Perioperative textbook outcomes of minimally invasive pancreatoduodenectomy: a multicenter retrospective cohort analysis in a Korean minimally invasive pancreatic surgery registry.

BACKGROUND: The aim of this study is to investigate the perioperative composite textbook outcomes of pancreatic surgery after minimally invasive pancreatoduodenectomy (MIPD). MATERIALS AND METHODS: The cohort study was conducted across 10 institutions and included 1552 patients who underwent MIPD registered with the Korean Study Group on Minimally Invasive Pancreatic Surgery between May 2007 and April 2020. We analyzed perioperative textbook outcomes of pancreatic surgery after MIPD. Subgroup analyses were performed to assess outcomes based on the hospital volume of MIPD. RESULTS: Among all patients, 21.8% underwent robotic pancreatoduodenectomy. High-volume centers (performing >20 MIPD/year) performed 88.1% of the procedures. The incidence of clinically relevant postoperative pancreatic fistula was 11.5%. Severe complications (Clavien-Dindo grade ≥IIIa) occurred in 15.1% of the cases. The 90-day mortality rate was 0.8%. The mean hospital stay was 13.7 days. Textbook outcomes of pancreatic surgery success were achieved in 60.4% of patients, with higher rates observed in high-volume centers than in low-volume centers (62.2% vs. 44.7%, P<0.001). High-volume centers exhibited significantly lower conversion rates (5.4% vs. 12.5%, P=0.001), lower 90-day mortality (0.5% vs. 2.7%, P=0.001), and lower 90-day readmission rates (4.5% vs. 9.6%, P=0.006) than those low-volume centers. CONCLUSION: MIPD could be performed safely with permissible perioperative outcomes, including textbook outcomes of pancreatic surgery, particularly in experienced centers. The findings of this study provided valuable insights for guiding surgical treatment decisions in periampullary disease.

Is 10 cm ileal resection sufficient in locally advanced caecal cancer surgery?

BACKGROUND: There is no consensus as to how much ileal resection is sufficient when performing a right hemicolectomy for right colon cancers. Locally advanced caecal cancer has the highest incidence of peri-ileal lymph node metastasis. Therefore, this study investigated whether the 10 cm ileum resection suggested by the Japanese Society for Cancer of the Colon and Rectum is oncologically safe in stage II and III caecal cancer. METHODS: The prospectively collected medical records of stage II and III caecal cancer patients who underwent a right hemicolectomy with at least D2 lymph node dissection were reviewed retrospectively. The patients were divided into two groups according to the length of proximal ileal resected: group 1 (≤10 cm) and group 2 (>10 cm). Factors contributing to the 5-year overall survival (OS) were analysed. RESULTS: The study enrolled 89 patients with pathological stage II or III caecal cancer. The >10 cm group tended to be younger (P = 0.0938) with higher pathological N stages (P = 0.0899) than the ≤10 cm group. The 5-year OS did not differ between the two groups. No significant difference was found between the two groups according to stage. Age (HR = 1.06, 95% CI = 1.02-1.10, P = 0.0069) and N2 stage (HR = 5.38, 95% CI = 1.90-15.28, P = 0.0016) were significantly associated with OS in both uni- and multivariate analyses. CONCLUSIONS: There was no OS benefit to resecting >10 cm of ileum in either stage II or III caecal cancer patients. Hence, we suggest that the '10 cm rule' is sufficient for stage II and III caecal cancer patients.

Doxifluridine versus Tegafur/Gimeracil/Oteracil (S-1) as adjuvant chemotherapy for patients with gastric cancer after gastrectomy: A propensity score-matched analysis.

INTRODUCTION: Doxifluridine (DF), an oral 5-FU prodrug, has been used for various solid cancers due to its efficacy and low toxicity. We aim to evaluate the effect of DF as adjuvant monotherapy in advanced gastric cancer. METHODS: We retrospectively reviewed the clinical data of 263 patients with advanced gastric cancer who underwent curative gastrectomy between January 2010 and December 2013 at our institute. Since previous randomized control trials have confirmed the efficacy of S-1 as adjuvant chemotherapy in advanced gastric cancer, we analyzed the oncologic effect and patient compliance of the DF group compared to the S-1 group. After propensity score matching, 48 patients were included in each group. RESULTS: There was no significant difference in 5-year overall survival (OS) and 5-year disease-free survival (DFS) between DF and S-1 groups (5-year OS; 77.1% vs 75.0%; p = 0.729, 5-year DFS; 76.6% vs 73.9%; p = 0.748). The completion rates of the DF and S-1 groups were 60.4% and 72.9%, respectively (p = 0.194). The mean relative dose intensity of the DF and S-1 groups were 76.2% and 84.2%, respectively (p = 0.195). After multivariate analysis, the chemotherapy regimen was not a risk factor for OS and DFS, whereas relative dose intensity and pathologic stage were independent prognostic factors. CONCLUSION: There was no significant difference in the oncologic effect and patient compliance between DF and S-1 groups. DF could be an alternative option for adjuvant chemotherapy in advanced gastric cancer. In addition, we confirmed that relative dose intensity is an important independent prognostic factor for survival.

Comparison between oxaliplatin therapy and capecitabine monotherapy for high-risk stage II - III elderly patients with colon cancer.

PURPOSE: 45% of colon cancer patients are elderly, yet they are often deviated from standard cancer management. The MOSAIC trial favored FOLFOX over FL with superior oncologic outcomes; however, which regimen is most beneficial in elderly population remains unclear. This study aimed to compare the efficacy of oxaliplatin-added chemotherapy and capecitabine monotherapy in high-risk stage II/stage III elderly colon cancer patients. METHODS: Colon cancer patients ≥70 years of age who received adjuvant chemotherapy at Inje University Busan Paik Hospital between February 2009 to April 2016 were included. Patients were separated into the oxaliplatin-added group and capecitabine monotherapy group. The primary outcomes were CSS and OS. RESULTS: Of 74 patients, 45 received oxaliplatin-added chemotherapy and 29 received capecitabine monotherapy. There was no difference between the two groups in CSS or OS (p = 0.9670 and p = 0.6801, respectively). The N stage was significantly associated with CSS in both uni/multivariate analysis (p = 0.0565 and p = 0.0347, respectively). The oxaliplatin-added group had more stage III patients, so we performed a subgroup analysis of CSS and OS based on stage, which also showed no significant difference. CONCLUSIONS: Capecitabine monotherapy is an oncologically safe regimen compared to oxaliplatin-added regimens in elderly patients with high-risk stage II/stage III colon cancer.

Comparing short-term outcomes after totally laparoscopic distal gastrectomy and laparoscopy-assisted distal gastrectomy with Billroth I anastomosis: early experience of a single institution.

Purpose: To determine the safety and feasibility of totally laparoscopic distal gastrectomy (TLDG) with modified delta-shaped anastomosis, we compared the short-term outcomes of TLDG to those of laparoscopy-assisted distal gastrectomy (LADG) with Billroth I anastomosis. Methods: We analyzed the characteristics of 85 patients with gastric cancer who underwent laparoscopic distal gastrectomy with Billroth I anastomosis between January 2013 and December 2018. After propensity score matching, each group had 35 patients. Results: Of these 85 patients, 44 underwent TLDG and 41 underwent LADG. Propensity score matching was performed with three covariates (age, underlying disease, and hypertension), and 35 patients from each group were matched 11. After matching, the TLDG group was older than the LADG group (64.5 ± 10.6 years vs. 56.3 ± 11.2 years, p = 0.003) and had more patients with hypertension (57.1% vs. 22.9%, p = 0.003). Tumors were larger in the TLDG group than in the LADG group (23.4 ± 16.2 mm vs. 16.0 ± 7.9 mm, p = 0.018). A greater proportion of patients had fever in the TLDG group than the LADG group (42.9% vs. 20.0%, p = 0.039), and C-reactive protein from postoperative days 3 to 6 was greater in the TLDG group (11.4 ± 5.7 mg/dL vs. 7.0 ± 5.0 mg/dL, p = 0.001). Conclusion: Although our data represent only our early experience performing TLDG with modified delta-shaped anastomosis, this procedure is relatively safe and feasible. Nevertheless, compared to LADG, which is the conventional method, the operative time for TLDG was longer. Surgeons must also watch out for anastomotic complications.

Over 500 Liver Transplants Including More Than 400 Living-Donor Liver Transplants in 2019 at Asan Medical Center.

BACKGROUND: More than 400 liver transplants were performed at Asan Medical Center (AMC) in 2011, and over 500 liver transplants including 420 living-donor liver transplants (LDLTs) were performed in 2019. Herein, we report the methodology of these procedures. METHODS: Since the first adult LDLTs at AMC using the left and right lobes were successfully performed, various innovative techniques and approaches have been developed: modified right lobe, dual graft, donor exchange for ABO incompatibility, expansion of indications and no-touch techniques for hepatocellular carcinoma, intraoperative cine-portogram and additional intervention for large collaterals, management of portal vein thrombosis (PVT) and stenosis, salvage LDLT after major hepatectomy, and timely LDLT for patients with acute-on-chronic liver failure. RESULTS: Four hundred twenty LDLTs in 403 adult and 17 pediatric patients and 85 deceased-donor liver transplants in 74 adult and 11 pediatric patients were performed. The number of deceased-donor liver transplants remained constant since 2011, but the number of LDLTs increased steadily. One hundred thirty patients (25.7%) required urgent liver transplantations and 24 patients with acute-on-chronic liver failure underwent LDLT. PVT including grade 1,2,3, and 4 was reported in 91 patients (18.0%), and Yerdel's grade 2, 3, and 4 PVT was reported in 47 patients (51.6%); all patients with PVT were successfully treated. Adult LDLTs for hepatocellular carcinoma and ABO incompatibility accounted for 52.6% and 24.3% of the cases, respectively. In-hospital mortality in 2019 was 2.97%. CONCLUSION: Continual efforts to overcome challenging problems in LDLT with various innovations and dedication of the team members during the perioperative period to improve patient outcomes were crucial in increasing the number of liver transplantations at Asan Medical Center.

Pretransplant Hepatic Malignancy Increases Risk of De Novo Malignancy after Liver Transplantation.

BACKGROUND: Hepatocellular carcinoma (HCC) recurrence and development of de novo malignancy (DNM) after liver transplantation (LT) are the major causes of late recipient death. METHODS: We analyzed the incidence of extrahepatic DNM following living donor LT according to the status of pretransplant hepatic malignancy. We selected 2,076 adult patients who underwent primary LDLT during 7 years from January 2010 to December 2016. RESULTS: The pretransplant hepatic malignancy group (n = 1,012) showed 45 cases (4.4%) of the following extrahepatic DNMs: posttransplant lymphoproliferative disease (PTLD) in 10; lung cancer in 10; stomach cancer in 6; colorectal cancer in 5; urinary bladder cancer in 3; and other cancers in 11. The pretransplant no hepatic malignancy group (n = 1,064) showed 25 cases (2.3%) of the following extrahepatic DNMs: colorectal cancer in 3; stomach cancer in 3; leukemia in 3; lung cancer in 3; PTLD in 2; prostate cancer in 2; and other cancers in 9. Incidences of extrahepatic DNM in the pretransplant hepatic malignancy and no hepatic malignancy groups were as follows: 1.1% and 0.5% at 1 year, 3.2% and 2.0% at 3 years, 4.6% and 2.5% at 5 years, and 5.4% and 2.8% at 8 years, respectively (P = 0.006). Their overall patient survival rates were as follows: 97.3% and 97.2% at 1 year, 91.6% and 95.9% at 3 years, 89.8% and 95.4% at 5 years, and 89.2% and 95.4% at 8 years, respectively (P < 0.001). Pretransplant hepatic malignancy was the only significant risk factor for posttransplant extrahepatic DNM. CONCLUSION: Our results suggest that patients who had pretransplant hepatic malignancy be followed up more strictly because they have a potential risk of primary hepatic malignancy recurrence as well as a higher risk of extrahepatic DNM than patients without pretransplant hepatic malignancy.

Prolonged hepatic inflow occlusion to reduce bleeding during recipient hepatectomy in living donor liver transplantation.

Background: Living donor liver transplantation (LDLT) causes bleeding in recipients during the careful preservation of most perihilar structures during this surgery. This case-control study aimed to analyze the effect of prolonged hepatic inflow occlusion (PHIO) when applied during recipient hepatectomy in LDLT. Methods: The study group comprised patients who underwent PHIO with Model for End-Stage Liver Disease (MELD) scores ranging from 26 to 35 (n=20). The following two control groups were selected according to their MELD scores: the low-MELD score group (MELD scores of 15-20, n=40) and the high-MELD score group (MELD scores of 26-35, n=40). Total dissection time for hepatic mobilization and dissection and blood loss during these procedures were compared between the two groups. Results: In the PHIO study group, mean total dissection time and mean PHIO duration were 226.3±59.4 and 68.2±19.1 minutes, respectively. Twelve patients underwent PHIO twice, and the other eight patients underwent PHIO once. The low-MELD score control group and the PHIO study group showed similar dissection duration (216.0±43.9 vs. 226.3±59.4 minutes, P=0.82) and similar blood loss volume during dissection (2,112.5±1,614.9 vs. 2,350.0±951.9 mL, P=0.17). The high-MELD score control group and the PHIO study group showed similar dissection duration (241.0±41.9 vs. 226.3±59.4 minutes, P=0.71), but the PHIO group showed a significantly lower blood loss during dissection than the high-MELD score group (2,350.0±951.9 vs. 2,815.0±1,813.9 mL, P=0.002). During and after PHIO, no adverse complication was observed, except for transient splanchnic congestion. Conclusions: Our findings suggest that PHIO is a simple effective method to reduce intraoperative bleeding during hepatic mobilization and dissection during LDLT operation requiring difficult dissection.

Changes in the indications for living donor liver transplantation: single-institution experience of 3,145 cases over 10 years.

Background: To understand the changing demands and recent trends in the indications for living donor liver transplantation (LDLT), the present study aimed to analyze the indications for LDLT performed in a high-volume transplantation center over 10 years. Methods: The liver transplantation database at our institution was searched to identify patients who underwent LDLT during a 10-year period from January 2008 to December 2017. The study subjects (n=3,145) were divided into two groups: adult patients (n=3,019, 92.7%) and pediatric patients (n=126, 3.9%). Results: In the adult recipients, the primary diagnoses were hepatitis B virus (HBV)-associated liver cirrhosis (n=1,898, 62.9%), alcoholic liver disease (n=482, 16.0%), hepatitis C virus-associated cirrhosis (n=203, 6.7%), acute liver failure (n=127, n=4.2%), and other diseases (n=157, 5.2%). The mean Model for End-Stage Liver Disease score was 15.6±8.8 (range, 6-40). The proportion of patients with HBV-associated liver disease gradually decreased, but the proportion of those with alcoholic liver disease increased. Hepatocellular carcinoma (HCC) was diagnosed in 1,467 patients (48.6%). The mean proportion of patients with HCC was 63.1% among those with HBV-associated liver disease. In pediatric recipients, the primary diagnoses were biliary atresia (n=51, 40.5%), liver failure of various causes (n=37, 29.4%), metabolic disease (n=22, 17.5%), hepatoblastoma (n=12, 9.5%), and infectious diseases (n=4, 3.2%). Conclusions: Our results showed that there were some significant changes in the indications of LDLT. We believe that our results may reflect the real changes in the indications of LDLT and they will be useful for predicting further changes in the future.

Wedged-patch venoplasty of the left liver graft portal vein for size matching in pediatric living donor liver transplantation.

Portal vein (PV) size matching between recipient and liver graft is important in preventing anastomotic stenosis in living donor liver transplantation (LDLT). In right liver grafts, the diameter of graft PV is usually >10 mm. Thus, PV size matching does not become critical in adult recipients. If the recipient PV is very large, funneling fence can be attached to graft PV. However, if the diameter of graft PV is <8 mm, it can induce anastomotic stenosis. We experienced a few cases of PV anastomotic stenosis due to small-sized graft PV in >5000 LDLT cases, but graft PV widening was not performed because graft PV is considered as being a no-touch area. In thinking out of the box, we performed wedged-patch venoplasty to exceptionally narrow graft PV. A 4 year-old female patient underwent second LDLT due to progressive deterioration of graft function after 3 years. At first LDLT operation for biliary stresia, an iliac vein conduit was interposed for PV reconstruction. At second LDLT operation, the diameter of interposed PV was 10 mm, but the left liver graft PV was only 6 mm-sized. Uniquely, the left PV was waist only at first-order PV. To resolve this PV waist, a longitudinal incision was made to release the waist. A cold-preserved fresh iliac vein patch was inserted to widen the PV orifice. The patch size was adjusted to match the size of the recipient PV. The patient recovered uneventfully. This wedged-patch venoplasty technique can be applied to small-sized graft PV, to cope with PV size mismatching in LDLT.

Cross-sectional analysis of immunosuppressive regimens focused on everolimus after liver transplantation in a Korean high-volume transplantation center.

Background: The mammalian target of the rapamycin inhibitor has dual inhibitory effects on cell growth and angiogenesis. This study aimed to analyze the usage of everolimus on actual immunosuppression (IS) regimens through a cross-sectional study in a high-volume liver transplantation (LT) center. Methods: Our institutional LT database was searched for adult patients who underwent primary LT surgery between January 2010 and December 2016. We identified 2,093 LT recipients with observation periods of 1 to 8 years. Results: We divided the 2,093 recipients into three groups according to the posttransplant follow-up period as follows: group A (12-36 months; n=680), group B (37-60 months; n=560), and group C (>60 months; n=853). The individual IS agents were tacrolimus in 1,807 patients (86.3%), cyclosporine in 169 patients (8.1%), mycophenolate mofetil (MMF) in 1,310 patients (62.6%), and everolimus in 115 patients (5.5%). The most common IS regimens were tacrolimus-MMF combination and tacrolimus monotherapy, regardless of the posttransplant period. Patients with pretransplant malignancies were administered everolimus more frequently than those without pretransplant malignancies (P<0.001). In 102 patients with hepatocellular carcinoma recurrence or de novo malignancies, IS regimens included everolimus-tacrolimus in 41 patients (40.2%), tacrolimus-MMF in 27 patients (26.4%), tacrolimus in 20 patients (19.6%), MMF in 10 patients (9.8%), cyclosporine in three patients (2.9%), and cyclosporine-MMF in one patient (1.0%). Conclusions: Administration of everolimus after LT has been gradually increasing with the expansion of indications in our institutional practice. Currently, the role of everolimus is minimal and not comparable to that of tacrolimus, but it has a unique position in the field of IS after LT.

Clinical Features and Surveillance of Very Late Hepatocellular Carcinoma Recurrence After Liver Transplantation.

BACKGROUND This study aimed to assess patterns of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) and to establish long-term surveillance protocols for late HCC recurrence. MATERIAL AND METHODS The 232 LT recipients experiencing subsequent HCC recurrence were categorized as Group 1, early recurrence (within 1 year of LT; n=117); Group 2, late recurrence (occurring in years 2-5; n=93); and Group 3, very late recurrence (after year 5; n=22). RESULTS Recurrence was detected by only elevated tumor marker levels in 11.1%, 30.1%, and 45.5% of patients in Groups 1, 2, and 3, respectively (p<0.001). The proportion of intrahepatic and extrahepatic metastases was similar in all 3 groups. Common sites of extrahepatic metastasis were the lung and bone; these were also similar across the 3 groups. Overall post-recurrence patient survival rates were 60.2% at 1 year, 28.2% at 3 years, 20.5% at 5 years, and 7.0% at 10 years. Median post-recurrence survival periods were 10.2, 23.8, and 37.0 months in Groups 1, 2, and 3, respectively. CONCLUSIONS While the pattern of HCC recurrence was similar regardless of time of recurrence, post-recurrence survival was significantly longer in patients with later recurrence. Long-term surveillance for HCC recurrence beyond 5 years after LT is recommended.

Prognostic comparison of the 7th and 8th editions of the American Joint Committee on Cancer staging system for intrahepatic cholangiocarcinoma.

BACKGROUND: Several important changes were made to the 8th edition of the American Joint Committee on Cancer (AJCC) tumor staging system for intrahepatic cholangiocarcinoma (ICC). We assessed the prognostic impact of this new tumor staging system compared to the 7th edition. METHODS: A retrospective single-institution study was performed with 626 patients who underwent R0 resection for ICC over 20-year period. RESULTS: Anatomical resection and concurrent bile duct resection were performed in 571 (91.2%) and 62 (9.9%) patients, respectively. Cumulative tumor recurrence and patient survival rates were 40.6% and 73.3% at 1 year; 66.7% and 43.8% at 3 years; 73.6% and 30.4% at 5 years; and 74.4% and 20.3% at 10 years, respectively. Independent prognostic factors for tumor recurrence and patient survival were multiple tumors, carbohydrate antigen 19-9 >200 U/ml, tumor size >5 cm, direct invasion to extrahepatic structure, and lymph node metastasis. For tumor-node-metastasis stages in the 7th versus the 8th editions, concordance index was 0.615 and 0.625 for tumor recurrence and 0.626 and 0.628 for patient survival, respectively. CONCLUSIONS: The 8th edition of the AJCC staging system appears to provide high prognostic contrast for T stage categories, except for T3. However, overall prognostic performance of the 8th edition was not markedly improved over the 7th edition.

Relationship between 15-hydroxyprostaglandin dehydrogenase and gastric adenocarcinoma.

PURPOSE: Prostaglandin E2 (PGE2) is a contributory carcinogen in gastric adenocarcinoma. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) catabolizes PGE2 by oxidizing its 15(s)-hydroxy group. The aim of this study was to investigate the expression of 15-PGDH in gastric adenocarcinoma tissue and the relationship between 15-PGDH expression and clinicopathologic features of gastric adenocarcinoma. METHODS: Ninety-nine patients who underwent surgical resection for gastric adenocarcinoma between January 2007 and December 2007 were enrolled and evaluated retrospectively. RESULTS: In 62 patients (62.6%), 15-PGDH expression was lower in gastric adenocarcinoma tissue than in nonneoplastic tissue. Regarding the relationship between 15-PGDH expression and clinicopathological features, 15-PGDH expression was significantly lower in tissues with poor differentiation (P = 0.002), advanced T stage (P = 0.0319), a higher number of lymph node metastases (P = 0.045), lymphatic invasion (P = 0.031), and vascular invasion (P = 0.036). CONCLUSION: 15-PGDH expression was associated with a subset of clinicopathologic features such as differentiation grade, T stage, lymphatic invasion, and vascular invasion.

Neuroendocrine carcinoma of the stomach: A case report.

Neuroendocrine carcinoma (NEC) is a rare tumor, comprising < 1% of stomach cancers. A 55-year-old woman was referred to our hospital with biopsy-proven gastric cancer. A shallow ulcerative lesion was detected in the lesser curvature of the lower body. It was suspected to be early gastric cancer IIA + IIC type. Thus, endoscopic submucosal dissection was performed. She was subsequently diagnosed with NEC, which is aggressive and carries a poor prognosis. We conducted a radical resection and a laparoscopic-assisted distal gastrectomy. The tumor had infiltrated the subserosal layer and 6/42 lymph nodes were involved. The mitotic index was 16/10 high power fields and the Ki-67 labeling index was 26%-50%. The final diagnosis of NEC was made according to the World Health Organization 2010 criteria. She was suspected of having jumping metastasis to the proximal margin. The patient was treated with an oral anticancer drug (5-flurouracil based drug) for 2 years. The patient has been followed up for 3 years without recurrence.