The clinical impacts of the prognostic nutritional index for the esophageal cancer patients who received curative treatment.

BACKGROUND: We investigated the impact of the prognostic nutritional index (PNI) on esophageal cancer survival and recurrence after curative treatment. METHODS: This study included 120 patients who underwent curative surgery followed by the adjuvant treatment for esophageal cancer between 2008 and 2018. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: The PNI of 49 was regarded to be the optimal critical point of classification considering the 1-year, 3-year, and 5-year survival rate. The OS rates at three and five years after surgery were 47.4% and 36.0% in the PNI low group, respectively, and 62.5% and 56.5% in the PNI high group, which amounted to a statistically significant difference (P = 0.020). The RFS rates at three and five years after surgery were 31.0% and 24.8% in the PNI low group, respectively, and 50.9% and 42.8% in the PNI high group, which amounted to a statistically significant difference (P = 0.020). A multivariate analysis demonstrated that the PNI was a significant independent risk factor for the OS and a marginally significant independent risk factor forRFS. CONCLUSION: The PNI was a risk factor for survival in patients who underwent curative treatment for esophageal cancer. It is necessary to develop the effective plan of the perioperative care and the surgical strategy according to the PNI.

A case of ventricular triple rupture after an acute myocardial infarction.

Cardiac rupture, such as ventricular free-wall rupture, ventricular septal perforation, and papillary muscle rupture, is a life-threatening complication of acute myocardial infarction. Herein, we report a very rare case of combining these three types of ventricular rupture. A 71-year-old woman underwent mitral valve replacement and left ventricular free-wall rupture repair after an acute myocardial infarction. She was transferred to our hospital under mechanical support by venoarterial extracorporeal membrane oxygenation and intra-aortic balloon pump due to circulatory collapse. Transthoracic echocardiography revealed a left-to-right shunt caused by ventricular septal perforation. The patient underwent endoventricular patch plasty for septal defect closure. Unfortunately, a prolonged postoperative course led to the development of multi-organ failure followed by fatal outcome on day 32 postoperatively. To our best knowledge, this is the first reported case of ventricular triple rupture associated with acute myocardial infarction.

The clinical impacts of lymphocyte-to-C-reactive protein ratio for esophageal cancer patients who receive curative treatment.

Background: We investigated the impact of the lymphocyte-to-C-reactive protein ratio (LCR) on esophageal cancer survival and recurrence after curative treatment. Patients and Methods: This study included 89 patients who underwent curative surgery followed by adjuvant treatment for esophageal cancer between 2008 and 2018. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. Results: LCR of 12,177 was regarded to be the optimal critical point of classification considering the 1-year, 3-year, and 5-year survival rates. The OS rates at 3 and 5 years after surgery were 33.2% and 29.9% in the LCR low group, respectively, and 74.0% and 60.9% in the LCR high group, which amounted to a statistically significant difference (P = 0.001). The RFS rates at 3 and 5 years after surgery were 25.3% and 21.7% in the LCR low group, respectively, and 52.1% and 47.4% in the LCR high group, which amounted to a statistically significant difference (P = 0.001). A multivariate analysis demonstrated that the LCR was a significant independent risk factor for both the OS and RFS. Conclusion: LCR was a risk factor for survival in patients who underwent curative treatment for esophageal cancer. It is necessary to develop the effective plan of the perioperative care and the surgical strategy according to the LCR.

Tumor DNA in Peritoneal Lavage as a Novel Biomarker for Predicting Peritoneal Recurrence in Patients With Gastric Cancer.

BACKGROUND: Peritoneal lavage cytology positivity (CY1) has been identified as a prognostic factor for distant metastases that is equivalent to peritoneal dissemination in Japan. Peritoneal lavage cytology is usually diagnosed by microscopic findings; a diagnostic procedure using a liquid biopsy (LB) technique has not yet been established. PATIENTS AND METHODS: We evaluated the feasibility of a LB approach using peritoneal lavage samples from 15 patients with gastric cancer. Samples were collected from both the Douglas pouch and the left subdiaphragmatic area, and cell-free DNA was extracted for analysis of TP53 mutations using droplet digital polymerase chain reaction. RESULTS: All 10 patients with CY1 had positive cytology for the left subdiaphragmatic specimen. However, only six out of the 10 patients had positive cytology for their Douglas pouch specimens, and these six patients had peritoneal tumor DNA (ptDNA) in these specimens. In all five patients with CY0, ptDNA was not detected. The overall survival was significantly shorter in the ptDNA-positive group than in the ptDNA-negative group. The survival of the group with a high amount of DNA from free intraperitoneal cells (ficDNA) was significantly worse than that of those with a low amount. In contrast, the group with a high amount of DNA from peritoneal cell-free DNA (pcfDNA) had significantly better survival than the group with a low amount. CONCLUSION: LB cytology showed equivalent utility to that of conventional microscopic examinations regarding its diagnostic ability. Therefore ptDNA, pcfDNA and ifcDNA are expected to be useful as prognostic factors.

Incidence and Risk of Venous Thromboembolism in Patients With Resectable Pancreatic Cancer Receiving Neoadjuvant Chemotherapy.

BACKGROUND/AIM: Pancreatic cancer has the highest risk of venous thromboembolism (VTE). Additionally, chemotherapy for cancer patients increases the risk of developing VTE. Due to recent advances in neoadjuvant chemotherapy (NAC) regimens, more patients with resectable pancreatic cancer will receive NAC. However, the incidence, risk, and predictors of developing VTE in these patients have not been fully evaluated. PATIENTS AND METHODS: We retrospectively evaluated the incidence, risk, and predictors of VTE among 67 consecutive patients with resectable pancreatic cancer who received neoadjuvant combination therapy with gemcitabine+S-1 (NAC-GS) followed by surgery and 45 patients with resectable pancreatic cancer who underwent upfront surgery (Up-S). RESULTS: The incidence of VTE in the NAC-GS and Up-S groups was 10.4% and 6.6%, respectively. Preoperative D-dimer levels were significantly higher in the NAC-GS group, and D-dimer levels were significantly increased during NAC-GS. Preoperative D-dimer level was the only predictor for VTE in patients with resectable pancreatic cancer who received NAC-GS. CONCLUSION: There is an increased risk of developing VTE during NAC. Screening with D-dimer and taking appropriate measures to suppress critical VTE is essential to provide NAC to patients with resectable pancreatic cancer.

Parathyroid carcinoma with pancreatitis causing hypercalcaemic emergency treated with extracorporeal membrane oxygenation-assisted parathyroid resection.

Summary: Emergencies due to malignancies usually have a severe clinical course and require urgent treatment. These scenarios are dubbed 'oncologic emergencies'. Parathyroid tumours often cause hypercalcaemia but not oncologic emergencies. We present a case of parathyroid carcinoma with severe hypercalcaemia and pancreatitis, resolved by surgical resection of the tumour assisted by extracorporeal membrane oxygenation (ECMO). A 66-year-old woman presented to our hospital because of haematuria. Laboratory findings were as follows: white blood cell count: 30 000, C-reactive protein: 17.7, calcium: 21.9, creatine kinase: 316, creatine kinase-myoglobin binding: 20, troponin I: 1415.8, amylase: 1046, lipase: 499, blood urea nitrogen: 57, and creatinine: 2.42. ECG was unremarkable. CT revealed a 4-cm low-density irregular tumour in the left lobe of the thyroid gland and severe pancreatitis. We diagnosed hypercalcaemia and pancreatitis due to parathyroid carcinoma. Volume expansion with isotonic saline was started immediately. Calcitonin, followed by denosumab, calcimimetic agents, and continuous hemodiafiltration were administered. The patient's general condition worsened due to uncontrolled hypercalcaemia. Urgent tumour resection was planned, assisted with ECMO for cardiopulmonary support and surgical field venous pressure reduction. Tumour histology was suggestive of parathyroid carcinoma. Hypercalcaemia and the patient's general condition improved gradually postoperatively. Hypercalcaemia is one of the oncologic emergency symptoms, commonly occurring because of lytic bone metastasis. However, reports about parathyroid carcinoma-causing life-threatening hypercalcaemia and pancreatitis are scarce; the fatality of this condition is estimated to be 30-70%. We report a case of survival of hypercalcaemia of malignancy. Learning points: Parathyroid carcinoma is relatively rare and sometimes causes emergent conditions such as hypercalcaemia and severe pancreatitis. General therapy for hypercalcaemia including aggressive saline dehydration, administration of furosemide, calcitonin, zoledronic acid, and evocalcet, and dialysis is sometimes ineffective for parathyroid carcinoma. Therefore, careful planning of therapy in case of exacerbation is important. During an emergency, rapid surgical treatment despite high calcium level is the best potential therapeutic strategy.

Should the splenic hilar lymph node be dissected for the management of adenocarcinoma of the esophagogastric junction?

BACKGROUND: Splenic hilar lymphadenectomy is not recommended for advanced proximal gastric cancer that does not invade the greater curvature according to the results of the previous studies. The efficacy of splenic hilar lymphadenectomy for type II and type III adenocarcinomas of the esophagogastric junction and easy spread to the greater curvature of the stomach remains unclear. This study aimed to investigate the efficacy of splenic hilar lymphadenectomy and identify the risk factors for metastasis to splenic hilar nodes. METHODS: We examined patients who underwent R0/1 gastrectomy for Siewert types II and III at a single high-volume center in Japan. We analyzed the metastatic incidence, therapeutic value index, and risk factors for splenic hilar lymph node metastasis. RESULTS: We examined 126 patients (74, type II; 52, type III). Splenectomy was performed in 76 patients. Metastatic incidence and the therapeutic value index of splenic hilar lymph nodes in patients with type II and type III tumors were 4.5% and 0, and 21.9% and 9.4, respectively. In the patients who underwent splenectomy, we identified Siewert type III tumors (odds ratio: 6.93, 95% confidence interval: 1.24-38.8, p = 0.027) and tumor location other than the lesser curvature (odds ratio: 7.36, 95% confidence interval: 1.32-41.1, p = 0.023) to be independent risk factors. The metastatic incidence (46.2%) and therapeutic value index (15.4) were high in patients with both risk factors. CONCLUSIONS: Splenic hilar lymphadenectomy may contribute to the survival of patients with Siewert type III tumors, especially when the predominant location is not the lesser curvature.

Clinical Significance of SEC11A Expression in Patients With Locally Advanced Gastric Cancer.

BACKGROUND/AIM: SEC11A gene encodes the SPC18 protein, which has been implicated in tumour progression by inducing the secretion of various growth factors. We investigated the clinical significance of SEC11A expression in gastric cancer (GC) tissues in patients with locally advanced gastric cancer (LAGC) after curative resection. PATIENTS AND METHODS: We estimated SEC11A expression in cancer tissues from 253 pStage II/III GC patients who underwent curative resection using quantitative polymerase chain reaction (PCR) and investigated the relationship of SEC11A expression with clinicopathological factors and survival. RESULTS: SEC11A expression was significantly related to serosal invasion, lymph node metastasis, lymphatic invasion, and pathological stage. The high-SEC11A expression group had a significantly lower survival rate than the low group (5-year survival 52.3% vs. 75.9%; p<0.005). Furthermore, in multivariate analysis, high-SEC11A expression was an independent factor of poor survival (hazard ratio, 2.010; 95% confidence interval=1.303-3.100; p=0.002). CONCLUSION: SEC11A expression in cancer tissue may be a useful prognostic marker in patients with LAGC after curative resection.

Store-operated calcium entry via ORAI1 regulates doxorubicin-induced apoptosis and prevents cardiotoxicity in cardiac fibroblasts.

Despite exhibiting cardiotoxicity, doxorubicin (DOX) is widely used for cancer treatments. Cardiac fibroblasts (CFs) are important in the pathogenesis of heart failure. This necessitates the study of the effect of DOX on CFs. The impairment of calcium (Ca2+) homeostasis is a common mechanism of heart failure. Store-operated Ca2+ entry (SOCE) is a receptor-regulated Ca2⁺ entry pathway that maintains calcium balance by sensing reduced calcium stores in the endoplasmic reticulum. ORAI1, a calcium channel protein and the most important component of SOCE, is highly expressed in human cardiac fibroblasts (HCFs). It is upregulated in CFs from failing ventricles. However, whether ORAI1 in HCFs is increased and/or plays a role in DOX-induced cardiotoxicity remains unknown. In this study, we aimed to elucidate the relationship between ORAI1/SOCE and DOX-induced heart failure. Induction of apoptosis by DOX was characterized in HCFs. Apoptosis and cell cycle analyses were performed by fluorescence-activated cell sorting (FACS). Reactive oxygen species (ROS) production was measured using fluorescence. YM-58483 was used as an ORAI1/SOCE inhibitor. ORAI1-knockdown cells were established by RNA interference. In vivo experiments were performed by intraperitoneally injecting YM-58483 and DOX into mice. We first demonstrated that DOX significantly increased the protein expression level of p53 in HCFs by western blotting. FACS analysis revealed that DOX increased early apoptosis and induced cell cycle arrest in the G2 phase in fibroblasts. DOX also increased ROS production. DOX significantly increased the expression level of ORAI1 in CFs. Both YM-58483 and ORAI1 gene knockdown attenuated DOX-induced apoptosis. Similarly, YM-58483 attenuated cell cycle arrest in the G2 phase, and ORAI1 knockdown attenuated DOX-induced ROS production in HCFs. In the animal experiment, YM-58483 attenuated DOX-induced apoptosis. In HCFs, ORAI1/SOCE regulates p53 expression and plays an important role in DOX-induced cardiotoxicity. ORAI1 may serve as a new target for preventing DOX-induced heart failure.

Outcomes of feeding jejunostomy after pancreaticoduodenectomy: A single-center experience.

Aims: Feeding jejunostomy tube (FJT) is one option for enteral nutrition after pancreaticoduodenectomy (PD); however, controversy regarding its clinical outcome(s) persists. The aim of the present study was to determine the safety and efficacy of FJT management. Materials and Methods: Data from 156 consecutive patients, who underwent PD between January 2015 and December 2017, were retrospectively reviewed. Safety was assessed according to postoperative and tube-related complications. Nutritional efficacy was evaluated based on improvement in serum albumin levels. Results: Thirty-day morbidity and mortality rates were 61.0% (n = 95) and 1.9% (n = 3), respectively. The rates of clinically relevant postoperative pancreatic fistula and delayed gastric emptying were 30.8% and 9.0%, respectively. In total, nine (5.8%) patients experienced complications directly related to FJT. Eight patients experienced surgical site infection adjacent to the catheter/skin interface. Although all required catheter removal at the bedside or in the office, none required reoperation. The improvement in serum albumin level 1 month after PD was 40.7% compared with 1 week after PD. Conclusion: FJT was useful in improving nutritional intake and status. Although FJT was associated with minor self-limiting complications, they could be managed by simple bedside or office treatment. As such, results of this study support the safety and efficacy of the FJT protocol used in the authors' department for nutritional management.

Malignant pleural mesothelioma in situ.

Although the diagnosis of malignant pleural mesothelioma at an in situ stage was traditionally challenging, it is now possible owing to advances in molecular biological methods such as P16 fluorescence in situ hybridization or BRCA1-associated protein 1 immunohistochemistry. Here, we report the first case, to our knowledge, of total parietal pleurectomy for mesothelioma in situ. Future follow-up and accumulation of cases are necessary to determine whether total parietal pleurectomy could be applied as a treatment for mesothelioma in situ or not.

[Vascular Prosthesis Perforation Caused by a Stent Graft Inserted into the Innominate Artery after Total Aortic Arch Replacement].

The patient was a 60-year-old woman who underwent thoracoabdominal aorta replacement for type B aortic dissection three years ago and aortic root replacement and total aortic arch replacement due to asymptomatic type A aortic dissection two years previously. Her clinical course was uneventful until follow-up computed tomography (CT) disclosed anastomotic insufficiency in the innominate artery and left main coronary artery stenosis owing to hematoma. Emergent percutaneous coronary intervention and stent graft insertion into the innominate artery were performed successfully. Seven months later, however, CT scan revealed a perforation in the posterior wall of the artificial graft damaged by the edge of the implanted stent graft. The patient underwent open surgery and perforation of artificial graft was sutured and redundant stent graft edge was resected. Artificial graft damage by stent graft placement is rare to date, but may increase in the future in accordance with broader application of endovascular treatment.

Laparoscopic-assisted surgery versus open surgery for transverse colon cancer: A multicenter retrospective study.

Introduction: Previous randomized controlled trials demonstrated similar oncological outcomes between laparoscopic-assisted (LA) and open (OP) colectomy; however, patients with transverse colon cancer were not analyzed. The aim of this study was to confirm the oncological safety and the advantages of the short- and long-term results of LA surgery for transverse colon cancer in comparison to OP surgery. Materials and Methods: The study data were retrospectively collected from the databases of four hospitals. Patients with transverse colon cancer who underwent LA or OP R0 or R1 resection were registered. Results: Among the 204 patients, 149 underwent OP colectomy and 55 underwent LA colectomy. The median follow-up period was 43 months. The rate of conversion to OP resection was 7.3%. The 5-year overall survival rate of the LA group was higher than that of the OP surgery group for all-stage patients (97.5% vs. 91.1%, P = 0.108), and it was similar in Stage II and Stage III patients (94.1% vs. 94.2%, P = 0.510). The LA group had significantly lower blood loss and a significantly longer operative time in comparison to the OP surgery group. Furthermore, the postoperative hospital stay was significantly shorter (9 vs. 13 days, P = 0.001) and the incidence of Grade ≥III complications was lower in the LA group (3.7% vs. 14.8%, P = 0.031). Conclusion: We concluded that LA surgery for transverse colon cancer is oncologically safe and yields better short-term results in comparison to OP surgery.

Clinical Significance of EREG Gene Expression in Gastric Cancer Tissue After Curative Surgery.

BACKGROUND/AIM: Epiregulin (EREG) is a ligand of the epidermal growth factor receptor (EGFR) and promotes tumour progression mainly by stimulating the EGF pathway. We investigated the clinical significance of EREG mRNA expression in cancer tissues from patients with gastric cancer (GC) in pathological (p) Stage II/III who have undergone curative surgery. PATIENTS AND METHODS: Expression of EREG mRNA was measured in cancer tissues obtained from 253 patients with pStage II/III GC who underwent curative surgery. Patients were divided into groups based on high or low expression of EREG mRNA. We examined the relationship between EREG mRNA expression levels and clinicopathological features and survival. RESULTS: Clinicopathological features did not vary between the high and low EREG mRNA expression groups. Overall survival was significantly lower in the high-expression group compared to that in the low-expression group (5-year survival probability: 55.0% vs. 73.0%; p=0.005). Multivariate analysis showed EREG mRNA expression to be an independent predictor of poor survival (hazard ratio=1.794; 95% confidence interval=1.186-2.712; p=0.006). CONCLUSION: Expression of EREG mRNA in cancer tissue from patients with pStage II/III GC may be a useful prognostic marker after curative surgery.

Rapid anticalcification treatment for glutaraldehyde-fixed autologous tissue in cardiovascular surgery.

BACKGROUND: Glutaraldehyde (GA)-fixed autologous tissues, including the pericardium, are widely used as patches and valve substitutes in cardiovascular surgery. However, GA treatment causes tissue calcification. No rapid anticalcification method has been established for use during surgery. Here, we aimed to establish a rapid anticalcification method using ethanol, as has already been demonstrated for bioprosthetic valves. METHODS: Thoracic aorta tissues were first fixed with GA for 3 min and then treated with ethanol for 0 (group 2), 10 (group 3), 20 (group 4), and 30 (group 5) min; untreated tissues (group 1) served as the control. The treated tissues were subdermally implanted into 3-week-old male Wistar rats and kept in place for 28 days. The calcification in each explant was semiquantitatively evaluated by annotating and measuring the area using virtual slides, and the data obtained were statistically analyzed. RESULTS: Semiquantitative analysis revealed that calcification of the implants from the untreated group (group 1; P = 0.0014) and groups 4 (P = 0.0014) and 5 (P = 0.0031) was significantly lower than that of implants from group 2. Moreover, implants from group 3 showed a tendency toward decreased calcification, although it was not significant (P = 0.0503). CONCLUSIONS: A rapid ethanol treatment prevents calcification of GA-fixed tissues in a rat model of subdermal implantation. This method may facilitate effective and rapid anticalcification of autologous tissues for use during cardiovascular surgery.

Gastric cancer biomarker analysis in patients treated with different adjuvant chemotherapy regimens within SAMIT, a phase III randomized controlled trial.

Biomarkers for selecting gastric cancer (GC) patients likely to benefit from sequential paclitaxel treatment followed by fluorinated-pyrimidine-based adjuvant chemotherapy (sequential paclitaxel) were investigated using tissue samples of patients recruited into SAMIT, a phase III randomized controlled trial. Total RNA was extracted from 556 GC resection samples. The expression of 105 genes was quantified using real-time PCR. Genes predicting the benefit of sequential paclitaxel on overall survival, disease-free survival, and cumulative incidence of relapse were identified based on the ranking of p-values associated with the interaction between the biomarker and sequential paclitaxel or monotherapy groups. Low VSNL1 and CD44 expression predicted the benefit of sequential paclitaxel treatment for all three endpoints. Patients with combined low expression of both genes benefitted most from sequential paclitaxel therapy (hazard ratio = 0.48 [95% confidence interval, 0.30-0.78]; p < 0.01; interaction p-value < 0.01). This is the first study to identify VSNL1 and CD44 RNA expression levels as biomarkers for selecting GC patients that are likely to benefit from sequential paclitaxel treatment followed by fluorinated-pyrimidine-based adjuvant chemotherapy. Our findings may facilitate clinical trials on biomarker-oriented postoperative adjuvant chemotherapy for patients with locally advanced GC.

Usefulness of Surgical Staging of Gastric Cancer in Neoadjuvant Chemotherapy Candidates: A Single-center Retrospective Study.

BACKGROUND: The current expectancy of long-term survival of patients with pathological stage (pStage) III gastric cancer (GC) is not satisfactory. However, neoadjuvant chemotherapy (NAC) is expected to improve survival rates in these patients. An appropriate pretherapeutic diagnostic strategy is necessary for selecting patients who are eligible for NAC. Surgical findings can often identify serosal invasion or metastatic lymphadenopathy, thereby facilitating the selection of candidates for NAC. Therefore, we aimed to evaluate the accuracy and potential of surgical staging in improving the management and survival of patients with GC. PATIENTS AND METHODS: We assessed the accuracy of surgical staging in comparison to preoperative staging using data from patients who underwent gastrectomy for GC. In addition, differences in survival after using the surgical staging criterion were assessed. RESULTS: A total of 915 patients were evaluated in this study. The sensitivity of surgical staging in detecting pStage III in the surgical T4N0-3 plus surgical T3N1-3 group was satisfactory (79.3%). The proportion of patients with pStage I using the surgical staging criterion was 7.8%. CONCLUSION: Surgical staging using laparoscopy or laparotomy may assist in selecting candidates for enrollment in clinical trials for NAC.

[A Case of Pregnancy-Associated Breast Cancer Which Underwent Surgical Treatment during Pregnancy and Chemotherapy after Delivery].

CASE: A 37-year-old pregnant woman arrived at our hospital with an abnormal mammogram. MEDICAL HISTORY: Mammography performed in June 2018 revealed an abnormal shadow on the left breast. Cytology from the 6-mm tumor in the left upper-outer quadrant revealed a malignancy. At the same time, a transvaginal echo revealed cysts, and the patient was diagnosed at 5 weeks gestation. Needle biopsy revealed a luminal A-like cStage Ⅰ, cT1bN0M0 invasive ductal carcinoma (IDC). Tumor resection and sentinel lymph node biopsy were performed under local anesthesia at 12 weeks gestation, and post-delivery adjuvant therapy was planned. Histologic examination of the resected tumor revealed that it was HER2-positive( immunohistochemistry score 3+); therefore, we had to reconsider the use of trastuzumab and decided to administer it to the patient after childbirth. The patient gave birth by cesarean section, and weekly paclitaxel plus trastuzumab was initiated 7 months after surgery. The patient is currently alive without recurrence. DISCUSSION: We faced several difficulties during the treatment of this patient. Postoperative adjuvant therapy is recommended to be administered 8 weeks after the surgical resection of the tumor. However, in our case, given that the tumor was HER2-positive, we could administer adjuvant therapy with trastuzumab only after delivery. Although the prevalence of breast cancer in women below the age of 40 years in Japan is currently as low as 4-6%, the incidence of pregnancy-associated breast cancer is predicted to increase as the number of elderly primigravida increases due to later marriage.

Prognostic Impact of Immune-related Adverse Events in Gastric Cancer Patients Treated With Nivolumab.

BACKGROUND/AIM: To evaluate the impact of development of nivolumab monotherapy-induced immune-related adverse events (irAEs) and continuing nivolumab with irAEs on the survival of patients with gastric cancer (GC). PATIENTS AND METHODS: Patients with unresectable advanced GC and recurrence after curative resection who received nivolumab monotherapy were included in the study. Survival was compared between patients who did and did not develop irAEs, and between those who continued and discontinued treatment due to irAEs. RESULTS: Of 110 GC patients, 22 developed irAEs. Grade ≥3 IrAEs included rash and diarrhoea associated with enteritis. Progression-free and overall survival (OS) were significantly better in patients with irAEs than in those without. The overall survival of patients who continued treatment despite irAEs was better than that of those who discontinued treatment. CONCLUSION: irAE development was associated with better survival in patients with GC who received nivolumab monotherapy. Continuing nivolumab with appropriate treatment in GC patients with irAEs may improve survival.

Postoperative acute pancreatitis after pancreatic resection in patients with pancreatic ductal adenocarcinoma.

INTRODUCTION: Postoperative pancreatic fistula (POPF) is one of the major critical complications after pancreatic resection. Recently, postoperative acute pancreatitis (POAP), a new concept for a pancreatic-specific complication following pancreatic resection, has been advocated, and its association with POPF has been reported. The present study examined the clinical features of POAP and identified the associations of POAP with POPF and other postoperative morbidities in pancreatic ductal adenocarcinoma (PDAC) patients undergoing pancreatic resection. METHODS: A total of 312 consecutive patients who underwent pancreatic resection for PDAC at our institution from 2013 to 2019 were enrolled in this study. POAP was defined as an elevated serum amylase level above the upper limit normal on postoperative day (POD) 0 or 1, based on Connor's definition. The severity of POPF was assessed by the International Study Group on Pancreatic Surgery definition. RESULTS: A total of 184 patients (58.9%) had POAP. POAP occurred in 58.5% of subtotal stomach-preserving pancreatoduodenectomy patients and 60% of distal pancreatectomy combined with splenectomy patients. The presence of POAP was significantly associated with the development of clinically relevant POPF, higher rates of severe morbidity, and a prolonged hospital stay after pancreatic resection. A multivariate analysis showed that the presence of POAP and elevated C-reactive protein levels on POD 3 were independent predictors of clinically relevant POPF after subtotal stomach-preserving pancreatoduodenectomy. CONCLUSIONS: POAP is associated with the development of POPF, higher rates of severe morbidity, and a prolonged hospital stay after pancreatic resection and is an independent risk factor for clinically relevant POPF after pancreatoduodenectomy. POAP represents an important indicator for planning treatment strategies to prevent serious complications, including POPF.