Management Of Colon Cancer Research Articles

Oncologic impact of colonic stents for obstructive left-sided colon cancer

Colonic stenting has had a significant positive impact on the management of obstructive left-sided colon cancer (OLCC) in terms of both palliative treatment and bridge-to-surgery (BTS). Notably, many studies have convincingly demonstrated the effectiveness of stenting as a BTS, resulting in improvements in short-term outcomes and quality of life, safety, and efficacy in subsequent curative surgery, and increased cost-effectiveness, whereas the safety of chemotherapy after stenting and the long-term outcomes of stenting as a BTS are controversial. Several studies have suggested an increased risk of perforation in patients receiving bevacizumab chemotherapy after colonic stenting. In addition, several pathological analyses have suggested a negative oncological impact of colonic stenting. In contrast, many recent studies have demonstrated that colonic stenting for OLCC does not negatively impact the safety of chemotherapy or long-term oncological outcomes. The updated version of the European Society of Gastrointestinal Endoscopy guidelines released in 2020 included colonic stenting as a BTS for OLCC as a recommended treatment. It should be noted that the experience of endoscopists is involved in determining technical and clinical success rates and possibly oncological outcomes. This review discusses the positive and negative impacts of colonic stenting on OLCC treatment, particularly in terms of oncology.

Identification and characterization of a first-generation inhibitor of claudin-1 in colon cancer progression and metastasis

Colorectal cancer (CRC) is a leading cause of the cancer-related deaths worldwide. Thus, developing novel and targeted therapies for inhibiting CRC progression and metastasis is urgent. Several studies, including ours, have reported a causal role for an upregulated claudin-1 expression in promoting CRC metastasis through the activation of the Src and β-catenin-signaling. In murine models of colon tumorigenesis, claudin-1 overexpression promotes oncogenic properties such as transformation and invasiveness. Conversely, the downregulation of claudin-1 inhibits colon tumorigenesis. Despite being a desirable target for cancer treatment, there are currently no known claudin-1 inhibitors with antitumor efficacy. Using a rigorous analytical design and implementing in- vitro and in-vivo testing and a brief medicinal chemistry campaign, we identified a claudin-1-specific inhibitor and named it I-6. Despite its high potency, I-6 was rapidly cleared in human liver microsomes. We, therefore, synthesized I-6 analogs and discovered a novel small molecule, PDS-0330. We determined that PDS0330 inhibits claudin-1-dependent CRC progression without exhibiting toxicity in in-vitro and in-vivo models of CRC and that it binds directly and specifically to claudin-1 with micromolar affinity. Further analyses revealed that PDS-0330 exhibits antitumor and chemosensitizer activities with favorable pharmacokinetic properties by inhibiting the association with metastatic oncogene Src. Overall, our data propose that PDS-0330 interferes with claudin-1/Src association to inhibit CRC progression and metastasis. Our findings are of direct clinical relevance and may open new therapeutic opportunities in colon cancer treatment and/or management by targeting claudin-1.

Consensus statement and clinical pathway for the management of colon cancer with peritoneal metastases in the state of Delaware

BackgroundIncreasing data suggests that the combination of modern systemic therapies and Cytoreductive surgery with or without Hyperthermic Intraperitoneal Chemotherapy (HIPEC) may improve the outcome of patients with colon cancer with peritoneal metastases. Patient selection and sequence of treatments remains ill-defined. Materials and methodsA working group, the State of Delaware Peritoneal Surface Malignancies Task Force (DE-PSM-TF), was created including representatives from medical and surgical oncology from the acute care hospitals in Delaware. An extensive review of all available literature was carried out. Virtual meetings were held, and interpretation and discussion of the data was conducted. ResultsA clinical pathway that includes a multidisciplinary evaluation at the time of diagnosis of colon cancer with peritoneal metastases and reflects a consensus from the Task Force on 7 key points that suggest the management of these patients based on the severity of their peritoneal metastases and incorporates all currently available therapies was created. The sequence of therapies of this multimodality treatment was determined by the Peritoneal Surface Disease Severity Score (PSDSS) (Fig. 1). ConclusionThe current pathway represents a comprehensive, team effort that should improve the outcome of patients with Colon Cancer with peritoneal metastases in the state of Delaware by having multidisciplinary discussions at the time of diagnosis, selecting the best order of sequence of currently available therapies in order to maximize benefits and minimize morbidity.

EPH144 The Impact of COVID-19 Pandemic on the Detection and Management of Cancer: A German Claims Data Analysis

The COVID-19 pandemic impacted the German healthcare system comprehensively. It is being widely discussed whether there was also a negative effect on cancer care, but evidence to quantify such an effect is lacking. This analysis aims to investigate the pandemic impact on the detection and management of breast cancer (BC), colon cancer (CC), lung cancer (LC), and prostate cancer (PC) in Germany. The analysis was based on anonymized claims data from a German statutory health insurance (AOK PLUS). Incidence was defined as at least one inpatient or two outpatient diagnoses of one of the four cancer types after a 24-month pre-index period without any cancer diagnoses. Standardized cumulative incidences and the proportions of patients with a metastatic diagnosis within the first three months after incident diagnosis were compared between 2019 and 2020. Differences in the time to treatment initiation (surgery, radiation, or systemic anticancer treatment) between 2019 and 2020 were investigated using Kaplan-Meier estimation. The standardized cumulative incidence of BC, CC, and LC in 2020 were significantly lower compared to 2019 (BC: 0.040%/0.038%; CC: 0.045%/0.037%; LC: 0.028%/0.025%; all p<0.001), while similar incidence of PC was observed (0.036%/0.036%; p>0.001). In all groups, the proportion of patients with metastases at the time of incident diagnosis did not differ considerably between the years. The time to treatment initiation after incident diagnosis did not differ significantly between 2019 and 2020 in the investigated populations. In incident BC/CC/LC/PC patients, the median time to therapy start was 42/47/59/90 days in 2019 versus 40/47/56/94 days in 2020 (HR [95%-CI]: 1.01 [0.92-1.10]/1.02 [0.92-1.3]/1.06 [0.94-1.20]/0.97 [0.88-1.07]). Significantly fewer patients were diagnosed with BC, CC, and LC in 2020 compared to 2019, possibly due to lower cancer screening rates. However, cancer therapy initiation and timing in newly diagnosed patients in 2020 were not substantially different from the pre-pandemic year.

Hybrid nanoparticulate system of Fluvastatin loaded phospholipid, alpha lipoic acid and melittin for the management of colon cancer

As a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, Fluvastatin (FLV) is used for reducing low-density lipoprotein (LDL) cholesterol as well as to prevent cardiovascular problems. FLV showed cell line cytotoxicity and antitumor effect. Melittin (MEL) exhibits antineoplastic activity and is known to be promising as a therapeutic option for cancer patients. The aim of this work was to investigate the combination of FLV with MEL loaded hybrid formula of phospholipid (PL) with alpha lipoic acid (ALA) nanoparticles to maximize anticancer tendencies. This study examines the optimization of the prepared formulation in order to minimize nanoparticles size and maximize zeta potential to potentiate cytotoxic potentialities in colon cancer cells (Caco2), cell viability, cell cycle analysis and annexin V were tested. In addition to biological markers as P53, Bax, bcl2 and Caspase 3 evaluation The combination involving FLV PL ALA MEL showed enhanced cytotoxic potentiality (IC50 = 9.242 ± 0.35 µg/mL), about twofold lower, compared to the raw FLV (IC50 = 21.74 ± 0.82 µg/mL). According to studies analyzing cell cycle, optimized FLV PL ALA MEL was found to inhibit Caco2 colon cancer cells more significantly than other therapeutic treatments, wherein a higher number of cells were found to accumulate over G2/M and pre-G1 phases, whereas G0/G1/S phases witnessed the accumulation of a lower number of cells. The optimized formulation may pave the way for a novel and more efficacious treatment for colon cancer.

MTOR as a Potential Target for the Treatment of Microbial Infections, Inflammatory Bowel Diseases, and Colorectal Cancer.

The mammalian target of rapamycin (mTOR) is the major controller of a number of important cellular activities, including protein synthesis, cell expansion, multiplication, autophagy, lysosomal function, and cellular metabolism. When mTOR interacts with specific adaptor proteins, it forms two complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The mTOR signaling system regulates gene transcription and protein manufacturing to control proliferation of cell, differentiation of immune cell, and tumor metabolism. Due to its vital role in case of microbial infections, inflammations and cancer development and progression, mTOR has been considered as a key therapeutic target for the development of targeted medication. As autophagy dysfunction is linked to changes in both innate and adaptive immune responses, bacterial clearance defects, and goblet and Paneth cell malfunction, all of these changes are linked to inflammatory bowel diseases (IBD) and colorectal cancer (CRC) pathogenesis. Preclinical and clinical data have shown that the inhibition and induction of autophagy have significant potential to be translated into the clinical applications. In IBD and several CRC models, mTORC1 inhibitors have been found effective. In the recent years, a number of novel mTOR inhibitors have been investigated in clinical trials, and a number of drugs have shown considerably enhanced efficacy when combined with mTOR inhibitors. The future developments in the mTOR targeting medications can benefit patients in individualized therapy. Advanced and innovative medicines that are more effective and have lower drug resistance are still in high demand. New findings could be relevant in medicine development, pharmacological modification, or future mTOR inhibitor research. Therefore, the goal of this review is to present a comprehensive account of current developments on the mTOR pathway and its inhibitors, with an emphasis on the management of microbial infections, the treatment of inflammatory bowel disease, and the management of colon cancer.

Payer-Negotiated Prices for Cancer Services Across National Cancer Institute-Designated Cancer Centers

INTRODUCTION: To promote price transparency and encourage insurer competition, recently implemented federal regulations require hospitals to publish payer-specific negotiated prices for all services. We sought to understand availability of payer-negotiated prices as well as how they vary within and across centers performing cancer operation. METHODS: We reviewed National Cancer Institute (NCI)-Designated Cancer Center (n = 64) websites to extract payer-negotiated prices and discounted cash prices for 131 services related to diagnosis and management of melanoma, colon, lung, pancreas, prostate, and rectal cancer. For each condition, we compared the highest and lowest payer-negotiated price within each center. We also compared centers with the highest median and lowest median payer-negotiated price for each condition. RESULTS: Of the 64 NCI-designated Cancer Centers, 34 (53.1%) had publicly available price data. Among these, there was wide variation in prices within and across centers and services. For example, median price for a pneumonectomy at 1 center demonstrated little variability ($7,423 to $9,000, median ratio 1.21) while another center for superficial axillary lymph node dissection demonstrated wide variation ($377 to $18,427, median ratio 31.7). Price variation also differed widely across different conditions with transanal excision demonstrating limited variability in median price across centers ($2,500.02 to $4,969.00, median ratio 1.99), while MLH1 gene analysis demonstrated wide variability in median price across centers ($2.80 to $2,631, median ratio 939.8) (Figure).FigureCONCLUSION: Adherence to federal regulations mandating hospital price transparency continues to be low. Significant variation in payer-negotiated prices exists both within and across hospitals for services related to diagnosis and treatment of the most common cancers.

Effects of suppressor of cytokine signaling 3 (SOCS3) on the development of colon cancer via regulation of HIF-1α

Purpose: To investigate the influence of suppressor of cytokine signaling 3 (SOCS3) on rats with colon cancer (CC).&#x0D; Methods: Sprague-Dawley (SD) rats were randomly divided into CC group and control group. CC models were constructed. The expression of SOCS3 in CC tissues was determined by quantitative real time-polymerase chain reaction (qRT-PCR). Hematoxylin-eosin staining (H&amp;E) was used to examine colon tissue morphology, while immunohistochemistry (IHC) staining assay was performed to determine the expression of SOCS3 protein in colon tissues. The content of HIF-1α, phosphorylated phosphatidylinositol 3-hydroxy kinase (p-PI3K), and phosphorylated protein kinase B (p-AKT) proteins was determined by Western blotting (WB).&#x0D; Results: Compared with that in the control group, the number of tumors in the CC group was significantly increased (p &lt; 0.05). Protein and messenger ribonucleic acid (mRNA) expressions of SOCS3 were down-regulated in CC group (p &lt; 0.05), while protein expressions of p-PI3K, p-AKT and HIF-1α were significantly elevated in CC group (p &lt; 0.05).&#x0D; Conclusion: SOCS3 is poorly expressed in CC rats, and promotes the expression of HIF-1α by activating PI3K/AKT signaling pathway. The findings, thus, provide a probable strategy for management of colon cancer.

324P Effects of screening and treatment improvement on colon cancer survival over 20 years in Korea

Although declines in colon cancer mortality were found worldwide, there is limited evidence to explain which improvements in treatment and management of colon cancer have been responsible for improved survival in the last 20 years. This study evaluated the treatment trajectories and aimed to explore the reasons for the improvement in colon cancer survival.

Colon and Rectal Cancer Management in Low-Resource Settings.

Colorectal cancer (CRC) incidence is rising in low- and middle-income countries, which also face disproportionate mortality from CRC, mainly due to diagnosis at late stages. Various challenges to CRC care exist at multiple societal levels in underserved populations. In this article, barriers to CRC care, strategies for screening, and treatment in resource-limited settings, and future directions are discussed within a global context.

Association of Rurality, Race and Ethnicity, and Socioeconomic Status With the Surgical Management of Colon Cancer and Postoperative Outcomes Among Medicare Beneficiaries

Rural patients with colon cancer experience worse outcomes than urban patients, but the extent to which disparities are explained by social determinants is not known. To evaluate the association of rurality with surgical treatment and outcomes of colon cancer and to investigate the intersection of rurality with race and ethnicity and socioeconomic status. This cohort study included fee-for-service Medicare beneficiaries 65 years or older diagnosed with incident, nonmetastatic colon cancer between April 1, 2016, and September 30, 2018, with follow-up until December 31, 2018. Data were analyzed from August 3, 2020, to April 30, 2021. Rurality of patient's residence, categorized as metropolitan, micropolitan, or small town or rural, using Rural-Urban Commuting Area codes. Receipt of surgery, emergent surgery, or minimally invasive surgery (MIS); 90-day surgical complications; and 90-day mortality. Among 57 710 Medicare beneficiaries with incident, nonmetastatic colon cancer, 46.6% were men, 53.4% were women, and the mean (SD) age was 76.6 (7.2) years. In terms of race and ethnicity, 3.7% were Hispanic, 6.4% were non-Hispanic Black (hereinafter Black), 86.1% were non-Hispanic White (hereinafter White), and 3.8% were American Indian or Alaska Native, Asian or Pacific Islander, or unknown race or ethnicity. Patients residing in nonmetropolitan areas were more likely to undergo surgical resection than those residing in metropolitan areas (69.2% vs 63.9%; P < .001). Black race was independently associated with lower hazard of surgical resection (hazard ratio, 0.92 [95% CI, 0.88-0.95]). Race and ethnicity and measures of socioeconomic status did not modify the association of rurality with surgery. Beneficiaries from small town and rural areas had higher odds of undergoing emergent surgery (adjusted odds ratio [OR], 1.32 [95% CI, 1.20-1.44]) but lower odds of undergoing MIS (adjusted OR, 0.75 [95% CI, 0.70-0.80]), with similar findings for patients residing in micropolitan areas. Members of racial and ethnic minority groups who resided in small town and rural settings experienced higher odds of postoperative surgical complications (P = .001 for interaction) and mortality (P = .001 for interaction). Notably, White patients who resided in small town and rural areas experienced lower odds of postoperative mortality than their White metropolitan counterparts (adjusted OR, 0.81 [95% CI, 0.71-0.92]), but Black patients who resided in small town and rural areas had significantly higher odds of postoperative mortality (adjusted OR, 1.86 [95% CI, 1.16-2.97]) than their Black metropolitan counterparts. These findings suggest that Medicare beneficiaries from small town and rural areas were more likely to undergo surgery for nonmetastatic colon cancer than metropolitan beneficiaries but also more likely to undergo emergent surgery and less likely to have MIS. The experiences of rural patients varied by race; rurality was associated with higher postoperative mortality for Black patients but not for other racial and ethnic groups.

Colon Targeted Eudragit Coated Beads Loaded with Optimized Fluvastatin-Scorpion Venom Conjugate as a Potential Approach for Colon Cancer Therapy: In Vitro Anticancer Activity and In Vivo Colon Imaging

Preclinical studies suggest that most of statins or 3‑hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors possess pleiotropic anticancer activity. The aim of the present work was to investigate the conjugation of the statin fluvastatin (FLV) with scorpion venom (SV), a natural peptide with proven anticancer properties, to enhance FLV cytotoxic activity and prepare colon targeted FLV-SV nanoconjugate beads for management of colon cancer. Response surface design was applied for the optimization of FLV-SV nanoconjugates. FLV-SV particle size and zeta potential were selected as responses. Cytotoxicity of optimized FLV-SV nanoconjugates was carried out on Caco2 cell line. Colon targeted alginate coated Eudragit S100 (ES100) beads for the optimized formula were prepared with the utilization of barium sulfate (BaSO4) as radiopaque contrast substance. Results revealed that optimized FLV-SV nanoconjugates showed a size of 71.21 nm, while the zeta potential was equal to 29.13 mV. Caco2 cells were considerably more sensitive to the FLV-SV formula (half-maximal inhibitory concentration (IC50) = 11.91 µg/mL) compared to SV and FLV used individually, as shown by values of IC50 equal to 30.23 µg/mL and 47.68 µg/mL, respectively. In vivo imaging of colon targeted beads, carried out by employing real-time X-ray radiography, confirmed the efficiency of colon targeted beads. Overall our results indicate that the optimized FLV-SV nanoconjugate loaded alginate coated ES100 beads could represent a promising approach for colon cancer with efficient colon targeting ability.

Effect of a combination of oxaliplatin and fluoropyrimidine derivative molecule S-1 on expression levels of IL-9 and CysLTR-1 in a rat model of colon cancer

Purpose: To investigate the effect of a combination of oxaliplatin and fluoropyrimidine derivative molecule S-1 on the expression levels of IL-9 and CysLTR-1 in rats with colon cancer.&#x0D; Methods: One hundred and eighty healthy Spraque Dawley rats were randomly assigned to groups A (healthy control), B (model), and C (treatment) with 60 rats in each group. Western blotting was used to determine contents of CysLTR-1 and related pathway proteins, while the levels of IL-9 and IFN-γ were evaluated by enzyme-linked immunosorbent assay (ELISA). Cell Counting Kit-8 (CCK-8) was used to determine cell proliferation, while cell apoptosis was assessed using flow cytometry.&#x0D; Results: Tumor volume was larger and tumor diameter was longer in group B than in group C (p &lt; 0.05). The expression levels of CysLTR-1, LTD4, β-catenin, COX-2, IL-9 and IFN-γ were significantly up-regulated in groups B and C, relative to group A (p &lt; 0.05). Cell proliferation was also significantly faster in groups B and C than in group A, while apoptotic rate was lower (p &lt; 0.05).&#x0D; Conclusion: Combined use of OX and S-1 inhibits CysLTR-1 expression level in colon cancer rats. Furthermore, it down-regulates IL-9 expression, thereby inhibiting the proliferation and apoptosis of tumor cells. Therefore, the combination treatment has potentials for development as a therapeutic strategy for the management of colon cancer.&#x0D; Keywords: Oxaliplatin; Fluoropyrimidine derivative molecule; Colon cancer; CysLTR-1

Modulating the Siah2-PHD3-HIF1α axis and/or autophagy potentially retard colon cancer proliferation possibly, due to the damping of colon cancer stem cells

BackgroundHypoxic microenvironment of colon cancer is associated with HIF-1α upregulation. HIF-1α response elements are responsible for autophagy induction that promotes tumor proliferation. Moreover, HIF-1α induces tumor cell proliferation via maintaining cancer stem cells (CSCs) survival. Siah2 is E3 ubiquitin ligase that indirectly stabilizes HIF-1α. We hypothesized that dual inhibition of Siah2 as well as autophagy could be a promising approach that may inhibit CSCs growth. Aim of the workThis study investigated the possible effect of vitamin K3 as a Siah2 inhibitor and hydroxychloroquine as an autophagy inhibitor in colon cancer management. The effect (if any) of these agents on CSCs growth will be also manipulated. MethodsColon cancer was induced by dimethylhydrazine. MDA and GSH were selected as oxidative stress markers, Expression of HIF-1α, Caspase-3, VEGF, MMP-9, EpCAM, SCF, and CA19.9 were assayed using immunoassay. The Western blot technique was used to assess LC3Ⅰ, CD44, and CD133 whereas RT-PCR was used to investigate PHD3 and CD44 in colon tissues. Additionally, Ki-67 and Siah2 were detected immunohistochemically. Resultsvitamin K3 and hydroxychloroquine either alone or in combination downregulated the expression of Siah2 and HIF-1α through upregulating PHD3 in colon tissues. This combination significantly downregulated MDA, Ki-67, VEGF, and MMP-9 expression and upregulated the expression of GSH and caspase-3. LC3Ⅰ was also upregulated. Interestingly, these therapeutic options were correlated with down-regulation of the cancer stem cell marker such as CD44 and EpCAM. ConclusionOur results suggested that suppression of both Siah2-PHD3-HIF-1α axis and autophagy retard colon cancer proliferation and dampened CSCs

Effects of SOCS3 on the development of colon cancer via regulation of HIF-1α

Purpose: To investigate the influence of suppressor of cytokine signaling 3 (SOCS3) on rats with colon cancer (CC).&#x0D; Methods: Sprague-Dawley (SD) rats were randomly divided into CC group and control group, and then CC rat model was constructed. The expression of SOCS3 in CC tissues was determined by quantitative real time-polymerase chain reaction (qRT-PCR). Hematoxylin-eosin staining (H&amp;E) was used to examine colon tissue morphology. Immunohistochemistry (IHC) staining assay was performed to determine the expression of SOCS3 protein in colon tissues. The contents of HIF-1α, phosphorylated phosphatidylinositol 3-hydroxy kinase (p-PI3K), and phosphorylated protein kinase B (p-AKT) proteins were determined by Western blotting (WB).&#x0D; Results: Compared with that in the control group, the number of tumors in CC group was significantly increased (p &lt; 0.05). 2). On the other hand, protein and message ribonucleic acid (mRNA) expressions of SOCS3 were down-regulated in CC group (p &lt; 0.05). 3), while protein expressions of p-PI3K, p-AKT and HIF-1α were raised in CC group (p &lt; 0.05).&#x0D; Conclusion: SOCS3 is lowly expressed in CC rats, and promotes the expression of HIF-1α by activating PI3K/AKT signaling pathway. Thus, SOCS3 provides a therapeutic strategy for the management of colon cancer.&#x0D; Keywords: Colon cancer; Suppressor of cytokine signaling protein 3 (SOCS3); Hypoxia inducible factor-1α

Oncological outcomes of open, laparoscopic and robotic colectomy in patients with transverse colon cancer.

Literature concerning surgical management of transverse colon cancer is scarce, since many key trials excluded transverse colon cancer. The aim of this study was to evaluate clinical and oncological outcomes comparing open, laparoscopic and robotic transverse colon cancer resection. Consecutivepatients who underwent elective surgery for transverse colon cancer between December 2005 and July 2021 were included. Data were kept in a prospective database approved by the institutional ethics committee. Primary outcome was overall and disease-free survival. Secondary outcomes included complications, operative time, length of stay and lymph node harvest. Statistical analysis was corrected for age and tumour localisation. Two hundred and forty-six (38 robotic, 71 open and 137 laparoscopic resections) were recruited in this study. There were five conversions during laparoscopic procedures. Operative time was significantly shorter in robotic vs laparoscopic procedures (195 vs 238min, p = 0.005) and length of stay was shorter in robotic vs laparoscopic and open group (7 vs 9 vs 15days, p < 0.001). There was no difference in overall complications. R0 resections were similar. Lymph node harvest was highest in the robotic group vs. laparoscopic or open (32 vs. 29 vs. 21, p < 0.001). Overall survival was 97%, 85% and 60% (p < 0.001) and disease-free survival was 91%, 78% and 56% (p < 0.001) for the robotic, laparoscopic and open groups, respectively. Minimally invasive surgery for transverse colon cancer is safe and offers good clinical and oncological outcomes. Robotic resection is associated with significantly shorter operating times, higher lymph node harvest, lower conversion rate and does not increase morbidity. Differences in disease-free and overall survival should be further explored in randomised controlled trials.

Localized Small Bowel Adenocarcinoma Management: Evidence Summary.

Simple SummarySmall bowel adenocarcinoma is a rare but aggressive disease that requires peri-operative treatment. Due to its rarity, there is little data on small bowel adenocarcinoma treatment, and most recommendations come from expert agreements or analogies to the management of colon cancer. In this Review, we summarize the current evidence on the management of localized small bowel adenocarcinoma, including future biomarker research perspectives that may help identify high-risk small bowel adenocarcinomas.Small bowel cancers are rare diseases whose prognosis is poorer than that of colon cancers. Due to disease rarity, there is little data on small bowel adenocarcinoma (SBA) treatment, and most recommendations come from expert agreements or analogies to the management of colon cancer. Although relatively high rates of local recurrence are observed for duodenal malignancies, distant metastatic relapse remains common and requires adjuvant systemic therapy. Given the similarities between SBA and colorectal cancer, radiotherapy and chemotherapy strategies used for the latter disease are frequently pursued for the former disease, specifically for tumors located in the duodenum. However, no previous randomized study has evaluated the benefit of adjuvant chemotherapy on the overall survival of SBA patients. Most previous studies on treatment outcomes and prognostic factors in this context were based on large international databases, such as the Surveillance, Epidemiology, and End Results or the National Cancer Database. Studies are required to establish and validate prognostic and predictive markers relevant in this context to inform the use of (neo) adjuvant treatment. Among those, deficient mismatch repair tumors represent 20% of SBAs, but their impact on chemosensitivity remains unknown. Herein, we summarize the current evidence on the management of localized SBA, including future perspectives.

Short- and long-term outcomes of subtotal/total colectomy in the management of obstructive left colon cancer.

Surgical management of obstructive left colon cancer (OLCC) is still a matter of debate. The classic Hartmann procedure (HP) has a disadvantage that requires a second major operation. Subtotal colectomy/total abdominal colectomy (STC/TC) with ileosigmoid or ileorectal anastomosis is proposed as an alternative procedure to avoid stoma and anastomotic leakage. However, doubts about morbidity and functional outcome and lack of long-term outcomes have made surgeons hesitate to perform this procedure. Therefore, this trial was designed to provide data for morbidity, functional outcomes, and long-term outcomes of STC/TC. This study retrospectively analyzed consecutive cases of OLCC that were treated by STC/TC between January 2000 and November 2020 at a single tertiary referral center. Perioperative outcomes and long-term outcomes of STC/TC were analyzed. Twenty-five descending colon cancer (45.5%) and 30 sigmoid colon cancer cases (54.5%) were enrolled in this study. Postoperative complications occurred in 12 patients. The majority complication was postoperative ileus (10 of 12). Anastomotic leakage and perioperative mortality were not observed. At 6 to 12 weeks after the surgery, the median frequency of defecation was twice per day (interquartile range, 1-3 times per day). Eight patients (14.5%) required medication during this period, but only 3 of 8 patients required medication after 1 year. The 3-year disease-free survival was 72.7% and 3-year overall survival was 86.7%. The risk of anastomotic leakage is low after STC/TC. Functional and long-term outcomes are also acceptable. Therefore, STC/TC for OLCC is a safe, 1-stage procedure that does not require diverting stoma.

Postoperative locoregional recurrence pattern and treatment management of stage pT4 sigmoid colon cancer: a retrospective cohort study

BackgroundThis study aimed to explore the pattern of locoregional recurrence after surgery in patients with non-metastatic stage pT4 sigmoid colon cancer and the role of adjuvant radiotherapy on survival.MethodsWe retrospectively analyzed data from 208 patients who underwent surgery in our hospital. The patients were randomly divided into training and validation groups at a 1:1 ratio. Patients at high risk for locoregional recurrence were screened using Cox regression analysis. Based on the data of 2,886 patients in the Surveillance, Epidemiology, and End Results (SEER) database, the effect of adjuvant radiotherapy on overall survival (OS) and cancer-specific survival (CSS) was evaluated by Kaplan–Meier curves.ResultsOf the 208 patients, 57 (27.4%) presented with locoregional recurrences (14 anastomotic and 43 abdominal or pelvic lymph node recurrences). Multivariate analysis showed that serum CEA, differentiation, lymph node dissection number, and N stage were independent predictors of locoregional recurrence-free survival (all p < 0.05). A risk-stratification model was constructed, and a total score of ≥ 6.5 points was considered the high-risk group for locoregional recurrence. Both the training and validation sets presented that the model had a good predictive ability (area under the curve = 0.828 and 0.724, respectively). Analysis of SEER data revealed that adjuvant radiotherapy significantly prolonged OS and CSS in the high-risk population (all p < 0.05, vs. no radiotherapy).ConclusionsPatients with a total risk score of 6.5 or more had a high likelihood of locoregional recurrence, and perhaps adjuvant radiotherapy could improve their survival.

Injectable Hydrogel Containing Cowpea Mosaic Virus Nanoparticles Prevents Colon Cancer Growth.

Despite advances in laparoscopic surgery combined with neoadjuvant and adjuvant therapy, colon cancer management remains challenging in oncology. Recurrence of cancerous tissue locally or in distant organs (metastasis) is the major problem in colon cancer management. Vaccines and immunotherapies hold promise in preventing cancer recurrence through stimulation of the immune system. We and others have shown that nanoparticles from plant viruses, such as cowpea mosaic virus (CPMV) nanoparticles, are potent immune adjuvants for cancer vaccines and serve as immunostimulatory agents in the treatment or prevention of tumors. While being noninfectious toward mammals, CPMV activates the innate immune system through recognition by pattern recognition receptors (PRRs). While the particulate structure of CPMV is essential for prominent immune activation, the proteinaceous architecture makes CPMV subject to degradation in vivo; thus, CPMV immunotherapy requires repeated injections for optimal outcome. Frequent intraperitoneal (IP) injections however are not optimal from a clinical point of view and can worsen the patient's quality of life due to the hospitalization required for IP administration. To overcome the need for repeated IP injections, we loaded CPMV nanoparticles in injectable chitosan/glycerophosphate (GP) hydrogel formulations, characterized their slow-release potential, and assessed the antitumor preventative efficacy of CPMV-in-hydrogel single dose versus soluble CPMV (single and prime-boost administration). Using fluorescently labeled CPMV-in-hydrogel formulations, in vivo release data indicated that single IP injection of the hydrogel formulation yielded a gel depot that supplied intact CPMV over the study period of 3 weeks, while soluble CPMV lasted only for one week. IP administration of the CPMV-in-hydrogel formulation boosted with soluble CPMV for combined immediate and sustained immune activation significantly inhibited colon cancer growth after CT26 IP challenge in BALB/c mice. The observed antitumor efficacy suggests that CPMV can be formulated in a chitosan/GP hydrogel to achieve prolonged immunostimulatory effects as single-dose immunotherapy against colon cancer recurrence. The present findings illustrate the potential of injectable hydrogel technology to accommodate plant virus nanoparticles to boost the translational development of effective antitumor immunotherapies.