Hepatoduodenal Ligament Research Articles

Robotic central hepatectomy: technical tips and tricks

Purpose: Minimal invasive (MI) central hepatectomy is considered a technical complex procedure. The robotic approach could provide benefits over traditional laparoscopy, thanks to 3D visualization, endowrist technology and tremor filtration. Based on three different cases, this video aims to demonstrate technical tips and tricks for robotic central hepatectomy. Methods: The cases consisted of an anatomic segment 4 resection for two hepatocellular carcinoma (HCC), a MI resection of segment 5 and part of segment 8 for a solitary colorectal liver metastasis, and a MI resection of segment 4, 5 and 8 for a mixed cholangiocarcinoma and HCC. Results: A series of tips and tricks are proposed. (1) Installation: supine anti-Trendelenburg position with four robotic ports and an AirSeal port. (2) Exposure: optimal instrument and gauze placement, and application of a percutaneous traction suture to facilitate resection of segment 8 lesions. (3) Intraoperative ultrasound: demarcation of the tumor margins with monopolar scissors. (4) Pringle maneuver: an extracorporeal method with an umbilical tape encircling the hepatoduodenal ligament inserted in a chest tube, versus an intracorporeal method based on the Huang loop technique with application of a vascular bulldog clamp instead of a locking clip to apply tension, allowing to Pringle intermittently. (5) Parenchymal transection: in both healthy and cirrhotic liver tissue the combination of bipolar sealing device, Kelly-crush technique with fenestrated bipolar forceps, and monopolar scissors, proved to be highly efficient. (6) Hemostasis: achieved by preoperative hypovolemic phlebotomy with blood salvage, locking polymer clips, barbed resorbable sutures, hemostatic matrix, fibrillar absorbable haemostat and fibrin sealant patch. Operative time was 198 ± 12.6 minutes. The Pringle maneuver was applied 52.3 ± 8.7 minutes. Blood loss was 60 ± 26.5 cc. No intraoperative complications were encountered. R0-resection was obtained in all patients. The postoperative course was uneventful. Discharge happened on postoperative day 3 ± 1. Conclusion: A systematic approach of robotic central hepatectomy provides a technically feasible and adequate alternative for laparoscopy.

Inferior pancreaticoduodenal artery pseudoaneurysm rupture caused by the pancreatic neuroendocrine tumor: a case report

Introduction: Inferior pancreaticoduodenal artery (IPDA) pseudoaneurysms rupture caused by the pancreatic neuroendocrine tumor (PNET) are extremely rare. Methods: Here we report an interesting case of emerging IPDA pseudoaneurysm rupture caused by PNET. Results: A 49-year-old man was referred to our hospital for epigastric pain. Dynamic computed tomography showed a heterogeneously enhancing pancreatic head mass measuring 12 cm in diameter with hypervascular lesion. In addition, an irregular aneurysm was found in the branch from the superior mesenteric artery (SMA) to the pancreatic head. Selective angiography of the SMA confirmed an aneurysm of the IPDA, from which a jet blood flow was observed into the pancreatic head mass. The high blood flow resulted in the cavernomatous transformation of the hepatoduodenal ligament. The next day, total pancreatectomy was performed in the hybrid operating room. Laparotomy revealed a large pancreatic head mass, 12 cm in diameter and highly vascular. Left side pancreas demonstrated necrotizing pancreatitis, so the distal pancreatosplenectomy was performed in advance. The intermittent inflow occlusion of IPDA was obtained by a balloon catheter, and pancreaticoduodenectomy was safely achievable. The pseudoaneurysm at the root of IPDA was blocked with vascular clip. The postoperative course was uneventful. Immunohistochemical examination was positive for chromogranin A and synaptophysin. The final pathological diagnosis was PNET G1. In addition, arterial invasion of tumor cells was observed. Conclusions: This case demonstrates that PNET can cause IPDA pseudoaneurysm rupture. The hybrid operation is advisable in pancreatic surgery for patients associating complicated vascular event.

An overview on diagnosis and surgical management of gallbladder cancer

Gallbladder cancer is among the most deadly cancers, and it continues to present surgeons with numerous challenges. Cholelithiasis, an abnormal pancreaticobiliary junction, and focal mucosal microcalcifications are all known risk factors for gallbladder carcinoma. The most common histologic type in most patients is adenocarcinoma, which is frequently associated with Kras and p53 mutations. Endoscopic ultrasonography, magnetic resonance cholangiopancreatography, as well as helical computed tomography, as well as radiologic or endoscopic improvements in endoscopic ultrasonography as well as magnetic resonance cholangialpancratia, have improved preoperative staging. Cholecystectomy (subsegmental surgical excision of segments IVB but instead V plus a hepatoduodenal ligament lymphadenectomy) for advanced disease without indications of distant metastasis (T2–4/N0-N2) or a radical cholecystectomy (subsegmental resection of segments IVB as well as V plus a hepatoduodenal musculotendinous lymphadenectomy) for severe stages without indications of distant metastasis More extensive hepatic resection, such as extended right hepatectomy or central segmentectomy with caudate lobectomy, has been recommended by certain surgeons. Patients who underwent a pancreaticoduodenectomy to enhance distal ductal margins as well as lymphadenectomy for T3 or T4 malignancies were studied by Japanese surgeons. These patients had a reduced incidence of tumor recurrence but no benefit in terms of survival. Adjuvant treatment options are still restricted. The most frequent postoperative treatment is radiation therapy with fluorouracil radio sensitization. Capecitabine, oxaliplatin, & bevacizumab are now being studied in the treatment of gallbladder cancer in clinical studies.

Perioperative risk factors of bleeding in extensive liver resections

To study the risk factors of severe blood loss in extensive liver resections, consequences of hemorrhagic problems and their correction. The study included 374 patients. Group 1 comprised 282 patients (118 men and 164 women aged 54.1±0.7 years) who underwent surgery between 2000 and 2012. Group 2 included 92 patients (34 women and 58 men aged 53.6±1.3 years) operated on for the period 2013-2019. Technical equipment for mobilization and dissection of hepatic parenchyma has fundamentally changed for the period 2013-2019. This processes reduced blood loss by more 50% and consumption of donor blood components (red blood cells by 2.8 times, FFP by 1.8 times). Compression of hepatoduodenal ligament (Pringle maneuver) and tumor type did not affect intraoperative blood loss. Neoplasms over 10 cm increased blood loss. An increase in the number of resected segments by 2 times contributed to increase of blood loss by 2.7 times. Body mass index >25 kg/m2 was also associated with higher blood loss.

Synchronous Gallbladder Cancer and Cholangiocarcinoma: Bad Luck or Good Chance?

Introduction: Biliary cancers are a diverse group of tumors that arise from the bile duct epithelium, that includes from intrahepatic or extrahepatic cholangiocarcinoma to gallbladder cancer. Despite improvements in treatment and diagnosis, they are often diagnosed at an advanced stage and associated with poor prognosis with limited treatment options. Simultaneous presence of cancer in the gallbladder and in the biliary tree could be due synchronous malignancies, local invasion (peri-neural, lymphatic or vascular) or to metastasis. Methods: Case report of synchronous gallbladder cancer and cholangiocarcinoma and literature review. Results: The authors present a clinical case of a 68 years old male patient referred to our hepatobiliary surgery unit because of an suspicious polyp on the anterior wall of the gallbladder diagnosed by ultrasound. MRI described a simple gallbladder polyp and no other doubtful findings. Patient was submitted to a laparoscopy cholecystectomy. Histopathology reveled a gallbladder adenocarcinoma. Patient was proposed to hepatoduodenal ligament lymphadenectomy and hepatic segmentectomy, of IV and V segments. There were no metastatic lymph nodes but a intrahepatic cholangiocarcinoma was noticed. Histopathology and metastatic workup revealed a moderately differentiated gallbladder adenocarcinoma (T2a G2 N0 ILV0 IPN0 M0) and moderately differentiated intrahepatic cholangiocarcinoma (T1a N0 ILV0 IPN0 M0). Conclusion: It is possible for two different foci of malignancy to arise within the same dysplastic environment. In this case, the absence of continuousness between the two tumors, the nonexistence lymph node extension, vascular or peri-neural invasion favors the hypothesis of synchronous neoplasms. It is essential for the clinician, as well as, the pathologist to maintain a high index of suspicion while evaluating such lesions.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in colorectal liver metastases: review of the literature

The liver is considered as one of the most common sites of metastasis and a key determining factor of survival in patients with isolated colorectal liver metastasis (CRLM). For longer survival of patients, surgical resection is the only available option. Especially in CRLM bilobar patients, to achieve R0 resection, maintaining an adequate volume of the future liver remnant (FLR) is the main technical challenge to avoid post-hepatectomy liver failure (PHLF). As standard procedures in the treatment of patients with severe metastatic liver disease, techniques such as portal vein embolization/portal vein ligation (PVE/PVL) accompanied by two-stage hepatectomy (TSH) have been introduced. These methods, however, have drawbacks depending on the severity of the disease and the capacity of the patient to expand the liver remnant. Eventually, implementation of the novel ALPPS technique ignited excitement among the community of hepatobiliary surgeons because ALPPS challenged the idea of unrespectability and extended the limit of liver surgery and it was reported that FLR hypertrophy of up to 80% was induced in a shorter time than PVL or PVE. Nonetheless, ALPPS techniques caused serious concerns due to the associated high morbidity and mortality levels of up to 40% and 15% respectively, and PHLF and bile leak are critical morbidity- and mortality-related factors. Carefully establishing the associated risk factors of ALPPS has opened up a new dimension in the field of ALPPS technique for improved surgical outcome by carefully choosing patients. The benefit of ALPPS technique is enhanced when performed for young patients with very borderline remnant volume. Adopting ALPPS technical modifications such as middle hepatic vein preservation, surgical management of the hepatoduodenal ligament, the anterior approach and partial ALPPS may lead to the improvement of ALPPS surgical performance. Research findings to validate the translatability of ALPPS’ theoretical advantages into real survival benefits are scarce.

Effect of gallic acid on liver injury during obstructive cholestasis after bile duct ligation in rat

Aim: To investigate the hepatoprotective, anti-inflammatory and antioxidant effects of gallic acid (GA) against obstructive cholestasis (OC) -induced liver damage in rats. Methods: Thirty female Sprague-Dawley rats were divided into three groups. Group 1 (n=10) was the sham-operated group. In group 2 and group 3, hepatoduodenal ligament dissection was performed after laparotomy. Once the common bile duct was made apparent, it was ligated with 4/0 silk surgical suture and cut between both sutures. Group 2 (n=10) was the control group. Group 3 (n=10) was the GA group. GA (50 mg/kg) was administered by oral gavage daily for 10 days. At the end of the experiment on day 10, the rats were anesthetized. Fibrosis, inflammation, ductal proliferation and necrosis were evaluated histopathologically. Serum levels of AST, ALT, TBIL, DBIL, LDH and GGT levels were determined. In the serum and liver, TAS, TOS, MDA, TNF-α, IL-1, IL-6, and IL 10 levels were evaluated. Results: When group 2 and group 3 were compared histopathologically, fibrosis and inflammation were significantly lower in group 3. In group 3, all LFTs (except DBIL), liver and serum IL-6, IL-1, TOS, MDA, and TNF-α levels were significantly lower than group 2, whereas IL-10 and TAS values were increased. Conclusion: Findings of this research indicate that GA may be effective against OC-induced liver damage in a rat model. We presume that the beneficial effects of GA are closely associated with its antioxidant and anti-inflammatory activities. Therefore, we think that using GA can save us time before resorting to the surgical method.

Ứng dụng dao siêu âm Sonastar trong phẫu thuật cắt gan

Background: Researching specification and evaluating early results after hepatectomy that it’s used with Sonastar ultrasonic tool. Materials and methods: We prospectively examined data of 19 patients who underwent hepatectomy at Hue Central Hospitalfrom 7/2019to 7/2020. Results: The mean ages was 60,7 ± 10,5 range (19 – 90) and males/females was 6:1.. Patients with solitary liver tumor accounted for 79%; while tumors that have satellite cores accounted for 21% of all cases. 68,4% of all patients have tumor that is more than 5cm in size. Blocking hepatic blood flow by clamping of hepatoduodenal ligament accounts for 57,9%, while right and left hepatic vein clamp accounted for 68,4% and 36,8% respectively. In 78,9% of the cases, surgicel was used to cover the liver resection margin, while the in the remainder 21,5% of the cases, BioGlue was used. Large liver resection (2 and more lobes resected) accounted for 73,7% of all cases. Mean liver resection time was 50 ( 45-110) minutes, mean operation time was 125 (90-280) minutes, mean blood loss amount was 250 (150-650)ml. On average, post-operative time was 8 days (7-23). Post-operative complications was observed in 15,9% of cases, and there was 5,3% deceased. Conclusion: Application of Sonastar ultrasonic tool in hepatectomy reduces blood loss, help better manage hepatic veins, thus reducing complications such as bile leakage. It also helps surgeons manage the liver resection margin, minimalizing recurrences cancer

Optimum marker selection of acute liver damage in rats in the experiment

Relevance. Assessment of liver damage and functional state is one of the leading tasks of clinical and laboratory diagnostics. Traditionally used methods for determining the activity of a number of indicator enzymes in blood with relative organ-specificity, such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, sorbitol dehydrogenase, alkaline phosphatase, and -glutamyl transferase, have low specificity for liver diseases. In this regard, the determination of the optimal marker of acute liver injury is an urgent problem. Aim. The purpose of the study is to determine the dynamics of changes in liver damage markers in rats at different periods of reperfusion after 20 minutes of ischemia in order to select the indicators that most informatively characterize the state of test-animals under conditions of correction of ischemia-reperfusion syndrome. Materials and methods: the study was performed on 120 white nonlinear male rats weighing 200250 grams. The animals were divided into 8 groups of 15 test-animals; all of them were simulated liver ischemia by clamping the analog of the hepatoduodenal ligament with a vascular clamp for 20 minutes. Then, blood was taken from different groups of rats at different reperfusion times 5, 15, 30, 60, 120, 180 minutes, 8 hours and a day. In the blood plasma of laboratory animals, the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), glutathione transferase (GST), and lactate concentration were determined. Results: the results obtained allowed us to characterize two main peaks of indicators: a 5-minute period after restoration of blood flow the maximum activity of glutathione transferase and lactate concentration, increased by 3.94.7 times; 60180 minutes of reperfusion is the peak of aminotransferase activity, a significant increase in the activity of which begins 60 minutes after the restoration of blood flow and reaches its maximum by the 3rd hour of reperfusion, and LDH, the peak of which is recorded already by the 60th minute of revascularization. At the same time, after 8 hours of reperfusion, an obvious tendency for a decrease in all studied parameters was determined, which ends a day after modeling ischemia with a decrease to the level of control values. Conclusion: the assessment of organ damage in the ischemic period and the anti-ischemic effect of metabolic drugs can be carried out with the determination of an increase in lactate concentration and glutathione transferase activity almost immediately after restoration of blood flow. The development of injuries during the reperfusion period is more expedient to assess by determining AST, ALT and LDH after a 3-hour period of blood flow restoration, at which time the maximum values of markers are recorded under the condition of 20-minute total liver ischemia.

Liver lymphatic drainage patterns follow segmental anatomy in a murine model

The liver’s cellular functions are sustained by a hierarchical, segmentally-organized vascular system. Additionally, liver lymphatic vessels are thought to drain to perihepatic lymph nodes. Surprisingly, while recent findings highlight the importance of organ-specific lymphatics, the functional anatomy of liver lymphatics has not been mapped out. In literature, no segmental or preferential lymphatic drainage patterns are known to exist. We employ a novel murine model of liver lymphangiography and in vivo microscopy to delineate the lymphatic drainage patterns of individual liver lobes. Our data from blue dye liver lymphangiography show preferential lymphatic drainage patterns: Right lobe mainly to hepatoduodenal ligament lymph node 1 (LN1); left lobe to hepatoduodenal ligament LN1 + LN2 concurrently; median lobe showed a more variable LN1/LN2 drainage pattern with increased (sometimes exclusive) mediastinal thoracic lymph node involvement, indicating that part of the liver can drain directly to the mediastinum. Upon ferritin lymphangiography, we observed no functional communication between the lobar lymphatics. Altogether, these results show the existence of preferential lymphatic drainage patterns in the murine liver. Moreover, this drainage can occur directly to mediastinal lymph nodes and there is no interlobar lymphatic flow. Collectively, these data provide the first direct evidence that liver lymphatic drainage patterns follow segmental anatomy.

The evaluation of B-SAFE and ultrasonographic landmarks in safe orientation during laparoscopic cholecystectomy.

IntroductionEven though the prevalence of bile duct injury (BDI) is nowadays lower than before and close to the era of open cholecystectomy, there is a strong need to make it even lower. B-SAFE is a group of five visual landmarks that may be used before dissection in the hepatocystic triangle for better orientation around the gallbladder. Another method is laparoscopic ultrasound (LUS), which enables confirmation of structures in the hepatoduodenal ligament and delineation of the safe plane of dissection.AimTo evaluate the use of B-SAFE and ultrasonographic landmarks during laparoscopic cholecystectomy in navigation around the gallbladder.Material and methodsThe study group consisted of 158 patients with symptomatic cholecystolithiasis. The methods of intraoperative orientation around the gallbladder attempted in every patient during laparoscopic cholecystectomy included B-SAFE and ultrasonographic landmarks.ResultsThe identification rate of ultrasonographic landmarks – the upper border of “Mickey Mouse” sign (MMS) (the equivalent of the Rouviere’s sulcus), the bile duct, and the hepatic artery – was significantly higher in patients with body mass index ≥ 30 kg/m2 and fibrosis and chronic inflammation in the gallbladder neck than B-SAFE. LUS was also significantly more successful in the identification of the bile duct in the whole study group than B-SAFE. There were no significant differences according to the identification of the duodenum. The conversion rate was 2.6%, and we did not observe any BDI.ConclusionsVisual landmarks defined in B-SAFE are not as reliable as ultrasonographic landmarks; thus, LUS should be taken into consideration in the first place as a method of navigation around the gallbladder.

Indocyanine green administration a day before surgery may increase bile duct detectability on fluorescence cholangiography during laparoscopic cholecystectomy.

The optimal indocyanine green (ICG) administration protocol for fluorescence cholangiography during laparoscopic cholecystectomy (LC) has yet to be determined. A prospective study including 20 cases of ICG fluorescence-navigated LC was conducted. Accordingly, the first 10 patients were administered 2.5mg of ICG on the day of surgery after intubation (surgery-day group), while the remaining 10 consecutive patients were administered 0.25mg/kg of ICG on the evening before surgery (one-day-before group). Fluorescence intensity (FI) of each tissue and FI ratios were then compared between both groups. The median interval between observation and ICG administration was 27minutes and 16hours 24minutes in the surgery-day and one-day-before group, respectively. Although FI values for the common bile duct (CBD), liver, and hepatoduodenal ligament (HDL) were significantly lower in the one-day-before group than in the surgery-day group, CBD- , 0.6-1.2 vs 2.5, 0.9 = -4.8; P<.001), and CBD-HDL contrast (1.7, 1.4-2.4 vs 2.3, 1.5-13.3; P=.038) were significantly higher in the one-day-before group than in the surgery-day group. ICG administration a day before LC may offer better CBD background contrast compared to administration just prior to surgery.

Liver Transection-First Approach in Hepatopancreatoduodenectomy for Hilar Cholangiocarcinoma: A Safe and Secure Technique for the Early Assessment of Curable Resection and Vascular Reconstruction.

Hepatopancreatoduodenectomy (HPD) is often indicated in the resection of cholangiocarcinoma but is associated with high mortality.1-3 From a risk-benefit perspective, HPD can be justified only when curative resection is achievable.4-6 METHODS: A liver transection-first approach is a surgical technique in which liver transection precedes pancreatoduodenectomy (PD) and skeletonization of the hepatoduodenal ligament in HPD. This approach enables an early assessment of resectability and curability. A 64-year-old with jaundice had a tumor located mainly in the proximal bile duct, spreading from the confluence of hepatic ducts (dominant in the left hepatic duct) to the intrapancreatic bile duct. The right hepatic artery and portal vein existed in close proximity to the tumor. HPD (left hemi-hepatectomy and subtotal stomach-preserving PD) with vascular resection was performed. After liver transection along the Cantlie line, the right Glissonean pedicle was collectively secured inside the liver. The right hepatic artery, right portal vein, and right hepatic duct (RHD) were isolated, and the feasibility of vascular reconstruction was confirmed. After the RHD was divided and the negative margin was confirmed, we proceeded to perform PD. The portal vein was reconstructed between the right portal vein and the portal vein trunk. The right hepatic artery was anastomosed to the second jejunal artery of the jejunal loop with the right gastroepiploic artery as an interposition graft. The liver transection-first technique in HPD facilitates early assessment of curability and resectability as well as a safe and secure manipulation and reconstruction of the hepatic artery and portal vein.

Ischemia reperfusion-induced metastasis is resistant to PPARγ agonist pioglitazone in a murine model of colon cancer

Ischemia reperfusion injury (IRI) during liver-metastasis resection for treatment of colon cancer may increase the risk of further metastasis. Peroxisome proliferator-activated receptor-γ (PPARγ) activation has been observed to exert a protective effect against IRI and IRI-induced metastasis of hepatocellular carcinoma. The present study aimed to investigate the effect of the PPARγ agonist pioglitazone on tumor metastasis and liver injury following IRI in a mouse model of colon cancer. Pioglitazone (30 mg/kg weight) was administered orally 1.5 h before and 2 h after the initiation of ischemia and was orally administrated daily to mice from day 0–21. SL4-cancer cells expressing red fluorescent protein (SL4-RFP) (1 × 106) were injected into the spleen. Fifteen minutes after injection, the hepatoduodenal ligament was clamped with a vessel clip, and released 5 min later. Liver, blood and tumor samples were taken from mice in order to determine if inflammation was induced by IRI. The effect of pioglitazone on liver metastasis was assessed. Furthermore, the effect of pioglitazone to control the inflammatory response during IRI progression was examined. Liver metastasis along with MMP-9 activation and the production of inflammatory cytokines were resistant to pioglitazone. Our results indicate that liver metastasis and associated inflammation in mice were resistant to pioglitazone.

Subtotal (segment II\u2013VIII) hepatectomy for bilateral diffuse hepatolithiasis with compensatory caudate lobe hypertrophy: a report of two cases

BackgroundHepatolithiasis often leads to atrophy–hypertrophy complex due to bile duct obstruction, inflammation or infection in the affected liver segments and compensatory response in the normal segments. In severe bilateral diffuse cases, main liver can all be atrophic, leaving the caudate lobe to be extremely hypertrophic. Subtotal (segment II–VIII) hepatectomy can be an option in selected patients under such circumstances. Since rare cases have been reported, our study aims to highlight the preoperative evaluation and key points of this procedure.Case presentationTwo patients with primary and secondary bilateral diffuse hepatolithiasis, respectively, were enrolled in this case series. The atrophy of the left and right liver with an exceeding hypertrophy of the caudate lobe were observed. Since the liver anatomy had completely been changed, contrast computed tomography, magnetic resonance imaging combined with 3D liver reconstruction were employed for comprehensive evaluation and pre-operational planning. The patients underwent standard subtotal (segment II–VIII) hepatectomy. During operation, the hepatoduodenal ligament around porta hepatis was dissected firstly to expose the hepatic artery, portal vein, bile duct and their branches successively. And then the vessels and bile duct to caudate lobe were preserved safely through cutting off the left and right hepatic artery, portal vein and bile duct at a safe point distal to the origin of the branches to caudate lobe. Operation time was 300 min and 360 min, respectively. Blood loss was 200 ml and 300 ml. No evidence of liver dysfunction, hepatolithiasis relapse or cholangitis was observed during the follow-up of 12 and 26 months.ConclusionsSubtotal (segment II–VIII) hepatectomy may be one of several treatments possible in selected patients with compensatory caudate lobe hypertrophy caused by bilateral diffuse hepatolithiasis.

S2455 Delayed-Onset Immunotherapy-Related Hepatitis Instigated by the Stress of Surgery

INTRODUCTION: Immune checkpoint inhibitors are prone to elicit immune-related adverse events that can affect many different organ systems. Specifically, hepatitis is relatively infrequent and may only present with elevated LFT’s and fever. We report a rare case of delayed immunotherapy-related hepatitis provoked by the acute immunologic stress of surgery. CASE DESCRIPTION/METHODS: Presenting a 63-year-old male with Stage 3A SCC of the lung who completed four cycles of neoadjuvant carboplatin, paclitaxel, and pembrolizumab followed by a recent left upper lobe lobectomy with mediastinal lymph node dissection. His initial post-operative course was uneventful; however, he presented two weeks later with intermittent fevers and vague abdominal complaints consisting of discomfort, distension, and early satiety. Labs showed a normal WBC, total bilirubin, and INR, but newly elevated labs with AST 66, ALT 111, and ALP 197. He was started on piperacillin-tazobactam, but continued to fever to a maximum temperature of 102°F. CT abdomen showed a normal liver and gallbladder with enlarged hepatoduodenal ligament lymph nodes. Infectious workup including blood and urine cultures, HSV, CMV, EBV, HIV, a hepatitis panel, and a respiratory viral panel was negative. Other labs included an elevated IgA, normal IgG and IgM, negative anti-nuclear antibody, and an anti-smooth muscle antibody positive at 1:40. The patient’s AST and ALT continued to gradually increase to a peak of 187 and 246 IU/L, respectively. Given the negative infectious workup and previous treatment with pembrolizumab, the patient was started on prednisone for presumed immunotherapy-related hepatitis resulting in complete resolution of his symptoms and elevated liver enzymes twelve days after beginning treatment (Figure 1). His prednisone was slowly tapered over an eight-week course. DISCUSSION: Immunotherapy-related hepatitis occurs in a very small percentage of patients on immune checkpoint inhibitors. Hepatitis typically occurs within a week to a few months of starting therapy, but can occur months after discontinuation of therapy as well. Given the extended half-life of anti-PD-1 therapy with a high percentage of sustained T-cell occupancy, our patient’s delayed immune reaction was thought to be instigated by the stress of his recent surgery. Since immunotherapy-related hepatitis has a vague and varying onset, it is important to keep this as a differential to allow for early initiation of steroids to prevent progression to liver failure.Figure 1.: Timeline of Altered LFT's.

PD-1 Expression by Lymph Node and Intratumoral Regulatory T Cells Is Associated with Lymph Node Metastasis in Pancreatic Cancer.

Simple SummaryPancreatic cancer is a devastating disease and among the most immune-resistant tumor types. Single-agent immunotherapy has not demonstrated clinical benefits in pancreatic cancer patients, and combinational therapies targeting multiple mechanisms of immunosuppression are likely needed. T cell activation in lymph nodes is required for the efficacy of immunotherapy. Here, we phenotypically and functionally analyze T cells from tumor-draining lymph nodes, blood and tumors from patients with pancreatic cancer to decipher unknown immunosuppressive mechanisms and to identify potential immunotherapeutic targets.Pancreatic ductal adenocarcinoma (PDAC) is characterized by a mostly immunosuppressive microenvironment. Tumor-draining lymph nodes (TDLN) are a major site for priming of tumor-reactive T cells and also tumor metastasis. However, the phenotype and function of T cells in TDLNs from PDAC patients is unknown. In this study, lymph nodes from the pancreatic head (PH), the hepatoduodenal ligament (HDL) and the interaortocaval (IAC) region were obtained from 25 patients with adenocarcinoma of the pancreatic head. Additionally, tumors and matched blood were analyzed from 16 PDAC patients. Using multicolor flow cytometry, we performed a comprehensive analysis of T cells. CD4+ T cells were the predominant T cell subset in PDAC-draining lymph nodes. Overall, lymph node CD4+ and CD8+ T cells had a similar degree of activation, as measured by CD69, inducible T cell co-stimulator (ICOS) and CD137 (4-1BB) expression and interferon-γ (IFNγ) secretion. Expression of the inhibitory receptor programmed death 1 (PD-1) by lymph node and tumor-infiltrating regulatory T cells (Tregs) correlated with lymph node metastasis. Collectively, Treg cells and PD-1 are two relevant components of the immunosuppressive network in PDAC-draining lymph nodes and may be particularly attractive targets for combinatorial immunotherapeutic strategies in selected patients with node-positive PDAC.

Reconsidering the Optimal Regional Lymph Node Station According to Tumor Location for Pancreatic Cancer.

A consensus regarding the optimal extent of lymph node dissection for pancreatic cancer has not yet been achieved. The purpose of this study was to evaluate the efficacy of lymph node dissection according to the location for pancreatic cancer. A total of 495 patients diagnosed with invasive ductal carcinoma of the pancreas who had undergone a pancreatectomy between October 2002 and December 2015 were analyzed. The efficacy index (EI) was calculated for each lymph node station via multiplication of the frequency of metastasis to the station and the 5-year survival rate of the patients with metastasis to that station. For pancreatic head (Ph) tumors, mesocolon lymph nodes had a high EI, although not regional. For pancreatic body (Pb) tumors, peri-Ph lymph nodes had a high EI, although not regional. For pancreatic tail (Pt) tumors, lymph nodes along the celiac axis and common hepatic artery had a zero EI, although regional. When the Ph was segmented into the pancreatic neck (Ph-neck), uncinate process (Ph-up), and periampullary regions, hepatoduodenal ligament lymph nodes had a zero EI for Ph-up, although regional; the mesojejunum lymph node also had a zero EI, even for Ph-up, regardless of a high incidence of metastasis. Regarding lymph node recurrence after surgery, recurrence was most frequently found at the peri-Ph lymph node (12%) in patients with Pb tumors who had undergone a distal pancreatectomy. The optimal extent of lymph node dissection should be estimated in regard to the tumor location.

Safety of bioabsorbable membrane (Seprafilim®) in hepatectomy in the era of aggressive liver surgery

BackgroundRepeat hepatectomy has been recognized as an effective treatment for hepatic malignancies, and a sheet type adhesion barrier, Seprafilm® has increasingly been used during hepatectomy to ease future relaparotomy. However, there is not yet sufficient evidence to support the safety of use of Seprafilm in liver surgery. MethodsData of 151 patients who had undergone open hepatectomy were retrospectively reviewed and the incidence of major abdominal morbidity was compared between patients in whom Seprafilm had and had not been used. ResultsSeprafilm was used in 108 patients (Seprafilm group) and no adhesion barrier was used in 43 patients (comparison group). There was no significant difference in the rate of major abdominal morbidities between the two groups (Seprafilm vs. comparison: 10% vs. 16%, P = 0.403). Although the Seprafilm group showed a tendency toward increased incidence of bile leakage (7% vs. 2%), and placement of Seprafilm on the hepatoduodenal ligament or on the visceral surface of the liver seemed to be associated with an increased incidence of major morbidity, multivariate analysis showed no significant correlation between the use of Seprafilm and postoperative major abdominal morbidity. ConclusionUse of Seprafilm may not increase the risk of major abdominal morbidity in liver surgery.

A case of inflammatory pseudotumour of the gallbladder presenting as a big mass of uncertain behavior

BackgroundInflammatory pseudotumour has been used to describe an inflammatory or fibrosing tumoral process of an undetermined cause that may involve a variety of organ systems, including the lungs, spleen, liver, lymph nodes, pancreas and extrahepatic bile duct with potential for recurrence and persistent local growth. In this article, we report a patient with a big mass of uncertain nature and behavior.Case presentationA 60-year-old woman presented with a 1-week history of abdominal pain, fever and jaundice. Six months before she had had right upper quadrant pain that was interpreted as biliary colic. A contrast-enhanced CT scan showed a big mass of soft tissue with diffuse infiltration of the gallbladder, displacement of the transverse colon, hepatic flexure and duodenum. For diagnostic distinction between a chronic inflammatory disease or a neoplasm, exploratory laparotomy was required. Intraoperative exploration disclosed a big mass of hard texture involving the gallbladder, with multiple concrements, hepatoduodenal ligament, right and transverse mesocolon, stomach and duodenum.Cholecystectomy was performed, preserving adjacent organs with macroscopic desmoplastic reaction. Histopathologic examination of the gallbladder showed a spindle cell proliferation with diffuse chronic inflammatory infiltrate of lymphocytes, plasma cells and hyalinized fibrous stroma. No vascular invasion or cellular atypia were evident.ConclusionInflammatory pseudotumour is a rare condition and diagnostic distinction from a chronic inflammatory disease or other neoplasm is only possible by histopathologic examination. There is a limited number of case reports in the literature indicating tumor location in the gallbladder.