Poly (ADP-ribose) polymerase-1 (PARP-1) is a good prognostic marker for pancreatic/periampullary cancers.

BACKGROUND: Periampullary cancer (PAC) is highly aggressive with no effective adjuvant therapy or prognostic markers. Recently, poly (ADP-ribose) polymerases-1 (PARP-1) have emerged as a target in solid cancers, and its relationship with epithelial-mesenchymal transition (EMT) has been observed. However, the relationship between PARP-1 and EMT in PAC has not explored well. METHODS: We assessed the prognostic significance of PARP1 in 190 PACs patients and correlated it with EMT markers, including FGF8, FGFR4, MMP2, MMP3, Snail, and ZEB1. Immunohistochemistry for PARP-1 and EMT markers was performed using a tissue microarray. RESULTS: PARP-1 and FGF8 expression were associated with better survival unlike other solid cancers (P = 0.006 and P = 0.003), and MMP3 and ZEB1 expression were associated with poor prognosis in multivariate and survival analyses (P = 0.009 and P < 0.001). In addition, PARP-1 is related negatively to Snail but not related with other EMT markers, implying an independent mechanism between PARP-1 and EMT in PACs. PARP-1 and FGF8 are independent good survival markers in PACs unlike other solid cancers. CONCLUSIONS: PARP-1 and FGF8 in PACs could not be related to the EMT pathway but must be rather understood in light of similar cancer-protective roles. Further studies are required on EMT-associated immune markers in PACs.

Accuracy of preoperative T2 gallbladder tumor localization and the adequate surgical resection.

INTRODUCTION: The agreement between the radiologic and histopathologic tumor locations in T2 gallbladder cancer is critical. There is no consensus regarding the extent of curative resection by tumor locations. METHODS: Between January 2010 and December 2019, a consecutive series of 118 patients with pathological T2 gallbladder cancer who underwent surgery were retrospectively analyzed in terms of the accordance between radiologic and histopathologic tumor locations, the extents of hepatic resection and the numbers of harvested lymph nodes. Radical resection was defined as liver resection with harvesting of at least four lymph nodes. RESULTS: The accuracy of preoperative tumor localization was only 68%. After radical resection, the 5-year overall survival (OS) was 59.4%; after nonradical resection, the figure was 46.1% (p = 0.092). In subanalyses, the 5-year OS was marginally better for patients who underwent liver resection or from whom at least four lymph nodes were harvested than those who did not undergo liver resection or from whom three or fewer lymph nodes were harvested (58.2% vs. 39.4%, p = 0.072; 59.9% vs. 50.0%, p = 0.072, respectively). In patients with peritoneal side tumor, the 5-year OSs of those who did and did not undergo liver resection were 67% and 41.2%, respectively (p = 0.028). In multivariate analysis, perineural invasion and radical resection were independently prognostic of OS. CONCLUSION: The accuracy of preoperative tumor localization was 68%. Hepatic resection, lymph node dissection harvesting of at least four lymph nodes are required for curative resection for gallbladder cancer, regardless of tumor location.

Laparoscopic common bile duct exploration following prior gastrectomy: surgical safety and feasibility.

PURPOSE: Previous gastrectomy (PG) can lead to an increased incidence of biliary stones. However, the success rate of endoscopic retrograde cholangiopancreatography after gastrectomy remains low. In such cases, laparoscopic common bile duct exploration (LCBDE) may be an alternative. The aim of this study was to evaluate the safety and feasibility of LCBDE for patients who underwent PG. METHODS: A retrospective analysis of patients with a history of LCBDE was conducted. Patients were divided into two groups according to their PG status, and their perioperative data were compared. RESULTS: The outcomes of 27 patients with a history of gastrectomy were compared with those of 155 without a history of gastrectomy who underwent LCBDE. PG patients experienced longer hospitalization times (P = 0.006), more postoperative bleeding (p = 0.021), a lower incidence of preoperative endoscopic retrograde cholangiopancreatography (P < 0.001), and a higher incidence of T-tube application (p = 0.002) than those without gastrectomy. However, there were no significant differences in estimated blood loss volume, operation time, bile leakage status, pancreatitis status, stone clearance rate, readmission rate, or recurrence rate. CONCLUSIONS: Although LCBDE following gastrectomy may require laborious perioperative management, a history of gastrectomy might not influence the feasibility or safety of LCBDE, as its perioperative outcomes are comparable to those in patients without a history of gastrectomy.

Safety of performing distal pancreatosplenectomy in patients who underwent distal gastrectomy previously: a multicenter cohort analysis with systematic literature review.

Purpose: In patients who have previously undergone subtotal gastrectomy (STG), the remnant stomach is supplied with arterial blood through the splenic artery. It is currently unclear whether the remnant stomach can be safely preserved when performing distal pancreatosplenectomy (DPS) in these patients. Thus, this study aimed to evaluate the safety and feasibility of performing DPS in patients who had undergone a previous STG. Methods: A multicenter cohort study was performed to identify patients who underwent DPS. Electronic medical data of Clinical Data Warehouse from 7 representative high-volume centers in 5 cities were retrospectively reviewed. A propensity score-matched analysis was performed to match patients who had no history of upper abdominal surgery with patients who had undergone a previous STG. Results: Fourteen DPS patients who had a history of STG (STG group) were studied and matched to 70 patients who underwent DPS without any history of upper abdominal surgery (non-STG group). All patients in the STG group had the remnant stomach preserved. In most patients, the blood vessel supplying blood to the remnant stomach was the left inferior phrenic artery. There was no significant difference in the incidence of stomach-related complications or length of hospital stay between the 2 groups. Conclusion: Our study results suggest that the remnant stomach could be safely preserved when performing DPS in patients with a prior STG. However, it is necessary to carefully evaluate the vascular structure of the remnant stomach through preoperative imaging study and closely observe changes to the blue stomach during the operation.

Korean Surgical Practice Guideline for Pancreatic Cancer 2022: A summary of evidence-based surgical approaches

Pancreatic cancer is the eighth most common cancer and the fifth most common cause of cancer-related deaths in Korea. Despite the increasing incidence and high mortality rate of pancreatic cancer, there are no appropriate surgical practice guidelines for the current domestic medical situation. To enable standardization of management and facilitate improvements in surgical outcome, a total of 10 pancreatic surgical experts who are members of Korean Association of Hepato-Biliary-Pancreatic Surgery have developed new recommendations that integrate the most up-to-date, evidence-based research findings and expert opinions. This is an English version of the Korean Surgical Practice Guideline for Pancreatic Cancer 2022. This guideline includes 13 surgical questions and 15 statements. Due to the lack of high-level evidence, strong recommendation is almost impossible. However, we believe that this guideline will help surgeons understand the current status of evidence and suggest what to investigate further to establish more solid recommendations in the future.

Is hepatectomy an appropriate option for bilobar liver metastasis with portal vein tumor thrombus of colorectal cancer?

The prognosis of patients with multiple liver metastasis of colorectal cancer (CLM) on both lobes accompanied by a portal vein tumor thrombus (PVTT) remains unclear. We report two patients with multiple CLM and PVTT who underwent liver resection. A 73-year-old man had successful extended right hemi-hepatectomy with a thrombectomy for a macroscopic tumor thrombus in the right portal branch and multiple CLM in both lobes. At 8 months after surgery, the patient had multiple CLM in the remnant lobe with left main PVTT and died 14 months after liver surgery. A 64-year-old woman who had previously undergone palliative chemotherapy for adenocarcinoma of the ascending colon presented with CLM accompanied by a macroscopic tumor thrombus in the left portal branch. Tumor and PVTT had progressed despite various regimens of chemotherapy. Left hemi-hepatectomy with radiofrequency ablation on right lobe and right hemicolectomy were performed. However, CLM occurred again within 3 months after the liver surgery. Considering these cases, a poor prognosis may be expected even though the tumor is successfully removed by liver resection.

Clinical implication of bactibilia in moderate to severe acute cholecystitis undergone cholecystostomy following cholecystectomy.

There is little evidence of clinical outcome in using antibiotics during the perioperative phase of acute cholecystitis with bactibilia. The aim of current study is to examine the effect of bactibilia on patients with acute cholecystitis and their perioperative clinical outcome. We performed a retrospective cohort analysis of 128 patients who underwent cholecystectomy for acute cholecystitis with moderate and severe grade. Patients who were positive for bactibilia were compared to bactibilia-negative group in following categories: morbidity, duration of antimicrobial agent use, in-hospital course, and readmission rate. There was no difference in morbidity when patients with bactibilia (n = 70) were compared to those without (n = 58) after cholecystectomy. The duration of antibiotics use and clinical course were also similar in both groups. In severe grade AC group (n = 18), patients used antibiotics and were hospitalized for a significantly longer period of time than those in the moderate grade AC group. The morbidity including surgical site infection, and readmission rates were not significantly different in moderate and severe grade AC groups. In moderate and severe AC groups, bactibilia itself did not predict more complication and worse clinical course. Antibiotics may be safely discontinued within few days after cholecystectomy irrespective of bactibilia when cholecystectomy is successful.

Reappraisal of clinical indication regarding total pancreatectomy: can we do it for the risky gland?

BACKGROUND: Although total pancreatectomy (TP) is performed at an increasing rate at major pancreatic centers, there is still debate regarding its indications and outcomes. This study aims to analyze the indications and outcomes of TP using our retrospective data. METHODS: We conducted a retrospective study on patients who underwent TP between January 2009 and December 2019 at two academic hospitals using data collected. Preoperative data, including demographics and clinical picture, operative details, and postoperative data, were collected and analyzed. Conventional indications of TP included positive margin on the neck, lesion of the central part of the pancreas, and diffuse lesions of the whole pancreas. The classification of the risky gland included pancreas remnants, which had higher risk for pancreaticoenterostomy after pancreatic head resection. RESULTS: During the study periods, a total of 72 TP were performed for benign and malignant pancreatic diseases. After excluding six TP undergone due to trauma or complication after partial pancreatectomy, 64 patients were grouped into 47 patients with existing conventional indications and 17 patients with predicted risky anastomosis. There was no significant difference in clinical data and surgical results between the conventional indication group and the risky gland group. Thirty-day major morbidity and mortality was 9.4% and 0%, respectively. Ninety-day mortality rate was 1.4% (n=1, conventional group), with the median follow-up length of 21.5 months. Overall 5-year survival rate was 67.7% for the total participants: 87.5% for the risk gland group and 57.9% for the conventional group. There was no significant difference in between the two groups. CONCLUSIONS: Total pancreatectomy appears to be a viable option for risky glands in terms of surgical safety.

High Expression of PD-L1 Is Associated with Better Survival in Pancreatic/Periampullary Cancers and Correlates with Epithelial to Mesenchymal Transition.

Periampullary cancers (PACs) are characterized by tumor-infiltrating lymphocytes (TILs), severe fibrosis, and epithelial to mesenchymal transition (EMT). The immune checkpoint marker programmed death-1 (PD-1) and its ligands 1 and 2 have gained popularity in cancers with TILs. Evidence suggests a strong relationship between immune checkpoint markers and EMT in cancers. Here, we evaluated the expression and prognostic significance of immune checkpoint and EMT markers in PAC using an automated image analyzer. Formalin-fixed, paraffin-embedded surgically excised PAC tissues from laboratory archives (1998-2014) were evaluated by immunohistochemical staining for PD-1, PD-L1, and PD-L2 in a tissue microarray. In total, 115 PAC patients (70 males and 45 females) with an average age of 63 years were analyzed. Location, gross type, size, radial resection margin, N-M stage, lymphatic invasion, vascular invasion, perineural invasion, histologically well-differentiated severe inflammation, and high PD-L1 expression were significantly associated with recurrence. Higher PD-L1 expression, but not PD-1 and PD-L2, was significantly related to better overall survival (OS) and disease-free survival (DFS). PD-L1 and PD-L2 were significantly related to EMT markers. Aside from other clinicopathologic parameters, high PD-L1 expression was significantly related to better OS and DFS of PAC patients. Moreover, immune checkpoint markers were significantly associated with EMT markers. Therefore, PD-L1 expression can be a good prognostic marker to guide future immune target-based therapies in PAC patients.

Amylase level after pancreaticoduodenectomy in predicting postoperative pancreatic fistula.

BACKGROUND: It is new clinical interest higher serum amylase level with pancreatitis after pancreaticoduodenectomy (PD) correlates with postoperative pancreatic fistula (POPF). Nevertheless, its evidence and study were scarce. We aimed to investigate correlation of serum amylase level immediate after PD and POPF occurrence. METHODS: Of 163 patients who underwent PD at between January 2009 and December 2019, retrospective analysis was conducted to identify risk factors including serum amylase level immediate after PD for POPF occurrence. RESULTS: Overall incidence of POPF (25/163) was 15.3%. The patients occurred a POPF had significantly higher level of serum amylase on POD0 compared to in whom without a POPF (414 vs 253, p < 0.001). In univariate analysis, ASA classification, post pancreatectomy acute pancreatitis (POAP, serum amylase on POD0 >285IU/L) and Fistula Risk Grade were correlated with POPF occurrence. In multivariable analysis, Fistula risk grade and POAP were significantly associated with developing POPF. CONCLUSION: In patients with higher serum amylase (>285IU/L) on POD0 with higher fistula risk grade, comprehensive management to achieve mitigation of POPF is important.

Appraisal of Laparoscopic Common Bile Duct Explorations Using Balloon-Assisted Stone Extraction Method: Seventeen Years Experiences.

Background: Balloon-assisted stone extraction (BASE) can be applied to remove the common bile duct (CBD) stones during laparoscopic CBD exploration (LCBDE). This study aimed to analyze the efficacy of BASE. Methods: A retrospective analysis of patients with CBD stone who underwent LCBDE using BASE from 2001 to 2017 was conducted. The outcomes of BASE and potential factor for failure of technique were also evaluated. Results: A total of 163 patients underwent LCBDE using BASE were enrolled. Success rate of BASE was 88.3% (144/163) and 19 (11.7%) patients with failed BASE underwent basket for lithotripsy additionally. The reason for aborting BASE were stone impaction (n = 6), small stone (n = 4), migration into intrahepatic duct (IHD) (n = 3), and others (n = 6). The overall success rate of stone clearance was 98.2% (160/163). The mean CBD diameter was 15.8 mm (range 7-34 mm), and the largest stone size was 13.8 mm (range 3-36 mm). The overall rate of complication related with procedure was 4.9% (8/163), including bile leakage in 2 patients (1.2%), bleeding in 2 patients (1.2%), and pancreatitis in 4 patients (2.4%). There was no procedure-related mortality. Conclusions: BASE for CBD stone is safe and effective technique for the treatment of CBD stones.

Lateral approach toward hepatoduodenal ligament during laparoscopic radical cholecystectomy for Gallbladder cancer.

BACKGROUND: The common approach of Lymph node dissection (LND) during laparoscopic radical cholecystectomy (LRC) is an anterior approach [1,2], which emulates the view of open surgery. However, isolating the post-pancreatic nodes and retro-portal nodes completely without any damage to neighboring organs can be difficult in laparoscopic surgery because the dorsal structures of hepatoduodenal ligament are embedded and it is difficult for a surgeon to expose them [3]. On the other hand, the lateral approach offers the better way to expose and dissect dorsal part of hepatoduodenal ligament and it can be useful for dissecting hilar during laparoscopic right hepatectomy without injury of left side vascular structures. METHODS: We performed retrospective analysis of consecutive 10 patients submitted to LRC for Gallbladder (GB) cancer and described a technical aspect regarding LND for those series of cases. Among them, we introduced a patient with 71 years old man in a surgical video clip. He had no symptom and was his lesion was detected during a regular health care screening. The preoperative computed tomography showed T2 cancer with suspicious involvement in liver. His liver function was normal and tumor marker level was in normal range. LRC with liver wedge resection were contemplated for his treatment. RESULTS: In the video clip, the patient was laid on an operating table in supine position. A zero degrees flexible laparoscope was used through the port on right subcostal angle. After identifying the common hepatic artery, #8 nodes were dissected and a 360-degree surrounding loop was applied to it for gentle retraction. Then gastroduodenal artery was identified with same manner. Cystic duct was isolated and frozen biopsy of its stump was done. After completing the isolation of common bile duct, another 360-degree loop was placed around it. The main trunk of the portal vein was exposed and followed superiorly up to the area of its bifurcation. Camera moved to lateral side of patient, to provide the better view of posterior and dorsal part of hepatoduodenal ligament. Careful dissection of retro-portal area with node dissection was then performed and portal vein was surrounded in 360°. Then, surgeon paid attention to dissecting retro-pancreatic #13 nodes, which was clearly identified and dissected. LRC was performed successfully by using lateral laparoscopic approach. Then liver wedge resection under laparoscopy was performed without any problem. This approach was not a great invention or innovation. Rather, this approach is commonly used technique in "liver and pancreatic minimally invasive procedures" including robotic procedures. However, this simple procedure can be useful for a surgeon to perform LRC. During last 20 years, we performed radical cholecystectomy for treating GB cancer in our institution. Since 2014, we changed the policy to treat early GB cancer (in the stage of T1b and T2) with "minimally invasive procedure". We performed only LND without liver resection for peritoneal side tumor. Most of all patients were diagnosed in preoperative manner. Only two cases of incidental cancer underwent additional operation of LND and liver resection. Half of cases went through the process of dissection of lymph nodes only and 5 liver resections were done. None of patients undergoing LRC required conversion to another view during hilar dissection. The retro-portal vein and pancreas head LND could be reached expeditiously and safely prior to parenchymal transection. Majority of them revealed T2 and T1b finally. Number of retrieved nodes were in between 1 and 17 and median was 7. There was one complication of small bowel perforation during adhesiolysis. CONCLUSION: Lateral approach during LRC appears to offer better way to visualize, expose and dissect the dorsal part of hepatoduodenal ligament and LND #12,13s.