Search Results (27)

Background/Objectives: Histopathological indicators, including desmoplastic reaction (DR) and tumour budding (TB), are significant prognostic indicators for metastatic liver lesions in patients with colorectal cancer (CRC). However, the relationship of DR and TB in primary CRC and metastatic lung lesions and their prognostic significance has not yet been examined. This study aimed to elucidate the association of DR and TB in primary CRC and metastatic lung lesions. Methods: Patients with pT3 or pT4 CRC with lung metastasis who underwent surgical resection of the primary CRC and synchronous or metachronous metastatic lung lesions were enrolled. DR was classified into immature (IM) and non-IM types, and TB was classified into TB1 (<4 buds), TB2 (5–9 buds) and TB3 (≥10 buds) in both the primary CRC and metastatic lung lesions. Results: Overall, 40 patients with CRC (males, 21; females, 19; median age, 70 years; right-side colon, 6; left-side colon, 9; rectum, 25; pT3, 31; pT4, 9) were evaluated. Six and thirty-four patients were classified as having IM and non-IM DR in the metastatic lung lesions, respectively. Thirty-one, seven, and two patients were classified as having TB1, TB2, and TB3, respectively. There was no significant correlation between primary and lung metastatic lesions for DR (κ = 0.08, p = 0.086), whereas TB demonstrated a moderate correlation (κ = 0.47, p = 0.015). The presence of IM DR and TB2/3 in metastatic lung lesions significantly correlated with poor overall survival (p = 0.0020 and 0.044, respectively). Conclusions: histological indicators of metastatic lung lesions in CRC may provide important prognostic information for better patient care. Full article

Background and Objectives: Multiple primary malignant tumors represent a small percentage of the total number of oncological cases and can involve either metachronous or synchronous development and represent challenges in diagnosis, staging, and treatment planning. Our purpose is to present a rare case of bladder adenocarcinoma in a female patient with multiple primary malignant tumors and to provide systematic review of the available literature. Materials and Methods: A 67-year-old female patient was admitted with altered general condition and anuria. The past medical history of the patient included malignant melanoma (2014), cervical cancer (2017), colon cancer (2021), obstructive anuria (2023), and liver metastasectomy (2023). Transurethral resection of bladder tumor was performed for bladder tumors. Results: Contrast CT highlighted multiple pulmonary metastases, a poly nodular liver conglomerate, retroperitoneal lymph node, II/III grade left ureterohydronephrosis, and no digestive tract tumor masses. The pathological result of the bladder resection showed an infiltrative adenocarcinoma. Conclusions: The difference between primary bladder adenocarcinoma tumor and metastatic colorectal adenocarcinoma is the key for the future therapeutic strategy. Identification and assessment of risk factors such as viral infection, radiotherapy, chemotherapy, smoking, and genetics are pivotal in understanding and managing multiple primary malignant tumors. Personalized prevention strategies and screening programs may facilitate the early detection of these tumors, whether synchronous or metachronous. The use of multicancer early detection (MCED) blood tests for early diagnosis appears promising. However, additional research is needed to standardize these techniques for cancer detection. Full article

Aim: The complex medical care of synchronous metastatic colorectal (smCRC) patients requires prudent multidisciplinary planning and treatments due to various challenges caused by the primary tumor and its metastases. The role of primary tumor resection (PTR) is currently uncertain; strong arguments exist for and against it. We aimed to define its effect and find its best place in our therapeutic methodology. Method: We performed retrospective data analysis to investigate the clinical course of 449 smCRC patients, considering treatment modalities and the location of the primary tumor and comparing the clinical results of the patients with or without PTR between 1 January 2013 and 31 December 2018 at the Institute of Oncotherapy of the University of Pécs. Results: A total of 63.5% of the 449 smCRC patients had PTR. Comparing their data to those whose primary tumor remained intact (IPT), we observed significant differences in median progression-free survival with first-line chemotherapy (mPFS1) (301 vs. 259 days; p < 0.0001; 1 y PFS 39.2% vs. 26.6%; OR 0.56 (95% CI 0.36–0.87)) and median overall survival (mOS) (760 vs. 495 days; p < 0.0001; 2 y OS 52.4 vs. 26.9%; OR 0.33 (95% CI 0.33–0.53)), respectively. However, in the PTR group, the average ECOG performance status was significantly better (0.98 vs. 1.1; p = 0.0456), and the use of molecularly targeted agents (MTA) (45.3 vs. 28.7%; p = 0.0005) and rate of metastasis ablation (MA) (21.8 vs. 1.2%; p < 0.0001) were also higher, which might explain the difference partially. Excluding the patients receiving MTA and MA from the comparison, the effect of PTR remained evident, as the mOS differences in the reduced PTR subgroup compared to the reduced IPT subgroup were still strongly significant (675 vs. 459 days; p = 0.0009; 2 y OS 45.9 vs. 24.1%; OR 0.37 (95% CI 0.18–0.79). Further subgroup analysis revealed that the site of the primary tumor also had a major impact on the outcome considering only the IPT patients; shorter mOS was observed in the extrapelvic IPT subgroup in contrast with the intrapelvic IPT group (422 vs. 584 days; p = 0.0026; 2 y OS 18.2 vs. 35.9%; OR 0.39 (95% CI 0.18–0.89)). Finally, as a remarkable finding, it should be emphasized that there were no differences in OS between the smCRC PTR subgroup and metachronous mCRC patients (mOS 760 vs. 710 days, p = 0.7504, 2 y OS OR 0.85 (95% CI 0.58–1.26)). Conclusions: The role of PTR in smCRC is still not professionally justified. Our survey found that most patients had benefited from PTR. Nevertheless, further prospective trials are needed to clarify the optimal treatment sequence of smCRC patients and understand this cancer disease’s inherent biology. Full article

Colorectal cancer is the third-most-diagnosed cancer in males and in females, representing 8% of estimated new cases, and the third cause of cancer-related death in both sexes, accounting for 9% of cancer deaths in men and 8% in women. About 20% of patients diagnosed with CRC present metastatic disease. Although lung metachronous or synchronous metastatic spread without other involved sites has been reported in only a small proportion of patients, considering that this tumor is frequently diagnosed, the clinical approach to CRC pulmonary metastases represents a major issue for thoracic surgeons and CRC oncologists. Among patients diagnosed with pulmonary metastases from CRC, about 9–12% are eligible for local treatments with radical intent, including surgical resection, SBRT (stereotactic body radiation therapy) and ablation therapy. Due to the lack of randomized controlled trials among different local strategies, there is no definitive evidence about the optimal approach, although surgical resection is considered the most effective therapeutic option in this clinical scenario. Oncological achievement of primary radical resection, the biology of primary tumor and metastatic sites, disease free interval and or progression free survival are independent prognostic factors which make it possible to define a cohort of patients which might significantly benefit from pulmonary metastasectomy. Full article

There is no clear evidence on the prevalence and clinical presentation of appendiceal mucinous neoplasm (AMN) among patients with inflammatory bowel disease (IBD), so a systematic review was performed to investigate the diagnosis, management and treatment of AMN in these patients. PubMed, Medline, Scopus and the Cochrane Library were searched for articles published up to September 2023. Twenty-three studies reporting data about 34 AMN patients were included. UC patients had a median age of 52 years and a median length of disease of 10 years; CD patients had a median age of 40.5 years and a median length of disease of 5 years. A pre-operative diagnosis was achieved in 44% of patients. Most patients were symptomatic (82.6%) and showed moderate–severe disease activity (61%). Surgical procedures were performed: laparoscopic appendectomy, ileocecal resection, right hemicolectomy and colectomy/proctocolectomy. Of the patients, 73.5% were diagnosed with low-grade mucinous neoplasm (LAMN) and nine with adenocarcinoma. Synchronous colorectal dysplasia/carcinoma was present in 23.5% of patients. IBD patients with long-standing disease should be routinely screened, not only for colorectal cancer but also for AMN, during gastro-enterologic follow-up. Laparoscopic appendectomy of unruptured LAMN as well as right hemicolectomy of non-metastatic adenocarcinoma are safe procedures in IBD patients. Full article

Surgery-induced tumor growth acceleration and synchronous metastatic growth promotion have been observed for decades. Surgery-induced wound healing, orchestrated through growth factors, chemokines, and cytokines, can negatively impact patients harboring residual or metastatic disease. We provide detailed clinical evidence of this process in surgical breast, prostate, and colorectal cancer patients. Plasma samples were analyzed from 68 cancer patients who had not received treatment before surgery or adjuvant therapy until at least four weeks post-surgery. The levels of plasma cytokines, chemokines, and growth factors were simultaneously quantified and profiled using multiplexed immunoassays for eight time points sampled per patient. The immunologic processes are induced immediately after surgery in patients, characterized by a drastic short-term shift in the expression levels of pro-inflammatory and angiogenic molecules and cytokines. A rapid and significant spike in circulating plasma levels of hepatocyte growth factor (HGF), interleukin-6 (IL-6), placental growth factor (PLGF), and matrix metalloproteinase-9 (MMP-9) after surgery was noted. The rise in these molecules was concomitant with a significant drop in transforming growth factor-β1 (TGF-β1), platelet-derived growth factor (PDGF-AB/BB), insulin-like growth factor-1 (IGF-1), and monocyte chemoattractant protein-2 (MCP-2). If not earlier, each plasma analyte was normalized to baseline levels within 1–2 weeks after surgery, suggesting that surgical intervention alone was responsible for these effects. The effects of surgical tumor removal on disrupting the pro-inflammatory and angiogenic plasma profiles of cancer patients provide evidence for potentiating malignant progression. Our findings indicate a narrow therapeutic window of opportunity after surgery to prevent disease recurrence. Full article

Background: The decision to resect or not the primary tumor in asymptomatic patients with synchronous metastatic colorectal cancer (mCRC) is a complex and challenging issue for oncologists, especially when an antiangiogenic-based therapy is planned. Methods: Patients enrolled in the phase III TRIBE and TRIBE2 studies that compared upfront FOLFOXIRI + bevacizumab to FOLFIRI or FOLFOX + bevacizumab, respectively, were included. We assessed the association of primary tumor resection (PTR) with progression-free survival (PFS), overall survival (OS), response rate (ORR), rate of grade > 2 adverse events (AEs), and serious gastrointestinal and surgical AEs in the overall population and according to the treatment arm. Results: Of the 999 patients included, 513 (51%) underwent PTR at baseline. Longer PFS and OS were observed in resected patients compared to those with unresected primary tumors: 11.2 vs. 10.0 months (p < 0.001) and 26.6 vs. 22.5 (p < 0.001), respectively. In multivariate models, PTR was confirmed as an independent prognostic factor for better PFS (p = 0.032) and OS (p = 0.018). Patients with PTR experienced a higher incidence of grade 3 or 4 diarrhea (p = 0.055) and lower incidence of anemia (p = 0.053), perforation (p = 0.015), and serious gastrointestinal and surgical AEs (p < 0.001). No statistically significant differences were noted in incidence of bleeding (p = 0.39). The benefit of FOLFOXIRI + bevacizumab in terms of PFS (p for interaction: 0.46), OS (p for interaction: 0.80), ORR (p for interaction: 0.36), and incidence of grade 3 or 4 AEs was independent of PTR. Conclusions: PTR at baseline was independently associated with good prognosis in synchronous mCRC patients and with lower incidence of serious gastrointestinal and surgical AEs during upfront chemotherapy plus bevacizumab. The benefit and toxicity profile of FOLFOXIRI plus bevacizumab was independent of PTR. Full article

The role of upfront primary tumor resection (PTR) in patients with unresectable metastatic colorectal cancer without severe symptoms remains controversial. We retrospectively analyzed the role of PTR in overall survival (OS) in this population. Among the 205 patients who enrolled, the PTR group (n = 42) showed better performance (p = 0.061), had higher frequencies of right-sided origin (p = 0.058), the T4 stage (p = 0.003), the M1a stage (p = 0.012), and <2 organ metastases (p = 0.002), and received fewer targeted agents (p = 0.011) than the chemotherapy group (n = 163). The PTR group showed a trend for longer OS (20.5 versus 16.0 months, p = 0.064) but was not related to OS in Cox regression multivariate analysis (p = 0.220). The male sex (p = 0.061), a good performance status (p = 0.078), the T3 stage (p = 0.060), the M1a stage (p = 0.042), <2 organ metastases (p = 0.035), an RAS wild tumor (p = 0.054), and the administration of targeted agents (p = 0.037), especially bevacizumab (p = 0.067), seemed to be related to PTR benefits. Upfront PTR could be considered beneficial in some subgroups, but these findings require larger studies to verify. Full article

Background and Aims: Colorectal cancer (CRC) represents 10% of all cancers worldwide with the highest incidence in developed countries; its incidence is also increasing in middle- and low-income countries. Population screening programs facilitate early diagnosis of the disease. When the diagnosis is carried out in advanced stages, approximately 80% of patients with liver metastases (LM) are considered unresectable at the time of diagnosis. In our study, variations in blood counts prior to CRC diagnosis were analyzed to assess whether they could be useful in identifying smaller, more manageable metastases at earlier stages for more effective treatment. Methods: A study was carried out using complete blood counts (CBCs) from CRC patients, obtained from primary health centers and the La Ribera University Hospital within La Ribera Health Department, Valencian Community, Spain, between July 2012 and September 2020. Data from CRC patients who presented synchronous liver metastasis (CRLM) were compared with those with CRC without LM at diagnosis (CRC patients). Results: Our analysis shows that at least 15 months before CRC diagnosis, a progressive alteration was observed in CBC parameters in both groups. A higher incidence of anemia (p < 0.001) was observed among CRLM patients in the three months prior to CRC diagnosis than in CRC patients showing no LM. Conclusions: A statistically significant deterioration of CBC was observed in patients with advanced-stage CRC and synchronous or early LM (CRLM) in the three months prior to diagnosis. The primary goal of incorporating CBC variations into predictive models is to identify individuals who are at a greater risk of developing metastatic colon cancer, leading to early diagnosis. Our research improves these models by highlighting a more pronounced and rapid decline in hemoglobin levels among CRLM patients. Identification of metastases at an earlier stage when they are smaller, more manageable, and more amenable to treatment may be a valuable tool to prevent their further progression. Full article

In 2020, the Global Cancer Observatory estimated the incidence of colorectal cancer (CRC) at around 10.7% coupled with a mortality rate of 9.5%. The explanation for these values lies in the tumor microenvironment consisting of the extracellular matrix and cancer-associated fibroblasts (CAFs). Fibroblast activation protein (FAP) offers a promising target for cancer therapy since its functions contribute to tumor progression. Immunohistochemistry examination of FAP, fibronectin ED-B, and CXCR4 in primary tumors and their respective synchronous and/or metachronous metastases along with semiquantitative analysis have been carried out on histological samples of 50 patients diagnosed with metastatic CRC. The intensity of FAP, articulated by both “Intensity %” and “Intensity score”, is lower in the first metastasis compared to the primary tumor with a statistically significant correlation. No significant correlations have been observed regarding fibronectin ED-B and CXCR4. Tumors that produce FAP have an ambivalent relationship with this protein. At first, they exploit FAP, but later they reduce its expressiveness. Although our study has not directly included FAP-Inhibitor (FAPI) PET/CT, the considerable expression of FAP reveals its potential as a diagnostic and therapeutic tool worthy of further investigation. This dynamic relationship between cancer and FAP has substantial diagnostic and therapeutic implications. Full article

Metastatic colorectal cancer (CRC) is a common cause of cancer-related mortality, of which peritoneal metastases (PMs) have the worse outcome. Metastasis-specific markers may help predict the spread of tumor cells and select patients for preventive strategies. This exploratory pilot study aimed to gain more insight into genetic alterations in primary CRC tumors, which might be a predictive factor for the development of PM. Forty patients with T3 stage CRC were retrospectively divided in three groups: without metachronous metastases during 5-year follow-up (M0, n = 20), with metachronous liver metastases (LM, n = 10) and with metachronous PM (PM, n = 10). Patients with synchronous metastases were excluded. Primary formalin-fixed paraffin-embedded tumor samples were analyzed via comprehensive genome sequencing (TSO500 analysis) to identify DNA alterations and RNA fusion transcripts in 523 genes and 55 genes, respectively. Thirty-eight samples were included for final analysis. Four M0 tumors and one PM tumor were microsatellite instable. BRAF mutations were uniquely identified in three microsatellite-stable (MSS) PM tumors (37.5%, p = 0.010). RNA analysis showed an additional FAM198A-RAF1 fusion in one PM sample. BRAF p.V600E mutations were only present in PM patients with MSS tumors. Greater attention should be paid to BRAF-mutated tumors in relation to the development of metachronous PM. Full article

Sporadic colorectal cancer (sCRC) initially presents as metastatic tumors in 25–30% of patients. The 5-year overall survival (OS) in patients with metastatic sCRC is 50%, falling to 10% in patients presenting with synchronous metastatic disease (stage IV). In this study, we systematically analyzed the mutations of RAS, PIK3CA and BRAF genes in circulating tumor DNA (ctDNA) and tumoral tissue DNA (ttDNA) from 51 synchronous metastatic colorectal carcinoma (SMCC) patients by real-time PCR, and their relationship with the clinical, biological and histological features of disease at diagnosis. The highest frequency of mutations detected was in the KRAS gene, in tumor biopsies and plasma samples, followed by mutations of the PIK3CA, NRAS and BRAF genes. Overall, plasma systematically contained those genetic abnormalities observed in the tumor biopsy sample from the same subject, the largest discrepancies detected between the tumor biopsy and plasma from the same patient being for mutations in the KRAS and PIK3CA genes, with concordances of genotyping results between ttDNA and ctDNA at diagnosis of 75% and 84%, respectively. Of the 51 SMCC patients in the study, 25 (49%) showed mutations in at least 1 of the 4 genes analyzed in patient plasma. From the prognostic point of view, the presence and number of the most common mutations in the RAS, PIK3CA and BRAF genes in plasma from SMCC patients are independent prognostic factors for OS. Determination of the mutational status of ctDNA in SMCC could be a key tool for the clinical management of patients. Full article

Introduction: Synchronous robotic colorectal and liver resection for metastatic colorectal cancer (mCRC) is gaining popularity. This case series describes our initial institutional experience. Methods: A retrospective study of synchronous robotic colorectal and liver resections for metastatic colorectal cancer (March 2020 to December 2021). Results: Eight patients underwent synchronous robotic resections. The median age was 59 (45–72), and the median body mass index was 29 (20–33). Seven received neoadjuvant chemotherapy, and five rectal cancers received neoadjuvant radiotherapy. One patient had a low anterior resection with major hepatectomy, two had low anterior resection with minor hepatectomy, and one had abdominoperineal resection with major hepatectomy. One patient had a left colectomy with minor hepatectomy, and two had right colectomies with minor hepatectomy. We used five robotic 8/12 mm ports in all cases. Extraction incisions were Pfannenstiel in four patients, colostomy site in two patients, one perineal incision, and one supra-umbilical incision. The median estimated blood loss was 200 mL (25–500), and the median operative time was 448 min (374–576). There were no intra-operative complications or conversions. Five patients had the liver resection first, and two of six anastomoses were performed before the liver resection. The Median length of stay was 4 days (3–14). There were two post-operative complications, prolonged ileus and DVT, with a Clavien-Dindo complication grade of I and II, respectively. There were no readmissions or reoperations. All colorectal and liver resection margins were negative. Conclusions: Synchronous robotic colorectal and liver resection can be performed effectively utilizing one port configuration with acceptable short-term outcomes and quality of oncologic resection. Full article

Colorectal cancer is the third most common cancer worldwide, and up to 50% of all patients diagnosed will develop metastatic disease. Management of colorectal liver metastases (CRLM) has been constantly improving, aided by newer and more effective chemotherapy agents and the use of multidisciplinary teams. However, the only curative treatment remains surgical resection of the CRLM. Although survival for surgically resected patients has shown modest improvement, this is mostly because of the fact that what is constantly evolving is the indication for resection. Surgeons are constantly pushing the limits of what is considered resectable or not, thus enhancing and enlarging the pool of patients who can be potentially benefited and even cured with aggressive surgical procedures. There are a variety of procedures that have been developed, which range from procedures to stimulate hepatic growth, such as portal vein embolization, two-staged hepatectomy, or the association of both, to technically challenging procedures such as simultaneous approaches for synchronous metastasis, ex-vivo or in-situ perfusion with total vascular exclusion, or even liver transplant. This article reviewed the major breakthroughs in liver surgery for CRLM, showing how much has changed and what has been achieved in the field of CRLM. Full article

Population-based data on the incidence and surgical treatment of patients with colorectal cancer (CRC) and synchronous liver and lung metastases are lacking as are real-life data on the frequency of metastasectomy for both sites and outcomes in this setting. This is a nationwide population-based study of all patients having liver and lung metastases diagnosed within 6 months of CRC between 2008 and 2016 in Sweden identified through the merging of data from the National Quality Registries on CRC, liver and thoracic surgery and the National Patient Registry. Among 60,734 patients diagnosed with CRC, 1923 (3.2%) had synchronous liver and lung metastases, of which 44 patients had complete metastasectomy. Surgery of liver and lung metastases yielded a 5-year OS of 74% (95% CI 57–85%) compared to 29% (95% CI 19–40%) if liver metastases were resected but not the lung metastases and 2.6% (95% CI 1.5–4%) if non-resected, p < 0.001. Complete resection rates ranged from 0.7% to 3.8% between the six healthcare regions of Sweden, p = 0.007. Synchronous liver and lung CRC metastases are rare, and a minority undergo the resection of both metastatic sites but with excellent survival. The reasons for differences in regional treatment approaches and the potential of increased resection rates should be studied further. Full article