Surgery For Metastatic Colorectal Cancer Research Articles

The Association between Preoperative Vitamin D Levels and Postoperative Complications in Patients Undergoing Colorectal Liver Metastasis Surgery.

(1) Background: Over the past several years, there has been a renewed interest with regard to the effect of pre-operative vitamin D levels on post-surgical outcomes. Pre-operative vitamin D deficiency has been associated with many negative post-operative outcomes. However, the role of vitamin D in postoperative outcomes in colorectal liver metastasis (CRLM) resection is relatively uninvestigated. Our study investigated the correlation between preoperative vitamin D levels and postoperative complications in patients undergoing resection for CRLM. (2) Methods: We retrospectively examined the post-operative course of 109 patients, who were evaluated based upon preoperative vitamin D levels: the first group had vitamin D levels less than 25 nmol/L (VIT D < 25 nmol/L) (n = 12) vs. the second group who had vitamin D levels equal to or greater than 25 nmol/L (VIT D ≥ 25 nmol/L) (n = 97). (3) Results: Patients with lower pre-operative vitamin D levels (VIT D < 25 nmol/L) had significantly higher rates of blood transfusions (33.3% vs. 10.3%, p = 0.01), post-operative surgical complications (50% vs. 17.5%, p = 0.009), and infectious complications (25% vs. 7.2%, p = 0.04). However, there was no difference in overall survival seen between the two groups. (4) Conclusions: The results of our study indicate that patients with preoperative vitamin D deficiency (defined as preoperative vitamin D levels less than 25 nmol/L) may have an increased risk of postoperative complications in patients undergoing liver surgery for metastatic colorectal cancer.

Improved outcomes after surgery for metastatic colorectal cancer by multimodal prehabilitation: a pilot study

Improved outcomes after surgery for metastatic colorectal cancer by multimodal prehabilitation: a pilot study

Clinical Validity of Tumor-Informed Circulating Tumor DNA Analysis in Patients Undergoing Surgery of Colorectal Metastases.

Accurate biomarkers to monitor tumor load and response in metastatic colorectal cancer patients undergoing surgery could optimize treatment regimens. This study explores the clinical validity of tumor-informed quantification of circulating tumor DNA in blood using ultra-deep sequencing. Resection specimens from 53 colorectal cancer patients were analyzed for tumor-specific mutations in 15 genes. These mutations were used to measure the presence of circulating tumor DNA in preoperatively collected plasma samples using hybrid capture-based sequencing. Additional postoperative measurements were performed one week after surgery in sixteen patients. The study was conducted at the Radboud university medical center. A total of 53 colorectal cancer patients undergoing surgery of metastases were included. The detection of circulating tumor DNA. At least one tumor-specific mutation was detected in all tumor samples. In preoperative plasma samples circulating tumor DNA was detected in 88% (37/42) of systemic treatment-naïve patients and in 55% (6/11) of patients who received preoperative chemotherapy. More specifically, in 0% (0/3) of cases with a subtotal or partial pathological response and in 75% (6/8) of cases without a pathological response in the resection specimen (p = 0.06). In postoperative plasma samples circulating tumor DNA was detected in 80% (4/5) of patients with an incomplete resection and in 0% (0/11) of those with a complete resection (p = 0.003). The study was limited by the heterogeneity of the cohort and the small number of postoperative plasma samples. These data indicate that tumor-informed circulating tumor DNA detection in plasma of patients undergoing surgery for metastatic colorectal cancer is feasible and may have clinical value in response monitoring and predicting residual disease. Prospective studies are needed to establish the clinical utility of circulating tumor DNA analysis to guide treatment decisions in these patients. See Video Abstract at http://links.lww.com/DCR/B990.

The Role of Preoperative Platelet-to-Lymphocyte Ratio as a Predictor for Incisional Hernias after Hand-Assisted Laparoscopic Liver Surgery for Metastatic Colorectal Cancer.

(1) Background: Hand-assisted laparoscopic surgery for liver resection is a globally established technique. In this study, we report on the incidence and risk factors for postoperative incisional hernia (IH) after hand-assisted laparoscopic surgery for colorectal liver metastasis. (2) Methods: This was retrospective analysis of 89 consecutive hand-assisted laparoscopic surgery for colorectal liver metastasis. (3) Results: Participants were 39 females and 50 males. Median age was 65 years, and in 63%, the BMI was ≥25. Postoperative complications were encountered in 18% of the patients. Seven patients (7.8%) had postoperative incisional hernia in the hand port site. There was significantly higher incidence of incisional hernia in overweight patients (BMI ≥ 25) (p = 0.04), and in cases with simultaneous liver and colon resection (p = 0.02). In univariant and multivariant analyses, simultaneous liver and colon resection (p = 0.004 and 0.03, respectively), and platelet-to-lymphocyte ratio ≤ 200 (p = 0.03, 0.04, respectively) were both independent risk factors for developing postoperative incisional hernia. (4) Conclusions: Both simultaneous liver and colon resection, and platelet-to-lymphocyte ratio ≤ 200 are independent risk factors for postoperative incisional hernia after hand-assisted laparoscopic surgery for colorectal liver metastasis.

The Role of Pre-Operative Platelet to Lymphocyte Ratio as a Predictor for Incisional Hernias after Hand-Assisted Laparoscopic Liver Surgery for Metastatic Colo-Rectal Cancer

Background: Minimally invasive techniques for liver resection has become a widespread procedure Through this study, we aimed to report the incidence of post-operative incisional hernia as well as to high mark the potential risk factors, including clinical data and inflammatory indexes, for post-operative hernias after Hand-assisted laparoscopic surgery (HALS) for liver metastatic colon cancer.

Who can benefit from a liver surgery for metastatic colorectal cancer in the era of modern chemotherapy? A post hoc analysis of the MIROX phase III trial.

3547 Background: Despite improvement in colorectal liver metastasis (CLM) treatment, survival after liver surgery remains highly variable. Several clinicopathologic prognostic factors have been reported whose validity in the era of modern chemotherapy remains to be defined. This study aimed to analyze the prognostic factors associated with survival after CLM resection. Methods: Clinicopathologic data of patients included in the MIROX phase III trial who underwent surgery for isolated CLMs were analyzed. The primary endpoints were 5-year overall survival (OS) and disease-free survival (DFS). Univariate Cox analysis was performed to identify associations with OS and DFS and select variables included in a multivariate model to determine their independent prognostic value. Results: A total of 181 patients were analyzed. The median follow-up period was 6.42 years (95% CI: 5.15-8.71), and the 5-year OS and DFS rates were 67.1% and 35.4%, respectively. On multivariate analysis, Fong's clinical risk score (CRS) as a categorical variable (CRS 0-1 vs 2-3 vs 4-5, p = 0.036) and polymorphonuclear neutrophil (PMN) count (&gt;6000/mm3vs ≤6000/mm3, p = 0.006) before chemotherapy were found to be independent prognostic factors for OS. However, only Fong's CRS remained significantly associated with DFS (p = 0.027). The final OS model was used to establish a nomogram that allows individual OS estimations at 1, 3, 5, and 10 years. Conclusions: Fong's CRS and PMN count were independently associated with poor OS after CLM resection. Fong's CRS was also associated with DFS. The established prognostic nomogram could predict OS more accurately before CLM treatment.

Liver surgery for metastatic colorectal cancer: the surgical oncologist perspective

Neoadjuvant/conversion chemotherapy has emerged as an indispensable tool to achieve resectability of initially unresectable metastatic colorectal cancer and improves oncological outcomes. In parallel, surgical strategy has adopted a more aggressive treatment approach to achieve complete tumor clearance. However, chemotherapy affects liver function and combined with extensive liver resection, morbidity has increased, thereby compromising oncological outcome. There is an imperative need for careful patient selection to optimize patient management. In this review, we discuss available evidence and indications for neoadjuvant treatment in the management of colorectal cancer liver metastases, on preoperative patient selection and identification of high-risk patients, potential treatment strategies to promote postoperative liver regeneration to avoid postoperative morbidity and potentially deleterious side effects of these therapies on tumor growth.

Primary lesion location influences postoperative survival in patients with metastatic colorectal spinal lesions

Spinal metastasis from colorectal cancer occurs rarely. However, with increasing incidence of colorectal cancer in the setting of improved therapies, physicians are more likely to encounter such patients. We performed a retrospective review of patients who underwent spine surgery for metastatic colorectal cancer from 2005–2011. Preoperative, operative and postoperative factors; functional outcome as determined by Karnofsky Performance Status (KPS) and modified Rankin scale (mRS); and survival were recorded. Univariate analysis was performed, with patients stratified into two groups based on the position of the primary cancer, either proximal (colon) or distal (rectum) to the rectosigmoid junction. Fourteen patients, with a median age of 52 (interquartile range [IQR] 48–66)years, underwent 21 spine surgeries for metastatic colorectal cancer. Pain was the common presenting symptom (n=11, 79%), followed by motor weakness (n=8, 57%). Twenty-seven postoperative complications occurred in 11 (52%) patients. Baseline KPS and mRS remained stable in four (29%), improved in two (14%), worsened in six (43%), and was unknown in two (14%) at last follow-up. Patients with spinal metastasis from a rectal primary (n=6) had a significantly longer survival compared to those with a colon primary (n=8), with a median survival of 84 (IQR 56–103) versus 26 (IQR 19–44)months after primary diagnosis (p=0.002), 19 (IQR 13–27) versus five (IQR 3–9)months after spine metastasis diagnosis (p=0.010), and six (IQR 4–14) versus three (IQR 2–4)months after surgery (p=0.030). Patients with spinal metastasis arising from rectal primary lesions display longer survival compared to colon lesions. Consideration of these factors is essential to appropriately assess surgical candidacy.

Hospital readmissions after liver surgery for metastatic colorectal cancer

Hospital readmission rates after surgery are increasingly used as a measure of quality of care. Numerous efforts to decrease these rates have been established by care providers and insurance companies. There is sparse information available regarding readmission rates after liver resection for metastatic colorectal cancer (mCRC). Data from hospital readmissions occurring within 30 days after liver resection and/or open ablation for mCRC between 2005 and 2010 were captured from the urgent care center (emergency room) database and were compared with data from the institutional database. Complications during the primary stay and those leading to readmission were analyzed and graded with an established scoring system. The time course of complications and their therapeutic management were analyzed as well. Of 746 patients who underwent surgery during this period, 277 (37%) developed medical or surgical complications within 30 days, and 97 (13%) required readmission after discharge. The most common causes for readmission were perihepatic or intra-abdominal collections (40%), wound issues (13%), and gastrointestinal issues (12%). Forty-four patients had complications grade 3 or higher during readmission, thus representing 34% of all major complications (grade 3 or higher). Seventy-four readmitted patients (27% of all patients with complications) had a complication of lesser grade during their primary stay. The median postoperative day of readmission was 15 (range, 6-30) with wide variation among complication types. Readmission is common after liver resection and/or ablation for mCRC. One quarter of patients who develop complications postoperatively will have their most significant complication as an outpatient and require rehospitalization.

Ras in digestive oncology: from molecular biology to clinical implications.

The modalities of Ras mutation detection, its role as a predictive biomarker, mechanisms of wild-type Ras activation, and the role of Ras-directed targeted therapies will be discussed mainly in colorectal cancer. RAS genotype is generally considered to be highly concordant between primary colorectal tumours and metastases. However, recent data show significant discordance between primary tumours and specific metastatic sites, but also heterogeneity within primary tumours. Moreover, the mechanisms of Ras activation expand far beyond mutations through altered expression or function of physiological Ras activators and inhibitors. Accordingly, genomic signatures of Ras or epidermal growth factor receptor (EGFR) activation are being developed and are potential predictive biomarkers of response to anti-EGFR antibodies. Finally, several recent clinical trials targeting Ras or its downstream signalling with statins or Raf inhibitors have shown promising activity in chemorefractory metastatic colorectal cancer. RAS mutation remains an important biomarker predicting response to anti-EGFR therapies and perhaps clinical outcomes after surgery for metastatic colorectal cancer, but new techniques including genomic signatures need to be validated to take into account the complexity of Ras activation. The importance of Ras signalling as a therapeutic target has recently been outlined by successful clinical trials with Raf inhibitors.

Acute leukemoid reaction associated with liver surgery for metastatic colorectal cancer

Dear Editor: A 48-year-old woman was referred to our department for management of colorectal cancer metastatic to the liver. Past medical and hematological history was nonsignificant. Past surgical history included sigmoidectomy for colonic adenocarcinoma with synchronous bilobar liver disease 1 year ago in a peripheral hospital. Following surgery, she had received first line chemotherapy ensued by treatment with bevazicumab due to a favorable K-ras status. At presentation to our hospital, liver disease showed a 60 % response to chemotherapy. We planned a two-staged hepatectomy, a right portal vein ligation combined with left liver lobe metastasectomies followed by a right hepatectomy 5 weeks later. The first operation ran uneventfully, and we proceeded to the next stage after a preoperative CT confirming an adequate left hemiliver volume. The patient underwent an anatomical right hemihepatectomy. During the immediate postoperative period, she gradually developed an obstructive jaundice (peak value: total bilirubin 12 mg/dl, direct bilirubin 9 mg/dl). Her white blood cell counts ranged between 7× 10/L and 16×10/L during the same time period. Due to persistent hyperbilirubinemia, an abdominal ultrasound exhibiting notable intrahepatic biliary tree dilatation and a MRCP not illustrating the extrahepatic biliary structures, we decided to proceed to surgery. At relaparotomy, we observed a 180° malrotation around the common bile duct due to malposition of the liver remnant into the abdominal cavity. A Rouxen-Y hepatojejunostomy was tailored across segments II and III, and the hemiliver was repositioned. The patient was directly extubated and transferred to the surgical ward. Surprisingly, her first blood counts postoperatively showed marked leukocytosis [white blood counts (WBC):53×10/L], with a neutrophilic differential (neutrophils 93 %). Her WBC continued to increase during the following hours, peaking at 93×10/L on the second postoperative day. Of note, the patient was afebrile without any septic-related symptoms or signs during this time period. A hematology consultation was pursued. Her clinical examination was non-remarkable. No hepatosplenomegaly or lymphadenopathy was present. The white blood cell differential was as follows: 95 % neutrophils, 2 % bands, 2 % lymphocytes and 1 % monocytes. The blood smear showed mature normally lobated neutrophils without toxic granulation. Occasional bands were noted without a left shift. Red blood cells were of normal morphology without the presence of schistocytes. Platelets were within normal limits regarding number and morphology. At this juncture, a detailed work-up was undertaken to rule out infection and sepsis. C-reactive protein, blood cultures, disseminated intravascular coagulation panel, urinalysis, and culture, as well as chest X-ray were within normal limits. Her WBC gradually declined to normal level during the following 5 days, and the patient was discharged 2 weeks later. Persistent neutrophilic leukocytosis exceeding 50×10/L and peaking as high as 180×10/L in noninfected patients with malignant, non-hematopoietic neoplasias is termed a leukemoid reaction. The exact pathophysiology underlying this excessive leukocytosis is yet unclear. Various reports on solid tumors associated with neutrophilic leukocytosis suggest that paraneoplastic cytokine production by the primary tumor induces granulocytic overproduction, therefore resulting in a leukemoid reaction. Indeed, production of granulocyte colony-stimulating factor, granulocyte–macrophage–CSF, interleukin-1, and/or interleukin-6 by several aerodigestive G. C. Sotiropoulos (*) : P. Charalampoudis :G. Kouraklis 2nd Department of Propedeutic Surgery, University of Athens Medical School, Laikon Hospital, 17 Agiou Thoma Street, Athens 11527, Greece e-mail: georgios.sotiropoulos@uni-due.de

Therapeutic potential of surgery for metastatic colorectal cancer

Evidence of the clinical benefit of surgery or metastasectomy for metastatic colorectal cancer to disease sites including the liver, lung, peritoneum, and pelvis as a potentially curative option is now available in the literature. The oncologic outcome of this treatment strategy achieves 5-year survival ranging between 20% and 50%. These survival gains have not been previously observed in the management of metastatic colorectal cancer. Treatment of potential surgical candidates requires a combined modality approach with systemic therapies to achieve macroscopic tumor removal and microscopic targeting of tumor deposits to achieve disease control. In nonsurgical candidates, systemic therapy, radiation therapy, and interventional oncology procedures may potentially facilitate sufficient disease downstaging for surgery. The purpose of this article is to provide a comprehensive review of the therapeutic advances in the surgical management of metastatic colorectal cancer.

Abstract SY24-02: Development of recombinant vaccines for the prevention and therapy of human carcinomas

Abstract SY24-02: Development of recombinant vaccines for the prevention and therapy of human carcinomas

Liver Resection for Metastatic Colorectal Cancer in the Presence of Extrahepatic Disease

Hepatic resection for metastatic colorectal cancer (CRC) with concomitant extrahepatic disease (EHD) is controversial. Earlier reports of the results of liver resection for metastatic CRC identified patients with EHD as a group with poor outcomes, suggesting that the presence of EHD was an absolute contraindication to resection. This has recently been challenged in several reports due to advances in systemic chemotherapy, surgical technique, and patient selection. This review was restricted to published data in the English language identified by searches of MEDLINE and Pubmed databases as well as reference lists of recent review articles on subjects of surgery for metastatic colorectal cancer. Five-year survival after resection is worse than patients with liver-only disease but approximates the survival rates seen in patients with resected liver-only metastases in the era prior to the use of modern chemotherapy. Recurrence occurs in the great majority of patients. At this time, there appears to be a role for surgery in highly selected patients with a single site of EHD amenable to complete resection. Unlike patients with liver-only disease, however, the goals of surgery must not be viewed as potentially curative.

Intensive Systemic Chemotherapy Combined With Surgery for Metastatic Colorectal Cancer: Results of a Phase II Study

To evaluate the efficacy and tolerability of the metastatic irinotecan plus oxaliplatin (MIROX) strategy (adjuvant FOLFOX-7 followed by FOLFIRI), in patients with resectable metastatic colorectal cancer. Forty-seven patients with resectable metastases of colorectal cancer were prospectively enrolled onto this study. Treatment consisted of six cycles of leucovorin 400 mg/m(2), oxaliplatin 130 mg/m(2) in a 120-minute infusion, and fluorouracil (FU) 2,400 mg/m(2) in a 46-hour infusion, every 2 weeks (FOLFOX-7), followed by six cycles of leucovorin 400 mg/m(2), irinotecan 180 mg/m(2) in a 90-minute infusion, bolus FU 400 mg/m(2), and FU 2,400 mg/m(2) as a 46-hour infusion, every 2 weeks (FOLFIRI). Surgery was performed before chemotherapy in 25 patients and after six cycles of FOLFOX-7 in 22 patients (six cycles of FOLFIRI were administered after surgery). All but one of the patients underwent curative surgery. Two patients refused postoperative chemotherapy. Tolerability was generally good. The main toxicities were grade 3 to 4 neutropenia (13%) and thrombocytopenia (11%); no febrile neutropenia or bleeding occurred, and there were no deaths caused by toxicity. Two pathologically confirmed complete responses and 15 partial responses were obtained with FOLFOX-7 in the 22 patients who received this regimen before surgery (overall response rate, 77%; 95% CI, 68 to 86). The median disease-free survival time was 21 months; the median overall survival has not yet been reached. The 2-year overall and disease-free survival rates were 89% and 47%, respectively. The MIROX strategy is feasible and well tolerated by patients with resectable metastatic colorectal cancer. Progression-free and overall survival rates are promising, with a median of 38 months of follow-up. This strategy currently is being compared with the leucovorin and FU regimen in a phase III trial.