[Zinc Suppresses Colorectal Cancer Development through Cell-mediated Immunity].

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, then 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 diet group compared to the normal zinc intake group, and about half the number in the high-zinc-intake group compared to 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. Collectively, we have shown that zinc exerts its tumor-suppressive effect by acting on cytotoxic T cells, the center of cellular immunity, and that it increases the transcription of granzyme B, one of the key molecules involved in tumor immunity. In this symposium, we would like to introduce our latest data on the relationship between zinc and tumor immunity.

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.

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.

Median arcuate ligament resection for a patient with ruptured pancreaticoduodenal artery aneurysm: A case report.

INTRODUCTION AND IMPORTANCE: Median arcuate ligament syndrome (MALS) is a rare disease characterized by compression of the celiac artery (CA) by the median arcuate ligament (MAL). A small proportion of pancreaticoduodenal artery (PDA) aneurysms are caused by compression of the CA by the MAL. Here, we report a case of rupture of a PDA aneurysm associated with MALS that was treated with coil embolization followed by MAL resection. CASE PRESENTATION: A 49-year-old man lost consciousness due to hypovolemic shock in the hospital two days after appendectomy. Contrast-enhanced multi-detector row computed tomography (MD-CT) showed a retroperitoneal hematoma and extravasation from the pancreaticoduodenal arcade vessels, therefore emergency angiography was performed. An aneurysm was detected in the anterior inferior PDA and coil embolization was performed for the inferior PDA. Three months after embolization, MAL resection was performed to prevent rebleeding from the PDA. Six months have passed after the surgery, the patient had no CA restenosis or PDA aneurysms. CLINICAL DISCUSSION: MALS is a rare disease that results from the compression of the CA by the MAL. PDA aneurysms are associated with CA stenosis, and compression of the CA by the MAL is the most frequently reported cause of CA stenosis. There is no established treatment for CA stenosis after a PDA aneurysm rupture due to MALS. CONCLUSION: It is suggested that MAL resection may be effective in reducing shear stress in the pancreaticoduodenal arcade. Improving blood flow through the CA by MAL resection might reduce risk of PDA aneurysm recurrence.

Reconsideration of the Appropriate Dissection Range Based on Japanese Anatomical Classification for Resectable Pancreatic Head Cancer in the Era of Multimodal Treatment.

Patients with resectable pancreatic cancer are considered to already have micro-distant metastasis, because most of the recurrence patterns postoperatively are distant metastases. Multimodal treatment dramatically improves prognosis; thus, micro-distant metastasis is considered to be controlled by chemotherapy. The survival benefit of "regional lymph node dissection" for pancreatic head cancer remains unclear. We reviewed the literature that could be helpful in determining the appropriate resection range. Regional lymph nodes with no suspected metastases on preoperative imaging may become areas treated with preoperative and postoperative adjuvant chemotherapy. Many studies have reported that the R0 resection rate is associated with prognosis. Thus, "dissection to achieve R0 resection" is required. The recent development of high-quality computed tomography has made it possible to evaluate the extent of cancer infiltration. Therefore, it is possible to simulate the dissection range to achieve R0 resection preoperatively. However, it is often difficult to distinguish between areas of inflammatory changes and cancer infiltration during resection. Even if the "dissection to achieve R0 resection" range is simulated based on the computed tomography evaluation, it is difficult to identify the range intraoperatively. It is necessary to be aware of anatomical landmarks to determine the appropriate dissection range during surgery.

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.

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.

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.

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.

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.

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.

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.

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.

Immunohistological evaluation of mismatch repair deficiency in pancreatic ductal adenocarcinoma treated with surgical resection.

BACKGROUND: The frequency and prognosis of resected deficient mismatch repair (dMMR) pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study was designed to assess the frequency of dMMR and its clinicopathological relevance in Japanese patients with PDAC treated with surgical resection. METHODS: A total of 400 consecutive patients with PDAC who underwent surgical resection at Hiroshima University were enrolled. Immunohistochemical staining with four antibodies including MLH1, MSH2, MSH6, and PMS2 was used to determine the presence of dMMR in PDAC specimens. Statistical analyses were applied to evaluate the frequency and clinical outcomes of these patients. RESULTS: Of these 400 patients, five (1.3%) had dMMR (two had MLH1 deficiency, two had PMS2 deficiency, and one had MSH2 deficiency). We found a significantly different histological differentiation pattern between patients with dMMR and those with proficient mismatch repair (pMMR) (P = .03). Univariate survival analysis revealed no significant differences between dMMR and pMMR in recurrence-free survival (P = .268) or overall survival (P = .173). CONCLUSIONS: The incidence of dMMR in Japanese patients with resected PDAC is low, and we found no ethnic-specific differences when comparing the incidence to that in Caucasian patients. In the current study, no significant difference was found in recurrence-free and overall survival between patients with dMMR and pMMR.

Reappraisal of the validity of surgery for patients with pancreatic cancer aged 80 years or older stratified by resectability status.

PURPOSE: The aim of this study was to assess the validity of surgical resection for patients with pancreatic ductal adenocarcinoma (PDAC) aged ≥80 years stratified by resectability status. METHODS: Medical records of 245 patients with resectable (R) and 169 with borderline resectable/unresectable (BR/UR) PDAC were reviewed retrospectively. Of the total of 414 patients, 56 (14%) were ≥80 years. The prognostic impact of age ≥80 years was analyzed with stratification by resectability status. RESULTS: No significant difference was found in the incidence of major complications between patients aged ≥80 versus <80 years (12% vs. 16% respectively; P = 0.53). However, patients aged ≥80 years were significantly less likely to receive adjuvant gemcitabine + S-1 chemotherapy than those <80 years (39% vs. 83%, respectively; P < 0.001). Multivariate analyses identified age ≥80 years as an independent risk factor for poor survival in the BR/UR group (P = 0.01), whereas it did not affect survival in the R group. CONCLUSION: Patients aged ≥80 years had a similar prognosis to <80 years in R PDAC, whereas they had significantly worse prognosis in BR/UR PDAC. These findings suggest that surgical resection for patients with PDAC aged ≥80 years is validated in R PDAC, whereas its survival benefit might be limited in BR/UR PDAC.

Prognostic Significance of Lymph Node Metastasis and Micrometastasis Along the Left Side of Superior Mesenteric Artery in Pancreatic Head Cancer.

BACKGROUNDS AND OBJECTIVES: Although metastasis in lymph nodes along the left side of superior mesenteric artery (SMA-LNs-lt) is sometimes found, survival benefit of SMA-LN-lt dissection for pancreatic head cancer is still unclear. The purpose of this study is to evaluate the prognostic significance of SMA-LN-lt metastasis and micrometastasis. METHODS: A total of 166 patients with pancreatic head cancer who underwent pancreatectomy with lymphadenectomy including SMA-LNs-lt between 2002 and 2017 were reviewed retrospectively. Micrometastasis was evaluated by immunohistochemistry. RESULTS: Twenty patients (12%) had SMA-LN-lt metastasis detected by hematoxylin and eosin (HE) staining, and eight patients (5%) had micrometastasis. Patients with SMA-LN-lt HE-positive or micrometastasis group experienced significantly shorter overall survival (OS) than those without (p = .015). In multivariate analysis, SMA-LN-lt HE-positive or micrometastasis (p = .034), portal vein resection (p = .002), histologic grade 2/3 (p = .046), LN metastasis (p = .002), and lack of adjuvant chemotherapy (p < .001) were independent risk factors. Within a subset of SMA-LN-lt HE-positive or micrometastasis group, lack of adjuvant chemotherapy (p = .003) was the independent poor prognostic factor. CONCLUSIONS: In pancreatic head cancer, the rate of SMA-LN-lt HE-positive and micrometastasis was found in 12% and 5%, respectively. Adjuvant chemotherapy may contribute to improvement of prognosis in patients with LN metastasis including SMA-LN-lt metastasis and micrometastasis.

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.