Simultaneous resection for colorectal cancer with synchronous liver metastases: current state-of-the-art.

BACKGROUND: A large proportion of patients with colorectal cancer (CRC) presents with synchronous colorectal liver metastases (sCRLM) at diagnosis. Surgical approaches for patients with sCRLM have evolved over the past decades. Simultaneous resection (SR) of CRC and sCRLM for selected patients has emerged as a safe and efficient alternative approach to traditional staged resections. METHODS: A comprehensive review of the literature was performed using MEDLINE/PubMed and Web of Science databases with the end of search date October 30, 2023. The MeSH terms "simultaneous resections" and "combined resections" in combination with "colorectal liver metastases," "colorectal cancer," "liver resection," and "hepatectomy" were searched in the title and/or abstract. RESULTS: SRs aim to achieve maximal tumor clearance, minimizing the risk of disease progression and optimizing the potential for long-term survival. Improvements in perioperative care, advances in surgical techniques, and a better understanding of patient selection criteria have collectively contributed to reducing morbidity and mortality associated with these complex procedures. Several studies have demonstrated that SR are associated with reduced overall length of stay and lower costs with comparable morbidity and long-term outcomes. In light of these outcomes, the proportion of patients undergoing SR for CRC and sCRLM has increased substantially over the past 2 decades. CONCLUSION: For patients with sCRLM, SR represents an attractive alternative to the traditional staged approach and should be selectively used; however, the decision on whether to proceed with a simultaneous versus staged approach should be individualized based on several patient- and disease-related factors.

[A Case of Stage â £ Gastric Cancer with Multiple Liver Metastases, Resected Primary Tumor after Chemotherapy, and Alive for 3.5 Years without Recurrence].

A 67-year-old man visited our hospital for epigastric pain. Esophagogastroduodenoscopy(EGD)revealed type 2 gastric cancer from the cardia to the gastric angle, and histopathological examination revealed papillary adenocarcinoma(pap), HER2-positive. Contrast-enhanced CT showed wall thickening mainly in the posterior wall of the gastric body, enlarged lymph nodes that were lumped together with the main lesion, and 8 low-absorption areas with ring shaped contrast effects in both lobes of the liver. The patient was diagnosed as gastric cancer cT4aN(+)M1[HEP], clinical Stage ⅣB. Six courses of capecitabine plus cisplatin plus trastuzumab(XP plus Tmab)therapy and 17 courses of capecitabine plus trastuzumab(X plus Tmab)therapy were performed. After chemotherapy, liver and lymph node metastases disappeared on CT and MRI. EGD showed residual gastric cancer, and the policy was to resect the primary tumor. Laparoscopic total gastrectomy with D2 lymph node dissection was performed. Pathological results showed T1b(SM)depth, no lymph node metastasis, and histologic response was Grade 2a. Six courses of X plus Tmab were administered as postoperative adjuvant chemotherapy, but were discontinued at the patient's request. Currently, 5 years have passed since the first chemotherapy and 3.5 years have passed since the surgery, and the patient is alive without recurrence, suggesting that the conversion surgery may have contributed to the prolonged survival.

[A Case of Solitary Inguinal Lymph Node Metastasis 15 Years after Colorectal Cancer Surgery].

The patient is a 69-year-old man. 17 years ago, a colectomy was performed for colorectal cancer, and a disseminated nodule was found during the operation, so the disseminated nodule was also resected. After the surgery, 12 courses of FOLFOX4 were administered, and there was no recurrence thereafter. He was diagnosed with hepatocellular carcinoma 12 years after the colectomy and underwent liver resection. Fifteen years after the colectomy, a mass shadow appeared in the right inguinal region, and inguinal lymph node metastasis of hepatocellular carcinoma or colorectal cancer was suspected. In the same year, he underwent the tumor resection and histopathological diagnosis revealed colon cancer inguinal lymph node metastasis. After the lymph node resection, he has been followed up for 2 years with no recurrence of colorectal cancer. It is extremely rare to have a solitary inguinal lymph node recurrence 15 years after colon surgery.

[A Case of Distal Gastrectomy and Left Segmentectomy for Hepatic Invasion of Gastric Cancer].

A 66-year-old male came to our hospital because of occult blood in stool and anemia. The patient was diagnosed as unresectable advanced gastric cancer,( ML/Less, type 2, tub2, cT4b[liver], cN+, cM0, cStage Ⅳ, HER2 negative). He was given oxaliplatin plus S-1 therapy. In the 3rd course of chemotherapy, he had severe anemia, and active bleeding from the tumor. To control the bleeding he underwent distal gastrectomy, lateral segmentectomy of the liver, and S4 partial hepatectomy. The patient underwent adjuvant chemotherapy with docetaxel plus S-1. Three months after surgery, lymph nodes recurrence was observed. He underwent second-line therapy with paclitaxel and ramucirumab. Seven months after surgery, lymph nodes recurrence was increased. He was switched to third-line therapy with nivolumab. He is currently arrive 12 months after surgery.

Troponin Elevation in Patients Undergoing Percutaneous Hepatic Perfusion for Metastatic Uveal Melanoma.

BACKGROUND: Percutaneous Hepatic Perfusion (PHP) is a liver directed regional therapy recently FDA approved for metastatic uveal melanoma to the liver involving percutaneous isolation of liver, saturation of the entire liver with high-dose chemotherapy and filtration extracorporeally though in line filters and veno-venous bypass. The procedure is associated with hemodynamic shifts requiring hemodynamic support and blood product resuscitation due to coagulopathy. OBJECTIVE: To assess the cardiac safety and subsequent clinically significant sequalae of this therapy. METHODS: Consecutive PHP procedures done at our center between 2010-2022 were assessed retrospectively. Cardiac risk factors, post procedural cardiac enzymes, electrocardiograms, and transthoracic echocardiograms along with 90-day cardiac outcomes were reviewed. All data were reviewed by cardio-oncologists at our institution. RESULTS: Of 37 patients reviewed, mean age was 63 years and 57% were women. 132 procedures were performed with an average of 3.57 procedures per patient. 68.6% of patients had elevated troponin during at least 1 procedure. No patients were found to have acute coronary syndrome, heart failure, unstable arrhythmias, or cardiac death. No patients had notable echocardiographic changes. 10.8% of patients with positive troponin had asymptomatic transient electrocardiographic changes not meeting criteria for myocardial infarction. One patient had non-sustained ventricular tachycardiac intra-operatively which did not recur subsequently. Three patients died from non-cardiac causes within 90-days. There was no oncology treatment interruption, even in those with troponin elevation. In multivariable analysis, a history of hyperlipidemia was a predictor of postoperative troponin elevation. (P = .042). CONCLUSION: Percutaneous Hepatic Perfusion is safe and associated with a transient, asymptomatic troponin elevation peri-operatively without major adverse cardiac events at 90 days. The observed troponin elevation is likely secondary to coronary demand-supply mismatch related to procedural hemodynamic shifts, hypotension, and anemia.

Percutaneous hepatic perfusion using melphalan in patients with uveal melanoma and liver metastases carries no significant cardiac adverse events.

New treatment alternatives for primary and metastatic colorectal cancer by an integrated transcriptome and network analyses.

Metastatic colorectal cancer (CRC) is still in need of effective treatments. This study applies a holistic approach to propose new targets for treatment of primary and liver metastatic CRC and investigates their therapeutic potential in-vitro. An integrative analysis of primary and metastatic CRC samples was implemented for alternative target and treatment proposals. Integrated microarray samples were grouped based on a co-expression network analysis. Significant gene modules correlated with primary CRC and metastatic phenotypes were identified. Network clustering and pathway enrichments were applied to gene modules to prioritize potential targets, which were shortlisted by independent validation. Finally, drug-target interaction search led to three agents for primary and liver metastatic CRC phenotypes. Hesperadin and BAY-1217389 suppress colony formation over a 14-day period, with Hesperadin showing additional efficacy in reducing cell viability within 48 h. As both candidates target the G2/M phase proteins NEK2 or TTK, we confirmed their anti-proliferative properties by Ki-67 staining. Hesperadinin particular arrested the cell cycle at the G2/M phase. IL-29A treatment reduced migration and invasion capacities of TGF-ß induced metastatic cell lines. In addition, this anti-metastatic treatment attenuated TGF-ß dependent mesenchymal transition. Network analysis suggests IL-29A induces the JAK/STAT pathway in a preventive manner.

Loss of Y in regulatory T lymphocytes in the tumor micro-environment of primary colorectal cancers and liver metastases.

Male sex is a risk factor for colorectal cancer (CRC) with higher illness burden and earlier onset. Thus, we hypothesized that loss of chromosome Y (LOY) in the tumor micro-environment (TME) might be involved in oncogenesis. Previous studies show that LOY in circulating leukocytes of aging men was associated with shorter survival and non-hematological cancer, as well as higher LOY in CD4 + T-lymphocytes in men with prostate cancer vs. controls. However, nothing is known about LOY in leukocytes infiltrating TME and we address this aspect here. We studied frequency and functional effects of LOY in blood, TME and non-tumorous tissue. Regulatory T-lymphocytes (Tregs) in TME had the highest frequency of LOY (22%) in comparison to CD4 + T-lymphocytes and cytotoxic CD8 + T-lymphocytes. LOY score using scRNA-seq was also linked to higher expression of PDCD1, TIGIT and IKZF2 in Tregs. PDCD1 and TIGIT encode immune checkpoint receptors involved in the regulation of Tregs function. Our study sets the direction for further functional research regarding a probable role of LOY in intensifying features related to the suppressive phenotype of Tregs in TME and consequently a possible influence on immunotherapy response in CRC patients.

Incidentally found parotid gland lesion in 18F-FDG PET/CT for staging evaluation of patients with hepatocellular carcinoma: remote possibility of metastatic tumor or second primary salivary gland malignancy.

OBJECTIVES: We primarily aimed to evaluate whether parotid incidental lesion (PIL) in 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for staging evaluation of patients with hepatocellular carcinoma (HCC) would represent a possibility of extrahepatic metastasis or second primary malignancy (SPM). Additionally, we explored the incidence of PIL in HCC patients and examined any associated risk factors. METHODS: We retrospectively analyzed patients with HCC who underwent 18F-FDG PET/CT at our institution from 2010 to 2022. The pathological findings of PILs in HCC patients were investigated for confirmatory identification of the risk of HCC metastasis or SPM in parotid gland. Healthy controls received 18F-FDG PET/CT for health screening were also enrolled to compare the incidence of PILs with HCC patients. Various parameters associated with patient demographics and characteristics of HCC were analyzed to find the related factors of PILs. RESULTS: A total of 17,674 patients with HCC and 2,090 healthy individuals who had undergone 18F-FDG PET/CT scans were enrolled in the analyses. Among the 54 HCC patients who underwent pathological confirmation for PILs, benign primary parotid tumor was most commonly observed (n = 43 [79.6%]); however, no malignant lesions were detected, including HCC metastasis. The incidence of PILs was higher in patients diagnosed with HCC compared with the control group (485 [2.7%] vs. 23 [1.1%], p = 0.002). Analysis for the risk factors for PILs revealed that patient age, sex, and positive viral markers were significantly associated with the incidence of PILs in patients with HCC (all p < 0.001). CONCLUSIONS: Our study demonstrates that PILs are more frequently identified in patients with HCC on 18F-FDG PET/CT. However, no malignant PIL, including extrahepatic metastasis of HCC, was identified. Therefore, the presence of PIL should not impede or delay the treatment process for patients with HCC. Additionally, we suggested that for future swift and straightforward differential diagnoses of PIL, the development of additional protocols within the PET/CT imaging could be beneficial.

[Pelvic radiotherapy strategy for rectal cancer with hepatic metastasis].

Hepatic metastasis is the most common in rectal cancer, and patients with resectable hepatic metastasis have better survival. Pelvic radiotherapy has become a key component of multidisciplinary management of rectal cancer with hepatic metastasis. For patients with unresectable hepatic metastasis, palliative radiotherapy to the primary lesion can reduce the risk of bleeding and obstruction and thus improve the quality of life. For patients with resectable hepatic metastasis, pelvic radiotherapy can effectively reduce the local recurrence rate, help some patients avoid surgery and improve their quality of life, and even improve the overall survival. At present, there is no consensus on the standardized treatment mode of pelvic radiotherapy for rectal cancer patients with hepatic metastasis, and it has become a hotspot for research on how to select the population benefiting from radiotherapy, how to optimize multidisciplinary collaboration and radiotherapy plans (long-course radiotherapy versus short-course radiotherapy) and how to preserve organs. This article reviews the research progress in pelvic radiotherapy for rectal cancer with hepatic metastasis in recent years, and provides ideas for individualized pelvic radiotherapy for rectal cancer with hepatic metastasis.

Renin-Angiotensin Inhibitor, Captopril, Attenuates Growth of Patient-Derived Colorectal Liver Metastasis Organoids.

The recurrence of colorectal liver metastasis (CRLM) following liver resection is common; approximately 40% of patients will experience tumor recurrence post-surgery. Renin-angiotensin inhibitors (RASis) have been shown to attenuate the growth and progression of CRLM in pre-clinical models following liver resection. This study examined the efficacy of the RASi captopril on patient-derived colorectal liver metastasis organoids. Patient-derived organoids (PDOs) were established using fresh samples of colorectal liver metastasis from appropriately consented patients undergoing liver resection. To mimic the regenerating liver post-CRLM liver resection, PDOs were cultured under hepatocyte regeneration conditions in vitro. CRLM PDOs were established from three patients' parent tissue. CRLM PDOs and parent tissue expressed markers of colorectal cancer, CDX2 and CK20, consistently. Furthermore, CRLM PDOs treated with captopril showed a dose dependent reduction in their expansion in vitro. In conclusion, CRLM PDOs recapitulate in vivo disease and displayed a dose-dependent response to treatment with captopril. RASis may be an additional viable treatment for patients with CRLM.

Size selection of intrahepatic lesions for cryoablation contributes to abscopal effect and long-term survival in patients with liver metastatic melanoma receiving PD-1 blockade therapy.

OBJECTIVES: In this study, we aimed to examine parameters of cryoablation, tumor characteristics, and their correlations with distant tumor response and survival of liver metastatic melanoma patients receiving cryoablation and PD-1 blockade (cryo-PD-1) combination treatment. MATERIALS AND METHODS: A retrospective study was conducted among 45 melanoma patients who received combined PD-1 blockade therapy and cryoablation for liver metastasis from 2018 to 2022. Cox regression was utilized to determine the associations between factors and overall survival (OS). Changes in cytokines and immune cell compositions in peripheral blood samples following the combined treatment were investigated, along with their correlations with treatment response. RESULTS: The mean cycle of cryo-PD-1 combination treatment was 2.2 (range, 1-6), and the 3-month overall response rate (RECIST 1.1 criteria) was 26.7%. Of the 21 patients who failed previous PD-1 blockade therapy after diagnosis of liver metastasis, 4 (19.0%) achieved response within 3 months since combination treatment. The diameter of ablated lesion ≤ 30 mm, metastatic organs ≤ 2, and pre-treatment LDH level ≤ 300 U/L were independent prognostic factors for favorable OS. Further analysis showed patients with intrahepatic tumor size of 15-45 mm, and ablated lesion size of ≤ 30 mm had significantly higher 3-month response rate (42.9% vs 12.5%; P = 0.022) and survival time (30.5 vs 14.2 months; P = 0.045) than their counterparts. The average increase in NLR among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 3.59 ± 5.01 and 7.21 ± 12.57, respectively. The average increase in serum IL-6 levels among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 8.62 ± 7.95 pg/ml and 15.40 ± 11.43 pg/ml, respectively. CONCLUSION: Size selection of intrahepatic lesions for cryoablation is important in order to achieve abscopal effect and long-term survival among patients with liver metastatic melanoma receiving PD-1 blockade therapy.

Colorectal metastases with intrabiliary growth: incidence, treatment, and outcomes.

Intrabiliary growth (IG) is an unusual modality for colorectal metastases to spread. Relatively little is known about this condition because large series are lacking. The aim of the study was to compare the surgical and oncological outcomes of patients with or without IG. From 01/2010 to 12/2020, 999 patients underwent hepatectomy for colorectal metastases. Clinicopathological variables were retrospectively analyzed from a prospective-collected database of patients with or without IG. A propensity score matched (PSM) analysis to compare OS and DFS was performed. At first hepatectomy, 29 patients (2.9%) had IG: 7 isolated IG and 22 mixed-type (mass-forming lesion with IG). 4 patients presented IG at repeat hepatectomy for recurrence, of whom 3 had no biliary invasion at initial surgery. IG resulted to be more common in older patients (median age 70 in IG vs 60 years of no-IG, p = 0.004). Mean time from colorectal tumor was longer in IG (20.4 months) than no-IG (12.9 months), p = 0.038. Major hepatectomies (55.2% IG vs 29.7% no-IG, p = 0.003) and anatomic resections (89.7% vs 58.2%, p = 0.001) were more frequently required to treat IG. In 5 (17%) of IG, a resection of main bile duct was performed. Overall postoperative mortality and complications were similar in the two groups, while bile leak was 17.2% IG vs 5.6% no-IG (p = 0.024). Median margin width was comparable in IG (1.4 mm) and no-IG (2 mm). Five-year overall survival (IG 45.9% vs no-IG 44.5%) and Disease-Free Survival (IG 35.9% vs no-IG 36.6%) were similar in the two groups. According to PSM, 145 patients with no-IG were compared to 29 of IG group. After PSM, OS and DFS did not show any statistically significant difference. IG has similar oncological outcomes of resected colorectal metastases without IG, although it affects surgical management.

Evolving survival gains in patients with young-onset colorectal cancer and synchronous resectable liver metastases.

We aimed to evaluate the practice and the associated outcomes of surgical treatment for young-onset colorectal cancer (YOCRC) patients presenting with synchronous liver metastases. The study cohort was divided into two groups according to surgery date: 131 patients in the early era (EE, 1998-2011) and 179 in the contemporary era (CE, 2012-2020). The CE had a higher rate of node-positive primary tumors, higher carcinoembryonic antigen level, and lower rate of RAS/BRAF mutations. The CE had higher rates of reverse or combined resection, multi-drug prehepatectomy chemotherapy, and two-stage hepatectomy. The median survival was 8.4 years in the CE and 4.3 years in the EE (p = 0.011). On multivariate analysis, hepatectomy in the CE was independently associated with improved overall survival (HR 0.48, p = 0.001). With a combination of perioperative systemic therapy, careful selection of treatment approach, and coordinated resections, durable cure can be achieved in YOCRC patients.

Influence of cancer-directed surgery on the prognosis of liver metastases from gastric cancer

There are controversial about the application of cancer-directed surgery (CDS) in patients with liver metastases from gastric cancer, with improved responses to chemotherapy and targeted treatments, the role of CDS in metastatic gastric cancer to the liver needs to be revisited. This study aimed to evaluate the effect of CDS on patients with liver metastases from gastric cancer. Data for patients with liver metastases from gastric cancer were extracted from the population-based Surveillance, Epidemiology, and End Results (SEER) database. A total of 958 individuals were enrolled, 285 in the CDS group and 673 in the non-cancer guided surgery (Non-CDS) group. Following propensity score matching (PSM) analysis at 1:1 in the two groups,285 were included in the survival analysis for each group. Kaplan–Meier values and Cox proportional risk models were used to estimate the effect of CDS on patients' prognoses. Compared with the Non-CDS group, the CDS group significantly prolonged the median overall survival from 4 months (95% confidence interval [CI] 3–5) to 11 months (95% CI 8–12), p value < 0.001. Overall survival (OS) at 1 year was higher in the CDS group than in the Non-CDS group, at 44% (95 CI 38–50) and 25% (95 CI 20–30), respectively. OS at 3 years was also higher in the CDS group than in the Non-CDS group, at 24% (95 CI 19–29) and 6% (95 CI 3–9), respectively. Multivariate analysis showed that Non-CDS (hazard ratio[HR] = 2.26, 95% CI 1.88–2.72, p value < 0.001) was an adverse independent prognostic factor for patients (AU)

Laparoscopic Caudate Resection: How to Safely Manage the Spiegel/IVC Interface.

BACKGROUND: Minimally invasive caudate lobectomy, or even paracaval caudate resection, can be associated with significant bleeding due to its abutment of inferior vena cava (IVC), portal pedicle and hepatic veins.1-3 This risk can be magnified by cirrhosis as well as response to neoadjuvant therapy (a common phenomenon after excellent response to neoadjuvant chemotherapy), leading to obliteration or even fusion of the hepato-caval space.4-7 PATIENT: A 68-year-old female with stage IVa colorectal adenocarcinoma was found to have a single liver metastasis (3.8 × 3.1 cm) in the paracaval caudate lobe. The patient received four cycles of neoadjuvant chemotherapy, leading to inflammatory fusion of the hepato-caval space. Despite this, the patient underwent a safe laparoscopic Spiegel process resection. TECHNIQUE: Prior to surgery, three-dimensional liver and port site modeling was performed to optimize the understanding of the spatial relationship between the tumor, IVC, and portal-hepatic veins. Following inflow control of portal veinous branches, the fused hepato-caval space was dissected. The adhesions were then sharply dissected to mobilize the paracaval caudate lobe off the IVC. Using scissors rather than an energy device reduced the risk of inadvertent thermal injury to the IVC. CONCLUSION: Preoperative virtual hepatectomy facilitates surgical planning, increasing the understanding of the tumor/vessel relationship and port placement. In case of a fused hepato-caval space, low central venous pressure and judicious management of short hepatic vein branches are the key for a successful dissection. Moreover, anticipation of a fused hepato-caval space and its strategic management are paramount when performing a minimally invasive caudate resection.

Prediction of transformation in the histopathological growth pattern of colorectal liver metastases after chemotherapy using CT-based radiomics.

Chemotherapy alters the prognostic biomarker histopathological growth pattern (HGP) phenotype in colorectal liver metastases (CRLMs) patients. We aimed to develop a CT-based radiomics model to predict the transformation of the HGP phenotype after chemotherapy. This study included 181 patients with 298 CRLMs who underwent preoperative contrast-enhanced CT followed by partial hepatectomy between January 2007 and July 2022 at two institutions. HGPs were categorized as pure desmoplastic HGP (pdHGP) or non-pdHGP. The samples were allocated to training, internal validation, and external validation cohorts comprising 153, 65, and 29 CRLMs, respectively. Radiomics analysis was performed on pre-enhanced, arterial phase, portal venous phase (PVP), and fused images. The model was used to predict prechemotherapy HGPs in 112 CRLMs, and HGP transformation was analysed by comparing these findings with postchemotherapy HGPs determined pathologically. The prevalence of pdHGP was 19.8% (23/116) and 45.8% (70/153) in chemonaïve and postchemotherapy patients, respectively (P < 0.001). The PVP radiomics signature showed good performance in distinguishing pdHGP from non-pdHGPs (AUCs of 0.906, 0.877, and 0.805 in the training, internal validation, and external validation cohorts, respectively). The prevalence of prechemotherapy pdHGP predicted by the radiomics model was 33.0% (37/112), and the prevalence of postchemotherapy pdHGP according to the pathological analysis was 47.3% (53/112; P = 0.029). The transformation of HGP was bidirectional, with 15.2% (17/112) of CRLMs transforming from prechemotherapy pdHGP to postchemotherapy non-pdHGP and 30.4% (34/112) transforming from prechemotherapy non-pdHGP to postchemotherapy pdHGP (P = 0.005). CT-based radiomics method can be used to effectively predict the HGP transformation in chemotherapy-treated CRLM patients, thereby providing a basis for treatment decisions.

Prediction of liver metastasis and recommended optimal follow-up nursing in rectal cancer.

We aimed to analyze and investigate the clinical factors that influence the occurrence of liver metastasis in locally advanced rectal cancer patients, with an attempt to assist patients in devising the optimal imaging-based follow-up nursing. Between June 2011 and May 2021, patients with rectal cancer at our hospital were retrospectively analyzed. A random survival forest model was developed to predict the probability of liver metastasis and provide a practical risk-based approach to surveillance. The results indicated that age, perineural invasion, and tumor deposit were significant factors associated with the liver metastasis and survival. The liver metastasis risk of the low-risk group was higher at 6-21 months, with a peak occurrence time in the 15th month. The liver metastasis risk of the high-risk group was higher at 0-24 months, with a peak occurrence time in the 8th month. In general, our clinical model could predict liver metastasis in rectal cancer patients. It provides a visualization tool that can aid physicians and nurses in making clinical decisions, by detecting the probability of liver metastasis.