What are the other Names for this Condition? (Also known as/Synonyms)

• Colorectal MiNENs
• MiNENs of the Colon and Rectum
• Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms of the Colon and Rectum

What is Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms? (Definition/Background Information)

• Colorectal neuroendocrine neoplasms (NENs) may be described as malignant epithelial cancers of the large intestine/colon and rectum. These are rare neoplasms of the colon and rectum with neuroendocrine differentiation
• According to the World Health Organization (WHO) classification of tumors of the colon and rectum, Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms (MiNENs) are subtypes of colorectal NENs, and all are categorized as grade 3 (G3, high-grade). This includes a variant known as mixed adenoneuroendocrine carcinoma (MANEC)
• Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms are diagnosed under a microscope, on examination of the cancer cells by a pathologist. The classification of the tumor is important, as it may dictate the type of treatments to be provided and the overall outcomes
• The cause of Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms is generally unknown. It is believed to be associated with genetic defects and certain food and lifestyle factors. The signs and symptoms of the tumor may include abdominal pain, bleeding from the rectum, fatigue, and weight loss. Advanced cancer cases can result in extensive tumor metastasis to distant sites
• The mainstay of treatment of Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms is a surgical excision of the tumor during the early stages. However, in many cases, a combination of treatment measures that includes surgery, chemotherapy, and radiation therapy may be necessitated
• The prognosis primarily depends upon a set of several factors including the stage of the tumor. The prognosis of Colorectal MiNENs is typically unfavorable; these tumors are known to aggressively invade and spread to other body sites and organs

Who gets Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms? (Age and Sex Distribution)

• Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms are rare neoplasms that are frequently observed in middle-aged and older adults
• Both males and females are affected; a slight male preference is noted
• All races and ethnic groups are at risk for the condition

What are the Risk Factors for Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms? (Predisposing Factors)

No specific risk factors are noted for Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms (MiNENs). According to reports, Colorectal MiNEN is generally observed in a setting of chronic inflammatory bowel condition of unknown cause.

The following risk factors are reported for neuroendocrine neoplasms (NENs) of the colon and rectum:

• Alcohol consumption - a higher risk is noted for colorectal NENs with this factor
• Smoking tobacco may increase the risk
• Obesity - increased body mass index (BMI)
• Positive family history of cancer

In general, the following factors may increase the risk for colorectal carcinoma (CRC):

• Aging: The greater the age, the higher is the risk
• Presence of a genetic disorder (such as Lynch syndrome, polyposis syndrome, etc.)
• Chronic inflammatory bowel disorders such as Crohn’s disease, ulcerative colitis, and schistosomiasis
• Consuming a high calorie diet and leading a sedentary lifestyle
• Meat consumption (including animal fat)
• Presence of premalignant lesions
• Radiation therapy to the pelvic region for cancer
• Procedure for bladder cancer treatment called ureterosigmoidostomy

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms? (Etiology)

The cause of development of Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms (MiNENs) is generally unknown.

• In general, it is known that cancers form when normal, healthy cells begin transforming into abnormal cells - these cancer cells grow and divide uncontrollably (and lose their ability to die), resulting in the formation of a mass or a tumor
• Many cancer types are caused by genetic mutations. These can occur, due to inherited mutations, or mutations that occur due to environmental factors 
• The transformation of normally healthy cells into cancerous cells may be the result of genetic mutations. Mutations allow the cancer cells to grow and multiply uncontrollably to form new cancer cells
• These tumors can invade nearby tissues and adjoining body organs, and even metastasize and spread to other regions of the body

Research scientists believe that the cause of the condition is mostly due to genetic mutations, influenced by factors that include food and lifestyle habits such as high-fat, high-calorie diet, sedentary lifestyle, and drinking alcohol or smoking.

According to research studies on gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), Colorectal MiNENs may show mutations in the APC, BCL9, FOXP2, KRAS, RB1, SMARCA4, and TP53 genes.

What are the Sign and Symptoms of Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms?

Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms (MiNENs) may present the following signs and symptoms:

• Typically, the presence of a single mass may be noted; ulceration of the tumor mass may occur when it is large
• It can cause narrowing of the colon
• The tumor may invade the intestinal submucosal surface
• Passing of fresh blood in stool (hematochezia) and anemia may be observed
• Change in bowel habits; increased episodes of constipation may be noted, due to stool being obstructed by large tumor masses
• Severe constipation can cause enlarged intestine (abdominal distention) and abdominal pain
• Sometimes, perforation of the intestinal walls may occur
• Fever, unintended weight loss, and fatigue/tiredness may be noted

Location of the tumor: Generally, MiNENs can be present anywhere in the colorectal region.

How is Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms Diagnosed?

A diagnosis of Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms may be undertaken via the following tests and exams:

• Complete evaluation of family (medical) history, along with a thorough physical examination
• Stool sample analysis
• Screening colonoscopy: Colorectal MiNENs may be diagnosed during colonoscopies. A colonoscopy is a test that allows the physician to look at the inner lining of the colon and rectum. A typical colonoscopy involves using a thin, flexible tube (called a colonoscope), with an attached video camera, to view the colon and rectum
• Lower gastrointestinal series, which are a combination of analysis methods, combining X-rays and barium to visualize the intestinal region
• Imaging studies, such as MRI scan, transrectal ultrasound scan (TRUS), scintigraphy, and PET scan, may be performed to detect tumor invasion and metastasis
• Molecular genetic studies, if available
• Tissue biopsy of the tumor:
  • A tissue biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
  • Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
  • Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, and very rarely, electron microscopic studies to assist in the diagnosis

On histological studies, in a vast majority of cases, it is observed that MiNENs have a poorly-differentiated component of neuroendocrine carcinoma together with an adenocarcinoma component of the colon and rectum. In extremely rare cases, these tumors have been observed with a low-grade neuroendocrine tumor component.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms?

Some potential complications of Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms include:

• Emotional and psychological stress due to cancer diagnosis
• Intussusception: When one part of the intestine pushes itself into another part of the intestine, causing obstruction of the bowel necessitating surgical correction
• Widespread metastasis to local and regional sites and to the lymph nodes is observed in most cases of mixed neuroendocrine-non-neuroendocrine neoplasm
• Recurrence of the tumor after treatment, especially due to partial surgical removal
• Anastomotic leak; leakage of GI tract contents following surgical procedures, which can result in severe infection and even sepsis
• Side effects due to cancer therapy

How is Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms Treated?

The treatment of Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms (MiNENs) may depend upon a consideration of the following set of factors:

• Stage of the tumor
• Size and location of the tumor
• Severity of the signs and symptoms
• Age of the individual
• Overall health status of the individual
• The treatment preferences of the individual

The staging system used for Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasm follows the criteria laid out for colorectal adenocarcinoma that is governed by the American Joint Committee on Cancer (AJCC) TNM system.

Colorectal MiNENs may be treated in the following manner:

• Surgery is performed in most cases, unless tumors are small and superficially located
• In case of lymph node metastasis, surgery is followed by chemotherapy and/or radiation therapy (adjuvant therapy)
• In case of rectal carcinoma, chemotherapy and/or radiation therapy, to shrink tumor before surgery may be considered (neoadjuvant therapy)

The treatment measures include the following:

• Surgical removal of the entire tumor may be the preferred method of treatment
• In case of cancer spread to local and distant region, ablation and embolization techniques may be used
  • In ablation, the cancer is destroyed without surgically removing them using high-energy radio waves (called radiofrequency ablation), injecting the tumor with ethanol (called ethanol/alcohol ablation), or by using extremely cold temperatures to freeze them using a probe (called cryotherapy)
  • In embolization, the blood flow to the tumor is minimized or obstructed through techniques termed as arterial embolization, chemoembolization, or radioembolization
• Chemotherapy: This approach uses a combination of drugs to kill the cancerous cells and can be used in patients for all stages of the tumor
  • There can be severe side effects including fatigue, nausea, hair loss, anemia, high risk of infection, and drug-specific reactions
  • Chemotherapy can be administered as a pill, liquid, shot, or intravenously
• Radiation: Radiation therapy is the use of high-energy radiation waves to kill cancer cells, by destroying their DNA
  • This treatment modality may be used in combination with chemotherapy
  • The radiation may be administered by a machine placed outside the body, or by placing a radioactive material inside the body
  • The side effects of radiation therapy include nausea, vomiting, fatigue, pain, risk of cancer later in life, and risk of heart disease
  • Radiation can damage healthy cells in addition to cancer cells, causing further complications
• Supportive treatment: Steroids, blood transfusions, anti-nausea medications, and antibiotics, may be used as supportive therapy. In combination with other treatment measures, these can help combat the symptoms of immunodeficiency
• Undertaking treatment of underlying inflammatory bowel diseases/genetic disorders, as necessary
• Targeted drug therapy: Specific medications are administered periodically to stop tumor growth, particularly for advanced stages. The medications that are given intravenously include Bevacizumab, Ramucirumab, Ziv-aflibercept, Cetuximab, and Panitumumab
• Immunotherapy: A patient’s immune system is activated to combat the cancer in this kind of therapy

Regular observation and periodic checkups to monitor the condition is strongly recommended following treatment.

How can Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms be Prevented?

Presently, there are no specific methods or guidelines available to prevent the formation of Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms. The following factors may help minimize the risk for the same:

• It is important to undergo routine colonoscopy screenings as one gets older (over the age of 45-50 years), to ensure early detection of any colonic tumors or polyps
• Avoidance of alcohol; drink only in moderation
• Smoking cessation
• Consuming a diet that is rich in whole grains, vegetables, and fruits
• Taking foods rich in vitamin D and calcium
• Physical activities and regular exercising; avoiding obesity or being overweight to lower one’s risk
• In women, estrogen replacement treatment as needed
• Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs)
• Taking early and appropriate treatment for inflammatory bowel diseases, as necessary
• In order to avoid a relapse or be prepared for a recurrence, the entire diagnosis, treatment process, drugs administered, etc. should be well-documented and follow-up measures initiated

Regular medical screening at periodic intervals with blood tests, scans, and physical examinations are mandatory. Often several years of active vigilance are crucial and necessary.

What is the Prognosis of Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms? (Outcomes/Resolutions)

The overall prognosis of Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms (MiNENs) depend on several factors including the stage of the tumor.

• The prognosis is usually poor for individuals with Colorectal MiNEN; it depends on the stage of the tumor and the Ki-67 proliferation index (a reliable prognostic cell proliferation marker in cancer patients). The recorded median overall survival time is about 12.2 months
• In general, the prognosis of colorectal tumors depend upon a set of several factors, which include: 
  • Stage of tumor: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
  • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
  • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
  • The size of the tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
  • Individuals with bulky disease have a poorer prognosis
  • Involvement of vital organs may complicate the condition
  • The surgical resectability of the tumor (meaning if the tumor can be removed completely) - it is a rare option
  • Whether the tumor is occurring for the first time or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur 
  • Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
  • Progression of the condition makes the outcome worse
• The combination chemotherapy drugs used, may have some severe side effects (such as cardio-toxicity). These chiefly impacts the elderly adults, or those who are already affected by other medical conditions. Tolerance to the chemotherapy sessions is a positive influencing factor

An early diagnosis and prompt treatment of Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasm generally yields better outcomes than a late diagnosis and delayed treatment.

Additional and Relevant Useful Information for Colorectal Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms:

The following article link will help you understand other cancers and benign tumors:

https://www.dovemed.com/diseases-conditions/cancer/