Pancreatic cancer tumor microenvironment is a major therapeutic barrier and target.

Pancreatic Ductal Adenocarcinoma (PDAC) is projected to become the 2nd leading cause of cancer-related deaths in the United States. Limitations in early detection and treatment barriers contribute to the lack of substantial success in the treatment of this challenging-to-treat malignancy. Desmoplasia is the hallmark of PDAC microenvironment that creates a physical and immunologic barrier. Stromal support cells and immunomodulatory cells face aberrant signaling by pancreatic cancer cells that shifts the complex balance of proper repair mechanisms into a state of dysregulation. The product of this dysregulation is the desmoplastic environment that encases the malignant cells leading to a dense, hypoxic environment that promotes further tumorigenesis, provides innate systemic resistance, and suppresses anti-tumor immune invasion. This desmoplastic environment combined with the immunoregulatory events that allow it to persist serve as the primary focus of this review. The physical barrier and immune counterbalance in the tumor microenvironment (TME) make PDAC an immunologically cold tumor. To convert PDAC into an immunologically hot tumor, tumor microenvironment could be considered alongside the tumor cells. We discuss the complex network of microenvironment molecular and cellular composition and explore how they can be targeted to overcome immuno-therapeutic challenges.

Risk factors and outcomes for cholangitis after hepatic resection.

INTRODUCTION: There is a paucity in the literature in regard to the incidence, risk factors, and outcomes for post-operative cholangitis following hepatic resection. METHODS: Retrospective review of the ACS NSQIP main and targeted hepatectomy registries for 2012-2016. RESULTS: A total of 11,243 cases met the selection criteria. The incidence of post-operative cholangitis was 0.64% (151 cases). Multivariate analysis identified several risk factors associated with the development of post-operative cholangitis, stratified out by pre-operative and operative factors. The most significant risk factors were biliary anastomosis and pre-operative biliary stenting with odds ratios (OR) of 32.39 (95% CI 22.91-45.79, P value < 0.0001) and 18.32 (95% CI 10.51-31.94, P value < 0.0001) respectively. Cholangitis was significantly associated with post-operative bile leaks, liver failure, renal failure, organ space infections, sepsis/septic shock, need for reoperation, longer length of stay, increased readmission rates, and death. CONCLUSION: Largest analysis of post-operative cholangitis following hepatic resection. While a rare occurrence, it is associated with significantly increased risk for severe morbidity and mortality. The most significant risk factors were biliary anastomosis and stenting.

Conditional Survival After Hepatectomy for Colorectal Liver Metastasis: Results from the Colorectal Liver Operative Metastasis International Collaborative (COLOMIC).

INTRODUCTION: Complete resection of colorectal liver metastasis (CLM) improves long-term survival in colorectal cancer. However, there is limited recent data on conditional survival (CS) as postoperative survival milestones are achieved post-hepatectomy. METHODS: A retrospective analysis was performed on the penta-institutional Colorectal Liver Operative Metastasis International Collaborative (COLOMIC), with 906 consecutive CLM hepatectomy cases. CS was calculated using Bayes' theorem and Kaplan-Meier analysis. Additional CS analyses were performed on additional clinicopathologic risk factors, including colon cancer laterality, KRAS mutation status, and extrahepatic disease. RESULTS: The 5-year CS was 40.6%, 45.3%, 52.8%, and 65.3% at 0, 1, 2, and 3 years postoperatively, with significant improvements each year (p < 0.005). CS was not significantly different between right-sided and left-sided colorectal cancers by 3 years postoperatively. Patients with KRAS mutations had worse CS at all timepoints (p < 0.001). Extrahepatic disease was a poor prognostic factor for OS and CS (p < 0.001). However, CS for patients with KRAS mutations or extrahepatic disease improved significantly as 2-year, postoperative survival was achieved (p < 0.05). CONCLUSIONS: Five-year CS after hepatectomy for CLM improved with each passing year of survival postoperatively. Although extrahepatic disease and KRAS mutations are poor prognostic factors for OS, these populations still had improved CS after 2 years postoperatively.

Machine Learning Models for Predicting the Outcomes of Surgical Treatment of Colorectal Liver Metastases.

BACKGROUND: Surgical intervention remains the cornerstone of a multidisciplinary approach in the treatment of colorectal liver metastases (CLM). Nevertheless, patient outcomes vary greatly. While predictive tools can assist decision-making and patient counseling, decades of efforts have yet to result in generating a universally adopted tool in clinical practice. STUDY DESIGN: An international collaborative database of CLM patients who underwent surgical therapy between 2000 and 2018 was used to select 1,004 operations for this study. Two different machine learning methods were applied to construct 2 predictive models for recurrence and death, using 128 clinicopathologic variables: gradient-boosted trees (GBTs) and logistic regression with bootstrapping (LRB) in a leave-one-out cross-validation. RESULTS: Median survival after resection was 47.2 months, and disease-free survival was 19.0 months, with a median follow-up of 32.0 months in the cohort. Both models had good predictive power, with GBT demonstrating a superior performance in predicting overall survival (area under the receiver operating curve [AUC] 0.773, 95% CI 0.743 to 0.801 vs LRB: AUC 0.648, 95% CI 0.614 to 0.682) and recurrence (AUC 0.635, 95% CI 0.599 to 0.669 vs LRB: AUC 0.570, 95% CI 0.535 to 0.601). Similarly, better performances were observed predicting 3- and 5-year survival, as well as 3- and 5-year recurrence, with GBT methods generating higher AUCs. CONCLUSIONS: Machine learning provides powerful tools to create predictive models of survival and recurrence after surgery for CLM. The effectiveness of both machine learning models varies, but on most occasions, GBT outperforms LRB. Prospective validation of these models lays the groundwork to adopt them in clinical practice.

Survival Outcomes of Optimally Treated Colorectal Metastases: The Importance of R0 Status in Surgical Treatment of Hepatic and Peritoneal Surface Disease.

BACKGROUND: Although colorectal hepatic metastases (HM) and peritoneal surface disease (PSD) are distinct biologic diseases, they may have similar long-term survival when optimally treated with surgery. METHODS: This study retrospectively reviewed prospectively managed databases. Patients undergoing R0 or R1 resections were analyzed with descriptive statistics, the Kaplan-Meier method, and Cox regression. Survival was compared over time for the following periods: 1993-2006, 2007-2012, and 2013-2020. RESULTS: The study enrolled 783 HM patients undergoing liver resection and 204 PSD patients undergoing cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). Compared with PSD patients, HM patients more often had R0 resections (90.3% vs. 32.4%), less often had pre-procedure chemotherapy (52.4% vs. 92.1%), and less often were functionally independent (79.7% vs. 95.6%). The 5-year overall survival for HM was 40.9%, with a median survival period of 45.8 months versus 25.8% and 33.4 months, respectively, for PSD (p < 0.05). When stratified by resection status, R0 HM and R0 PSD did not differ significantly in median survival (49.0 vs. 45.4 months; p = 0.83). The median survival after R1 resection also was similar between HM and PSD (32.6 vs. 26.9 months; p = 0.59). Survival between the two groups again was similar over time when stratified by resection status. The predictors of survival for HM patients were R0 resection, number of lesions, intraoperative transfusion, age, and adjuvant chemotherapy. For the PSD patients, the predictors were peritoneal cancer index (PCI) score, estimated blood loss (EBL), and female gender. CONCLUSION: The study showed that R0 resections are associated with improved outcomes and that median survival is similar between HM and PSD patients when it is achieved. Surveillance and treatment strategies that facilitate R0 resections are needed to improve results, particularly for PSD.

Outcomes after repeat hepatectomy for colorectal liver metastases from the colorectal liver operative metastasis international collaborative (COLOMIC).

BACKGROUND: Resection of colorectal liver metastasis (CLM) is beneficial when feasible. However, the benefit of second hepatectomy for hepatic recurrence in CLM remains unclear. METHODS: The Colorectal Liver Operative Metastasis International Collaborative retrospectively examined 1004 CLM cases from 2000 to 2018 from a total of 953 patients. Hepatic recurrence after initial hepatectomy was identified in 218 patients. Kaplan-Meier analysis was performed for overall survival (OS) and recurrence-free survival (RFS). Propensity score matching (PSM) was performed to offset selection bias. Cox proportional-hazards regression was performed to identify risk factors associated with OS. RESULTS: A total of 51 patients underwent second hepatectomy. Unadjusted median OS was 60.1 months in repeat-hepatectomy versus 38.3 months in the single-hepatectomy group (p = 0.015). In the PSM population, median OS remained significantly better in the repeat-hepatectomy group (60.1 vs. 33.1 months; p = 0.0023); median RFS was 12.4 months for the repeat-hepatectomy group, versus 9.8 months in the single-hepatectomy group (p = 0.0050). Repeat hepatectomy was associated with lower risk of death (hazard ratio: 0.283; p = 0.000012). Obesity, tobacco use, and high intraoperative blood loss were associated with significant risk of death (p < 0.05). CONCLUSION: In CLM with hepatic recurrence, second hepatectomy was beneficial for OS. With PSM, the OS benefit of performing a second hepatectomy remained significant.

Perioperative chemotherapy for resectable colorectal liver metastases: Analysis from the Colorectal Operative Liver Metastases International Collaborative (COLOMIC).

BACKGROUND: Chemotherapy has been increasingly combined with surgery as multimodality treatment for resectable colorectal-liver metastases (CLM). There is paucity of clinical data addressing optimal timing of chemotherapy relative to surgery. We examined outcomes of patients undergoing hepatectomy for resectable CLM. METHODS: Seven hundred and eighteen patients treated with hepatectomy for CLM were analyzed from five hepatobiliary institutions between 2000 and 2018. Overall survival (OS) was measured from time of hepatectomy for patients receiving: surgery alone, neoadjuvant, adjuvant, and neoadjuvant-plus-adjuvant (perioperative) chemotherapy. Kaplan-Meier analysis was performed to detect differences in OS between treatment groups. Single- and multi-variable analysis with Cox proportional hazards were run for OS between groups. RESULTS: One hundred and thirty-seven patients (19.08%) received surgery, 104 (14.48%) received neoadjuvant-only, 214 (29.81%) received adjuvant-only, and 263 (36.63%) received perioperative chemotherapy; with median OS of 48.20, 46.83, 56.27, and 49.93 months, respectively. No differences in median OS were seen between groups on Kaplan-Meier analysis. No significant difference in Charlson-Deyo comorbidity status was seen between groups (p = 0.853), while significant difference was seen in maximum tumor size (p = 0.0023). On multivariate analysis, adjuvant (p = 0.010) and perioperative (p = 0.020) chemotherapy were independently associated with OS compared to surgery alone. DISCUSSION: Despite group differences, chemotherapy after surgery was independently associated with improved OS in CLM.

Repeat Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Cancers with Peritoneal Metastasis: A 30-year Institutional Experience.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) improves survival in abdominal cancer patients with metastatic disease limited to the peritoneal cavity. Patients are increasingly being offered repeat CRS-HIPECs for peritoneal recurrence. However, in this rare clinical scenario, the survival benefit of performing repeat CRS-HIPEC operations remains unclear. METHODS: A retrospective review of the CRS-HIPEC database at Wake Forest Baptist Medical Center was performed over a 30-year timespan. From 1547 patients with appendix cancers, colorectal cancers, mesotheliomas, and other miscellaneous cancers, 156 received more than one CRS-HIPEC. Kaplan-Meier survival analysis was performed using overall survival (OS) from the time of surgery as the primary endpoint. Multi-variable Cox proportional hazards regression modelling was performed on pertinent clinical variables. RESULTS: Patients who received multiple CRS-HIPECs had significantly better median OS (10.7 years) versus those who received one CRS-HIPEC (2.5 years), with appendix cancers faring best (12.9 years). Resection status R2a or better was achieved in 76.4% of repeat CRS-HIPECs. There were no significant changes in complication rates after repeat CRS-HIPEC. On multivariate analysis of repeat CRS-HIPEC, patients with appendix and colorectal cancers, heart disease, and poor functional status were independently associated with poor OS. Factors not independently associated with OS were age, sex, body mass index, race, diabetes, lung disease, smoking history, and systemic chemotherapy between CRS-HIPECs. CONCLUSIONS: Performing multiple CRS-HIPEC operations on appropriate surgical candidates may significantly prolong survival. Appendix cancers derived the greatest benefit. Satisfactory resection margins and complication rates are comparable to first cases and achievable in repeat CRS-HIPEC procedures.

Association of primary tumor laterality with surgical outcomes for colorectal liver metastases: results from the Colorectal Liver Operative Metastasis International Collaborative (COLOMIC).

BACKGROUND: Primary laterality of colorectal cancer is thought to be associated with differences in outcomes. Liver metastasis is the most common site of solitary colorectal cancer spread. However, how primary colorectal cancer laterality affects outcomes in colorectal liver metastasis remains unclear. METHODS: The Colorectal Liver Operative Metastasis International Collaborative (COLOMIC) of operative hepatectomy cases for colorectal liver metastasis was compiled from five participating institutions. This included consecutive cases from 2000 to 2018 at all sites. A total of 884 patients were included in this study. Univariate, multivariate, and Kaplan-Meier analyses were performed. RESULTS: Patients with left-sided versus right-sided cancers had significantly better overall survival: 49.4 vs. 41.8 months (p < 0.05). Patients with KRAS mutations had significantly worse median overall survival compared to KRAS wild-type (43.6 vs 56.1 months; p < 0.001). In left-sided cancers, KRAS mutations were associated with significantly worse median overall survival compared to KRAS wild-type cancers (43.6 vs 56.6 months; p < 0.01). This association was absent in patients with right-sided primary tumors. Multivariate Cox regression analysis revealed different variable sets (non-overlapping) were associated with overall survival, when comparing left-sided and right-sided cancers. CONCLUSION: Understanding how primary tumor laterality and related biological aspects affect long-term outcomes can potentially inform treatment decisions for patients with colorectal liver metastases.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Management of Colorectal Cancer with Peritoneal Dissemination: 30 Years of Experience at a Single Institution.

BACKGROUND: Cytoreductive surgery (CRS) is at the forefront of treatment for colorectal cancer with peritoneal metastasis or "carcinomatosis" (CRC-PC). We report outcomes of the operative management of CRC-PC at a single center. STUDY DESIGN: We retrospectively reviewed our database from 1992 through 2021. The Kaplan-Meier method was used to estimate survival. Proportional hazards regression and multivariable models were used for assessments. RESULTS: This study included 345 patients with mean age 53.5 years. Multivariate analysis revealed performance and resection status were associated with overall survival (OS; p < 0.001). Within the R0/R1 group, adverse impact on OS was found with increasing Peritoneal Cancer Index (PCI) score starting at 9 (hazard ratio [HR] = 1.98, CI 1.39-2.82, p = 0.0001) with the most significant hazard noted at PCI >14 (HR = 2.35, CI 1.52-3.63, p = 0.0001). Incomplete resection (R2) had significantly worse OS compared with complete CRS 33.4 (n = 206) vs R2: 12.7 months (n = 139; p < 0.0001. When stratified by PCI for the R0/R1 group, median OS for PCI less than 10, 10 to 15, and greater than 15 was 38.2, 19.7, and 22.2 m, respectively (p = 0.0007 comparing PCI less than 10 and greater than 15). Ten-year increments-1991 through 2000, 2001 through 2010, 2011 through 2020-revealed improvement in median OS (13.4 [n = 66], 19.3 [n = 139], and 29.1 months [n = 140]). However, by resection status, median OS remained stable for R0/R1 (32.3 [n = 23], 31.1 [n = 76], and 34.1 months [n = 107]) and improved for R2 (5.2 [n = 43], 14.4 [n = 63], and 14.6 months [n = 33]). Clavien-Dindo complication rate (greater than or equal to grade III) was 29.4%. CONCLUSION: CRS improves outcomes for CRC-PC compared with historic outcomes with nonoperative management. This benefit is greatest with complete resection and lower disease burden. Results of CRS (with or without heated intraperitoneal chemotherapy) are improving, and surgery for CRC-PC should be routinely considered.

Utility of Neoadjuvant Chemotherapy for Peritoneal Carcinomatosis Secondary to High-Grade Appendiceal Neoplasms for Patients Undergoing Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

INTRODUCTION: Neoadjuvant chemotherapy (NAT) is frequently utilized before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for high-grade appendiceal neoplasms. The proposed benefits of NAT do not correlate with the limited literature. METHODS: Retrospective review of our CRS-HIPEC registry. Primary outcomes were the effect of NAT on disease burden, cytoreduction scores, overall survival (OS), disease-free survival (DFS), and recurrence patterns. RESULTS: A total of 126 cases of high-grade disease met selection criteria; 73 cases received NAT before referral, and 53 cases received no therapy before referral and went directly to CRS-HIPEC. For those cases who received NAT 89% received a FOLFOX-based regimen. Mean PCI scores were 16.47 and 16.07 (P = 0.843) with complete cytoreductions rates of 79.5% and 75% (P = 0.556) for NAT and non-NAT cases, respectively. NAT cases were associated with significantly decreased OS and DFS rates. Mean OS was 3.6 and 2.5 years (P = 0.005) with actual 5-year OS rates of 24.2% versus 5% (P = 0.017) for non-NAT and NAT cases respectively. Mean DFS was 2.8 and 1.7 years (P = 0.015) with actual 5-year DFS rates of 18.6% versus 5.7% (P = 0.048) for non-NAT and NAT cases respectively. Lastly, the use of NAT had no impact on recurrence patterns (P = 0.221). CONCLUSIONS: This is the largest study to evaluate high-grade appendiceal neoplasms in regard to CRS-HIPEC and NAT. NAT had no impact in regard to disease burden, cytoreduction, or recurrence patterns. Utilization of NAT was associated with decreased OS and DFS.

Utility of hyperthermic intraperitoneal chemotherapy in cases of incomplete cytoreductive surgery.

INTRODUCTION: Hyperthermic intraperitoneal chemotherapy (HIPEC) during cytoreductive surgery (CRS) is typically reserved for a complete or optimal cytoreduction. There is the potential for therapeutic effect of HIPEC with an incomplete cytoreduction, particularly for near optimal cytoreductions. METHODS: Retrospective review of incomplete cytoreductions (R2b, R2c) for appendiceal and colorectal primaries. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Subgroup analysis for primary etiology and specific cytoreductive score. RESULTS: A total of 121 cases of incomplete CRS, 74 CRS alone, and 47 CRS-HIPEC. For the entire study group there was a survival benefit with HIPEC. OS and PFS were 2.3 versus 1.4 (p = 0.001) and 1.6 versus 0.7 (p < 0.0001) respectively for cases with and without HIPEC. Subgroup analysis of appendiceal neoplasms, 43 CRS-HIPEC and 50 CRS alone, found HIPEC benefit persisted; OS and PFS were 2.4 versus 1.5 (p = 0.016) and 1.7 versus 0.8 (p < 0.0001), respectively for cases with and without HIPEC. Benefit most pronounced in low-grade cases with doubling of the OS and PFS (p = 0.004). With colorectal primary cases, 10 CRS-HIPEC and 18 CRS alone, no difference in OS and PFS. When stratifying out by cytoreduction scores, R2b and R2c, HIPEC only provided a benefit for R2b cases; OS and PFS for R2b cases were 2.28 versus 1.01 (p = 0.011) and 1.67 versus 0.75 (p = 0.001), respectively for cases with and without HIPEC. CONCLUSION: HIPEC has utility for incomplete cytoreductions with appendiceal neoplasms, greatest effect with low-grade appendiceal neoplasms. HIPEC is only beneficial for near optimal cytoreductions (R2b).

Evolving Role of Oncolytic Virotherapy: Challenges and Prospects in Clinical Practice.

Selective oncotropism and cytolytic activity against tumors have made certain viruses subject to investigation as novel treatment modalities. However, monotherapy with oncolytic viruses (OVs) has shown limited success and modest clinical benefit. The capacity to genetically engineer OVs makes them a desirable platform to design complementary treatment modalities to overcome the existing treatment options' shortcomings. In recent years, our knowledge of interactions of the tumors with the immune system has expanded profoundly. There is a growing body of literature supporting immunomodulatory roles for OVs. The concept of bioengineering these platforms to induce the desired immune response and complement the current immunotherapeutic modalities to make immune-resistant tumors responsive to immunotherapy is under investigation in preclinical and early clinical trials. This review provides an overview of attempts to optimize oncolytic virotherapy as essential components of the multimodality anticancer therapeutic approach and discusses the challenges in translation to clinical practice.

Strategies to Develop Potent Oncolytic Viruses and Enhance Their Therapeutic Efficacy.

Despite advancements in cancer therapy that have occurred over the past several decades, successful treatment of advanced malignancies remains elusive. Substantial resources and significant efforts have been directed toward the development of novel therapeutic modalities to improve patient outcomes. Oncolytic viruses (OVs) are emerging tools with unique characteristics that have attracted great interest in developing effective anticancer treatment. The original attraction was directed toward selective replication and cell-specific toxicity, two unique features that are either inherent to the virus or could be conferred by genetic engineering. However, recent advancements in the knowledge and understanding of OVs are shifting the therapeutic paradigm toward a greater focus on their immunomodulatory role. Nonetheless, there are still significant obstacles that remain to be overcome to enhance the efficiency of OVs as effective therapeutic modalities and potentially establish them as part of standard treatment regimens. In this review, we discuss advances in the design of OVs, strategies to enhance their therapeutic efficacy, functional translation into the clinical settings, and various obstacles that are still encountered in the efforts to establish them as effective anticancer treatments.

Optimal Adjuvant Treatment Approach After Upfront Resection of Pancreatic Cancer: Revisiting the Role of Radiation Based on Pathologic Features.

OBJECTIVE: To identify the survival benefit of different adjuvant approaches and factors influencing their efficacy after upfront resection of pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA: The optimal adjuvant approach for PDAC remains controversial. METHODS: Patients from the National Cancer Database who underwent upfront PDAC resection from 2010 to 2014 were analyzed to determine clinical outcomes of different adjuvant treatment approaches, stratified according to pathologic characteristics. Factors associated with overall survival were identified with multivariable logistic regression and Cox proportional hazards were used to compare overall survival of different treatment approaches in the whole cohort, and propensity score matched groups. RESULTS: We included 16,709 patients who underwent upfront resection of PDAC. On multivariable analysis, tumor size, grade, positive margin, nodal involvement, lymphovascular invasion (LVI), stage, lymph node ratio, not receiving chemotherapy, and/or radiation were predictors for worse survival. In the presence of at least 1 high-risk pathologic feature (nodal or margin involvement or LVI) chemotherapy with subsequent radiation provided the most significant survival benefit (median survivals: 24.8 vs 21.0 mo for adjuvant chemotherapy; HR = 0.81; 95% CI: 0.77-0.86; P < 0.001 in propensity score matching). The addition of radiation to adjuvant chemotherapy did not significantly improve overall survival in those with no high-risk pathologic features (median survivals: 54.6 vs 42.7 mo for adjuvant chemotherapy; HR=0.90; 95% CI: 0.75-1.08; P = 0.25 in propensity score matching). CONCLUSIONS: In the presence of any high-risk pathologic features (nodal or margin involvement or LVI), adjuvant chemotherapy followed by radiation provides a better survival advantage over chemotherapy alone after upfront resection of PDAC.

Quality analysis of operative reports and referral data for appendiceal neoplasms with peritoneal dissemination.

BACKGROUND: Peritoneal metastasis from appendiceal neoplasms is a rare disease usually found unexpectedly and is associated with deficits in quality reporting of findings. METHODS: Retrospective review of our appendiceal peritoneal metastases carcinomatosis database evaluating quality of index operative and pathology reports. Operative report quality was graded by 2 standards; general quality, based on Royal College of Surgeons quality metrics and peritoneal metastases assessment. Pathology report quality was assessed by the accuracy of diagnosis. RESULTS: Three hundred and seventy-five index operative reports and 490 outside pathology reports were reviewed. General quality of the index operative reports was excellent, with nearly 80% of reports encompassing all the Royal College of Surgeons quality metrics. Peritoneal metastases assessment was poor. Forty-four percent of the reports performed no peritoneal evaluation, while 48.3% only involved partial peritoneal evaluation. Only 7.7% of the reports performed a complete evaluation. Of the pathology reports, 48.4% had discrepancies with final pathologic findings. Low-grade disease and high-grade disease were misdiagnosed 36.06% and 62.7% of the time, respectively. Discordant treatment occurred in 15.3% and 30.0% of cases for misdiagnosed low-grade and high-grade disease, respectively. Incomplete cytoreduction was attempted in nearly a third of referral cases, which was associated with a significantly increased risk for ultimate incomplete cytoreduction with an odds ratio of 4.72. CONCLUSION: This review finds that referral operative reports' descriptions of the technical aspects of a procedure is usually complete. However, oncologic parameters and descriptions of peritoneal metastases are frequently incomplete. Further, pathology reports from outside institutions can lead to inappropriate clinical management decisions. We propose a simplified algorithm to assist nonperitoneal surface malignancy surgeons.

Precision Approaches in the Management of Colorectal Cancer: Current Evidence and Latest Advancements Towards Individualizing the Treatment.

The genetic and molecular underpinnings of metastatic colorectal cancer have been studied for decades, and the applicability of these findings in clinical decision making continues to evolve. Advancements in translating molecular studies have provided a basis for tailoring chemotherapeutic regimens in metastatic colorectal cancer (mCRC) treatment, which have informed multiple practice guidelines. Various genetic and molecular pathways have been identified as clinically significant in the pathogenesis of metastatic colorectal cancer. These include rat sarcoma (RAS), epithelial growth factor receptor (EGFR), vascular endothelial growth factor VEGF, microsatellite instability, mismatch repair, and v-raf murine sarcoma viral oncogene homolog b1 (BRAF) with established clinical implications. RAS mutations and deficiencies in the mismatch repair pathway guide decisions regarding the administration of anti-EGFR-based therapies and immunotherapy, respectively. Furthermore, there are several emerging pathways and therapeutic modalities that have not entered mainstream use in mCRC treatment and are ripe for further investigation. The well-established data in the arena of targeted therapies provide evidence-based support for the use or avoidance of various therapeutic regimens in mCRC treatment, while the emerging pathways and platforms offer a glimpse into the future of transforming a precision approach into a personalized treatment.