Minimally invasive pancreatoduodenectomy by junior surgeon: Initial experience of the next generation.

BACKGROUND: Several guidelines exist for minimally invasive pancreatoduodenectomy (MIPD) regarding its prerequisites and learning curve. However, these guidelines are based on the experience of the pioneers of MIPD; minimal data exist on the experience of the next generation of surgeons. The aim of this study was to compare the two surgeon types (veteran and junior) for MIPD in terms of immediate postoperative outcomes. METHODS: The postoperative outcomes of 22 patients who underwent robot-assisted pancreatoduodenectomy (RAPD) by a junior surgeon from July 2021 to December 2022 were retrospectively reviewed. The outcomes were compared with the initial postoperative outcomes and the contemporary postoperative outcomes of RAPD by a veteran surgeon. RESULTS: In comparing the initial outcomes between the two surgeon types, the veteran surgeons showed a shorter operation time (junior surgeon vs. veteran surgeon: 606 ± 89 vs. 467 ± 77 min, p < 0.001). However, there was no significant difference in terms of postoperative outcomes, such as blood loss (300 [200-600] ml. vs. 200 [100-500] ml, p = 0.208), major complications (≥CDC IIIa: 4 (18.2%) vs. 4 (18.2%), p = 1.000), postoperative pancreatic fistula (POPF; ≥ISGPF Grade B: 2 (9.1%) vs. 3 (13.6%), p > 0.999), and length of hospital stay (18.0 ± 8.9 days vs. 18.3 ± 7.9 days, p = 0.915), between the two surgeon types. In addition, in a comparison of the contemporary outcomes, there was no significant difference in terms of postoperative outcome (complications: 4 (18.2%) vs 11 (11.1%), p = 0.580; POPF: 2 (9.1%) vs. 3 (3.0%), p = 0.484; length of hospital stay: 18.0 ± 8.9 vs. 15.0 ± 6.5 days, p = 0.065). CONCLUSION: The initial outcomes of MIPD by a well-trained junior surgeon were found to be comparable to those of MIPD by a veteran surgeon.

Optimal surgical management of unifocal vs. multifocal NF-PNETs: a respective cohort study.

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) represent 1-2% of pancreatic tumors, with recent guidelines recommending active surveillance for non-functioning PNETs (NF-PNETs) smaller than 2 cm. However, the management of multiple NF-PNETs, as well as the influence of tumor number on prognosis, remains under-researched. METHODS: This retrospective study analyzed NF-PNET patients who underwent pancreatic resection at Severance Hospital between February 1993 and August 2023, comparing the characteristics of patients diagnosed with multifocal tumors and those with unifocal tumors. A subgroup analysis of overall survival (OS) and recurrence-free survival (RFS) was performed based on multifocality employing the Kaplan-Meier method and the log-rank test. RESULTS: Of 187 patients, 169 (90.4%) had unifocal and 18 (9.6%) had multifocal tumors. Multifocal tumors were more likely to be diffusely spread, necessitating more total pancreatectomies (diffuse tumor location: 4.7% in unifocal vs. 38.9% in multifocal cases, p < 0.001; total pancreatectomy: 4.1% in unifocal vs. 33.3% in multifocal cases, p < 0.001). In patients with NF-PNET who underwent the same extent of pancreatic resection, no significant difference in the incidence of complication was observed regardless of multifocality. Moreover, no significant difference in OS was seen between the unifocal and multifocal groups (log-rank test: p = 0.93). However, the multifocal group exhibited a poorer prognosis in terms of RFS compared to the unifocal group (log-rank test: p = 0.004) Hereditary syndrome, tumor grade, size, lymphovascular invasion, and lymph node metastasis were key factors in the recurrence. CONCLUSION: This study's findings suggest that the presence of multiple tumors was associated with poorer recurrence-free survival but did not affect long-term survival following surgery. Given the long-term oncologic outcome and quality of life following surgery, resection of tumors over 2 cm is advisable in patients with multifocal PNETs, while a cautious "wait-and-see" approach for smaller tumors (under 2 cm) can minimize the extent of resection and improve the quality of life. In cases with only small multifocal NF-PNETs (< 2 cm), immediate resection may not be crucial, but the higher recurrence rate than that in solitary NF-PNET necessitates intensified surveillance.

Effect of local treatment in patients with oligo-recurrence after surgery of distal bile duct cancer: A bi-institutional study.

BACKGROUND: Distal extrahepatic bile duct (EHBD) cancer is highly recurrent. More than 50% of patients suffer from disease relapse after curative resection. Some patients present with oligo-recurrence which could be a single loco-regional mass or lesions limited to a single solid organ. The aim of this study was to examine the effect of local control (surgical resection or radiofrequency ablation) on survival outcomes in patients with oligo-recurrent distal EHBD cancer. METHODS: Data of 1219 patients who underwent surgery for distal EHBD cancer from 2000 to 2018 were retrospectively reviewed. Clinicopathological characteristics and survival outcomes of patients with recurrence were investigated. Post-recurrence survival (PRS) was analyzed according to modalities of re-treatment (local treatment or systemic therapy alone). RESULTS: Among 654 patients with recurrence, 90 patients who had oligo-recurrence showed better recurrence-free and overall survival than patients with non-oligo-recurrent disease. Lymph node ratio and perineural invasion at initial pathology, timing of recurrence, and platelet-to-lymphocyte ratio at recurrence were independent risk factors for PRS in the oligo-recurrent group. Patients with local treatment for oligo-recurrence had better 3- and 5-year PRS than those with systemic treatment alone (38.3% vs. 14.1%, p = 0.04; 28.3% vs. 7.1%, p = 0.04, respectively). Recurrence within 24 months after initial surgery was the only significant factor for PRS in the local treatment group. CONCLUSION: In patients with oligo-recurrence after resection of distal EHBD cancer, post-recurrence local treatment could improve survival outcomes, particularly for those with recurrence more than 2 years after initial resection.

Pancreatoduodenectomy following neoadjuvant chemotherapy in duodenal adenocarcinoma.

A 51-year-old male patient had four times of massive hematochezia episode three days before arrival. Carbohydrate antigen (CA) 19-9 level was extremely elevated. Computed tomography, magnetic resonance imaging, and positron emission tomography-computed tomography identified 5.7 cm sized periampullary duodenal cancer with regional metastatic lymph nodes and vascular invasion to aberrant right hepatic artery, main portal vein, and superior mesenteric vein. Diagnosed as duodenal adenocarcinoma through endoscopic biopsy, 16 times of FOLFIRI (5-fluorouracil, leucovorin, irinotecan) was conducted. The regimen changed to XELOX (capecitabine, oxaliplatine), four times of administration was done, and the CA19-9 level dramatically decreased. The tumor decreased to 2.1 cm. After R0 laparoscopic pylorus preserving pancreatoduodenectomy, no adjuvant therapy was given. No sign of recurrence or metastasis was reported, and the patient reached complete remission after five years. We reported a case where neoadjuvant chemotherapy for locally advanced duodenal adenocarcinoma was shown to be effective.

Left-sided Hepatectomy Leads to Less Postoperative Liver Failure and Comparable Overall Survival to Right-sided Hepatectomy in Type II or IV Perihilar Cholangiocarcinoma.

INTRODUCTION: Right-side hepatectomy (RH) is used in oncological resection for perihilar cholangiocarcinoma (PHC); however, the decision between performing left-side hepatectomy (LH) or RH is still controversial. We compared surgical and oncologic outcomes of LH and RH in PHC type II or IV where either hepatectomy was expected to have a negative margin. METHODS: From 2001 to 2020, 99 patients underwent major liver resection for type II or IV PHC. Patients with unilateral vascular invasion, unilateral tumor growth, and atrophy of unilateral liver were excluded. Preoperative characteristics, perioperative, and long-term outcomes were compared between the remaining RH and LH patients. RESULTS: After excluding 47 cases with side predominance, the RH group (n = 29) and LH group (n = 23) were compared. Clinical characteristics and disease severity did not differ between the groups. Portal vein embolization (RH: 48.3% vs. LH: 0.0%, p < 0.001) and days from diagnosis to operation (RH: 31.0 ± 16.2 vs. LH: 18.8 ± 13.4, p = 0.006) were significantly higher in the RH group. The RH group had statistically higher rate of postoperative hepatic failure (RH: 55.2% vs. LH: 21.7%, p = 0.015) and a higher mortality rate that was not significant (RH: 13.8% vs. LH: 0%, p = 0.120). The R0 resection rate (RH: 72.4% vs. LH: 78.3%, p = 0.629), median disease-free (p = 0.620), and overall (p = 0.487) survival did not differ between groups. R1 resection and lymph node metastasis were significant risk factors for disease-free survival in multivariate analysis. CONCLUSIONS: In type II or type IV PHC where either LH or RH was feasible, LH provided a shorter period of preoperative preparation, lower postoperative hepatic failure rate, similar R0 rate, and comparable long-term outcomes. LH should be considered a reasonable option in type II or IV PHC.

Neoadjuvant FOLFIRINOX Followed by Pancreatoduodenectomy for Pancreatic Cancer in Patients with Previous Transhiatal Esophagectomy for Esophageal Cancer.

During pancreaticoduodenectomy after transhiatal esophagectomy, the preservation of the blood supply to the gastric conduit is technically difficult due to adhesion. Here, we present a case of successful pancreaticoduodenectomy after neoadjuvant chemotherapy in a patient with pancreatic head cancer who previously underwent subtotal esophagectomy with gastric reconstruction for esophageal cancer. A 69-year-old man who had undergone cholecystectomy 20 years prior and transhiatal esophagectomy 6 years prior for esophageal cancer presented to our hospital for indigestion. Computed tomography and magnetic resonance imaging revealed a 2.8-cm pancreatic head cancer, with focal abutment with the gastroduodenal artery, right gastroepiploic artery, and right colic vein. After discussion with the multidisciplinary team, the patient underwent neoadjuvant chemotherapy with six cycles of FOFIRINOX. The patient successfully underwent pancreatectomy, which preserved the pylorus. We preserved the gap between the gastric tube and the left lateral segment of the liver to avoid injuring the right gastric artery and vein. The tumor was found to be invading the gastroduodenal artery; thus, we performed R0 resection of the gastroduodenal artery and an end-to-end anastomosis between the gastroduodenal artery and the right gastroepiploic artery. After completing the surgical procedure, we added Braun anastomosis to reduce the incidence of delayed gastric emptying. Pancreaticoduodenectomy after transhiatal esophagectomy can be performed with preservation of the blood supply to the neogastric tube by reconstructing the major vessels, even in cases in which the tumor is invading or abutting the major vessels.

Laparoscopic distal pancreatosplenectomy for left-sided pancreatic cancer in patients with radical subtotal gastrectomy for gastric cancer.

After radical subtotal gastrectomy (RSTG) for stomach cancer, the remnant stomach is supposed to be perfused through the short gastric vessels. What if a patient who received previous RSTG is diagnosed with resectable distal pancreatic cancer? Can radical distal pancreatosplenectomy (DPS) be performed safely without ischemic damage to the remnant stomach? Unfortunately, there are limited studies on this specific clinical issue. Notably, in spite of rare clinical presentation, it is expected to increase due to prolonged survival of patients with resected gastric cancer. Therefore, we aimed to demonstrate the safety and feasibility of the radical DPS in patients with previous RSTG. In this study, we investigated perioperative and long-term survival outcomes of DPS for left-sided pancreatic cancer in patients with previous RSTG.

A Prognostic Impact of Splenectomy in Laparoscopic Distal Pancreatectomy on Benign/Borderline Pancreatic Tumors: A Change of the Era.

PURPOSE: In the past, spleen preservation during distal pancreatectomy (DP) was preferred; however, more recent studies reported comparable results between splenectomy and spleen preserving. We retrospectively reviewed patients in a single center who underwent laparoscopic DP with/without splenectomy, and evaluated the chronologic changes of surgical outcomes of the two procedures. MATERIALS AND METHODS: Patients who underwent laparoscopic DP with or without splenectomy due to benign/borderline tumor from 2005 to 2019 were included in this study. We divided this period into Era 1 (2005-2012) and Era 2 (2013-2019), and compared the chronological evolution of surgical outcomes of laparoscopic distal pancreatosplenectomy (LDPS) to those of laparoscopic spleen-preserving distal pancreatectomy (LSpDP), including the long-term postoperative immunologic profiles. RESULTS: A total of 198 cases were included (LSpDP: 80 cases; LDPS: 118 cases). As the period changed from Era 1 to Era 2, the ratio of LSpDP decreased and the surgical outcomes of LDPS improved. In Era 1, LSpDP group showed superior results compared to LDPS group in terms of hospital days and postoperative pancreatic fistula ratio; however, in Era 2, the surgical outcomes showed no statistical differences. No significant differences were observed in all of the immunologic markers. CONCLUSION: We carefully conclude that during laparoscopic DP, combined splenectomy can be equivalent to spleen preserving in surgical and immunological outcomes, and inevitable splenectomy can be safely conducted.

Anticancer effect of locally applicable aptamer-conjugated gemcitabine-loaded atelocollagen patch in pancreatic cancer patient-derived xenograft models.

We investigated the anticancer effect of the aptamer-conjugated gemcitabine-loaded atelocollagen patch in a pancreatic cancer patient-derived xenograft (PDX) model to propose a future potential adjuvant surgical strategy during curative pancreatic resection for pancreatic cancer. A pancreatic cancer PDX model was established. Animals were grouped randomly into a no-treatment control group; treatment group treated with intraperitoneal gemcitabine injection (IP-GEM) or aptamer-conjugated gemcitabine (APT:GEM); and transplant with three kinds of patches: atelocollagen-aptamer-gemcitabine (patch I), atelocollagen-inactive aptamer-gemcitabine (patch II), and atelocollagen-gemcitabine (patch III). Tumor volumes and response were evaluated based on histological analysis by H&E staining and Immunohistochemistry (IHC) was performed. Anticancer therapy-related toxicity was evaluated by hematologic findings. The patch I group showed the most significant reduction of tumor growth rate, compared with the no-treatment group (p < 0.05). However, other treatment groups were not found to show significant reduction in tumor growth rate (0.05 < p < 0.1). There was no microscopic evidence suggesting potential toxicity, such as inflammation, nor necrotic changes in liver, lung, kidney, and spleen tissue. In addition, no leukopenia, anemia, or neutropenia was observed in the patch I group. This implantable aptamer-drug conjugate system is thought to be a new surgical strategy to augment the oncologic significance of margin-negative resection in treating pancreatic cancer in near future.

Surgical Outcomes and Comparative Analysis of Transduodenal Ampullectomy and Pancreaticoduodenectomy: A Single-Center Study.

BACKGROUND: Transduodenal ampullectomy (TDA) is performed for adenoma or early cancer of the ampulla of Vater (AoV). This study aimed to analyze the short- and long-term outcomes of TDA (TDA group) when compared with conventional pancreaticoduodenectomy (PD) or pylorus-preserving pancreaticoduodenectomy (PD group). METHODS: Patients who underwent TDA between January 2006 and December 2019, and PD cases performed for AoV malignancy with carcinoma in-situ (Tis) (high-grade dysplasia, HGD) and T1 and T2 stage from January 2010 to December 2019 were reviewed. RESULTS: Forty-six patients underwent TDA; 21 had a benign tumor, and 25 cases with malignant tumors were compared with PD cases (n = 133). Operation time (p < 0.001), estimated blood loss (p < 0.001), length of hospital stays (p = 0.003), and overall complication rate (p < 0.001) were lower in the TDA group than in the PD group. Lymph node metastasis rates were 14.6% in pT1 and 28.9% in pT2 patients. The 5-year disease-free survival and 5-year overall survival rates for HGD/Tis and T1 tumor between the two groups were similar (TDA group vs PD group, 72.2% vs 77.7%, p = 0.550; 85.6% vs 79.2%, p = 0.816, respectively). CONCLUSION: TDA accompanied with lymph node dissection is advisable in HGD/Tis and T1 AoV cancers in view of superior perioperative outcomes and similar long-term survival rates compared with PD.

Adverse Impact of Intraoperative Conversion on the Postoperative Course Following Laparoscopic Pancreaticoduodenectomy.

PURPOSE: The aim of the current study was to evaluate the adverse clinical impact of intraoperative conversion during laparoscopic pancreaticoduodenectomy (LPD). MATERIALS AND METHODS: The medical records of patients who underwent pancreaticoduodenectomy (PD) were retrospectively reviewed. Perioperative clinical variables were compared between patients who underwent converted PD (cPD) and initially planned open PD (OPD) to investigate the clinical impact and predictive factors of intraoperative conversion during LPD. RESULTS: A total of 171 patients were included. Among them, 31 patients (19.3%) were found to have intraoperative conversion during LPD. Failure of progression due to severe adhesion (12 patients, 7%) and major vessel invasion (7 patients, 4%) were the two most frequent reasons for conversion. On multivariate analysis, age [Exp(ß)=1.044, p=0.044] and pancreatic texture [Expa(ß)=2.431, p=0.039) were found to be independent factors for predicting intraoperative conversion during LPD. In comparative analysis with the OPD group, the cPD group had a longer operation time (516.8 min vs. 449.9 min, p=0.001), higher rate of postoperative hemorrhage (12.1% vs. 0.85%, p=0.008), higher reoperation rate (9.1% vs. 0%, p=0.01), and higher cost (21886.4 USD vs. 17168.9 USD, p=0.018). CONCLUSION: Intraoperative conversion during LPD can have an adverse clinical impact on the postoperative course following LPD. Appropriate patients selection and improvement of surgical techniques will be crucial for unnecessary intraoperative conversion and safe LPD.

Comparison of Oncologic Outcomes between Transduodenal Ampullectomy and Pancreatoduodenectomy in Ampulla of Vater Cancer: Korean Multicenter Study.

This study used multicenter data to compare the oncological safety of transduodenal ampullectomy (TDA) with that of pylorus-preserving pancreatoduodenectomy (PPPD) in early ampulla of Vater (AoV) cancer. Data for patients who underwent surgical resection for AoV cancer (pTis-T2 stage) from January 2000 to September 2019 were collected from 15 institutions. The clinicopathologic characteristics and survival outcomes were compared between the PPPD and TDA groups. A total of 486 patients were enrolled (PPPD, 418; TDA, 68). The oncologic behavior in the PPPD group was more aggressive than that in the TDA group at all T stages: larger tumor size (p = 0.034), advanced T stage (p < 0.001), aggressive cell differentiation (p < 0.001), and more lymphovascular invasion (p = 0.002). Five-year disease-free survival (DFS) and overall survival (OS) did not differ between the two groups when considering all T stages or only the Tis+T1 group. Among T1 patients, PPPD produced significantly better DFS (PPPD vs. TDA, 84.8% vs. 66.6%, p = 0.040) and superior OS (PPPD vs. TDA, 89.1% vs. 68.0%, p = 0.056) than TDA. Lymph node dissection (LND) in the TDA group did not affect DFS or OS (TDA + LND vs. TDA-only, DFS, p = 0.784; OS, p = 0.870). In conclusion, PPPD should be the standard procedure for early AoV cancer.

Laparoscopic pancreaticoduodenectomy reduces incidence of clinically relevant postoperative pancreatic fistula in soft pancreas with a smaller than 2 mm pancreatic duct.

BACKGROUND: Soft pancreas with small pancreatic duct is a known risk factor for postoperative pancreatic fistula (POPF). This study demonstrated the safety and feasibility of laparoscopic duct-to-mucosa pancreaticojejunostomy (PJ) and compared perioperative outcomes of laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) in patients with soft pancreas and small pancreatic duct. METHODS: From January 2014 to December 2019, 183 patients underwent LPD and 91 patients underwent OPD by a single surgeon. Data on patients with soft pancreas and combined small pancreatic duct (≤ 2 mm) were retrospectively reviewed. Clinicopathologic characteristics, and perioperative outcomes were compared between LPD and OPD. We evaluated risk factors affecting clinically relevant POPF (CR-POPF). We also correlated calculated risks of POPF and CR-POPF between the two groups. RESULTS: We compared 62 patients in the LPD group and 34 patients in the OPD group. Perioperative outcomes showed less blood loss, shorter hospital stays, and less postoperative pain score on postoperative day (POD)#1 and #5 in LPD compared with OPD. Postoperative complications showed no differences between LPD and OPD. LPD group showed significantly reduced CR-POPF rates compared to the OPD group (LPD 11.3% vs. OPD 29.4%, p = 0.026). Multivariate analysis identified obesity (BMI ≥ 25), thick pancreas parenchyma and open surgery as independent predicting factors for CR-POPF. The LPD group showed less CR-POPF than the OPD group according to POPF risk groups. This difference was more prominent in a high-risk group. CONCLUSION: With appropriate laparoscopic technique, LPD is feasible and safe and reduces CR-POPF in soft pancreas with a small pancreatic duct.

Feasibility and Safety of Laparoscopic Radical Distal Pancreatosplenectomy with Adrenalectomy in Advanced Pancreatic Cancer.

INTRODUCTION: Pancreatic adenocarcinoma is a lethal condition with poor outcomes and an increasing incidence.1 However, recent meta-analysis reported improved survival and R0 resection rate following neoadjuvant chemotherapy with subsequent surgery in initially unresectable pancreatic cancer.2 In addition, as a result of technological advances during the past 2 decades, even in pancreatic cancers, minimally invasive surgery (MIS) approaches are being used more frequently and safely.3-5 This video shows the feasibility and safety of laparoscopic resection in advanced left-sided pancreatic cancer. METHOD: The patient was a 63-year-old male with hypertension and diabetes. Initial computed tomography (CT) scan showed a 31 mm-sized pancreatic tail cancer with celiac artery and left adrenal gland abutment. The patient underwent neoadjuvant chemotherapy due to the risk of retroperitoneal cancer infiltration. After four cycles of FOLFIRINOX chemotherapy, follow-up CT scan showed the tumor decreased to 2.6 cm and celiac artery abutment became less prominent. Based on the CT scan, laparoscopic radical distal pancreatosplenectomy with left adrenalectomy was planned. RESULTS: A five-port laparoscopic approach was performed, including three 12 mm trocars and an additional two 5 mm trocars. Initial intra-abdominal exploration showed no peritoneal seeding or micro liver metastasis. Gastric wedge resection was added due to cancer invasion for margin-negative resection. Operation time was 215 min and estimated blood loss was 200 cc without transfusion. The patient was discharged on postoperative day 6 without any complications, including postoperative pancreatic fistula. CONCLUSION: Laparoscopic distal pancreatosplenectomy can be technically feasible and safe to obtain negative resection margins in well-selected patients following neoadjuvant therapy in locally advanced pancreatic cancer.6.

Comparison study for surgical outcomes of right versus left side hemihepatectomy to treat hilar cholangiocellular carcinoma.

PURPOSE: Major liver resection and radical lymph node dissection has been accepted as a definite treatment of choice for hilar cholangiocarcinoma (HC). However, the perioperative and survival outcomes of right hemihepatectomy (RH) and left hemihepatectomy (LH) still remain controversial. Thus, this study aimed to compare the surgical and oncological outcomes of RH and LH in HC patients. METHODS: From January 2000 to January 2018, a total of 326 patients underwent surgical resection for HC at Yonsei University College of Medicine in Seoul, Korea. Among the 326 patients, we excluded 130 patients and selected 196 patients, who underwent hemihepatectomy with caudate lobectomy. Among these 196 patients, 114 patients underwent RH, and 82 patients underwent LH. We compared the clinicopathological features as well as the surgical and oncologic outcomes of the RH and LH groups. RESULTS: There were no significant differences in disease-free survival (P = 0.473) or overall survival (P = 0.946) in the RH and LH groups. The LH group had fewer complications compared with the RH group, including postoperative ascites (RH: 15 [13.2%] vs. LH: 3 [3.7%], P = 0.023); however, the LH group had more bile leakage complications (RH: 5 [4.4%] vs. LH: 12 [14.6%], P = 0.012). The average time lag from portal vein embolization to operation was 25.80 ± 12.06 days (n = 45). There was no difference in postoperative liver failure (P = 0.402), although there were significantly more frequent ascites after RH (P = 0.023). CONCLUSION: LH might be a good alternative option for the surgical treatment of HC given appropriate tumor location and biliary anatomy indications.

Comparison of the immunogenicity and safety of 3 inactivated hepatitis A vaccines in Korean children aged 12 to 18 months: An open-label, randomized, prospective, multicenter study.

Several approved inactivated hepatitis A (HA) vaccines are available in Korea. These have been shown to be immunogenic and safe in European children; however, their immunogenicity and safety have not been investigated among Korean children. We aimed to compare the immunogenicity and safety of the most commonly used HA vaccines in ethnic Korean children aged 12 to 18 months.In this open-label, randomized, prospective, multicenter study, 108 children were enrolled and randomized to receive a pediatric form of Avaxim, Epaxal, or Havrix. The 2nd dose was administered after an interval of 6 months. Anti-HA virus (HAV) immunoglobulin (Ig) G was measured to assess geometric mean concentrations (GMCs) and seropositvity rates (≥20 mIU/mL anti-HAV IgG). To assess safety, local solicited adverse events (AEs), systemic solicited AEs, unsolicited AEs, and serious AEs (SAEs) were graded.Among the 108 participants enrolled, 37, 34, and 37 received Avaxim, Epaxal, and Havrix, respectively. After administration of 2 doses, the seropositivity rates in the Avaxim, Epaxal, and Havrix groups were all 100% (95% confidence intervals [CIs]: 99.0-100, 98.9-100, and 99.0-100, respectively; P < .001). The anti-HAV GMCs in the Avaxim, Epaxal, and Havrix groups were 5868.4 (95% CI: 4237.2-8126.6), 1962.1 (95% CI: 1298.0-2965.9), and 2232.9 mIU/mL (95% CI: 1428.4-3490.4), respectively, after administration of 2 doses (P < .001). There were no significant differences in the proportions of participants reporting local solicited AEs, systemic solicited AEs, unsolicited AEs, and SAEs among the 3 vaccine groups after the 1st and 2nd doses. All local solicited and unsolicited AEs were grade 1 or 2. Grade 3 systemic solicited AE occurred in 5.4% and 2.9% of the participants in the Havrix group after the 1st and 2nd doses, respectively. SAEs after the 1st and 2nd doses were reported in 2 participants and 1 participant, respectively, but none was assessed as being related to vaccination.The results indicate that these vaccines were safe and immunogenic in ethnic Korean children. The results have contributed to the establishing of an HA vaccination policy in Korea and will be informative to countries that plan to initiate vaccination programs against HAV.

Final report on the key comparison, CCM.P-K15 in the pressure range from 1.0 × 10-4 Pa to 1.0 Pa.

The comparison CCM.P-K15 is a key comparison in pressure involving six laboratories in three regional metrological organizations (RMO). The measurand of the comparison is the accommodation coefficient of two spinning rotating gauge characterized in nitrogen from 0.1 mPa up to 1.0 Pa. The two transfer standards were circulated from November 2009 until March 2011. The circulation consisted of three loops, one for each RMO, and a new calibration by the pilot between each loop. The stability of one of the transfer standards was poor and was worse than expected based on the previous history of the transfer standard while the other transfer standard demonstrated good stability while circulated in Europe and America and a fair stability while circulated in Asia. All the participants demonstrated equivalence to the definition of pressure in their respective primary standards.