Oncologic outcomes according to the location and status of resection margin in pancreas head cancer: role of radiation therapy in R1 resection

Purpose@#The clinical significance of margin status in pancreatic head cancer is still controversial due to the nonstandardized definition of R status and pathologic reporting. This study aims to evaluate the impact of the margin status including location and the role of radiation therapy in pancreatic head cancer. @*Methods@#A total of 314 patients who underwent curative-intent surgery for pancreatic head cancer between 2010 and 2017 were analyzed. Demographics, survival, and local recurrences were compared according to 2 definitions: 0-mm R1 as direct involvement and 1-mm R1 as close resection margin less than 1 mm. The specific margins were divided into 4 groups according to the location around the pancreas: pancreas transection, anterior surface, posterior surface, and vessel (superior mesenteric artery/superior mesenteric vein) margin. @*Results@#The 0-mm R1-rate was 15.6%, and increased to 36.3% in 1-mm R1. The median overall survival rate of 0-mm R0 vs. R1 was 26 months vs. 16 months (P = 0.052) and that of 1-mm R0 vs. R1 was 27 months vs. 18 months, respectively (P = 0.016). In individual margins, posterior, anterior surface, and pancreas transection margin involvement were associated with poor outcome, and the 1 mm posterior surface involvement was an independent risk factor for disease-free survival (hazard ratio, 1.63). Adjuvant radiation therapy had oncologic benefits, especially in R1 patients (P = 0.011) compared to R0 patients (P = 0.088). @*Conclusion@#Margin status, especially 1-mm R1 status is an important predictive factor, and involved posterior surface has a clinical impact. Patients with positive margins should be considered adjuvant radiation therapy.

Risk factors deteriorating severe exocrine pancreatic insufficiency measured by stool elastase after pancreatoduodenectomy and the risk factors for weight loss

Purpose@#The measurement of stool elastase (SE) level is useful for evaluating pancreatic exocrine function. This study aimed to determine the risk factors for severe exocrine pancreatic insufficiency (EPI) after pancreatoduodenectomy (PD), and analyze serial changes in nutritional markers and weight based on the SE level. @*Methods@#Among patients who underwent PD for periampullary disease, patients whose preoperative and postoperative SE levels were measured were included in the study. The deteriorated (exocrine function) group comprised patients whose SE levels decreased from ≥100 µg/g preoperatively to <100 µg/g postoperatively. Patients whose weight 12 months postoperatively was greater than that 3 months postoperatively were classified into the weight-recovery group. @*Results@#Of the 202 included patients, the deteriorated group had a higher incidence of preoperative SE level above 200 μg/ g, benign pathology, and the presence of a clinically relevant postoperative pancreatic fistula than the maintained group. Patients who did not undergo weight recovery had a higher rate of history of adjuvant radiotherapy compared to the norecovery group. @*Conclusion@#The evaluation of EPI by measuring SE alone is not sufficient because it does not reflect the nutritional status of patients, and a comprehensive approach that considers other parameters is required for EPI management.

In vivo study for the hemostatic efficacy and foreign body reaction of a new powder-type polysaccharide hemostatic agent

Purpose@#Various hemostatic agents have been introduced in therapy as postoperative bleeding is a poor prognostic factor for postoperative outcomes. These products can be divided into those that directly promote the hemostatic cascade and those that physically form a barrier by absorbing blood. The latter, powder-type hemostatic agents have the advantages of being inexpensive and more absorbable with less foreign body reactions (FBRs) and are applicable to a relatively wide area. This study was conducted to verify the safety and efficacy of a newly invented polysaccharide product (OOZFIX, Theracion Biomedical), which improves blood absorption and hemostatic effects. @*Methods@#Two separate animal experiments were performed. The first evaluated FBRs histologically at 3 days, 2 weeks, and 4 weeks, after implantation of OOZFIX in rats, and the second compared hemostatic performance of OOZFIX and Arista AH (Bard) in the porcine liver punch biopsy model. @*Results@#We found minimal FBRs in the 3-day group and no reactions in both the 2-week and 4-week groups after implantation of hemostatic agents. The time to hemostasis of OOZFIX was not significantly different from that of Arista AH (median [interquartile range]: 9 [6–10] minutes vs. 8 [6–10] minutes, respectively; P = 0.522). When comparing the serial bleeding grade tendency, there was no statistical difference between OOZFIX and Arista AH (P = 0.656). @*Conclusion@#OOZFIX caused a minimal FBR that disappeared within 2 weeks in vivo, and its hemostatic performance was comparable with that of an existing agent, Arista AH. Further clinical studies are required in the future.

Comparison of oncologic outcomes of extrahepatic cholangiocarcinoma according to tumor location: perihilar cholangiocarcinoma versus distal bile duct cancer

Purpose@#Extrahepatic cholangiocarcinoma is distinguished into perihilar cholangiocarcinoma (PHC) and distal bile duct cancer (DBC). The studies for each subtype have been conducted separately. This study compared oncological outcomes between PHC and DBC. @*Methods@#From 2001 to 2017, patients who underwent surgery at Seoul National University Hospital for PHC or DBC were enrolled. T stage was reclassified for tumor extent as ‘confined to’ or ‘beyond’ the bile duct (BD). In survival analysis, stage matching was performed based on tumor extent and lymph node (LN) metastasis. @*Results@#There were 680 patients enrolled: 295 with PHC and 385 with DBC. The R0 resection rate was higher in DBC (77.3% vs. 89.9%, P = 0.001). Tumors confined to BD were more common in PHC (61.7% vs. 37.7%, P = 0.001). The 5-year survival rate (5YSR) was higher in DBC patients (30.8% vs. 47.8%, P = 0.001). After stage matching, DBC patients showed better 5YSR for tumors confined to BD/LN(–) (47.1% vs. 64.3%), confined to BD/LN(+) (22.0% vs. 35.0%), beyond BD/LN(–) (21.9% vs. 49.8%), and beyond BD/LN(+) (9.6% vs. 26.9%). The overall recurrence rate was higher in PHC (59.7% vs. 51.9%, P = 0.045), with no difference in the recurrence types between two groups. Radiation therapy was effective for patients with advanced stage disease (5YSR: 35.8% vs. 29.5%, P = 0.022); adjuvant chemotherapy was effective for patients receiving R1 resection (5YSR: 37.3% vs. 13.2%, P = 0.040). @*Conclusion@#Differences were identified in oncological outcomes between PHC and DBC, including pathologic findings and survival outcomes.

Predicting prognosis and evaluating the benefits of adjuvant chemotherapy depending on the tumor location in intrahepatic cholangiocarcinoma: focusing on the involvement of below 2nd bile duct confluence

Purpose@#Intrahepatic cholangiocarcinoma (ICC) has various characteristics according to anatomical, histologic classifications, and its prognoses are different. This study aimed to compare oncologic outcomes according to tumor location (second bile duct confluence) and evaluate the effect of adjuvant chemotherapy. @*Methods@#Clinical data of 318 patients who underwent curative resection for ICC was reviewed. Central type ICC (C-ICC) and peripheral type ICC (P-ICC) were defined when the tumor invades the intrahepatic secondary biliary confluence and when located more peripherally, respectively. @*Results@#A larger tumor size, higher rate of elevated CA 19-9 level, vascular invasion, R1 resection, advanced T stage, and lymph node metastasis were found in C-ICC. C-ICC had poorer overall survival (median, 33 months vs. 58 months; P = 0.001), and the difference was more prominent in the early stage. C-ICC had a higher recurrence rate (68.7% vs. 55.1%, P = 0.014); otherwise, there was no difference in the recurrence patterns. There were no survival benefits of adjuvant chemotherapy in the entire cohort, but there were benefits in advanced stages (T3–4, N1 stage), especially in C-ICC. @*Conclusion@#C-ICC has more aggressive tumor characteristics and poor survival compared to P-ICC. Adjuvant chemotherapy seems to have survival benefits in the advanced stages, especially in the central type.

The development and clinical efficacy of simulation training of open duct-to-mucosa pancreaticojejunostomy using pancreas and intestine silicone models

Purpose@#As pancreaticojejunostomy (PJ) is a challenging anastomosis, an education program is needed to train young surgeons to perform PJ. This study evaluated the effects of simulation-based training of open PJ using pancreas and intestine silicone models. @*Methods@#Five videos pancreatobiliary clinical fellows who did not perform PJ participated in this study. After watching the master video created by a senior pancreatobiliary surgeon, each trainee performed the PJ using silicone models and recorded them 10 times using a video camera. Of these videos, 5 were randomly duplicated due to the validation of the scoring system. The scoring system developed consisted of 20 scores. Three pancreatobiliary professors scored their performance by watching videos. @*Results@#The mean procedure time of the 5 trainees was 25.4 minutes (range, 23.5–27.3 minutes) in the first video and 15.8 minutes (range, 13.8–19.1 minutes) in the 10th video. The mean score was 12.6 (range, 5–19) and 18.3 (range, 15–20) in the first and 10th videos, respectively. The scores were similar among the duplicated videos for each supervisor. @*Conclusion@#This education system would help pancreatobiliary trainees to overcome learning curves efficiently without ethical issues related to animal models or direct practice to human patients.

Limits of serum carcinoembryonic antigen and carbohydrate antigen 19-9 as the diagnosis of gallbladder cancer

Purpose@#Although serum CEA and CA 19-9 have been widely utilized for the diagnosis of gallbladder cancer (GBC), few studies have examined the diagnostic performance of them. This study aimed to investigate the diagnostic performance of these 2 biomarkers and demonstrate their clinical usefulness in diagnosing GBC. @*Methods@#Between January 2000 and March 2020, a total of 751 GBC patients and 2,310 normal controls were included. Serum CEA and CA 19-9 were measured preoperatively. Receiver operating characteristic curves were obtained, and the sensitivity and specificity of each biomarker were evaluated. @*Results@#In terms of differentiating GBC from the control, the sensitivity and specificity of serum CEA at 5 ng/mL was 12.1% and 99.1%, respectively, and those of serum CA 19-9 at 37 IU/mL were 28.7% and 94.5%, respectively. The optimal cutoff values of CEA and CA 19-9 were set to 2.1 ng/mL and 26 IU/mL in the receiver operating characteristic curves, respectively.The sensitivities of CEA and CA 19-9 at new cutoff values slightly increased but remained low (CEA, 42.9%; CA 19-9, 38.2%). When differentiating early-stage GBC from advanced tumor, the sensitivity and specificity, were 14.2% and 96.1% for CEA (cutoff value, 5 ng/mL) and 33.6% and 90.1% for CA 19-9 (cutoff value, 37 IU/mL), respectively. @*Conclusion@#Serum CEA and CA 19-9 levels are not suitable for screening GBC patients from controls. New promising biomarkers with higher sensitivity should be explored.

Clinical characteristics of patients with malignancy and long-term outcomes of surgical treatment of patients with choledochal cyst

Purpose@#There are few reports of postoperative long-term malignant risk or postoperative sequelae after surgery for choledochal cysts (CCs). This study aimed to analyze the clinical characteristics of patients with malignancy and the longterm results of operated CC. @*Methods@#The patients who underwent surgical treatments for CC between 2003 and 2020 at Seoul National University Hospital were enrolled. Clinicopathologic factors and pre-/postoperative computed tomography or magnetic resonance imaging were reviewed. @*Results@#Of the 153 patients, Todani classification Ic (36.6%), C-P type (43.8%) anomalous pancreaticobiliary duct union were the most common type respectively. Fourteen patients (9.2%) had biliary tract cancer and a comparison of patients with and without malignancy showed that the diameter of cyst was significantly lower in malignant patients and malignancy was observed to be significantly higher in P-C type. The incidence of long-term complications was 9.8%, and the median time interval was 30 months. The 2 most common complications were cholangitis and stricture (60.0%). There was one case of new cancer near the intrapancreatic remnant bile duct. @*Conclusion@#Of the resected CCs, 9.2% had a combined malignancy on the biliary tracts. Long-term complications such as cholangitis, anastomotic stricture, and new cancers may occur. Therefore, continuous surveillance is required.

Comparison of perioperative short-term outcomes and oncologic long-term outcomes between open and laparoscopic distal pancreatectomy in patients with pancreatic ductal adenocarcinoma

Purpose@#Laparoscopic distal pancreatectomy (LDP) is widely performed but its efficacy and safety are not established for malignant lesions. This study was aimed to compare outcomes of LDP and open distal pancreatectomy (ODP) in pancreatic ductal adenocarcinoma (PDAC). @*Methods@#Patients who underwent distal pancreatectomy for PDAC between 2009 and 2017 were enrolled. The preoperative clinical stage was evaluated and propensity score matching (PSM) was performed using age, sex, The American Joint Committee on Cancer 8th clinical T stage, and other organ involvement. @*Results@#In 186 patients enrolled, 35 (18.8%) received LDP. The ODP group showed larger tumor size and frequent involvement of other organs in preoperative images. However, after PSM, these differences were balanced. R0 resection (90.5% vs. 94.3%, P = 0.730), harvested lymph nodes (14.3 vs. 12.6, P = 0.380) and pathologic T stage (P = 0.474) were comparable between ODP and LDP groups, respectively. LDP demonstrated shorter operation time, less postoperative pain, and shorter hospitalization (14.4 days vs. 11.1 days, P = 0.026). In terms of long-term oncologic outcomes, median overall survival (32 months vs. 28 months, P = 0.724) and disease-free survival (18 months vs. 19 months, P = 0.926) were comparable. @*Conclusion@#LDP demonstrated better short-term outcomes and comparable long-term outcomes compared with ODP.LDP is a safe and feasible procedure for PDAC.

Comparison of perioperative short-term outcomes and oncologic long-term outcomes between open and laparoscopic distal pancreatectomy in patients with pancreatic ductal adenocarcinoma

Purpose@#Laparoscopic distal pancreatectomy (LDP) is widely performed but its efficacy and safety are not established for malignant lesions. This study was aimed to compare outcomes of LDP and open distal pancreatectomy (ODP) in pancreatic ductal adenocarcinoma (PDAC). @*Methods@#Patients who underwent distal pancreatectomy for PDAC between 2009 and 2017 were enrolled. The preoperative clinical stage was evaluated and propensity score matching (PSM) was performed using age, sex, The American Joint Committee on Cancer 8th clinical T stage, and other organ involvement. @*Results@#In 186 patients enrolled, 35 (18.8%) received LDP. The ODP group showed larger tumor size and frequent involvement of other organs in preoperative images. However, after PSM, these differences were balanced. R0 resection (90.5% vs. 94.3%, P = 0.730), harvested lymph nodes (14.3 vs. 12.6, P = 0.380) and pathologic T stage (P = 0.474) were comparable between ODP and LDP groups, respectively. LDP demonstrated shorter operation time, less postoperative pain, and shorter hospitalization (14.4 days vs. 11.1 days, P = 0.026). In terms of long-term oncologic outcomes, median overall survival (32 months vs. 28 months, P = 0.724) and disease-free survival (18 months vs. 19 months, P = 0.926) were comparable. @*Conclusion@#LDP demonstrated better short-term outcomes and comparable long-term outcomes compared with ODP.LDP is a safe and feasible procedure for PDAC.

Improved motility in the gastrointestinal tract of a postoperative ileus rat model with ilaprazole

Postoperative ileus (POI), a symptom that occurs after abdominal surgery, reduces gastrointestinal motility. Although its mechanism is unclear, POI symptoms are known to be caused by inflammation 6 to 72 h after surgery. As proton pump inhibitors exhibit protective effect against acute inflammation, the purpose of this study was to determine the effect of ilaprazole on a POI rat model. POI was induced in rats by abdominal surgery. Rats were divided into six groups: control: normal rat + 0.5% CMC-Na, vehicle: POI rat + 0.5% CMC-Na, mosapride: POI rat + mosapride 2 mg/kg, ilaprazole 1 mg/kg: POI rat + ilaprazole 1 mg/kg, ilaprazole 3 mg/kg: POI rat + ilaprazole 3 mg/kg, and ilaprazole 10 mg/kg: POI rat + ilaprazole 10 mg/kg. Gastrointestinal motility was confirmed by measuring gastric emptying (GE) and gastrointestinal transit (GIT). In the small intestine, inflammation was confirmed by measuring TNF-α and IL-1β; oxidative stress was confirmed by SOD, GSH, and MDA levels; and histological changes were observed by H&E staining. Based on the findings, GE and GIT were decreased in the vehicle group and improved in the ilaprazole 10 mg/kg group. In the ilaprazole 10 mg/kg group, TNF-α and IL-1β levels were decreased, SOD and GSH levels were increased, and MDA levels were decreased. Histological damage was also reduced in the ilaprazole-treated groups. These findings suggest that ilaprazole prevents the decrease in gastrointestinal motility, a major symptom of postoperative ileus, and reduces inflammation and oxidative stress.

Reliability of Core Needle Biopsy in Evaluating Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor 2, and Ki-67 Status

PURPOSE: The preoperative determination of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), and Ki-67 expression status is crucial because these factors influence the therapeutic response to endocrine therapy, chemotherapy, and HER2-targeted therapy and help in the selection of adjuvant or neoadjuvant treatment. To evaluate the accuracy of core needle biopsy (CNB) in determining ER, PR, and HER2 status, and Ki-67 level status, we compared the results of CNB with those of surgical specimens. METHODS: We retrospectively reviewed data from 191 patients with breast cancer whose ER, PR, and HER2 status, and Ki-67 level status was analyzed using both CNB and surgical specimens between 2013 and 2015. Patients who received neoadjuvant chemotherapy were excluded from this study. ER, PR, and Ki-67 were detected using immunohistochemistry (IHC) and reported as the percentage of positively stained cells. The cutoff point was 1% for ER and PR, and 14% for Ki-67. HER2 was determined by IHC and/or fluorescence in situ hybridization (FISH). HER2 positivity was defined as IHC 3+ or FISH (+). RESULTS: In correlation analysis, Pearson correlation coefficients were 0.950 for ER expression, 0.813 for PR expression, 0.847 for HER2 grade, and 0.817 for Ki-67 expression level (p<0.0001). According to criteria for ER, PR, HER2, and Ki-67, the sensitivities of ER, PR, HER2, and Ki-67 assessment in CNB were 92.6%, 88.8%, 100%, and 80.6%, respectively. The specificities of ER, PR, HER2, and Ki-67 assessments in CNB were 90.7%, 86.0%, 99.1%, and 88.7%, respectively. CONCLUSION: The ER, PR, HER2, and Ki-67 status in CNB specimens correlated well with their status in surgical specimens. The HER2 status was the most accurately assessed factor in CNB specimens when compared to its assessment in surgical specimens. However, Ki-67 levels in CNB specimens were lower than those in surgical specimens.

Meckel diverticulum in exomphalos minor

A congenital hernia into the base of the umbilical cord is known as an exomphalos and when the size of the defect is 5 cm or less and containing only bowel, it is called as exomphalos minor. We present a case of a newborn with an exomphalos minor within a Meckel diverticulum. He underwent surgical resection of the Meckel diverticulum and repair of the abdominal wall defect. To our knowledge, this is the first reported case of Meckel diverticulum in an exomphalos minor in Korea.