Homogeneity in immune features between colorectal liver metastases better identifies patients with good prognosis compared to pathological response to preoperative chemotherapy.

In colorectal cancer liver metastases (CRLM), the density of tumor-infiltrating lymphocytes, the expression of class I major histocompatibility complex (MHC-I), and the pathological response to preoperative chemotherapy have been associated with oncological outcomes after complete resection. However, the prognostic significance of the heterogeneity of these features in patients with multiple CRLMs remains under investigation. We used a tissue microarray of 220 mismatch repair-gene proficient CRLMs resected in 97 patients followed prospectively to quantify CD3+ T cells and MHC-I by immunohistochemistry. Histopathological response to preoperative chemotherapy was assessed using standard scoring systems. We tested associations between clinical, immunological, and pathological features with oncologic outcomes. Overall, 29 patients (30.2%) had CRLMs homogeneous for CD3+ T cell infiltration and MHC-I. Patients with immune homogeneous compared to heterogeneous CRLMs had longer median time to recurrence (TTR) (30 vs. 12 months, p = .0018) and disease-specific survival (DSS) (not reached vs. 48 months, p = .0009). At 6 years, 80% of the patients with immune homogeneous CRLMs were still alive. Homogeneity of response to preoperative chemotherapy was seen in 60 (61.9%) and 69 (80.2%) patients according to different grading systems and was not associated with TTR or DSS. CD3 and MHC-I heterogeneity was independent of response to pre-operative chemotherapy and of other clinicopathological variables for their association with oncological outcomes. In patients with multiple CRLMs resected with curative intent, similar adaptive immune features seen across metastases could be more informative than pathological response to pre-operative chemotherapy in predicting oncological outcomes.

Prognostic implications of adaptive immune features in MMR-proficient colorectal liver metastases classified by histopathological growth patterns.

BACKGROUND: After resection, colorectal cancer liver metastases (CRLM) surrounded by a desmoplastic rim carry a better prognosis than the metastases replacing the adjacent liver. However, these histopathological growth patterns (HGPs) are insufficient to guide clinical decision-making. We explored whether the adaptive immune features of HGPs could refine prognostication. METHODS: From 276 metastases resected in 176 patients classified by HGPs, tissue microarrays were used to assess intratumoral T cells (CD3), antigen presentation capacity (MHC class I) and CD73 expression producing immunosuppressive adenosine. We tested correlations between these variables and patient outcomes. RESULTS: The 101 (57.4%) patients with dominant desmoplastic HGP had a median recurrence-free survival (RFS) of 17.1 months compared to 13.3 months in the 75 patients (42.6%) with dominant replacement HGP (p = 0.037). In desmoplastic CRLM, high vs. low CD73 was the only prognostically informative immune parameter and was associated with a median RFS of 12.3 months compared to 26.3, respectively (p = 0.010). Only in dominant replacement CRLM, we found a subgroup (n = 23) with high intratumoral MHC-I expression but poor CD3+ T cell infiltration, a phenotype associated with a short median RFS of 7.9 months. CONCLUSIONS: Combining the assessments of HGP and adaptive immune features in resected CRLM could help identify patients at risk of early recurrence.

Effect of intraoperative hypovolemic phlebotomy on transfusion and clinical outcomes in patients undergoing hepatectomy: a retrospective cohort study.

BACKGROUND: There is no consensus on how to best achieve a low central venous pressure during hepatectomy for the purpose of reducing blood loss and red blood cell (RBC) transfusions. We analyzed the associations between intraoperative hypovolemic phlebotomy (IOHP), transfusions, and postoperative outcomes in cancer patients undergoing hepatectomy. METHODS: Using surgical and transfusion databases of patients who underwent hepatectomy for cancer at one institution (11 January 2011 to 22 June 2017), we retrospectively analyzed associations between IOHP and RBC transfusion on the day of surgery (primary outcome), and with total perioperative transfusions, intraoperative blood loss, and postoperative complications (secondary outcomes). We fitted logistic regression models by inverse probability of treatment weighting to adjust for confounders and reported adjusted odds ratio (aOR). RESULTS: There were 522 instances of IOHP performed during 683 hepatectomies, with a mean (standard deviation) volume of 396 (119) mL. The IOHP patients had a 6.9% transfusion risk on the day of surgery compared with 12.4% in non-IOHP patients (aOR, 0.53; 95% confidence interval [CI], 0.29 to 0.98; P = 0.04). Total perioperative RBC transfusion tended to be lower in IOHP patients compared with non-IOHP patients (14.9% vs 22.4%, respectively; aOR, 0.72; 95% CI, 0.44 to 1.16; P = 0.18). In patients with a predicted risk of ≥ 47.5% perioperative RBC transfusion, 24.6% were transfused when IOHP was used compared with 56.5% without IOHP. The incidence of severe postoperative complications (Clavien-Dindo scores ≥ 3) was similar in patients whether or not IOHP was performed (15% vs 16% respectively; aOR, 0.97; 95% CI, 0.53 to 1.54; P = 0.71). CONCLUSIONS: The use of IOHP during hepatectomy was associated with less RBCs transfused on the same day of surgery. Trials comparing IOHP with other techniques to reduce blood loss and transfusion are needed in liver surgery.

RéSUMé: CONTEXTE: Il n'existe pas de consensus quant à la meilleure façon d'obtenir une pression veineuse centrale basse pendant une hépatectomie dans le but de réduire les pertes et les transfusions sanguines. Nous avons analysé les associations entre la phlébotomie hypovolémique peropératoire, les transfusions, et les résultats cliniques postopératoires chez les patients qui subissent une hépatectomie pour cancer. MéTHODE: À l'aide de bases de données chirurgicales et transfusionnelles de patients ayant subi une hépatectomie pour cancer dans un seul établissement (du 11 janvier 2011 au 22 juin 2017), nous avons rétrospectivement analysé les associations entre la phlébotomie hypovolémique peropératoire et les transfusions érythrocytaires le jour de la chirurgie (critère d'évaluation principal) et avec les transfusions périopératoires totales, les pertes sanguines peropératoires, et les complications postopératoires (critères d'évaluation secondaires). Nous avons utilisé des modèles de régression logistique avec pondération de probabilité inverse de traitement afin de tenir compte des facteurs de confusion et rapporté les rapports de cotes ajustés (RCa). RéSULTATS: Il y a eu 522 phlébotomies hypovolémiques peropératoires exécutées au cours de 683 hépatectomies, avec un volume moyen (écart type) de 396 (119) mL. Les patients ayant eu une phlébotomie hypovolémique peropératoire avaient un risque transfusionnel de 6,9 % le jour de la chirurgie, comparativement à 12,4 % pour les patients sans phlébotomie (RCa, 0,53; intervalle de confiance [IC] de 95 %, 0,29 à 0,98; P = 0,04). Les transfusions périopératoires totales d'érythrocytes tendaient à être moins fréquentes chez les patients ayant subi une phlébotomie hypovolémique peropératoire par rapport aux patients sans phlébotomie (14,9 % vs 22,4 %, respectivement; RCa, 0,72; IC 95 %, 0,44 à 1,16; P = 0,18). Pour les patients présentant un risque prédit de transfusion périopératoire d'érythrocytes ≥ à 47,5 %, 24,6 % de ceux qui ont eu une phlébotomie hypovolémique peropératoire ont été transfusés, comparativement à 56,5 % sans phlébotomie. L'incidence des complications postopératoires graves (scores de Clavien-Dindo ≥ 3) était semblable chez tous les patients, avec ou sans phlébotomie hypovolémique peropératoire (15 % vs 16 % respectivement; RCa, 0,97; IC 95 %, 0,53 à 1,54; P = 0,71). CONCLUSIONS: L'utilisation de la phlébotomie hypovolémique peropératoire pendant une hépatectomie était associée à un moins grand nombre de transfusions érythrocytaires le jour de la chirurgie. Des études qui compareront la phlébotomie hypovolémique peropératoire à d'autres techniques visant à réduire les pertes et les transfusions sanguines sont nécessaires en chirurgie hépatique.

Treatment of mycotic superior mesenteric vein pseudoaneurysm via placement of covered endovascular stent.

Vascular pseudoaneurysms are a rare yet life-threatening complication of untreated pancreatic pseudocysts related to their high risk of rupture and bleeding. Several studies and reports have established endovascular approaches as a successful first-line therapy in the management of arterial pancreatic pseudoaneurysms. However, no reports have been published describing endovascular repair of a venous pseudoaneurysm that developed after infection of a chronically stable pancreatic pseudocyst, most likely due to its rare occurrence. We report in this technical note the treatment of a superior mesenteric vein pseudoaneurysm that developed as a result of an infected small pancreatic pseudocyst, by radiologic placement of a covered endovascular stent.

The Use of Three-Dimensional Printing Model in the Training of Choledochoscopy Techniques.

AIM: To evaluate the application value of a three-dimensional (3D) printing model in the training of choledochoscopy techniques. MATERIALS AND METHODS: Imaging data from two patients with biliary dilatation were used to produce two 3D reconstruction models which were subsequently constructed into 3D printing models (No. 1 and No. 2). Four hepatobiliary surgeons evaluated the anatomical accuracy and academic teaching value of the printed models. Twenty resident trainees with no prior experience in any kind of endoscopic techniques were randomly and symmetrically divided into two groups. The training group (A) used the 3D model No. 1 in the learning of biliary tract anatomy and practice techniques of choledochoscopy. The control group (B) got the virtual 3D image of the same model on computer for learning. After 4 weeks, the model No. 2 was used to reassess the trainees' subjective and objective progress in anatomy familiarity and choledochoscopy manipulations. RESULTS: All consulted surgeons agreed that the 3D models realistically reproduced the anatomy of the biliary system. All trainees in group A agreed or strongly agreed that the 3D models provided good anatomical realism, enhanced their experience in the training of choledochoscopy techniques, and aided in their learning of biliary anatomy. With the practice went on, they increased the accuracy and showed a reduction in operation time on the model No. 1. During final examination with model No. 2, the rate of correct anatomical structure identification in training group was significantly higher than group B (p < 0.05). CONCLUSION: The 3D printed biliary tract model is an excellent teaching tool in the training of choledochoscopy techniques. The 3D model is anatomically realistic and can improve the trainee's anatomical knowledge and endoscopic skills.

Choledochoscopic Examination of a 3-Dimensional Printing Model Using Augmented Reality Techniques: A Preliminary Proof of Concept Study.

BACKGROUND: We applied augmented reality (AR) techniques to flexible choledochoscopy examinations. METHODS: Enhanced computed tomography data of a patient with intrahepatic and extrahepatic biliary duct dilatation were collected to generate a hollow, 3-dimensional (3D) model of the biliary tree by 3D printing. The 3D printed model was placed in an opaque box. An electromagnetic (EM) sensor was internally installed in the choledochoscope instrument channel for tracking its movements through the passages of the 3D printed model, and an AR navigation platform was built using image overlay display. The porta hepatis was used as the reference marker with rigid image registration. The trajectories of the choledochoscope and the EM sensor were observed and recorded using the operator interface of the choledochoscope. RESULTS: Training choledochoscopy was performed on the 3D printed model. The choledochoscope was guided into the left and right hepatic ducts, the right anterior hepatic duct, the bile ducts of segment 8, the hepatic duct in subsegment 8, the right posterior hepatic duct, and the left and the right bile ducts of the caudate lobe. Although stability in tracking was less than ideal, the virtual choledochoscope images and EM sensor tracking were effective for navigation. CONCLUSIONS: AR techniques can be used to assist navigation in choledochoscopy examinations in bile duct models. Further research is needed to determine its benefits in clinical settings.

Augmented reality technology for preoperative planning and intraoperative navigation during hepatobiliary surgery: A review of current methods.

BACKGROUND: Augmented reality (AR) technology is used to reconstruct three-dimensional (3D) images of hepatic and biliary structures from computed tomography and magnetic resonance imaging data, and to superimpose the virtual images onto a view of the surgical field. In liver surgery, these superimposed virtual images help the surgeon to visualize intrahepatic structures and therefore, to operate precisely and to improve clinical outcomes. DATA SOURCES: The keywords "augmented reality", "liver", "laparoscopic" and "hepatectomy" were used for searching publications in the PubMed database. The primary source of literatures was from peer-reviewed journals up to December 2016. Additional articles were identified by manual search of references found in the key articles. RESULTS: In general, AR technology mainly includes 3D reconstruction, display, registration as well as tracking techniques and has recently been adopted gradually for liver surgeries including laparoscopy and laparotomy with video-based AR assisted laparoscopic resection as the main technical application. By applying AR technology, blood vessels and tumor structures in the liver can be displayed during surgery, which permits precise navigation during complex surgical procedures. Liver transformation and registration errors during surgery were the main factors that limit the application of AR technology. CONCLUSIONS: With recent advances, AR technologies have the potential to improve hepatobiliary surgical procedures. However, additional clinical studies will be required to evaluate AR as a tool for reducing postoperative morbidity and mortality and for the improvement of long-term clinical outcomes. Future research is needed in the fusion of multiple imaging modalities, improving biomechanical liver modeling, and enhancing image data processing and tracking technologies to increase the accuracy of current AR methods.

Totally laparoscopic radiofrequency-assisted liver partition with portal vein ligation for hepatocellular carcinoma in cirrhotic liver.

RATIONALE: Adequate future liver remnant (FLR) volume is often a concern for patients with hepatocellular carcinoma (HCC). Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure can rapidly lead to impressive growth of FLR. We describe the technique of an entirely laparoscopic radiofrequency-assisted liver partition with portal vein ligation for staged hepatectomy (RALPP) in a cirrhotic patient with HCC. PATIENT CONCERNS: A 33 year-old female cirrhotic patient with HCC in the right liver was indicated for RALPP as the predicted future liver remnant (FLR) was 21%. DIAGNOSES: HCC with liver cirrhosis. INTERVENTIONS: The first surgery consisted of ligation of the right portal vein and radiofrequency ablation of the liver without parenchymal transection. Three weeks postoperatively, FLR reached 42%, and the patient underwent right hepatectomy. OUTCOMES: Operative times for the both surgeries were 60 and 240 minutes respectively, with negligeable blood loss. The patient had an uneventful postoperative course, and the FLR reached 53% 1 week after the second procedure. No recurrence occurred at 10 months. LESSONS: Laparoscopic RALPP is feasible in some cirrhotic patients with liver cancer that in line with the indications and this method may be a superior choice for selected cirrhotic patients with HCC, as it decreases potential morbidity associated with open surgery.

Impact of peri-operative bevacizumab on survival in patients with resected colorectal liver metastases: an analysis of the LiverMetSurvey.

BACKGROUND: Peri-operative chemotherapy is recommended for the management of colorectal liver metastases (CRLM). The aim of this study was to examine the impact of peri-operative bevacizumab on survival in patients with resected CRLM. METHODS: A multicentre retrospective cohort of patients with resected CRLM was analysed from the LiverMetSurvey Registry. Patients who received peri-operative FOLFOX (group A) were compared with those who received peri-operative FOLFOX and bevacizumab (group B). RESULTS: In total, 501 patients were compared (A, n = 384; B, n = 117). Group A was older (68.3 versus 62.5 years, P < 0.01), had more rectal cancers (30.7 versus 18.8%, P < 0.01) and higher carcinoembryonic antigen (CEA) levels at diagnosis (17.0 versus 9.7 ng/ml, P = 0.043). No difference was observed regarding primary tumour stage, synchronicity and the number or size of metastases. Post-operative infections were more frequent in group B (4.7% versus 12.8%, P < 0.01). Peri-operative bevacizumab had no effect on 3-year overall survival (OS) (76.4% versus 79.8%, P = 0.334), or disease-free survival (DFS) (7.4% versus 7.9%, P = 0.082). DFS was negatively associated with primary tumour node positivity (P = 0.011) and synchronicity (P = 0.041). CONCLUSIONS: The addition of bevacizumab to standard peri-operative chemotherapy does not appear to be associated with improved OS or DFS in patients with resected CRLM.

Polyhemoglobin-superoxide dismutase-catalase-carbonic anhydrase: a novel biotechnology-based blood substitute that transports both oxygen and carbon dioxide and also acts as an antioxidant.

Polyhemoglobin-superoxide dismutase-catalase-carbonic anhydrase (PolyHb-SOD-CAT-CA) is a therapeutic antioxidant that also transports both oxygen and carbon dioxide. This is formed by crosslinking Hb with SOD, CAT, and CA using glutaraldehyde. Crosslinking stroma-free Hb from red blood cell (RBC) reduces CA activity to 55%. Addition of more CA resulted in a preparation with the same CA activity as RBC. PolyHb in the complex acts as a buffer to prevent large pH changes as carbon dioxide is converted to carbonic acid. We then prepare and optimize a novel PolyHb-SOD-CAT-CA, a therapeutic antioxidant that also transports both oxygen and carbon dioxide.

Polyhemoglobin-superoxide dismutase-catalase-carbonic anhydrase: a novel biotechnology-based blood substitute that transports both oxygen and carbon dioxide and also acts as an antioxidant.

Polyhemoglobin-superoxide dismutase-catalase-carbonic anhydrase (PolyHb-SOD-CAT-CA) is a therapeutic antioxidant that also transports both oxygen and carbon dioxide. This is formed by crosslinking Hb with SOD, CAT, and CA using glutaraldehyde. Crosslinking stroma free Hb from red blood cell (rbc) reduces CA activity to 55%. Addition of more CA resulted in a preparation with the same CA activity as RBC. PolyHb in the complex acts as a buffer to prevent large pH changes as carbon dioxide is converted to carbonic acid. We then prepare and optimize a novel PolyHb-SOD-CAT-CA, a therapeutic antioxidant that also transports both oxygen and carbon dioxide.