Description of the condition
Based on worldwide statistics, ovarian cancer is the seventh most frequent cancer for both incidence and mortality with age-standardised rates (ASR) respectively of 6.3 and 3.8 per 100,000 women. Within these rates is significant geographical variation with an ASR of incidence of 9.3 per 100,000 in more developed regions and 4.9 per 100,000 in less developed regions of the world (GLOBOCAN 2008). Approximately 90% of ovarian cancers originate in the epithelial (or surface) layers of the ovary; other types of ovarian cancer can occur in the sex cord-stroma (inner structure of the ovary) and in the germ cells (where the eggs develop).
The presenting symptoms of ovarian cancer are often of a non-specific nature such as abdominal pain, abdominal bloating, changes in bowel habit, extreme fatigue or back pain and may be attributed to other reasons. As a consequence, patients may often be found to have advanced disease at the time of diagnosis. The treatment and prognosis of ovarian cancer are indicated by the staging of the disease classified using the International Federation of Gynecology and Obstetrics (FIGO) system (Benedet 2000). Staging may be evaluated from ultrasound, computerised tomography (CT) or other scanning techniques or from the finding of malignant cells in ascites (abnormal fluid collection in the abdomen); staging is confirmed when surgery occurs. The surgical treatment of ovarian cancer diagnosed at an early stage entails the removal of one or both ovaries and the uterus, depending on the extent of the disease and the need to preserve fertility. Where abnormal tissue is more widespread, for example in other pelvic organs, cytoreductive surgery is used with the aim of surgically removing all visible tumour tissue (optimal cytoreduction). If optimal cytoreductive surgery cannot be undertaken as a primary treatment, due to the presence of disease at inaccessible sites or poor performance status, chemotherapy may be commenced (neoadjuvant chemotherapy), prior to subsequent surgical reduction of the tumour (interval debulking) (Tangitgamol 2010). Surgical intervention may also be indicated where intestinal obstruction occurs as a complication of the disease.
Causes of malnutrition and weight loss in people with cancer have been described and these may include: tumour-induced anorexia; catabolic effects of the tumour; abnormal metabolism of nutrients; physical obstruction of the gastrointestinal tract by a tumour; reduced food intake as a side effect of radiotherapy or chemotherapy and diminished intake due to pain, anxiety or depression (Henry 2011). Specifically in ovarian cancer, common presenting symptoms include abdominal discomfort or pain, abdominal distension, nausea, dyspepsia, early satiety and constipation (Brooks 1994). In one UK study, more than 50% of 35 women recruited were reported to have a visibly distended abdomen due to ascites or ovarian mass (Balogun 2011).These factors are liable to influence food intake and consequently nutritional status within this patient group. Malnutrition in association with ovarian cancer has been identified as a problem for many years particularly in women with advanced cancer (FIGO stages III and IV) (Tunca 1983). Within a group of 33 women with ovarian cancer requiring an operation for a bowel obstruction, 75% were identified as having severe nutritional deprivation (Larson 1989).
A variety of methods have been used to identify malnutrition. Subjective global assessment (SGA) is a method of evaluating nutrition status combining weight change, diet history and physical examination. In a Brazilian study of women with gynaecological cancers, SGA identified malnutrition in four out of 14 (28%) women with ovarian cancer (Zorlini 2008), while the same method found 50% of 132 women with ovarian cancer in a US study were malnourished (Gupta 2008). In Australia, using the patient-generated SGA (PG-SGA), malnutrition was identified in two-thirds of 48 women with ovarian cancer in comparison with 12% of women with other gynaecological cancers. The mean body mass index (BMI) of the malnourished women (27.4 kg/m
Evidence of malnutrition in women with ovarian cancer has been related to outcomes from surgery. When surgery has been required for intestinal obstruction, poor nutritional status (identified either by weight loss, low serum albumin or low lymphocyte count) was a factor that significantly correlated with poor surgical outcome (Krebs 1983), poor postoperative survival (Clarke-Pearson 1988) and an increased incidence of postoperative infectious complications (Donato 1992). In a study of older women (aged 75 years or over) with ovarian and primary peritoneal cancer, serum albumin was used as a surrogate measure for nutritional status and was significantly associated with lower rates of optimal cytoreduction. Women with sub-optimal cytoreductive surgery had a lower median survival time in comparison with the women who underwent optimal cytoreduction (17 months versus 62 months) (Alphs 2006). Although serum albumin may reflect chronic protein deficiency, it is also an indicator of acute clinical stress, hydration status, liver dysfunction and inflammation, so requires careful evaluation. In a study where prealbumin was used as a nutrition assessment marker, a significant relationship was shown between low serum prealbumin and the risk of complications after primary radical cytoreductive surgery for ovarian cancer, with significantly greater risk of blood loss, morbidity and mortality where serum prealbumin was lower than 10 mg/dL (Geisler 2007).
Current guidelines recommend the use of nutrition screening in hospital to identify individuals at risk of malnutrition. Identification of patients found to be malnourished or at risk of malnutrition should be linked to further assessment and implementation of an appropriate nutrition care plan, which may include nutrition support (ASPEN 2011; Kondrup 2003; NICE 2006). Women with ovarian cancer may have co-existing excess weight or obesity with or without ascites, therefore appropriate screening and assessment methods are required to ensure that malnutrition is identified and treated.
Description of the intervention
In this context, nutrition interventions include nutrition screening, nutrition assessment or nutrition advice, which may be combined with nutrition support (additional or alternative provision of nutrients), with the intention to improve or maintain nutrient intake. Nutrition support may be provided as supplementary foods and drinks, fortified foods or oral nutrition supplements; also nutrition formulations given by tube into the gastrointestinal tract (enteral feeding) or given by infusion intravenously (parenteral feeding or PN). Nutrition support may compensate in part or in full for inadequate food consumption. In this review, nutrition interventions do not include the use of nutrition formulations given routinely in 'Enhanced Recovery after Surgery (ERAS)' programmes, which have been recently reviewed in the context of gynaecological oncology (Lv 2010). Nutrition interventions may occur at any stage in the perioperative period with the intention to identify, prevent or treat malnutrition. It is important that the risk of adverse effects associated with the provision of nutrition support are considered. Risks associated with nutrition support interventions may range from minor effects such as taste dislike or nausea to life-threatening effects such as PN catheter-related sepsis.
How the intervention might work
Nutrition screening and assessment may identify women at risk of malnutrition and enable nutrition support to be implemented. Nutrition support may improve the nutrient intake of women undergoing surgical intervention for the investigation or treatment of ovarian cancer or associated complications. The nutrition intervention may prevent further nutritional losses at a time of increased metabolic requirements due to the stresses of surgery and the requirement for postoperative wound healing.
Nutrition interventions may improve quality of life (QoL) as perceived by the patient. In other patient groups undergoing radiotherapy for cancer treatment, randomised controlled trials (RCTs) have shown that nutrition counselling improved nutrition intake, nutritional status and QoL (Ravasco 2005; Ravasco 2005a).
Nutrition interventions may reduce the length of hospital stay. Malnutrition has been identified as a factor contributing to prolonged length of stay following surgery for gynaecological cancer (Laky 2010).
Nutrition interventions may affect clinical outcome by reducing postoperative complications. Parenteral nutrition has been successfully used to raise prealbumin levels above 10 mg/dL in women with ovarian cancer; this reduced the incidence of surgical complications, which occurred in women when prealbumin levels were lower than 10 mg/dL. Prealbumin levels were subsequently used to determine the prescription of nutritional support and the timing of surgical intervention (Geisler 2007).
Women who are unable to eat due to ovarian cancer-related intestinal obstruction can be given nutrients by an alternative route (PN) either pre- or perioperatively (Rubin 1989). Nutrition support techniques may be used as an alternative to normal food intake where gastroparesis has occurred as a side effect of cytoreductive surgery in ovarian cancer (Caprino 2006).
The identification of malnutrition may provide useful prognostic information. Mean survival time has been shown to be longer in well-nourished women than in malnourished women with similar cancer staging (Gupta 2008). Nutrition status can improve. Some women with ovarian cancer identified as being malnourished at diagnosis, were subsequently noted to be nourished three months later and they had a median survival time similar to that of women who were identified as well nourished both at diagnosis and at three months. Nutritional interventions may have contributed to improved nutritional status (Gupta 2010).
Why it is important to do this review
Malnutrition has been shown to be a significant risk in women with ovarian cancer and therefore requires purposeful identification and treatment. Nutrition interventions may positively improve clinical outcomes, nutritional status or QoL measures in women with ovarian cancer. There is a need to develop practical guidance on the use of nutrition interventions derived from a systematic review of high quality studies undertaken in this patient group.
- To assess the effects of nutrition interventions in the perioperative period for women with ovarian cancer.
- To evaluate whether the effects are modified by nutritional status at baseline or by type of nutrition intervention.
Criteria for considering studies for this review
Types of studies
Only RCTs were included.
Types of participants
Adult women (aged 18 years and over) in the perioperative phase of surgical treatment for ovarian cancer. Although the perioperative period may be considered to extend from the time when the patient is admitted to hospital for surgery until they are discharged, the term can also cover the period of time in which a patient is prepared physically (and psychologically) for surgery (i.e. from the time that surgery is planned as a treatment for ovarian cancer). The latter broader time period was considered for inclusion. Studies could include surgery at any stage in the treatment of ovarian cancer including recurrent cancer.
If studies included patients with cancer other than ovarian cancer, such as other gynaecological cancers, we only included studies where all patients were being surgically treated for cancer and where at least 75% of participants were women with ovarian cancer. No studies were found where information was reported by separate types of cancer and where data on ovarian cancer only could be extracted.
Types of interventions
We examined trials where any type of nutrition interventions was provided at any stage in the perioperative period where surgery was used as a treatment for ovarian cancer. Nutrition interventions were defined as any of the following: nutrition screening/assessment, nutrition counselling/advice, supplementary foods or drinks, fortified foods, oral nutrition supplements, enteral or parenteral feeds. Nutrition support would include a mixture of nitrogen and non-nitrogen energy with vitamins and minerals and be either supplementary to the usual food and drink provision or be the sole source of nourishment. Nutrition interventions were considered in comparison with no nutrition intervention or were comparisons of alternative types of nutrition intervention.
Types of outcome measures
- Overall survival (OS) recorded up to five years.
- Length of hospital stay.
- Infective and non-infective complications that occurred subsequent to the surgery including haemorrhage, sepsis, wound breakdown, anastomatic leak, bowel obstruction, paralytic ileus, pulmonary embolism and deep vein thrombosis, chest infection and urinary infection. Complications were included in relation to the route of access (line infection, nasogastric tube misplacement) or in relation to the substrate (such as metabolic abnormalities). Details about whether complications were recorded prospectively or retrospectively and how they were defined were noted.
- Nutrition measures including nutrient intake, anthropometry (physical measures of the body), subjective global assessment (SGA) or other validated nutrition assessment tools or minor complications related to the nutrition including nausea, vomiting or diarrhoea.
- Functional measures such as change in performance status, hand grip strength or sit-to-stand time.
- QoL measures including patient-reported outcomes.
- Biochemical measures of nutritional status (blood tests), e.g. prealbumin, transferrin, retinol-binding protein, urinary nitrogen balance.
Search methods for identification of studies
The following electronic databases were searched:
- the Cochrane Gynaecological Cancer Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2012, Issue 7) and DARE (2012, Issue 3) (Appendix 1),
- Medline (1946 to July week 4 2012) (Appendix 2, Appendix 2)
- Embase (1980 to 2012 week 31) (Appendix 3),
- AMED (1985 to April 2012), BNI (1992 to April 2012), CINAHL (1981 to April 2012)
All relevant articles were identified on PubMed and using the ‘related articles’ feature, a further search was carried out for newly published articles. Papers in all languages were sought and translations were carried out as necessary.
Searching other resources
Unpublished and grey literature
Metaregister (http://www.controlled-trials.com/rct), Physicians Data query (http://nci.nih.gov), http://www.clinicaltrials.gov and http://www.cancer.gov/clinicaltrials were searched for ongoing trials. An ongoing trial that had not been published was identified; we approached the principal investigator to ask for information concerning the protocol and likely date of publication of results. Conference proceedings and abstracts were searched through ZETOC (http://zetoc.mimas.ac.uk) and WorldCat Dissertations.
Handsearching was undertaken of the citation lists of included studies and a previous systematic review to identify further relevant trials.
Data collection and analysis
Selection of studies
All titles and abstracts retrieved by electronic searching were examined by two review authors to determine relevance and eligibility. Papers that did not meet the eligibility criteria were excluded. When there was insufficient information to make a decision based on the abstract and title, the full article was obtained in order to make a decision. Two review authors independently reviewed relevant references and discussed with the team of review authors to ensure they met the eligibility criteria. The reasons for exclusion of studies were documented.
Data extraction and management
A data collection form devised for the study to facilitate data collection from the included studies was piloted and modified. Data extraction was undertaken by review authors (JC, VLD, LK, LJL) independently with discrepancies discussed. The following information was recorded:
- authorship, year of publication, country of origin and source of funding;
- patient details, number of participants, age, inclusion and exclusion criteria;
- cancer diagnosis including staging if indicated, type of surgery used, details of prior chemotherapy;
- details of nutrition status of women including BMI, the proportion of malnourished women (and definition of malnutrition);
- details of nutrition intervention (including type of food or nutrition support product, route of intervention, time period of intervention and quantity delivered);
- details of primary and secondary outcomes including the time points when these were collected and reported.
Data on outcomes were extracted:
For dichotomous outcomes, we examined the number of women in each treatment arm who experienced the outcome of interest and the number of women assessed at endpoint, in order to estimate a risk ratio (RR).
For continuous outcomes, we recorded the final value and standard deviation (SD) of the outcome of interest and the number of women assessed at endpoint in each treatment arm at the end of follow-up, in order to estimate the mean difference (MD) between treatment arms and its standard error.
All data extracted were relevant to an intention-to-treat analysis, in which participants were analysed in the groups to which they were assigned.
Assessment of risk of bias in included studies
The risk of bias in included studies was assessed using The Cochrane Collaboration's tool (Higgins 2011). This included assessment of:
- selection bias:
- random sequence generation;
- allocation concealment;
- performance bias:
- blinding of participants and personnel (women and treatment providers) - although blinding may not have been possible due to the nature of the interventions;
- detection bias:
- blinding of outcome assessment;
- attrition bias:
- incomplete outcome data: the proportion of participants whose outcomes were not reported at the end of the study was noted; a level of loss to follow-up for each outcome was coded as:
- low risk of bias, if fewer than 20% of women were lost to follow-up and reasons for loss to follow-up were similar in both treatment arms;
- high risk of bias, if more than 20% of women were lost to follow-up or reasons for loss to follow-up differed between treatment arms;
- unclear risk of bias, if loss to follow-up was not reported;
- reporting bias:
- selective reporting of outcomes
- other possible sources of bias.
The 'Risk of bias' tool was independently applied and differences resolved by discussion. Results were summarised in a 'Risk of bias' summary. Results of meta-analyses in future updates of the review will be interpreted in light of the findings with respect to risk of bias.
Measures of treatment effect
The following measures of the effect of treatment were used: for dichotomous outcomes RR was used and for continuous outcomes the MD between treatment arms.
Dealing with missing data
If missing data were identified, it had been planned to contact study authors to seek relevant information. There was no imputation of missing data for any outcome.
Sensitivity analyses were planned to be performed, excluding studies at high risk of bias
Description of studies
Results of the search
The results of the search are summarised in Figure 1. Following the initial review of titles and abstracts and after handsearching, it was noted that the search strategy had not been sufficiently broad to identify all available studies in this area, in some studies, patients with ovarian cancer were categorised as having 'gynaecological cancer'. The title search was therefore repeated to include the broader term of 'gynaecological cancer', when a further 2642 titles were examined for relevance. A total of 4092 titles were therefore screened. Fourteen papers were examined in detail to determine relevance where this could not be determined from the abstract. Thirteen studies were excluded as they did not meet the criteria of the protocol, one study met the protocol criteria and was included.
|Figure 1. Study flow diagram.|
See Characteristics of included studies. In this RCT (Minig 2009a) a comparison was made of postoperative feeding regimens for women who were undergoing intestinal resection in conjunction with surgery for gynaecological malignancy; 88% of the women had ovarian cancer (n = 35); FIGO staging was not reported. This was a single-centre trial conducted in Milan, Italy with the aim of investigating the feasibility of early postoperative oral feeding in this patient group and evaluating whether this would result in a reduced length of hospital stay. Baseline characteristics of the women in the two comparison groups were similar; the median age of the women in the intervention and the control group was 54 and 58 years respectively. The nutritional intervention included nutritional assessment prior to surgery using a standardised subjective global assessment questionnaire that classified women as well nourished, moderately nourished or severely malnourished. This assessment was used to determine eligibility for the trial and women who were found to be severely malnourished were excluded. Postoperatively, the nutritional intervention comprised an early oral feeding (EOF) regimen in comparison with a "traditional" oral feeding regime (TOF) where nourishment was withheld until normal bowel function resumed, evidenced by bowel sounds and passage of flatus.
See Characteristics of excluded studies. All of the excluded studies included some women with ovarian cancer. One RCT examined the provision of oral and parenteral nutrition supplementation in women with advanced ovarian cancer undergoing chemotherapy, however, the chemotherapy was given after the surgical phase of treatment rather than prior to surgery (Nuutinen 1982). The use of postoperative parenteral nutrition for women with advanced ovarian cancer was studied in a group of women in comparison with a similar group of women who did not receive parenteral nutrition, but the trial was excluded as there was no reported evidence of randomisation (Tan 2002). Two studies, which were not RCTs, examined early postoperative feeding as part of a new clinical pathway and compared data from the prospective trials with data extracted retrospectively on earlier patients (Gerardi 2008; Marx 2006). Four RCTs examining early postoperative oral feeding in contrast to traditional postoperative regimens in women undergoing major abdominal gynaecological surgery were not included, as the study groups included women with benign disease in addition to women with malignant disease and there was an insufficient proportion of women with ovarian cancer (Pearl 1998; Pearl 2002; Schilder 1997; Steed 2002). The effects of early postoperative feeding were also observed in three RCTs including only women with gynaecological cancer, the proportion of women with ovarian cancer ranged from 18% to 58%, this was lower than the protocol inclusion rate of 75% (Cutillo 1999; Feng 2008; Minig 2009b). An earlier RCT included an intervention group who were given postoperative elemental feeding via jejunostomy tube. Although all the women in the study had gynaecological malignancies, only half had ovarian cancer (Spirtos 1988). More recently perioperative enteral feeding using standard and immune-enhancing feeds was compared in an RCT of women with gynaecological cancers; this trial included 32% of patients with ovarian cancer (Celik 2009).
Risk of bias in included studies
In the included study (see Characteristics of included studies), a web-based randomisation system was used (TENALEA 2013) where patient details were entered prior to the randomisation. Allocation to groups was made after surgery was completed and when it had been verified that no intraoperative exclusion criteria had occurred (exclusions were: if total or anterior pelvic exenteration had occurred or if intestinal bowel resection had not been performed). No information was reported concerning whether those who cared for the women, measured outcomes and analysed the data were aware of which intervention the women were receiving; due to the nature of the intervention, blinding may not have been possible. Postoperative exclusion from the trial was to occur if intensive care unit (ICU) admission equalled or exceeded 24 hours, or if the malignancy was found to be non-gynaecological. Eleven of 51 women (22%) were excluded from the trial postoperatively, with similar numbers and reasons in both study groups. It is reported that these women received the intervention, although it is unclear for what length of time. Post-randomisation exclusion may have increased the risk of bias and raises the possibility that the intervention may be associated with an outcome that resulted in exclusion from the trial. As the nutrition intervention is a supportive therapy rather than a primary treatment, the welfare of the patient undergoing prolonged ICU admission may not be compatible with the continuing administration of the intervention.
The authors reported both their primary and secondary end-points. Although it was noted that there was a significant difference in estimated blood loss (EBL), which was greater in the group receiving the traditional feeding regimen compared with those receiving early oral feeding, the authors state that EBL did not have a significant impact on length of hospital stay. FIGO stage was also reported as not being associated with length of hospital stay but details of FIGO staging were not reported. Although subjective global assessment score was evaluated, it was not reported so it is unclear if there were differences in nutritional status between the comparison groups.
Other potential sources of bias
There is a potential risk of bias associated with the small size of the study. The women in the study were carefully selected for inclusion in the RCT; although they all had gynaecological cancer, not all of them had ovarian cancer.
Effects of interventions
In the included study, most women in the early intervention group (78%, n = 14) were able to consume drinks within 24 hours of surgery and solid food one day after surgery, this was at least two days prior to those in the traditional feeding group. The primary outcome of the study was length of stay which was significantly shorter in the EOF group (9.1 ± 4.5 (mean days ± SD) compared to 6.9 ± 2.6 ). After adjustment for postoperative complications, the mean reduction in stay was 1.7 days. Overall survival was evaluated until 30 days following discharge from hospital. In this period, there was one death of a woman who had been in the group receiving traditional oral feeding (TOF), cause of death was not noted. The incidence of postoperative complications did not differ statistically between the groups, 44% of the patients in the EOF group had complications, none of which were infectious complications; in the TOF group, complications occurred in 55% of the patients of which a quarter had infectious complications. No complications were reported to result from the nutrition intervention. The incidence of nausea and vomiting during the postoperative stay was similar in both groups and was noted in slightly more than half of the women. Scores were similar between the two groups on the two health-related quality of life questionnaires used at 30 days after hospital discharge and overall postoperative satisfaction was noted to be similar in both groups. Half of the women in the TOF group reported a wish to eat sooner than was allowed by the protocol. Nutrient intake, anthropometric measures, functional and biochemical measures were not evaluated as outcomes in this study.
Summary of main results
Results from the included study showed evidence that a small group of women with ovarian cancer who were undergoing surgery including intestinal resection could tolerate an early introduction of oral fluids and foods postoperatively, and that this resulted in a reduced length of hospital stay and no difference in postoperative complication rates in comparison with women who had a traditional postoperative feeding regimen. One of the strengths of the study was that alternative feeding regimens were the only aspects of the perioperative management of the patients that differed between the randomised groups.
Overall completeness and applicability of evidence
The most striking observation from this review concerns the absence of information on this topic. While it has been reported that the incidence of malnutrition in women with ovarian cancer may vary between 28% (Zorlini 2008) and 67% (Laky 2008) and may extend to 75% where there is associated bowel obstruction (Larson 1989), there are currently no published RCTs specifically addressing the treatment of malnutrition in women with ovarian cancer or investigating the use of nutrition assessment linked to preoperative nutritional interventions in this patient group. This situation will be partly addressed by a trial currently underway where randomisation to early postoperative enteral feeding is being trialled in women identified as being at nutritional risk (Characteristics of ongoing studies). The included study is of limited applicability to women with ovarian cancer, as the 35 women in the study with ovarian cancer were all undergoing surgery that included intestinal resection.
Quality of the evidence
Results from the included study indicate that women with ovarian cancer who are undergoing surgery with associated intestinal resection may be able to manage selected fluids within 24 hours of operation and solid foods on the following day. The small number of women with gynaecological cancer (n = 40) included in the study was calculated on the basis of demonstrating a significant difference in the length of hospital stay in relation to the feeding regimens. There was no reported quantification of the amount of foods consumed, information concerning the use of intravenous fluids or measurement of nutrition outcomes. The study was conducted in a single centre and therefore may not be generalisable. Additionally, there were several reasons why women were not eligible for the trial, including women with significant other presenting conditions including an ASA (American Society of Anesthesiologists) score of four or more, severe concomitant medical condition, metabolic disease such as type 1 diabetes, infection or intestinal obstruction. Women were also excluded if found to be severely malnourished, although this was reported to be determined only on the criteria of recent weight loss greater than 10%, an assessment which may not be applicable to women with ovarian cancer; within this study, 42% of the women (n = 17) were noted to have ascites, which may disguise significant weight loss. There is no evidence from the included trial that can be applied to women who have ovarian cancer in association with these exclusion criteria or who require surgery without intestinal resection.
Potential biases in the review process
We undertook to minimise bias in this review by the breadth of our search for relevant papers including handsearching and by repeating the electronic searches when it became evident that some studies, which included patients with ovarian cancer, were categorised as having 'gynaecological cancer'. Titles, abstracts and papers were all reviewed by at least two review authors. Bias in the review process may have been influenced by the decision to exclude studies where fewer than 75% of included patients had ovarian cancer in an attempt to secure information relevant to women with ovarian cancer. It became evident from our data selection process that most studies relevant to this topic include women with differing types of gynaecological cancer or where groups of women may have either a benign or malignant tumour and that data are not reported separately for differing types of disease. Although malnutrition has been noted in association with other types of gynaecological cancer, it is most prevalent in association with ovarian cancer and therefore, data were sought that was specific to women with ovarian cancer. If we had lowered the inclusion rate selected to include studies where a majority of the women in a mixed study (more than 50%) had ovarian cancer, this would only have resulted in the inclusion of one additional study.
Agreements and disagreements with other studies or reviews
Our review concurs with a recent systematic review which was unable to identify any RCTs that evaluated the use of nutrition supplementation or nutrition counselling in women with ovarian cancer (Balogun 2012). A Cochrane systematic review on the topic of early versus delayed oral fluids and food after major abdominal gynaecologic surgery included three studies including some patients undergoing surgery for ovarian cancer (Charoenkwan 2007). The conclusion of Charoenkwan 2007 was that early feeding after major abdominal gynaecologic surgery was safe even though associated with an increased risk of nausea, and that early feeding was associated with a reduced length of hospital stay.
Implications for practice
There is limited evidence from one small randomised controlled trial (RCT) that some women with ovarian cancer undergoing surgery, including bowel resection, may manage to commence oral fluids within 24 hours of surgery and may manage to eat normal foods on the following day without increasing the risk of postoperative complications.
Implications for research
Women with ovarian cancer may be at risk of malnutrition but there is an absence of research concerning the identification and treatment of malnutrition in this patient group. Studies are needed which examine whether nutrition interventions such as good quality nutrition counselling with or without the use of oral supplements following diagnosis and before and during the perioperative period may be efficacious in improving nutrition status, treatment outcomes and quality of life for women with ovarian cancer. Particular effort should be given to identifying, supporting and treating women identified as being most at risk of malnutrition.
Further analysis of data from RCTs, which include large sub-groups of women with ovarian cancer (such as RCTs where women with other types of gynaecological cancer are also included), could provide more information concerning the effect of nutrition interventions specific to this population group.
Replication of the early feeding intervention in a further RCT and with the inclusion of women who may have additional co-morbidities will confirm whether early oral fluids and foods should be recommended as standard practice for women with ovarian cancer undergoing surgery either with or without bowel surgery.
We thank Chris Williams and Jo Morrison for clinical and editorial advice, Jane Hayes for designing the search strategy and Gail Quinn and Clare Jess for their contribution to the editorial process. We additionally thank Janice Lui for study translation. Dr Sorrel Burden was supported by a Post Doctoral Fellowship Grant from Macmillan Cancer Support.
The National Institute for Health Research (NIHR) is the largest single funder of the Cochrane Gynaecological Cancer Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NIHR, NHS or the Department of Health.
Data and analyses
This review has no analyses.
Appendix 1. CENTRAL/DARE search strategy
#1 MeSH descriptor Perioperative Care explode all trees
#2 MeSH descriptor Perioperative Period explode all trees
#3 peri-operative or perioperative
#4 MeSH descriptor Surgical Procedures, Operative explode all trees
#5 Any MeSH descriptor with qualifier: SU
#6 surg* or operat* or procedure*
#7 (#1 OR #2 OR #3 OR #4 OR #5 OR #6)
#8 MeSH descriptor Nutrition Therapy explode all trees
#9 MeSH descriptor Nutrition Disorders explode all trees
#10 MeSH descriptor Nutritional Status, this term only
#11 MeSH descriptor Nutrition Assessment, this term only
#12 MeSH descriptor Cachexia, this term only
#13 weight or underweight or cachexi* or malnutrition
#14 nutrition* or nutrient* or macronutrient* or micronutrient* or immunonutrition or immunonutrition
#15 MeSH descriptor Foodexplode all trees
#16 food* or feed* or supplement* or vitamin* or mineral* or protein* or fat* or carbohydrate* or calorie* or energy
#17 MeSH descriptor Dietexplode all trees
#18 Any MeSH descriptor with qualifier: DH
#20 MeSH descriptor Fish Oils explode all trees
#21 MeSH descriptor Amino Acids explode all trees
#22 amino acid* or fatty acid* or fish oil* or omega 3 or glutamin* or arginine or novel substrate* or nitrogen
#23 MeSH descriptor Feeding Methods explode all trees
#24 enteral or parenteral of PN or TPN or naso-gastric or nasogastric or gastrostomy or jejunostomy
#25 (#8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24)
#26 MeSH descriptor Genital Neoplasms, Female explode all trees
#27 MeSH descriptor Ovarian Neoplasms explode all trees
#28 (gynaecologic* or gynecologic* or ovar*) near/5 (cancer* or tumor* or tumour* or malignan* or carcinoma* or adenocarcinoma*)
#29 (#26 OR #27 OR #28)
#30 (#7 AND #25 AND #29)
Appendix 2. Medline search strategy
1 exp Perioperative Care/
2 exp Perioperative Period/
3 (peri-operative or perioperative).mp.
4 exp Surgical Procedures, Operative/
6 (surg* or operat* or procedure*).mp.
7 1 or 2 or 3 or 4 or 5 or 6
8 exp Nutrition Therapy/
9 exp Nutrition Disorders/
10 Nutritional Status/
11 Nutrition Assessment/
13 (weight or underweight or cachexi* or malnutrition).mp.
14 (nutrition* or nutrient* or macronutrient* or micronutrient* or immunonutrition or immuno-nutrition).mp.
15 exp Food/
16 (food* or feed* or supplement* or vitamin* or mineral* or protein* or fat* or carbohydrate* or calorie* or energy).mp.
17 exp Diet/
18 diet therapy.fs.
20 exp Fish Oils/
21 exp Amino Acids/
22 (amino acid* or fatty acid* or fish oil* or omega 3 or glutamin* or arginine or novel substrate* or nitrogen).mp.
23 exp Feeding Methods/
24 (enteral or parenteral or TPN or naso-gastric or nasogastric or gastrostomy or jejunostomy).mp.
25 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24
26 exp Genital Neoplasms, Female/
27 exp Ovarian Neoplasms/
28 ((gynaecologic* or gynecologic* or ovar*) adj5 (cancer* or tumor* or tumour* or malignan* or carcinoma* or adenocarcinoma*)).mp.
29 26 or 27 or 28
30 randomized controlled trial.pt.
31 controlled clinical trial.pt.
34 clinical trials as topic.sh.
37 30 or 31 or 32 or 33 or 34 or 35 or 36
38 7 and 25 and 29 and 37˜
39 exp animals/ not humans.sh.
40 38 not 39
mp=protocol supplementary concept, rare disease supplementary concept, title, original title, abstract, name of substance word, subject heading word, unique identifier
Appendix 3. Embase search strategy
1 perioperative period/
2 (peri-operative or perioperative).mp.
3 exp surgery/
5 (surg* or operat* or procedure*).mp.
6 1 or 2 or 3 or 4 or 5
7 exp diet therapy/
8 exp nutritional disorder/
9 exp nutritional status/
10 nutritional assessment/
12 (weight or underweight or cachexi* or malnutrition).mp.
13 (nutrition* or nutrient* or macronutrient* or micronutrient* or immunonutrition or immuno-nutrition).mp.
14 exp Food/
15 (food* or feed* or supplement* or vitamin* or mineral* or protein* or fat* or carbohydrate* or calorie* or energy).mp.
16 exp diet/
18 fish oil/
19 exp amino acid/
20 (amino acid* or fatty acid* or fish oil* or omega 3 or glutamin* or arginine or novel substrate* or nitrogen).mp.
21 exp food intake/
22 (enteral or parenteral or PN or TPN or naso-gastric or nasogastric or gastrostomy or jejunostomy).mp.
23 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22
24 exp female genital tract tumor/
25 exp ovary tumor/
26 ((gynaecologic* or gynecologic* or ovar*) adj5 (cancer* or tumor* or tumour* or malignan* or carcinoma* or adenocarcinoma*)).mp.
27 24 or 25 or 26
28 crossover procedure/
29 double-blind procedure/
30 randomized controlled trial/
31 single-blind procedure/
34 (crossover* or cross over* or cross-over*).mp.
36 (double* adj blind*).mp.
37 (singl* adj blind*).mp.
41 28 or 29 or 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40
42 6 and 23 and 27 and 41
43 (exp Animal/ or Nonhuman/ or exp Animal Experiment/) not Human/
44 42 not 43
[mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword]
Last assessed as up-to-date: 31 July 2013.
Contributions of authors
The protocol and review was drafted by HAB who also co-ordinated the review and undertook data entry. CH provided specialist advice that the focus of the review should be on women with ovarian cancer and provided a clinical perspective to the review and to the interpretation of data. JC was involved in designing the review, screening search results and screening retrieved papers for eligibility, VLD was involved in designing the review, screening retrieved papers, extracting data from papers and appraising the quality of papers. LK was involved in designing the review, screening retrieved papers for eligibility, liaison with the interpreter, extracting data from papers and appraising the quality of papers, LJL was involved in designing the review, screening retrieved papers for eligibility, the design of data extraction forms, liaison with the interpreter, extracting data from papers and appraising the quality of papers, AJW was involved in the design of the review and the design of data extraction forms. SB supervised HAB, conceived and initiated the review to examine the nutritional requirements of patients with gynaecological cancer, screened retrieved papers and provided methodological perspective to the review. All authors reviewed both the draft protocol and draft review, which was subsequently amended to reflect their comments.
Declarations of interest
Sources of support
- This work was supported by the NIHR Manchester Biomedical Research Centre, UK.
- No sources of support supplied
Differences between protocol and review
Some minor clarification of methods was made at the request of reviewers which did not affect how the present review was undertaken but would be incorporated into future updates of this review. Due to time constraints, some tasks were undertaken by different authors than originally planned. As only one study was identified for inclusion, it was not necessary to use some statistical analysis as detailed in the protocol. If we had obtained further studies, then the following elements of the protocol would have been used and these will be incorporated in future updates as appropriate
Assessment of heterogeneity
We planned to assess heterogeneity between studies by visual inspection of forest plots, by estimation of the percentage heterogeneity between trials that could not be ascribed to sampling variation (Higgins 2003), by a formal statistical test of the significance of the heterogeneity (Deeks 2001) and, if possible, by subgroup analyses (Subgroup analysis and investigation of heterogeneity). If there was evidence of substantial heterogeneity, we planned to investigate and report the possible reasons for this.
Assessment of reporting biases
We intended to examine funnel plots corresponding to meta-analysis of the primary outcome to assess the potential for small-study effects such as publication bias. If these plots suggested that treatment effects were not sampled from a symmetric distribution, as assumed by the random-effects model, we would have performed further meta-analyses using fixed-effect models.
If sufficient, clinically similar studies were available, their results would have been pooled in meta-analyses.
For time-to-event data, we planned to pool hazard ratios (HRs) using the generic inverse variance facility of RevMan 5.
For any dichotomous outcomes, the RR would have been calculated for each study and these were then to be pooled.
For continuous outcomes, we planned to pool the mean differences between the treatment arms at the end of follow-up if all trials measured the outcome on the same scale, otherwise standardised mean differences would have been used.
If any trials had multiple treatment groups, the ‘shared’ comparison group would have been divided into the number of treatment groups and comparisons between each treatment group and the split comparison group would have been treated as an independent comparison.
We planned to use random-effects models with inverse variance weighting for all meta-analyses (DerSimonian 1986) if data allowed.
If possible, studies making different comparisons would have been synthesised using the methods of Bucher 1997.
Subgroup analysis and investigation of heterogeneity
We planned to undertake subgroup analysis on studies if data allowed grouping the trials by:
- malnourished versus non-malnourished; trials conducted before and after 1990 (since when there have been significant developments in artificial feeding and nutrition support);
- factors such as age, stage, type of intervention, length of follow-up, adjusted/unadjusted analysis were planned to be considered in the interpretation of any heterogeneity.
Medical Subject Headings (MeSH)
*Food; Elective Surgical Procedures; Fluid Therapy [*methods]; Malnutrition [*diet therapy; etiology]; Ovarian Neoplasms [complications; *surgery]; Perioperative Care [*methods]; Postoperative Nausea and Vomiting [epidemiology]; Randomized Controlled Trials as Topic
MeSH check words
Adult; Female; Humans