Chronic inflammation is an aberrantly prolonged form of a protective response to a loss of tissue homeostasis and it is involved in several steps of the carcinogenesis process. As a result, many ...cancers are inflammation-related. The systemic inflammatory response is associated with survival in advanced and localized cancers. Two categories of scores have been proposed to monitor the systemic inflammatory response, those derived from protein measurement and those based on counting inflammatory cells. This review aims to provide a critical appraisal of these 2 categories of surrogate markers. The 3 scale modified Glasgow prognostic score (mGPS) is based on the combination of C-reactive protein and albumin and is graded 0 to 2. It has been validated worldwide showing an independent prognostic value in patients with cancer in a variety of tumour types and tumour stages. Leukocytes-based scores are mainly neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR). Elevated NLR and/or PLR and lower LMR seem to be associated with decreased survival, but the studies about these markers are very heterogeneous. The main limit is the variety of thresholds used to dichotomize patients, so that reproducibility and reliability of leukocytes-based scores can be questioned. Hence, there is no sufficient evidence to support their use in clinical practice. Comprehensive management of patients with operable and advanced cancer should integrate the host systemic inflammatory response by calculating the mGPS. It could be a helpful tool to tailor patients' management.
Abstract
Background
Understanding the changes occurring in biological tissue during thermal ablation is at the heart of many current challenges in both therapy and medical imaging research.
Purpose
...The objective of this work is to quantitatively interpret the scattering response of human liver samples, before and after thermal ablation. We report acoustic measurements performed involving
n
= 21 human liver samples. Thermal ablation is achieved at temperatures between 45 and 80°C and quantification of the irreversible changes in acoustic attenuation and Backscattering Coefficient (BSC) is reported, with a particular attention to the latter.
Methods
Both attenuation coefficient and BSCs were measured in the frequency range from 10 to 52 MHz. Scans were performed before heating and after cooling down. Attenuation coefficients were calculated using spectral difference method and BSC estimated using the reference phantom method.
Results
Strong increases of attenuation coefficients and BSCs with heating temperature were observed. Quantitative ultrasonic parameters obtained with the polydisperse structure factor model (poly‐SFM)are compared to histological observations and seen to be close to hepatocyte mean diameter (HMD).
Conclusions
The results presented in this study provide a description of the impact of thermal ablation in human liver tissue on acoustic attenuation and the BSC. For the first time, quantitative agreement between the Effective Scatterer Diameter (ESD) estimated from BSC and HMD was shown, highlighting the important role of cellular network in the scattering response of the medium. This core result is an important step toward the determination of the nature of scattering sources in biological tissues.
A toroidal high-intensity focused ultrasound (HIFU) transducer was used to non-invasively treat liver tissues in vivo in a pig model. The transducer was divided into 32 concentric rings with equal ...surface areas operating at 2.5 MHz. First, attenuation of skin, fat, muscle and liver tissues was measured in fresh animal samples to adjust the energy delivered to the focal zone. Then, 8 animals were included in the present protocol and placed in a dorsal decubitus proclive position at an angle of 15°. The device was held by hand, and sonications were performed during apnea. Two thermal HIFU lesions were created in 40 s in each animal. The average abdominal wall thickness was 14.8 ± 1.3 mm (12.5-17.6 mm). The longest and shortest axes of the HIFU ablations were 20.9 ± 6.3 mm (14.0-33.7 mm) and 14.2 ± 5.5 mm (7.0-22.0 mm), respectively. All HIFU lesions were visible on sonograms. The correlation between the dimensions of the HIFU lesions observed on sonograms and those obtained during gross examination was r = 0.84. Creating large and fast ablations with reliable ultrasound imaging guidance in the liver using this handheld device may represent a new therapeutic option for patients with liver tumors.
Minimally invasive resection of segment VIII is a technically challenging procedure, made even more challenging when the resection is extended to segment IV and/or segment VII. Parenchymal-sparing ...resections are frequently used in the management of liver metastases but expose to the risk of R1 resection, especially with a minimally invasive approach. Preoperative surgical planning with 3D reconstruction and intraoperative guidance with hepatic vein is helpful for laparoscopic oncological liver resection.1-3 PATIENT AND METHODS: We present the case of a 58-year-old female with three metachronous liver metastases from epidermoid anal cancer. The disease was stable 6 months after cessation of chemotherapy. Metastases were mainly located in segment VIII (with a large segment VIII dorsal) but also in the territory of glissonian pedicles from segments IV and VII. Prior to surgery, three-dimensional (3D) reconstruction showed that a segmentectomy VIII would not be sufficient to have a safety margin and showed the relation between metastases and hepatic veins. Transection of the liver was performed with an ultrasonic dissector. Exposure of the hepatic veins was performed by gently pulling of the hepatic tissue from the vein, using the nonactive blade of the ultrasonic device. Activation of ultrasonic energy was performed only for sealing and dividing small collateral veins. Three transection lines were necessary. The posterior transection line, in segment VII, was determined with intraoperative ultrasound (IOUS), at 1 cm below the metastasis. The liver was transected superficially only. The medial transection line, in segment IV, was determined with IOUS, at 1 cm on the left of the metastasis, parallel to the middle hepatic vein. Finally, the inferior transection line, between segment V and segment VIII, was approximately determined with IOUS, vertically aligned with the hepatic vein of segment V. The transection line was further corrected after clamping the glissonian pedicle of segment VIII, according to fluorescence. The surgical procedure began with the mobilization of the right liver, including division of the hepato-caval ligament, followed by the superficial transection of the posterior margin in segment VII. Then, transection of segment IV was performed near the termination of the middle hepatic vein, which was further exposed with a cranio-caudal approach to minimize the risk of vein injury. The hepatic vein of segment V was then used as a landmark for the identification of the Glissonian pedicle of segment VIII, which was transected.4 Termination of the right hepatic vein (RHV) was then identified, and the ventral branch of the RHV was transected. The dorsal branch of the RHV was exposed with a cranio-caudal approach. Finally, transection of segment VII was performed toward the transection line made initially.INTRODUCTIONMinimally invasive resection of segment VIII is a technically challenging procedure, made even more challenging when the resection is extended to segment IV and/or segment VII. Parenchymal-sparing resections are frequently used in the management of liver metastases but expose to the risk of R1 resection, especially with a minimally invasive approach. Preoperative surgical planning with 3D reconstruction and intraoperative guidance with hepatic vein is helpful for laparoscopic oncological liver resection.1-3 PATIENT AND METHODS: We present the case of a 58-year-old female with three metachronous liver metastases from epidermoid anal cancer. The disease was stable 6 months after cessation of chemotherapy. Metastases were mainly located in segment VIII (with a large segment VIII dorsal) but also in the territory of glissonian pedicles from segments IV and VII. Prior to surgery, three-dimensional (3D) reconstruction showed that a segmentectomy VIII would not be sufficient to have a safety margin and showed the relation between metastases and hepatic veins. Transection of the liver was performed with an ultrasonic dissector. Exposure of the hepatic veins was performed by gently pulling of the hepatic tissue from the vein, using the nonactive blade of the ultrasonic device. Activation of ultrasonic energy was performed only for sealing and dividing small collateral veins. Three transection lines were necessary. The posterior transection line, in segment VII, was determined with intraoperative ultrasound (IOUS), at 1 cm below the metastasis. The liver was transected superficially only. The medial transection line, in segment IV, was determined with IOUS, at 1 cm on the left of the metastasis, parallel to the middle hepatic vein. Finally, the inferior transection line, between segment V and segment VIII, was approximately determined with IOUS, vertically aligned with the hepatic vein of segment V. The transection line was further corrected after clamping the glissonian pedicle of segment VIII, according to fluorescence. The surgical procedure began with the mobilization of the right liver, including division of the hepato-caval ligament, followed by the superficial transection of the posterior margin in segment VII. Then, transection of segment IV was performed near the termination of the middle hepatic vein, which was further exposed with a cranio-caudal approach to minimize the risk of vein injury. The hepatic vein of segment V was then used as a landmark for the identification of the Glissonian pedicle of segment VIII, which was transected.4 Termination of the right hepatic vein (RHV) was then identified, and the ventral branch of the RHV was transected. The dorsal branch of the RHV was exposed with a cranio-caudal approach. Finally, transection of segment VII was performed toward the transection line made initially.Operative time was 360 min with 450 mL blood loss. The Pringle maneuver was used during 148 min. The patient was discharged on the seventh postoperative day. Pathological examination confirmed R0 resection, with 20-60% necrosis of the three liver metastases. The resected liver weight was 225 g. Six months after liver resection, the patient had a recurrence in a celiac lymph node, which was treated by radiotherapy. Fifteen months after liver resection, the patient is free of disease without active treatment.RESULTSOperative time was 360 min with 450 mL blood loss. The Pringle maneuver was used during 148 min. The patient was discharged on the seventh postoperative day. Pathological examination confirmed R0 resection, with 20-60% necrosis of the three liver metastases. The resected liver weight was 225 g. Six months after liver resection, the patient had a recurrence in a celiac lymph node, which was treated by radiotherapy. Fifteen months after liver resection, the patient is free of disease without active treatment.Preoperative virtual hepatectomy facilitates surgical planning by increasing the understanding of the tumors-vessels relationship. Intraoperative hepatic vein guidance with a cranio-caudal approach enables to follow preoperative surgical planning and to perform safe complex laparoscopic liver resection.CONCLUSIONPreoperative virtual hepatectomy facilitates surgical planning by increasing the understanding of the tumors-vessels relationship. Intraoperative hepatic vein guidance with a cranio-caudal approach enables to follow preoperative surgical planning and to perform safe complex laparoscopic liver resection.
This document is a summary of the French intergroup guidelines regarding the management of metastatic colorectal cancer (mCRC) published in January 2019, and available on the French Society of ...Gastroenterology website (SNFGE) (www.tncd.org).
This collaborative work was realized by all French medical and surgical societies involved in the management of mCRC. Recommendations are graded in three categories (A, B and C), according to the level of evidence found in the literature, up until December 2018.
The management of metastatic colorectal cancer has become complex because of increasing available medical, radiological and surgical treatments alone or in combination. The therapeutic strategy should be defined before the first-line treatment, mostly depending on the presentation of the disease (resectability of the metastases, symptomatic and/or threatening disease), of the patient’s condition (ECOG PS, comorbidities), and tumor biology (RAS, BRAF, MSI). The sequence of targeted therapies also seems to have an impact on the outcome (angiogenesis inhibition beyond progression). Surgical resection of metastases was the only curative intent treatment to date, joined recently by percutaneous tumor ablation tools (radiofrequency, microwave). Localized therapies such as hepatic intra-arterial infusion, radioembolization and hyperthermic intraperitoneal chemotherapy, also have seen their indications specified (liver-dominant disease and resectable peritoneal carcinomatosis). New treatments have been developed in heavily pretreated patients, increasing overall survival and preserving quality of life (regorafenib and trifluridine/tipiracil). Finally, immune checkpoint inhibitors have demonstrated high efficacy in MSI mCRC.
French guidelines for mCRC management are put together to help offer the best personalized therapeutic strategy in daily clinical practice, as the mCRC therapeutic landscape is complexifying. These recommendations are permanently being reviewed and updated. Each individual case must be discussed within a multidisciplinary team (MDT).
Data regarding clinical outcomes of patients undergoing hepatic resection for BRAF-mutated colorectal liver metastases (CRLM) are scarce. Most of the studies report an impaired median overall ...survival (OS) in BRAF-mutated patients, but controversial Results regarding both recurrence-free survival (RFS) and recurrence patterns. The purpose of this updated meta-analysis was to better precise the impact of BRAF mutations on clinical outcomes following liver surgery for CRLM study, especially on recurrence.
A systematic literature review was performed to identify articles reporting clinical outcomes including both OS and RFS, recurrence patterns, and clinicopathological details of patients who underwent complete liver resection for CRLM, stratified according to BRAF mutational status.
Thirteen retrospective studies, including 5192 patients, met the inclusion criteria. The analysis revealed that both OS (OR = 1.981; 95% CI = 1.613–2.432) and RFS (OR = 1.49; 95% CI 1.01–2.21) were impaired following liver surgery for CRLM in BRAF-mutated patients. Risks of both hepatic (OR = 0.42; 95% CI 0.18–0.98) and extrahepatic recurrences (OR = 0.53; 95% CI 0.33–0.83 were significantly higher in BRAF-mutated patients. These patients tended to have higher rates of right-sided colon primary tumors, primary positive lymph nodes, and multiple CRLM.
This meta-analysis confirms that BRAF mutations impair both OS and RFS following liver surgery. Therefore, BRAF mutational status should probably be included in further prognostic scores for the assessment of the expected clinical outcomes following surgery for CRLM.
For tumors involving inferior vena cava (IVC), surgery with complete resection remains the first line treatment. Management of IVC after resection, either ligation without reconstruction or primary ...reconstruction, is debated. Our study aimed to evaluate type of venous reconstruction, anticoagulation management and morbidity.
A French single center database of patients who underwent partial or total circumferencial resection of the IVC for malignant disease was analyzed. Inclusion criteria were any oncologic procedure for a retroperitoneal neoplasm requiring concomitant resection of the IVC with or without venous reconstruction with prosthesis. Exclusion criteria were surgery before year 2000. Data were descriptive and reverse Kaplan Meier was used for follow-up calculation. The endpoints were the rate of prosthetic reconstruction, the use of anticoagulation and the post-operative outcomes.
Fifty – one patients were included with a median duration of follow-up of 54.8 months. The majority of patients were men (56.9%). Median age of the population was 44.1 years. Most of the patients underwent surgery for primary testicular cancer and for sarcoma. Complete IVC resections were performed in 46 (90,2%) patients, 32 having a concomitant prosthetic replacement. Eight patients underwent aortic resection in the same operative time. Postoperative morbidity was 33.3%. Post-operative anticoagulation was done in 24 patients. At 1 month, four patients developed thrombosis in the prosthesis.
IVC resections are feasible and safe. Venous reconstruction and postoperative management were planned according to the preoperative imaging and intraoperative findings. We propose a decision-tree for peri-operative management and anticoagulation.
Purpose
Pelvic exenteration remains the only curative treatment for advanced pelvic malignancies. However, identification of predictive factors for successful surgical outcomes is still a ...controversial issue at present time.
Methods
This retrospective study included data from all adult patients with colorectal or anal advanced pelvic malignancy registered for pelvic exenteration at the Leon Berard Cancer Center (Lyon, France). The primary endpoint was the surgical outcomes and aimed to define the predictive factors for postoperative complications. Secondary endpoints included overall survival and progression free survival in patients having experienced pelvic exenteration (PE).
Results
Data from 141 patients with locally advanced tumor (
N
= 81) or recurrent malignancies (
N
= 60) diagnosed between May 1994 and November 2018 were collected. The median age was 63.3 years (95%CI 20.0–92.0). Malignancies included different locations (rectal: 69.5%, left colon: 17.0% and anal: 13.5%). Posterior pelvectomy was the most frequent surgery (81.6%). The median length of hospital stay was 23.3 days (95%CI 3.0–82.0). The major complication rate at 30 days was 24.8% and 38.1% at 90 days. The median overall survival was 54.5 months (95%CI 41.5–104.1) and the median PFS was 34.5 months (95%CI 19.6-NA).
Conclusion
In selected patients, pelvic exenteration is associated with good surgical and survival outcomes.
Apart from palliative chemotherapy, no other therapy has been proven effective for the treatment of locally advanced pancreatic tumors. In this study, an intraoperative high-intensity focused ...ultrasound (HIFU) device was tested in vivo to demonstrate the feasibility of treating the pancreatic parenchyma and tissues surrounding the superior mesenteric vessels prior to clinical translation of this technique. Twenty pigs were included and treated using a HIFU device equipped with a toroidal transducer and an integrated ultrasound imaging probe. Treatments were performed with energy escalation (from 30 kJ to 52 kJ). All treatments resulted in visible (macroscopically and in ultrasound images) homogeneous thermal damage, which was confirmed by histology. The dimensions of thermal lesions measured in ultrasound images and those measured macroscopically were correlated (r = 0.82,
< 0.05). No arterial spasms or occlusion were observed at the lowest energy setting. Temporary spasm of the peripancreatic artery was observed when using an energy setting greater than 30 kJ. The possibility of treating the pancreas and tissues around mesenteric vessels without vascular thrombosis holds great promise for the treatment of locally advanced pancreatic cancers. If clinically successful, chemotherapy followed by HIFU treatment could rapidly become a novel treatment option for locally advanced pancreatic cancer.
PDF