Nutritional Interventions in Gynaecological Malignancies

VARLAS Valentin 1,2, DUMITRU Andreea 1*, POP Anca Lucia3, BORȘ Roxana 1

1 Department of Obstetrics and Gynaecology, Filantropia Clinical Hospital, Bucharest

2 Department of Obstetrics and Gynaecology, Carol Davila University of Medicine and Pharmacy, Bucharest

3 University of Medicine and Pharmacy”Carol Davila” Bucharest (ROMANIA)

Corresponding author: helena_dumitru20@yahoo.com

Abstract

A healthy diet is vital for the proper functioning of the body. The effects of dietary factors in terms of cancer survival rates or the prevention of disease recurrence are insufficiently studied. Proper nutrition can help cancer patients maintain their body weight, nutrient stores, and improve their quality of life. Gynaecological malignancies and adverse side effects of treatment usually cause symptoms that affect eating habits and nutritional needs, thus increasing the risk of malnutrition, metabolic disorders, and muscle loss. Malnutrition is a common problem in cancer patients and is recognized as an essential component of adverse effects, including increased morbidity, mortality, and decreased quality of life. This review aims to understand the importance of early detection and prompt treatment of malnutrition and metabolic disorders in cancer patients and cancer survivors. Nutritional intervention should be considered a supportive measure in terms of the overall cancer strategy.

Keywords: nutritional intervention, cancer, oncologic gynaecology, malnutrition. 

Introduction

Cancers are the leading cause of mortality and morbidity worldwide, and besides the progress made in therapy, it is impeded by the frequent manifestation of malnutrition and metabolic problems [1][2]. The tumour itself utilizes nutritional substrates preferentially so that nutritional stores usually adequate can be directed to the demands of a growing malignancy [1]. Due to this fact, cancer is often associated with anorexia, which can lead to cancer-related malnutrition (cachexia). The consequences are the impairment of the ability to heal wounds, bacterial resistance development, and decreased metabolic storage [3]. The decision to provide nutritional supplementation to a patient with a gynaecologic malignancy must be made with a good understanding of the treatment goals. Although it may seem right to give nutrition to the malnourished, an understanding of the underlying disease process is required before exposing patients to the discomfort and risks of nutritional supplementation.

Materials and methods 

We searched databases like Pubmed, Cochrane Library, Medscape and UptoDate for recent systematic reviews and meta-analyses about the topic. We focused on studies that follow nutritional intervention for ovarian, endometrial, cervical and breast cancer, and we presented the best alternatives for patients, combined with our guidelines. 

Oncological patient and treatment effects

Patients with gynaecological cancer may also experience fatigue, urinary or bowel issues, lymphedema, psychological breakdown, sleep disorder, menopausal symptoms, and sexuality issues. Side effects of treatment, cumulative organ toxicities, and complications can also alter the patient’s physique function, interfere with day-by-day activities, and have a negative impact on quality life [4]. 

Surgery

Surgical complexity, haemoglobin levels, and the presence of comorbidities are associated with severe complications. Surgical infections are associated with increased patient morbidity and mortality, and appear in up to 20–30% of gynaecologic oncology patients undergoing surgery [5].

Enhanced recovery after surgery (ERAS) program in cancer patients undergoing surgery helps reduce surgical stress, preserve nutritional status, decrease complications, and optimize the recovery rate. Pre-operative and psychological education can limit anxiety and increase patient satisfaction, which can also reduce pain, nausea, and fatigue, and facilitate early discharge [6].

Core principles of nutritional intervention of the ERAS program in gynaecologic cancer patients include: 

  • pre-operative bowel preparation should no longer be used routinely in gynaecologic oncologic surgery and should be limited to patients in which a colon resection is planned. 
  • nutritional components.

The stress due to major surgery induces a marked post-operative metabolic response that can be reduced with oral carbohydrates and avoiding fasting by clear fluids given up to 2 hours, and a light meal up to 6 hours pre-operative. Administration of oral carbohydrates 2–3 hours before surgery attenuates the catabolic response and is associated with reduced post-operative insulin resistance, earlier return of bowel function, and shorter hospitalization, without effect on post-operative complication rates.

  • perioperative goal-directed fluid therapy reduces the length of stay and complications in high-risk patients undergoing abdominal surgery. 
  • when patients rely on opioids alone for post-operative analgesia, this may cause nausea, sedation, and fatigue while increasing the risk of addiction.
  • maintenance of appropriate nutritional status post-operatively: up to 2.0 g of protein/ kg/day and 25–30 kcal/kg/day. Perioperative nutritional supplementation, or immune nutrition, may identify the roles of antioxidants, polyunsaturated fatty acids, arginine, and nucleotides on the effects of inflammatory response and post-operative healing. Early feeding, coffee consumption, and gum chewing are effective in decreasing the time to bowel function return [5][6].

Data suggest that when all patients receive such optimized nutritional and metabolic care, the metabolic response to surgery can be minimized, and some indices of moderate nutritional risk are no longer associated with adverse outcomes [6].

Chemotherapy

An oncological treatment, such as chemotherapy, may additionally interfere with a patient’s diet due to the fact of its secondary effects. These outcomes may generate a poor impact on the patient’s dietary intake and choice of nutrient sources, as well as on the patient’s dietary status, with an extension in waist circumference and body weight [7].

Extended fasting periods are frequent after chemotherapy sessions; however, if fasting lasts >48 h, the muscle-mass loss can also be promoted, following in deterioration of the patient’s dietary status related to progressive weight loss and cancer cachexia [8].

Cancer- and chemotherapy-induced poor appetite is typically the result of taste changes, mouth sores, nausea and vomiting, increased satiety, medication side effects, pain, fatigue, depressed mood, and anxiety [10]. Excessive emetogenic agents (>90% of patients) include i.e., cisplatin, cyclophosphamide, and dacarbazine. Nausea, vomiting, and secondary anorexia reduced oral intake, and also produced fluid and electrolyte imbalance, general weakness, and weight loss [11] [12]. 

Factors such as food regimen (deficiency of vitamin A and zinc, excess of vitamin C, excessive fibre diet, high osmolar dietary supplements, milk or milk products), infection, inflammatory factors, malabsorption and medications appear to be related with an elevated incidence of chemotherapy-induced diarrhoea (CID) [12]. Cinausero et al. describe the pathobiology and treatment of cancer treatment-related mucosal injury. Oral and gastrointestinal mucositis may also cause local ulceration and pain, which may also lead to anorexia, malabsorption, weight loss, anemia, and fatigue [11]. Mouth sores, related pain, and poor diet can place immunocompromised patients at high risk for infection [10].

Some of the patients can present chemotherapy-related fluid retention edema, which might also lead to considerable weight gain throughout chemotherapy [10]. Asthenia often leads to a decrease in appetite, constant fatigue has been associated with weight gain [9][10].

Radiotherapy

Over 50% of women diagnosed with gynecologic malignancies annually will acquire external and/or internal radiotherapy either as their primary treatment or together with surgery or chemotherapy [13]. Side-effects, like fatigue, food intolerance, and diarrhea appear through the second and third weeks of treatment [14].

King and her colleagues found that by the third week, most gynecologic patients report considerable problems with diarrhoea (86%), nausea (30%), anorexia (45%), and fatigue (75%). Such problems are very weakening and can produce dietary imbalances, and may also be linked to third difficulty, radiation-induced taste aversions [14].

Pelvic radiation therapy has numerous acknowledged acute and long period toxicities on the gastrointestinal tract: enteritis, proctitis, hemorrhoids, fistula, stricture, obstruction, manifested by nausea, diarrhoea, constipation, malabsorption, tenesmus, mucus, rectal bleeding, pain, fecal incontinence [13]. Significant gastrointestinal (GI) signs and symptoms vary from 3% to 8% of women who get postoperative radiotherapy to the pelvis and up to 20% of patients with locally advanced and unresectable tumours who require external–beam RT (EBRT) with each dose escalation and brachytherapy [13] [15].

Indications and benefits of nutritional support

Given the high incidence of nutritional deficits and metabolic disorders among cancer patients, it seems equitable to regularly monitor relevant parameters and initiate interventions early to prevent excessive deficits. Indications, where it is used as primary therapy, are: cutaneous gastrointestinal fistula, renal failure, short-bowel syndrome, acute burns, hepatic failure [16]. Before radical and ultra radical surgery, in gynaecologic oncology, there is a routine to benefit from nutritional support as a pre-operative measure in patients with low protein storage [3] [17]. Another category that benefits from nutritional support are those with impaired oral intake or enteral absorption, as an example, patients with stomatitis or candidal esophagitis resulting from chemotherapy can not swallow. Nutritional support can be offered to intra-abdominal metastasis, a carcinomatous ileus may result as the tumour is disseminating through the peritoneal cavity [18].

By using nutritional interventions, patients benefit from: adequate energy supply and protein intake, a stable body weight, relieve of metabolic disorders, maintenance of body mass and adequate performance status, increased tolerance to treatment, decreased rate of post-operative infections, decreased duration of hospitalization, and improvement of life quality.

Management

A. Patient evaluation 

Cancer-associated malnutrition or cachexia is defined as the presence of reduced food intake and metabolic disorders. Estimating the prevalence of nutritional deficits in patients with breast and other solid tumours, Bruera &MacDonald [19] reported that up to 80% of patients with advanced solid tumours met objective criteria for malnutrition. For early detection of nutritional disturbances, it is recommended to regularly evaluate the nutritional

intake, weight change, and BMI [17]. Assessment starts with a thorough history and physical evaluation looking for signs of metastatic disease or another status that would make nutritional sustenance unnecessary. Reasons suggestive for malnutrition may include emetogenic chemotherapy and multiple surgical procedures. Information about baseline weight and nutritional status is of important use. 

Another issue is about the multiple vitamin deficiencies that arises in patients with long periods of decreased oral intake or with underlying eating disorders (e.g., anorexia, bulimia). An example is cutaneous sores, such as stomatitis and xerostomia, which are the result of malnutrition caused by vitamin B deficiencies. Patients with food intolerance may need to have their dietary supplements adjusted properly. Patients diagnosed with diarrhoea determined by fatty foods may have associate a malabsorption syndrome which predisposes them to essential fatty acid and lipid-soluble vitamin deficiencies. 

Patients with radiation enteritis may experience food intolerance due to the lack of absorptive surfaces, and they may develop dysmotility or limited obstruction, especially in the terminal ileum, which becomes more susceptible to injury [20]. Estimation of protein deposits can be made on physical examination to identify characteristics of the nutritional deficiency known as kwashiorkor. Another kind of malnutrition known as marasmus due to the deficiency in energy stores, which is characterized by loss of muscle mass, temporal atrophy, and a scaphoid abdomen with prominent skeletal contours [20][21].

In progressive stages, cancer affects the body’s capacity to grow and regenerate protein and may result in a hypermetabolic state. Liver metastases can destroy the metabolism and transport of amino acids, proteins, and other vital nutrients, producing modifications in coagulation factors, serum albumin, and liver enzymes. Low fats in diet cause deficiency in vitamins and minerals, and may affect prostaglandin and steroid hormone biosynthesis due to lack of essential precursors. The osteoclast activation, by bone metastases and paraneoplastic factors, may determine abdominal cramping and constipation related to hypercalcemia. For end-stage cancer patients, perhaps there may be no benefit to nutritional support [21].

Paraclinical investigations includes full blood count, serum albumin, and transferrin concentrations. Circulating transport proteins reflect the liver’s good function and can be used as markers for the nutritional deficit, which is useful for monitoring the liver’s synthetic capacity. Usually, a normal value for albumin level is considered to be greater than 3.5 g/dL, but a level less than 3 g/dL is identified at patients severely malnourished. Thus, it is possible to detect the beneficiaries of nutritional support by combining clinical history with a physical examination [21].

B. Planification . Nutritional requirements. 

It is essential to determine the right amount of proteins and energy supply. The stresses caused by the disease and therapy may accelerate protein wasting and may result in essential nutrient and vitamin deficiencies, which should be replaced in the right proportions to bypass excess. The total daily amount of energy is appreciated to be ranging between 25 and 30 kcal/kg/day. The estimating daily energy requirements for women utilize the Harris-Benedict Equation a well-known population-based formula. Dextrose supplies 3.4 kcal for every 1g metabolized. It must be adapted to patients with energy requirements for protein turnover or underlying diseases [21].

Protein requirements are more difficult to predict; they provide approximately 4.1 kcal/g substrate. An assessment can be made by collecting a 24-hour urine specimen and measuring urine urea nitrogen excretion. It is proved that a post-operative diet high in proteins may reduce complications [5]. Lipid requirements, great energy storage are also a source of essential nutrients. They provide approximately 9 kcal/g enteral lipid substrate [22].  Vitamins act as cofactors for essential chemical reactions. The daily requirements are quickly met by patients with an intact gastrointestinal tract and a reasonably balanced diet. Metabolism of vitamin B12 is damaged in patients with surgical ileal resection, bypass, functional malabsorption related to radiation enteritis or blind loop syndrome [22].

C. Intervention – Nutritional Therapy

A preliminary step in treating such patients is determining their desire to be supported, because many patients reject the idea of being “tube fed” or parenteral nutrition, primarily if they associate nutritional support with loss of autonomy at the end of life. Most gynaecologic oncology patients who require support, receive parenteral nutrition. Parenteral feeding is preferred because their nutritional depletion is based on primary gastrointestinal dysfunction due to metastatic tumor, radiation, or surgery and also because of difficult access to the stomach and small intestine for tube feedings due to peritoneal disease or ascites [22]. The number of calories appropriate for maintaining homeostasis is given in the form of proteins, carbohydrates, and lipids. The basal metabolic rate should be evaluated in patients with weight loss due to inadequate intake of calories using the Harris-Benedict formula. At patients with secondary malnutrition, like those with severe surgical wounds, infections, cancer, or burns, the requirements are probably 35–40 kcal/kg/day [21][22].

Complications

Tardily complications associated with long-term CVCs are common, occurring in up to 10% of cancer patients who have these devices [23][24]. Electrolytes such as calcium, phosphate, magnesium, potassium, sodium, and chloride imbalances should be carefully monitored, recognized, and corrected to prevent problems, such as CO2 retention, hyperammonemia, and deficiencies in essential fatty acids and vitamins [22]. A little understood metabolic complication of nutritional therapy is the “refeeding syndrome.” It is encountered in patients with chronic malnutrition, when the infusion of protein, energy, and electrolytes may cause profound disturbance of metabolic routes and lead to the development of electrolyte-wasting syndromes with osmotic diuresis and acidosis. It is treated, in the first 24–48 hours, by slowly infusing enteric and intravenous nutritional solutions [21].

Results and discussion 

From a total of 50 studies, we selected 26 studies centred on the post-operative management and nutritional care of gynaecological patients with malignant affections. Main criteria consists of: references of the most frequent gynaecological cancers, types of nutritional intervention, recent recommendations for postoperative care, effects of chemo and radiotherapy, nutritional issues and long term effects. We consider that the objectives of this review are met due to the fact that we understand the early detection and prompt treatment of malnutrition and metabolic disorders in gynaecological cancer patients and survivors. Through the studies researched we observed that the ERAS program offers benefits to the patients by reducing surgical stress, decreasing complications, preserving nutritional status and optimizing the recovery rate. Before establishing nutritional support to this patients, it is important to evaluate the patient history and perform paraclinical investigations in accordance with it. The plan should include all nutritional requirements for a healthy diet. It was observed that parenteral feeding is preferred because the nutritional depletion is based on primary gastrointestinal dysfunction due to metastasis, surgery and radiation. 

Conclusions

Complications can result from lousy patient medical history and drug administration management, so it is important to have careful monitoring of energy supplies. Special attention must be offered to this type of patient due to additional complications that accompany the disease. Quality of life must be preserved and maintained as the main objective, furthermore, any type of therapy must be used with the consent and clear understanding of the patient. Thus, the assistance provided by a multidisciplinary team with a good understanding is required to allow the gynaecologic cancer patient to have maximum benefits. Nutritional intervention remains controversial in gynaecologic cancer treatment and it should be provided only by following evidence-based criteria, taking into account benefits and adverse effects. Finally, it must be taken into account that there are types of cancer that convert into chronic diseases, and for management of end-stage cancer patients it is still little influence known, so it must be handled prudently. 

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