A Systematic Review of Clinical Response and Survival Outcomes of Downsizing Systemic Chemotherapy and Rescue Liver Surgery in Patients with Initially Unresectable Colorectal Liver Metastases

Background  

Selected patients with unresectable colorectal liver metastases (CLM) may be rendered resectable after systemic chemotherapy. We reviewed the evidence of downsizing systemic chemotherapy followed by rescue liver surgery in patients with initially unresectable CLM.     

The Utility of PET/CT in the Management of Patients With Colorectal Liver Metastases Undergoing Laparascopic Radiofrequency Thermal Ablation

Background  

There are scant data in the literature about the use of PET in the management of patients undergoing RFA of colorectal liver metastases (CLM). The aim of this study is to look at the use of PET versus contrast-enhanced CT (ce CT) scans on the initial assessment and follow-up of patients with CLM undergoing laparoscopic RFA.     

Liver Resection of Colorectal Liver Metastases in Elderly Patients

Background  

The percentage of elderly patients with colorectal liver metastases (CLM) has increased. Liver resection remains the only curative therapy; data evaluating the outcome in this age group is limited. Aim of the present study was to determine if postoperative morbidity, mortality, and other independent predictors influence survival in patients ≥70 years undergoing liver resection for CLM.     

Anatomical versus nonanatomical resection of colorectal liver metastases: is there a difference in surgical and oncological outcome?

Background  

The increased use of neoadjuvant chemotherapy and minimally invasive therapies for recurrence in patients with colorectal liver metastases (CLM) makes a surgical strategy to save as much liver volume as possible pivotal. In this study, we determined the difference in morbidity and mortality and the patterns of recurrence and survival in patients with CLM treated with anatomical (AR) and nonanatomical liver resection (NAR).     

Two Decades of Experience with Hepatic Cryotherapy for Advanced Colorectal Metastases

Introduction  

Only 15% of patients with colorectal liver metastases (CLM) are candidates for curative hepatectomy at time of diagnosis, limited by anatomical location and tumor burden. Ablative therapies may extend this. This study reports a single institution’s long-term experience with hepatic cryotherapy for advanced CLM.     

Resection of Colorectal Liver Metastases

Introduction  

The gold-standard treatment for colorectal liver metastases (CLM) is liver resection. Advances in staging, surgical technique, perioperative care and systemic chemotherapy have contributed to steady improvement in oncologic outcomes for patients following surgery in this subset of patients with stage IV colorectal cancer. The limits of resection continue to expand to include patients with more, larger and bilateral CLM, yet outcomes continue to improve with 5-year overall survival exceeding 50% following resection. Chemotherapy is an important element of treatment for patients with CLM, and chemotherapy can be combined safely with surgery to improve outcomes further.     

Histological and Immediate Postoperative Outcome after Preoperative Cetuximab: Case-Matched Control Study

Background  

The aim of this study was to analyze the effects of preoperative cetuximab (cetu) on nontumorous liver parenchyma and the clinical and biological outcomes after liver resection for colorectal liver metastases (CLM).     

Impact of Biomarkers Expression Before and After Portal Vein Embolization on Recurrence After Two-Stage Hepatectomy for Colorectal Liver Metastases

Background  

The adverse oncological effect of portal vein embolization (PVE) in patients with colorectal liver metastases (CLM) remains controversial. This study was designed to evaluate the effect of PVE on change of tumor characteristics using tumor specimens obtained from sequential hepatectomy before and after PVE.     

Preoperative evaluation of the depth of anal canal invasion in very low rectal cancer by magnetic resonance imaging and surgical indications for intersphincteric resection

Purpose  

The present study was performed to evaluate the depth of anal canal invasion (DACI), and determine whether magnetic resonance imaging (MRI) assessment of the conjoined longitudinal muscle (CLM) can be used to identify the surgical indication for intersphincteric resection.     

Eradication of Missing Liver Metastases After Fiducial Placement

Background

The risk of colorectal liver metastases (CLM) disappearing on cross-sectional imaging has increased with advances in preoperative chemotherapy, but <50 % of disappearing CLM demonstrate complete pathological response.

Objective

The aim of this study was to evaluate the role of fiducial marker placement before potentially curative treatment of CLM at risk of disappearing with chemotherapy.

Methods

All consecutive patients who underwent fiducial placement for tracking of CLM at a tertiary center were reviewed.

Results

Among 1377 patients undergoing CLM resection between 2005 and 2015, 35 patients underwent fiducial placement. Three patients were excluded due to disease progression. The study population comprised 32 patients who underwent fiducial placement in 41 CLM. Among the 41 marked CLM, 34 (83 %) were located >10 mm deep in the liver parenchyma, 25 (61 %) were in the right liver, and median size was 12 mm (range, 6–20 mm). No complication occurred after fiducial placement. After chemotherapy, 19 (46 %) of the 41 marked metastases disappeared on cross-sectional imaging. All fiducial-tracked CLM were treated with resection (n?=?31) or ablation (n?=?10). After median follow-up of 14 months (range, 0–64 months), no local recurrences were observed.

Conclusion

Fiducial placement represents a safe procedure that facilitates accurate localization for resection or ablation of small CLM at risk of disappearing with chemotherapy.

     

Cyclooxygenase Isoenzyme-2 and Vascular Endothelial Growth Factor are Associated with Poor Prognosis in Esophageal Adenocarcinoma

Background  

Cyclooxygenase isoenzyme-2 (COX-2) and vascular endothelial growth factor (VEGF) contribute to angiogenesis and are overexpressed in various malignancies. The aim of the study was to evaluate expression, prognostic value and correlation between COX-2 and VEGF expression in esophageal adenocarcinoma (EAC).     

Tumor Marker Evolution: Comparison with Imaging for Assessment of Response to Chemotherapy in Patients with Colorectal Liver Metastases

Background  

As the real clinical significance of carcinoembryonic antigen (CEA) and carbohydrate antigen 19.9 (CA19.9) evolution during preoperative chemotherapy for colorectal liver metastases (CLM) is still unknown, we explored the correlation between biological and radiological response to chemotherapy, and their comparative impact on outcome after hepatectomy.     

Colorectal Liver Metastasis in the Setting of Lymph Node Metastasis: Defining the Benefit of Surgical Resection

Background  

For patients with colorectal liver metastasis (CLM), the presence of concomitant perihepatic/para-aortic lymph node metastasis (LNM) is considered a contraindication to liver resection. We sought to determine the benefits of liver resection among patients with CLM + LNM by examining long-term outcomes among a large cohort of patients.     

Systematic Review of Randomized and Nonrandomized Trials of the Clinical Response and Outcomes of Neoadjuvant Systemic Chemotherapy for Resectable Colorectal Liver Metastases

Background  

Neoadjuvant chemotherapy prior to hepatectomy in patients with resectable colorectal liver metastases (CLM) may facilitate the resectability of the liver lesions and treat occult metastasis but may also lead to hepatic parenchyma damage. There is argument over the oncologic benefit of this practice in patients who would already be suitable for a curative hepatectomy.     

Postoperative complications following aggressive repeat hepatectomy for colorectal liver metastasis have adverse oncological outcomes

Purposes

Repeat hepatectomy remains the only curative treatment for recurrent colorectal liver metastasis (CLM) after primary hepatectomy. However, the repeat resection rate is still low, and there is insufficient data on the outcomes after repeat hepatectomy. The aim of this study was to investigate the feasibility and prognostic benefit of aggressive repeat hepatectomy for recurrent CLM.

Methods

Data were reviewed from 282 consecutive patients who underwent primary curative hepatectomy for CLM between January 1994 and March 2015. The short- and long-term outcomes were analyzed.

Results

One hundred ninety-three patients (68 %) developed recurrence, and repeat hepatectomy was conducted in 62 patients. Overall, 62 s, 11 third, 4 fourth, and 1 fifth hepatectomies were performed. The postoperative morbidity and mortality rates were low (11.5 and 1.3 %, respectively). The overall survival rates at 3 and 5 years after primary hepatectomy for CLM in the repeat hepatectomy group were 79.5 and 57.4 %, respectively. A multivariate analysis indicated that postoperative complications were independently associated with overall survival after repeat hepatectomy.

Conclusions

Repeat hepatectomy for CLM is feasible, with acceptable rates of perioperative morbidity and mortality, and the potential for long-term survival. However, postoperative complications following aggressive repeat hepatectomy for CLM are associated with adverse oncological outcomes.

     

Minimally invasive colon resection for malignant colonic conditions is associated with a transient early increase in plasma sVEGFR1 and a decrease in sVEGFR2 levels after surgery

Introduction  

Plasma VEGF levels increase after minimally invasive colorectal resection (MICR) and remain elevated for 2–4 weeks. VEGF induces physiologic and pathologic angiogenesis by binding to endothelial cell (EC) bound VEGF-Receptor-1 (VEGFR1) and VEGFR2. Soluble forms of these receptors sequester plasma VEGF, decreasing the amount available to bind to EC-bound receptors. Ramifications of surgery-related plasma VEGF changes partially depend on plasma levels of sVEGFR1 and sVEGFR2. This study assessed perioperative sVEGFR1 and sVEGFR2 levels after MICR in patients with colorectal cancer.     

R1 Resection for Colorectal Liver Metastases: a Survey Questioning Surgeons about Its Incidence,Clinical Impact,and Management

Background

A ≥?1-mm margin is standard for resection of colorectal liver metastases (CLM). However, R1 resection is not rare (10–30%), and chemotherapy could mitigate its impact. The possibility of detaching CLM from vessels (R1 vascular margin) has been described. A reappraisal of R1 resection is needed.

Methods

A 19-question survey regarding R1 resection for CLM was sent to hepatobiliary surgeons worldwide. Seven clinical cases were included.

Results

In total, 276 surgeons from 52 countries completed the survey. Ninety percent reported a negative impact of R1 resection (74% local recurrence, 31% hepatic recurrence, and 36% survival), but 50% considered it sometimes required for resectability. Ninety-one percent of responders suggested that the impact of R1 resection is modulated by the response to chemotherapy and/or CLM characteristics. Half considered the risk of R1 resection to be an indication for preoperative chemotherapy in patients who otherwise underwent upfront resection, and 40% modified the chemotherapy regimen when the tumor response did not guarantee R0 resection. Nevertheless, 80% scheduled R1 resection for multiple bilobar CLM that responded to chemotherapy. Forty-five percent considered the vascular margin equivalent to R0 resection. However, for lesions in contact with the right hepatic vein, right hepatectomy remained the standard. Detachment from the vein was rarely considered (10%), but 27% considered detachment in the presence of multiple bilobar CLM.

Conclusions

A negative margin is still standard for CLM, but R1 resection is no longer just a technical error. R1 resection should be part of the modern multidisciplinary, aggressive approach to CLM.

     

Expression and clinical significance of hepaCAM and VEGF in urothelial carcinoma

Purpose  

Investigate the expression of hepatocyte cell adhesion molecule (hepaCAM) and vascular endothelial growth factor (VEGF) mRNA in 55 cases of urothelial carcinoma to examine the potential relationship between hepaCAM and VEGF in urothelial carcinoma.     

Impact of microvessel density on lymph node metastasis and survival after curative resection of pancreatic cancer

Purpose  

The roles of angiogenesis and the most prominent angiogenic vascular endothelial growth factor (VEGF) in diseases of the pancreas remain controversial. We compared microvessel density (MVD) and VEGF status in normal pancreatic, chronic pancreatic, and pancreatic cancer (PC) tissues to establish their prognostic relevance.     

Glucose-regulated protein 78 silencing down-regulates vascular endothelial growth factor/vascular endothelial growth factor receptor 2 pathway to suppress human colon cancer tumor growth

Background

Up to 20% of colorectal cancer (CRC) is diagnosed with distant metastasis. The combination of chemotherapy with anti-vascular endothelial growth factor (VEGF) antibody can improve patient survival. Glucose-regulated protein 78 (GRP78) has an important role in cancer progression, but little is known about its role in VEGF production in CRC. The aim of this study was to explore the mechanism of GRP78 in two human colon cancer cell lines.

Methods

We first checked the expression of GRP78 in human normal and colon cancer tissues and two colon cancer cell lines. Glucose-regulated protein 78 was knocked down using GRP78 small interfering RNA (siRNA) in HT29 and DLD-1 cells. We examined knockdown cells by the cell growth kinetics in vitro and tumor growth rate in vivo, respectively. We also investigated the effect of GRP78 siRNA on the expression of hypoxia inducible factor (HIF-1α), VEGF, and VEGF receptor 2 (VEGFR2).

Results

Compared with their adjacent normal tissue, we detected high expression levels of GRP78 of surgically removed colon cancer tissues. Using GRP78 siRNA, we reduced the expression of GRP78 in HT29 and DLD-1 cells. The GRP78 knockdown cells had a lower proliferation rate with fewer colony-forming units in vitro and produced smaller tumors in vivo. In dissecting the mechanism underlying the reduced cell growth, we found that the down-regulation of GRP78 decreased the production of HIF-1α, VEGF, and VEGFR2 and suppressed angiogenesis.

Conclusions

Silencing GRP78 not only inhibits tumor, but also decreases the expression of VEGF and VEGFR2. Collectively, therapy targeting for GRP78 may inhibit the formation of colon cancer tumors via the HIF-1α/VEGF/VEGFR2 pathway.