• Humans
• Female
• Male
• Aged
• Colonic Neoplasms/pathology
• Colonic Neoplasms/drug therapy
• Colonic Neoplasms/mortality
• Middle Aged
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Neoplasm Staging
• Neoplasm Metastasis
• Aged, 80 and over
• Adult

• cancer
• drug delivery
• focused ultrasound
• image-guided therapy
• microbubble contrast agents
• optical imaging

• Animals
• Female
• Mice
• Antineoplastic Agents
• Blood-Brain Barrier
• Contrast Media
• Drug Delivery Systems/methods
• Microbubbles
• Models, Animal
• Neoplasms/drug therapy
• Tumor Microenvironment

• R01 CA269973 NCI NIH HHS
• R01 EB025841 NIBIB NIH HHS

• Colorectal cancer
• Palliative primary tumor resection
• Palliative systemic treatment
• Peritoneal metastases

• SEER database
• cutaneous melanoma
• nomogram
• stage IV
• surgery

• RNA-seq
• WES
• colorectal cancer
• expression
• mutation
• prognosis
• transcription

In patients with metastatic colorectal cancer (mCRC) with an asymptomatic primary tumor, there is no consensus on the indication for resection of the primary tumor.

The PubMed, Embase and the Cochrane Library databases were searched from inception to November 30,2021. A meta-analysis was performed using RevMan (version 5.3.3; The Cochrane Collaboration) on the outcome of mCRC patients with or without resection of the primary tumor in 8 selected studies.

This meta-analysis included 2805 colorectal cancer patients with an asymptomatic primary tumor from 8 selected studies. Primary tumor resection (PTR) patients had longer overall survival (OS: MD =6.76 [3.39, 10.12], I² = 77%, P < 0.0001), compared with non-primary tumor resection (NPTR) patients. In the subgroup, the randomized controlled trials (RCT) PTR group didn’t have longer overall survival (OS: MD =3.79 [-3.49, 11.08], I² = 69%, P= 0.31); the Non-RCT PTR group had longer overall survival (OS: MD =8.42 [3.14, 13.70], I² = 89%, P= 0.002). In the meanwhile, compared with NPTR group, the 2-year overall survival rate, the 3-year overall survival rate, 5-year overall survival rate in the PTR group is higher (OR=2.35 [1.74, 3.18], I² = 0%, P < 0.00001; OR=3.61 [2.35, 5.54], I² = 0%, P < 0.00001; OR=3.02 [1.72, 5.33], I² = 48%, P= 0.0001, respectively).

Our results from studies demonstrate that the resection of primary tumor is a prognostic factor for survival in mCRC patients. However, 2 RCTs showed the resection of primary tumor was not related with a significant survival benefit in subgroup. Therefore, a larger RCT in the era of modern chemotherapy and liver resection techniques would be helpful.

• asymptomatic
• colorectal cancer
• meta-analysis
• primary tumor
• resection

Approximately 20% of patients with colorectal cancer are initially diagnosed with stage IV disease. This study aims to examine the role of regional lymph node (LN) status in metastatic colorectal cancer (mCRC) with respect to clinicopathologic features and survival outcomes.

We investigated 1147 patients diagnosed with mCRC and had undergone surgical resection of the primary CRC. A total of 167 patients were placed in the LN-negative (LN−) group and another 980 in the LN-positive (LN+) group.

LN+ patients exhibited a significantly higher rate of T4 tumors (p = 0.008), poorly differentiated adenocarcinoma (p < 0.001), lymphovascular invasion (p < 0.001), and perineural invasion (p < 0.001) than those in the LN− group. LN− patients had a significantly higher rate of lung metastasis (p < 0.001), whereas the rate of peritoneal seeding (p < 0.001) and systemic node metastasis (p < 0.001) was both significantly higher in the LN+ group. The 5-year overall survival (OS) in the LN+ group was significantly poorer than that in the LN− group (LN− vs. LN+ 23.2% vs. 18.1%; p = 0.040). In patients with curative resection, the 5-year OS rate has no significant difference between the two groups (LN− vs. LN+ 19.5% vs. 24.3%; p = 0.890).

Metastatic CRC patients with LN+ who underwent primary tumor resection may present with more high-risk pathological features, more peritoneal seeding, and systemic node metastasis, but less lung metastasis than LN− patients. LN+ patients had poorer long-term outcomes compared with that in LN− patients. Nevertheless, with curative resection, LN+ patients could have similar survival outcomes as LN− patients.

• Chemotherapy
• metastatectomy
• metastatic rectal cancers
• resectability
• short-course radiotherapy

• Colorectal cancer
• chemotherapy
• comparative effectiveness research
• instrumental variable
• selection bias
• surgery

Colorectal cancer is the third leading cause of death worldwide. Currently, novel chemotherapeutic agents are first-line therapy for unresectable stage IV colorectal cancer, while benefits of noncurative primary tumor resection in advanced disease remain debatable.

This meta-analysis evaluated outcomes of patients with unresectable stage IV colorectal cancer receiving systemic chemotherapy with or without primary tumor resection.

A database search of PubMed and Cochrane Library databases identified 167 studies that were screened for relevance. After 119 were excluded, 48 were assessed for eligibility and 26 were included for meta-analysis, including 24 retrospective studies, one prospective study, and one randomized, controlled trial. Extracted data included patient demographics (age, sex), clinical data (tumor stage, metastasis), targeted therapy agents, and surgical data (with/without tumor resection). Patients’ overall and progression-free survival was compared between groups with/without primary tumor resection.

The 26 studies included 43,903 patients with colorectal cancer, with 29,639 receiving chemotherapy/radiotherapy plus primary tumor resection, and 14,264 managed medically with chemotherapy/chemoradiotherapy alone without primary tumor resection. Patients receiving primary tumor resection plus chemotherapy/radiotherapy had longer overall survival (hazard ratio [HR 0.59], 95% confidence interval [CI] 0.51–0.68; P<0.001), with significant differences in overall survival between patients with and without primary tumor resection (HR 0.58, 95% CI 0.49–0.68; P<0.001). Longer overall survival was also found among patients receiving primary tumor resection who were treated with bevacizumab/cetuximab targeted therapy agents (HR 0.63, 95% CI 0.46–0.86; P=0.003). Patients from three studies who received primary tumor resection had longer progression-free survival (HR 0.73, 95% CI 0.58–0.91; P=0.005). Results are limited by retrospective data, inconsistent complications data, and publication bias.

Study results support primary tumor resection in stage IV colorectal cancer, but significant biases in studies suggest that randomized trials are warranted to confirm findings.

• chemotherapy
• colorectal cancer
• outcomes
• tumor resection

• Colorectal neoplasms
• Colorectal surgery
• Palliative care

• CEA
• Colorectal cancer
• SEER
• Stage IV
• Surgery

There is no consensus regarding resection of the primary tumour with few or absent symptoms in patients with synchronous unresectable metastatic colorectal cancer (CRC). A potential benefit of resection of the primary tumour is to prevent complications of the primary tumour in later stages of the disease. We here propose a randomized trial in order to demonstrate that resection of the primary tumour improves overall survival.

The CAIRO4 study is a multicentre, randomized, phase III study of the Dutch Colorectal Cancer Group (DCCG). Patients with synchronous unresectable metastases of CRC and few or absent symptoms of the primary tumour are randomized 1:1 between systemic therapy only, and resection of the primary tumour followed by systemic therapy. Systemic therapy will consist of fluoropyrimidine-based chemotherapy in combination with bevacizumab. The primary objective of this study is to determine the clinical benefit in terms of overall survival of initial resection of the primary tumour. Secondary endpoints include progression free survival, surgical morbidity, quality of life and the number of patients requiring resection of the primary tumour in the control arm.

The CAIRO4 study is a multicentre, randomized, phase III study that will assess the benefit of resection of the primary tumour in patients with synchronous metastatic CRC.

The CAIRO4 study is registered at clinicaltrials.gov (NCT01606098)

Colorectal cancer (CRC) is a common neoplasia in the Western countries, with considerable morbidity and mortality. Every fifth patient with CRC presents with metastatic disease, which is not curable with radical intent in roughly 80% of cases. Traditionally approached surgically, by resection of the primitive tumor or stoma, the management to incurable stage IV CRC patients has significantly changed over the last three decades and is nowadays multidisciplinary, with a pivotal role played by chemotherapy (CHT). This latter have allowed for a dramatic increase in survival, whereas the role of colonic and liver surgery is nowadays matter of debate. Although any generalization is difficult, two main situations are considered, asymptomatic (or minimally symptomatic) and severely symptomatic patients needing aggressive management, including emergency cases. In asymptomatic patients, new CHT regimens allow today long survival in selected patients, also exceeding two years. The role of colonic resection in this group has been challenged in recent years, as it is not clear whether the resection of primary CRC may imply a further increase in survival, thus justifying surgery-related morbidity/mortality in such a class of short-living patients. Secondary surgery of liver metastasis is gaining acceptance since, under new generation CHT regimens, an increasing amount of patients with distant metastasis initially considered non resectable become resectable, with a significant increase in long term survival. The management of CRC emergency patients still represents a major issue in Western countries, and is associated to high morbidity/mortality. Obstruction is traditionally approached surgically by colonic resection, stoma or internal by-pass, although nowadays CRC stenting is a feasible option. Nevertheless, CRC stent has peculiar contraindications and complications, and its long-term cost-effectiveness is questionable, especially in the light of recently increased survival. Perforation is associated with the highest mortality and remains mostly matter for surgeons, by abdominal lavage/drainage, colonic resection and/or stoma. Bleeding and other CRC-related symptoms (pain, tenesmus, etc.) may be managed by several mini-invasive approaches, including radiotherapy, laser therapy and other transanal procedures.

• Colorectal cancer
• Palliative care
• Multimodal treatment
• Chemotherapy
• Surgery
• Stenting
• Radiotherapy

• Antineoplastic Agents/adverse effects
• Antineoplastic Agents/therapeutic use
• Chemotherapy, Adjuvant
• Colectomy/adverse effects
• Colorectal Neoplasms/mortality
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/surgery
• Colorectal Neoplasms/therapy
• Cooperative Behavior
• Humans
• Interdisciplinary Communication
• Neoadjuvant Therapy
• Neoplasm Staging
• Palliative Care
• Patient Care Team
• Patient Selection
• Treatment Outcome

• Chemotherapy
• Colorectal cancer
• Colorectal primary tumor
• Colorectal surgery
• Liver metastases
• Survival

• humans
• antineoplastic agents
• antineoplastic agents/therapeutic use
• asymptomatic diseases
• asymptomatic diseases/mortality
• asymptomatic diseases/therapy
• case‐control studies
• cohort studies
• colorectal neoplasms
• colorectal neoplasms/mortality
• colorectal neoplasms/pathology
• colorectal neoplasms/therapy
• controlled clinical trials as topic
• neoplasm staging

• Antineoplastic Agents/therapeutic use
• Asymptomatic Diseases/mortality
• Asymptomatic Diseases/therapy
• Case-Control Studies
• Cohort Studies
• Colorectal Neoplasms/mortality
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/therapy
• Controlled Clinical Trials as Topic
• Humans
• Neoplasm Staging