-9, SPan-1, and DUPAN-II levels in patients with resectable PDAC. METHODS: Pre-operative CA19-9, SPan-1, and DUPAN-II levels were analyzed to compare their prognostic values for resectable PDAC in 198 patients whose pre-operative tumor markers were available. The relationships of clinicopathological factors, including pre- and postoperative CA19-9, SPan-1, and DUPAN-II levels, with overall survival (OS) were analyzed using univariate and multivariate analyses in 149 patients for whom both pre- and postoperative tumor markers were available. RESULTS: Elevated pre-operative CA19-9 (≥37 U/mL), SPan-1 (≥30 U/mL), and DUPAN-II (≥150 U/mL) levels were found in 113 (60%), 96 (51%), and 82 (43%) patients, respectively. In multivariate analysis, absence of adjuvant chemotherapy (hazard ratio [HR], 4.17; p = 0.001), R1 resection (HR, 1.90; p = 0.03), higher histological grade (HR, 1.99; p = 0.02), advanced UICC T factor (HR, N/A; p = 0.04) and elevated postoperative CA19-9 (HR, 3.39; p = 0.009) were identified as independent predictors for worse OS. CONCLUSION: When the prognostic impacts of pre- and post-operative serum CA19-9, SPan-1, and DUPAN-II levels in patients with resectable PDAC were compared, elevated postoperative CA19-9 was the strongest predictive marker of poor survival in the pre- and post-operative period.

Sarcopenia is closely associated with pancreatic exocrine insufficiency in patients with pancreatic disease.

BACKGROUND/OBJECTIVES: The loss of skeletal muscle mass (sarcopenia) is associated with the poor prognosis of pancreatic cancer. It has been reported pancreatic exocrine insufficiency (PEI) is associated with serum nutritional markers in chronic pancreatitis. However, there has been no report about the relationship between sarcopenia and PEI. The aim of this study is to determine whether body composition, including skeletal muscle (SM), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), intramuscular adipose tissue content (IMAC), and serum nutritional markers are associated with pancreatic exocrine function in patients with pancreatic disease. METHODS: Data were collected prospectively on 132 patients with pancreatic disease. SM, SAT, VAT and IMAC were assessed by computed tomography. Patients underwent a 13C-labeled mixed triglyceride breath test to measure pancreatic exocrine function. Serum nutritional markers were measured at the same time of 13C-labeled mixed triglyceride breath test. Patients were stratified by quartiles according to each body component, and for each component the lowest group was defined as the lowest quartile, treating men and women separately. The lowest group for SM was defined as sarcopenia. PEI was defined as a percentage 13CO2 cumulative dose at 7 h below 5%. RESULTS: Sarcopenia was associated with PEI in both men (P < 0.001) and women (P = 0.012). Serum albumin was associated with PEI in men only (P = 0.005). Among all patients, sarcopenia (P = 0.001) and serum albumin (P = 0.058) were associated with PEI. On multivariate analysis, only sarcopenia remained independently associated with PEI (P < 0.001). CONCLUSIONS: Sarcopenia is independently associated with PEI in patients with pancreatic disease.

Prognostic value of circulating tumour DNA in patients undergoing curative resection for pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is frequently diagnosed at an advanced stage, leading to a poor prognosis. Therefore, interest in the development of non-invasive biomarkers for prognostic prediction has grown rapidly. Here, we assessed the clinical implications of v-Ki-ras2 kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated circulating tumour DNA (ctDNA) as a useful surrogate biomarker in patients with resectable PDAC. METHODS: We used droplet digital polymerase chain reaction to detect rare mutant tumour-derived KRAS genes in plasma cell-free DNA (cfDNA) as ctDNA. Samples were collected from 105 patients who underwent pancreatoduodenectomy for PDAC at a single institution. Overall survival (OS) was analysed according to the presence of ctDNA. RESULTS: Among the 105 cases, ctDNA was detected in 33 (31%) plasma samples. The median OS durations were 13.6 months for patients with ctDNA (ctDNA+) and 27.6 months for patients without ctDNA. Patients who were ctDNA+ had a significantly poorer prognosis with respect to OS (P<0.0001). CONCLUSIONS: Our findings suggested that the presence of ctDNA in plasma samples could be an important and powerful predictor of poor survival in patients with PDAC. Accordingly, ctDNA detection might be a promising approach with respect to PDAC treatment.