Chemotherapy, surgery and radiotherapy for locally advanced breast cancer

Background

Breast cancer is the most common cause of cancer death in women world wide. In the developed world it is estimated that approximately 1 in 11 women will develop the disease over their lifetime. Most new diagnoses are at an early stage of disease (especially in countries with mammographic screening programs), where all macroscopic evidence of malignancy can be removed, and there is a reasonable prospect of long term survival with standard treatments. However, breast cancer can sometimes present as a mass that is large, diffuse or attached to surrounding tissues, making initial surgery very difficult. Such "locally advanced" breast cancer accounts for between 5-30% of all cases of breast cancer, depending on the population group studied (Therasse 2003).

To date the results of treatment of locally advanced breast cancer have been poor, with 5 year survival rates often as low as 30%. Progress in this area has been limited by the relative infrequency of the disease, and resultant lack of clinical trials evaluating its management (Hortobagyi 1998). Furthermore, the definition of what constitutes "locally advanced breast cancer" is broad, and includes those with inoperable stage IIIB, potentially operable T3 tumours, positive supraclavicular lymphadenopathy and inflammatory subtypes. Thirdly chemotherapy, surgery and radiotherapy have often been used in different combinations and sequences across different treatment centres. This variability in disease definition and treatment strategies makes assessment of efficacy very complex.

The aim of this review is to identify and synthesise data from all published randomized trials that compare the effects of different local and systemic therapies on patient outcomes in women with locally advanced breast cancer.

Objectives

1. To assess the impact of different combinations of local therapies and systemic therapies on survival and locoregional disease control in locally advanced breast cancer.

Specifically, for local therapies,
the effect of differing amounts and type of local therapy (surgery and radiotherapy, either alone or in combination)
the effect of different sequences of local therapy (surgery then radiotherapy or vice versa)

and for systemic therapies
the effect of differing amounts and duration of treatment (for example, more chemotherapy versus less or chemotherapy with or without endocrine therapy)
the effect of sequence in relation to local therapy (chemotherapy before or after local therapy)

2. To determine if overall duration or amount of therapy influences treatment outcome

Methods

Criteria for considering studies for this review

Types of studies

Randomized controlled trials involving

women with "locally advanced breast cancer" as classified by the investigators
women with inoperable non-inflammatory breast cancer
women with inflammatory breast cancer as defined by the investigator

Properly randomized controlled trials that evaluate

amount of local therapy (surgery, radiotherapy or both)
amount of systemic therapy (dose, duration, intensity)
sequence of modalities

Local therapies may include surgery and/or radiotherapy.
Systemic therapies may include chemotherapy and/or endocrine therapy and/or molecularly targeted therapy.
Trials that study a mixed population of women with "early or locally advanced" or "locally advanced or metastatic" disease will be excluded, unless the proportion of patients with locally advanced disease represents the majority (>85%), or patients with locally advanced disease can be identified clearly and outcomes extracted.

Types of participants

Women with "locally advanced breast cancer" as defined above:
Any age of patient
Any menopausal status
Any hormone receptor status (ER or PR)
Any Her 2 status

Types of interventions

Interventions include the use of any of:

Surgery
Radiotherapy (in the neoadjuvant, definitive or adjuvant setting, using conventional external beam techniques and including the use of boosts, and dose fractionation)
Chemotherapy (in the neoadjuvant, definitive or adjuvant setting, given systemically, using conventional cytotoxic agents, with or without colony stimulating factors [excluding cytokines or monoclonal antibodies used alone, and high-dose chemotherapy requiring stem cell support])
Endocrine manoeveres (including anti-oestrogens, oestrogens, androgens, aromatase inhibitors, progestogens and ablations [ovarian , adrenal]
Molecularly targeted therapy (herceptin)

in single agent, or combined modality comparison.

Types of outcome measures

Primary outcomes

Overall survival

Local control (proportion free of local disease progression)

Secondary outcomes

Disease free survival

Time to, or proportion with local disease progression

Time to, or proportion with distant disease progression

Response rate

Quality of life

Toxicity

Subgroup analyses
Will be performed if there are sufficient data to justify them, in particular to identify differences in the effectiveness of treatments between:

inflammatory and non-inflammatory subtypes

Search methods for identification of studies

The Cochrane Breast Cancer Group's specialized register will be searched. Trials coded as potentially relevant to locally advanced or inflammatory breast cancer will be assessed by both investigators, first by abstract, then blinded methods section then full manuscript as appropriate. Details of the search strategy applied by the Group to create the register, and the procedure used to code references, are described in the Group's module on the Cochrane Library.

Data collection and analysis

Study selection

Study selection will be undertaken independently by the reviewers (CM and NW), both of whom are content experts. The above selection criteria will be applied to each trial, initially based on title, with the subsequently agreed pool of potentially eligible trials screened with the results section (and any other area where the results appeared) masked. For unpublished trials, available information from conference proceedings will be screened.

Assessment of trial quality

A quality score will be applied to describe the adequacy of allocation concealment:
A. low risk of bias in the randomization process (eg randomization by telephone call to central office).
B. moderate risk of bias (eg sealed envelopes)
C. high risk of bias
D. trials where there was insufficient information to score allocation concealment

Data extraction

Initial data will be extracted independently by CM and NW. This will include baseline characteristics of the patients, the interventions being tested, tumour response rates, median survivals, and information about toxicity and quality of life. Hazard ratios and confidence intervals will be derived by extracting and combining study estimates according to the method described in Parmar 1998.

Analysis

Results of eligible studies will be statistically synthesised (meta-analysis) if appropriate. It is inevitable that some post hoc judgment will be required, because a number of different questions may be posed, and there may only be one or two trials addressing particular questions. Tumour response rates as reported will be analysed as categorical variables and a pooled relative risk derived if appropriate. It is unlikely that anything other than a narrative review of toxicity and quality of life data will be possible.

Background

Objectives

1. To assess the impact of different combinations of local therapies and systemic therapies on survival and locoregional disease control in locally advanced breast cancer.

2. To determine if overall duration or amount of therapy influences treatment outcome

Methods

Criteria for considering studies for this review

Types of studies

Randomized controlled trials involving

women with "locally advanced breast cancer" as classified by the investigators
women with inoperable non-inflammatory breast cancer
women with inflammatory breast cancer as defined by the investigator

Properly randomized controlled trials that evaluate

amount of local therapy (surgery, radiotherapy or both)
amount of systemic therapy (dose, duration, intensity)
sequence of modalities

Types of participants

Women with "locally advanced breast cancer" as defined above:
Any age of patient
Any menopausal status
Any hormone receptor status (ER or PR)
Any Her 2 status

Types of interventions

Interventions include the use of any of:

Surgery
Radiotherapy (in the neoadjuvant, definitive or adjuvant setting, using conventional external beam techniques and including the use of boosts, and dose fractionation)
Chemotherapy (in the neoadjuvant, definitive or adjuvant setting, given systemically, using conventional cytotoxic agents, with or without colony stimulating factors [excluding cytokines or monoclonal antibodies used alone, and high-dose chemotherapy requiring stem cell support])
Endocrine manoeveres (including anti-oestrogens, oestrogens, androgens, aromatase inhibitors, progestogens and ablations [ovarian , adrenal]
Molecularly targeted therapy (herceptin)

in single agent, or combined modality comparison.

Types of outcome measures

Primary outcomes

Overall survival

Local control (proportion free of local disease progression)

Secondary outcomes

Disease free survival

Time to, or proportion with local disease progression

Time to, or proportion with distant disease progression

Response rate

Quality of life

Toxicity

Subgroup analyses
Will be performed if there are sufficient data to justify them, in particular to identify differences in the effectiveness of treatments between:

inflammatory and non-inflammatory subtypes

Search methods for identification of studies

Data collection and analysis

Study selection

Assessment of trial quality

Data extraction

Analysis

Hydrocolloid dressings for treating pressure ulcers

Description of the condition

Pressure ulcers are an internationally recognised patient safety problem, estimated to affect 2.5 million people annually (House 2011). The development of pressure ulcers in any patient is a serious complication resulting in pain, decreased quality of life and significant expenditure of both time and money for the healthcare industry (VanGilder 2009). Also known as pressure injury, pressure sores, decubitus ulcers, or bedsores, pressure ulcers are a localised injury to the skin, underlying tissue, or both, usually occurring over a bony prominence, as a result of pressure, or pressure in combination with shear stress (EPUAP/NPUAP 2009).

The main factors associated with the development of pressure ulcers are exposure of the skin to excessive pressure, and a reduced tolerance of the skin to pressure. Pressure is exerted on the skin, soft tissue, muscle, and bone by the weight of an individual or a device applied against the surface. Tissue tolerance is the ability of the skin and its supporting structures to tolerate the effects of pressure by distributing it (cushioning) and by the transfer of pressure loads from the skin surface to the skeleton (AWMA 2012). Tissues are capable of withstanding enormous pressures briefly, but prolonged exposure to pressure initiates a series of events that potentially leads to necrosis and ulceration of tissue.

Factors that increase pressure on the skin include impairments in mobility, activity or sensory perception, because then the pressure is not relieved by movement or changes to body position. Intrinsic risk factors for the development of pressure ulcers include advancing age, poor nutrition, poor perfusion and oxygenation, whereas, extrinsic risk factors include increased moisture, shear and friction. Shear forces and friction aggravate the effects of pressure upon tissue and are important components of the mechanism of injury. The combination of pressure, shear forces, and friction causes microcirculatory occlusion, resulting in ischemia and tissue anoxia (lack of oxygen) and stimulation of inflammatory processes, which may lead to necrotic cell death, and ulceration. Irreversible tissue damage may occur in a vulnerable patient with as little as 30 minutes of uninterrupted pressure (Kirman 2008). In addition, excessive contact of the skin to fluids impairs its barrier function, causes maceration and an increased risk of the development of pressure ulcers.

Global prevalence rate of pressure ulcers ranges from 8% to 30%, depending on patient factors and treatment setting. Prevalence surveys in European acute care settings found an overall prevalence of 18.1%, with individual countries reporting prevalence of between 8.3% to 23% (Vanderwee 2007). A recent US study estimated pressure ulcer prevalences of approximately 13.3% in acute care settings and 29% to 30% in long-term care settings (VanGilder 2009). Within Australia, pressure ulcer prevalence is currently estimated at between 5% to 15% in acute care settings and between 13% and 37% in aged care (DoH 2006). These international studies of prevalence illustrate the extent of the burden of all grades of pressure ulcers, however, variability in prevalence in similar settings suggests pressure ulcers are amenable to intervention, with substantial potential for improvement in patient and financial outcomes.

A number of systems for describing the amount of tissue damage exist, but pressure ulcers are generally graded 1, 2, 3 and 4, according to the depth of tissue damage, with category/stage 1 being the least severe, and category/stage 4 indicating complete tissue destruction (Moore 2005), as illustrated in Table 1 (EPUAP/NPUAP 2009). The majority of pressure ulcers occur on the sacrum or heel, but they also occur frequently over the elbow, hip, ischium, shoulder, spinous process, ankle, toe, head or face (Lahmann 2006; Shanin 2008; Vanderwee 2007).

Internationally, substantial investment has occurred over recent decades in monitoring, preventing and treating pressure ulcers. For example, it is estimated that the annual cost of treating pressure ulcers in Australia is between AUD 300-350 million with the cost of treating a stage 4 ulcer at nearly AUD 22, 000 (AUD) (Graves 2005; Young 1997). The total annual cost for pressure ulcer management in the UK has been estimated to be approximately GBP 1.4 to 2.1 billion annually. This equates to 4% of the total UK healthcare expenditure (Bennett 2004). The main costs incurred for the treatment and management of pressure ulcers are due to prolonged hospitalisation and the extent of nursing care required. The average length of acute hospital stay for a patient with a pressure ulcer is 12 days. In comparison, the average length of stay for patients without a pressure ulcer is 4.6 days (VanGilder 2009). Furthermore, discomfort and pain, increased time spent in hospital, increased risk of mortality, altered body image and reduced quality of life, together with the potential cost associated with litigation, compounds the cost to health services and the burden upon the patient with the pressure ulcer (VQC 2004).

In spite of the level of investment in prevention and monitoring of pressure ulcers, many people continue to develop them. This is the case particularly in acute care settings where people may present with an increased number of high risk factors such as decreased mobility, impaired perfusion, poor nutrition, and fluctuating patient status. Pressure ulcer treatment strategies can be costly and complex.

Description of the intervention

Treatment of pressure ulcers is primarily two-fold involving the relief of pressure allied with wound management. Other general strategies include patient education, pain management, optimising circulation/perfusion, optimising nutrition and the treatment of clinical infection (AWMA 2012). Wound management may involve surgical or chemical debridement (removal of dead tissue) and dressings to protect the wound and promote healing. Dressings can be divided into four main categories, namely, basic wound dressings, advanced wound dressings, anti-microbial dressings and specialist dressings. Classification of a dressing depends on its purpose and the key material used. Key attributes of a dressing have been described (BNF 2010), and include:

the ability of the dressing to absorb and contain exudate without leakage or strike-through (saturation);
lack of particulate contaminants left in the wound;
thermal insulation;
level of permeability to water and bacteria;
avoidance of wound trauma on dressing removal;
frequency with which the dressing needs to be changed;
provision of pain relief;
comfort.

The focus of this review is hydrocolloid dressings, the properties of which are described below. However, as hydrocolloid dressings are likely to be evaluated against one of the many wound dressings available, a description of potential comparators has been categorised, according to the British National Formulary (BNF 2010). These are listed alphabetically below, by their generic names and, where possible with their corresponding trade names and manufacturers. Dressing names, manufactures and distributors may vary between countries.

Absorbent dressings are applied directly to the wound and may be used as secondary absorbent layers in the management of heavily exuding wounds. Examples include Primapore (Smith & Nephew), Mepore (Mölnlycke) and absorbent cotton gauze (BP 1988).

Alginate dressings are highly absorbent fabrics/yarns that come in the form of calcium alginate or calcium sodium alginate and can be combined with collagen. The alginate forms a gel when in contact with the wound surface; this can be lifted off at dressing removal, or rinsed away with sterile saline. Bonding to a secondary viscose pad increases absorbency. Examples include: Curasorb (Covidien), SeaSorb (Coloplast) and Sorbsan (Unomedical).

Capillary-action dressings consist of an absorbent core of hydrophilic fibres held between two low-adherent contact layers. Examples include: Advadraw (Advancis) and Vacutex (Protex).

Films - permeable film and membrane dressings - are permeable to water vapour and oxygen, but not to water or micro-organisms. Examples include Tegaderm (3M) and Opsite (Smith & Nephew).

Soft polymer dressings are composed of a soft silicone polymer held in a non-adherent layer; they are moderately absorbent. Examples include: Mepitel (Mölnlycke) and Urgotul (Urgo).

Foam dressings contain hydrophilic polyurethane foam and are designed to absorb wound exudate and maintain a moist wound surface. There is a variety of versions and some include additional absorbent materials, such as viscose and acrylate fibres, or particles of superabsorbent polyacrylate, which are silicone-coated for non-traumatic removal. Examples include: Allevyn (Smith & Nephew), Biatain (Coloplast) and Tegaderm (3M).

Honey-impregnated dressings contain medical-grade honey that is purported to have antimicrobial and anti-inflammatory properties and can be used for acute or chronic wounds. It is important to note that, when such dressings are used on patients with diabetes, the patients should be monitored for changes in blood-glucose concentrations. Examples include: Medihoney (Medihoney) and Activon Tulle (Advancis).

Hydrocolloid dressings are usually composed of an absorbent hydrocolloid matrix on a vapour-permeable film or foam backing. Examples include: Granuflex (ConvaTec) and NU DERM (Systagenix). Fibrous alternatives have been developed that resemble alginates and are not occlusive: Aquacel (ConvaTec).

Hydrogel dressings consist of a starch polymer and up to 96% water. These dressings can absorb wound exudate or rehydrate a wound depending on the wound moisture levels. They are supplied in either flat sheets, an amorphous hydrogel or as beads. Examples include: ActiformCool (Activa) and Aquaflo (Covidien).

Iodine-impregnated dressings release free iodine, which is thought to act as a wound antiseptic, when exposed to wound exudate. Examples include Iodoflex (Smith & Nephew) and Iodozyme (Insense).

Low-adherence dressings and wound contact materials usually consist of cotton pads that are placed directly in contact with the wound. They can be non-medicated (e.g. paraffin gauze dressing) or medicated (e.g. containing povidone iodine or chlorhexidine). Examples include paraffin gauze dressing, BP 1993 and Xeroform (Covidien) dressing - a non-adherent petrolatum blend with 3% bismuth tribromophenate on fine mesh gauze.

Odour-absorbent dressings contain charcoal and are used to absorb wound odour. Often this type of wound dressing is used in conjunction with a secondary dressing to improve absorbency. An example is CarboFLEX (ConvaTec).

Other antimicrobial dressings are composed of a gauze or low-adherent dressing impregnated with an ointment thought to have antimicrobial properties. Examples include: chlorhexidine gauze dressing (Smith & Nephew) and Cutimed Sorbact (BSN Medical).

Protease-modulating matrix dressings alter the activity of proteolytic enzymes in chronic wounds. Examples include: Promogran (Systagenix) and Sorbion (H & R).

Silver-impregnated dressings are used to treat infected wounds, as silver ions are thought to have antimicrobial properties. Silver versions of most dressing types are available (e.g. silver foam, silver hydrocolloid etc). Examples include: Acticoat (Smith & Nephew) and Urgosorb Silver (Urgo).

The diversity of dressings available to clinicians (including variation within each type listed above) makes evidence-based decision-making difficult when determining the treatment regime for the patient. Some dressings are formulated with an 'active' ingredient such as silver that is promoted as a dressing treatment option to reduce infection and possibly to promote healing. With increasingly sophisticated technology being applied to wound care, practitioners need to know how effective these, often expensive, dressings are compared with more traditional, and usually less costly, dressings. However, far from providing critical evaluation of dressing types for clinical use, studies have shown wide variation in practice and wound (pressure ulcer) care knowledge (Maylor 1997; Pieper 1995).

How the intervention might work

The principle of moist wound healing governs wound care practice today. This is optimised through the application of occlusive or semi-occlusive dressings and preparation of the wound bed (AWMA 2012). Animal experiments performed 50 years ago suggested that acute wounds healed more quickly when their surface was kept moist, rather than being left to dry and to scab (Winter 1962; Winter 1963a; Winter 1963b). Winter 1962 examined the rate of epithelialisation in experimental wounds cut into the skin of healthy pigs, comparing wounds with a natural scab exposed to the air against wounds that were covered with polythene film. He found that epithelialisation occurred more quickly in the latter.

Wounds exposed to the air lose water vapour, the upper dermis dries and healing takes place beneath a dry scab. Covering a wound with an occlusive dressing prevents scab formation and radically alters the pattern of epidermal wound healing. Winter’s (1962) research focused only on acute, superficial wounds, but the results have been used to generate a theory of moist wound healing for all types of wound of varying aetiologies. However, the theory of moist wound healing may not provide a basis for satisfactory management of every type of wound encountered. Whilst a moist environment at the wound site has been shown to aid the rate of epithelialisation in superficial wounds, excess moisture at the wound site can cause maceration of the peri wound (surrounding) skin (Cutting 2002). Some early studies also suggested that keeping wounds moist might predispose them to infection (Hutchinson 1991). It is not entirely clear which type(s) of wound should be kept moist, how much moisture is required, when it should be applied, and in what combination with other factors it actually confers benefit. However, Bishop and colleagues have proposed a general principle of moisture balance (Bishop 2003), that is, that dressings must absorb exudate away from the wound surface, while ensuring that the wound surface remains moist. Despite a plethora of research into wound care, the optimal level of exudate to promote wound healing has yet to be established.

The principle of moist wound healing has led to the development of several commercially available wound dressings to support optimal healing processes. These have revolutionised wound management (Benbow 2005); products include hydrogels that retain moisture in contact with the wound, hydrocolloids that absorb small amounts of excess moisture without drying the wound bed, absorbent foams, alginates, adhesive dressings, non-adhesive dressings and silicone-based low-adherent dressings. Hydrocolloid dressings (the subject of this review) are composed of a layer of sodium carboxymethylcellulose (or similar material that forms a gel when wet) bonded onto a vapour-permeable film or foam pad. These occlusive dressings absorb exudate whilst maintaining a moist wound environment. Fibrous hydrocolloids are a sub-set of dressings that are designed for use in wounds with heavy exudate in lieu of alternate dressing types such as alginates (BNF 2010; Pan Pacific Clinical Guidelines 2011).

Why it is important to do this review

Pressure ulcer prevention and management is a significant burden to all healthcare systems. It is an internationally recognised patient safety problem and serves as a clinical indicator of the standard of care provided. Pressure ulcers are the second most reported incident that leads to patient harm in the health system, and are a significant source of suffering for patients and their care givers (PSC 2009; Reddy 2008). Over recent decades significant investment has been placed in strategies aimed at pressure ulcer prevention. Treatment strategies for pressure ulcers can also be costly and complex, and there is a large range of wound care products available. Despite a growing amount of literature concerned with wound care interventions, relatively few research studies have used clinical trial methodology to evaluate clinical effectiveness. The complexity of suggested interventions, and range of options available suggests that the evidence requires evaluation and presentation to the clinician to assist with effective decision making. This review is part of a suite of reviews investigating the use of individual dressing types in the treatment of pressure ulcers. Each review will focus on a particular dressing type. These reviews will then be summarised in an overview of reviews which will draw together all existing Cochrane review evidence regarding the use of dressing treatments for pressure ulcers.

There is a plethora of wound care products available, however, the evidence base to support use of some of these products remains incomplete. Thus, there is a clear need to provide clinicians with a reliable evidence base with which to make sound decisions for the treatment of pressure ulcers, if we are to reduce their prevalence and burden.

Published Online: 28 FEB 2013

DOI: 10.1002/14651858.CD010364

Incision and drainage of perianal abscess with or without treatment of anal fistula

Background

The perianal abscess is a common surgical problem. A third of perianal abscesses may manifest a fistula-in-ano which increases the risk of abscess recurrence requiring repeat surgical drainage. Treating the fistula at the same time as incision and drainage of the abscess may reduce the likelihood of recurrent abscess and the need for repeat surgery. However, this could affect sphincter function in some patients who may not have later developed a fistula-in-ano.

Objectives

We aimed to review the available randomised controlled trial evidence comparing incision and drainage of perianal abscess with or without fistula treatment.

Search methods

Randomised trials were identified from MEDLINE, EMBASE, the Cochrane Library, and reference lists of published papers and reviews.

Selection criteria

Trials comparing outcome after fistula surgery with drainage of perianal abscess compared with drainage alone were included in the review.

Data collection and analysis

The primary outcomes were recurrent or persistent abscess/fistula which may require repeat surgery and short-term and long-term incontinence. Secondary outcomes were duration of hospitalisation, duration of wound healing, postoperative pain, quality of life scores. For dichotomous variables, relative risks and their confidence intervals were calculated.

Main results

We identified six trials, involving 479 subjects, comparing incision and drainage of perianal abscess alone versus incision and drainage with fistula treatment. Metaanalysis showed a significant reduction in recurrence, persistent abscess/fistula or repeat surgery in favour of fistula surgery at the time of abscess incision and drainage (RR=0.13, 95% Confidence Interval of RR = 0.07-0.24). Transient manometric reduction in anal sphincter pressures, without clinical incontinence, may occur after treatment of low fistulae with abscess drainage. Incontinence at one year following drainage with fistula surgery was not statistically significant (pooled RR 3.06, 95% Confidence Interval 0.7-13.45) with heterogeneity demonstrable between the trials (Chi² =5.39,df=3, p=0.14, I² =44.4%).

Authors' conclusions

The published evidence shows fistula surgery with abscess drainage significantly reduces recurrence or persistence of abscess/fistula, or the need for repeat surgery. There was no statistically significant evidence of incontinence following fistula surgery with abscess drainage. This intervention may be recommended in carefully selected patients.

Published Online: 7 JUL 2010

Assessed as up-to-date: 29 JAN 2010

DOI: 10.1002/14651858.CD006827.pub2

Pylorus-preserving pancreaticoduodenectomy (pp Whipple) versus pancreaticoduodenectomy (classic Whipple) for surgical treatment of periampullary and pancreatic carcinoma

Background

Pancreatic cancer is the fourth leading cause of cancer death for men and the fifth for women. The standard treatment for resectable tumours is either a classic Whipple (CW) operation or a pylorus-preserving pancreaticoduodenectomy (PPW). It is unclear which of the procedures is more favourable in terms of survival, mortality, complications and quality of life.

Objectives

The objective of this systematic review is to compare the effectiveness of each operation.

Search methods

We conducted searches on 28 March 2006 and 11 January 2011 to identify all randomised controlled trials (RCTs), applying no language restrictions. We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL), CDSR and DARE from The Cochrane Library (2010, Issue 4), MEDLINE (1966 to January 2011), and EMBASE (1980 to January 2011). Abstracts from Digestive Disease Week and U nited European Gastroenterology Week (1995 to 2010). No additional studies were indentified upon updating the systematic review in 2011.

Selection criteria

We considered RCTs comparing the CW with PPW to be eligible if they included patients with periampullary or pancreatic carcinoma.

Data collection and analysis

Two authors independently extracted data from the included studies. We used a random-effects model for pooling data. We compared binary outcomes using odds ratios (OR), pooled continuous outcomes using mean differences (MD) and used hazard ratios (HR) for meta-analysis of survival. Two authors independently evaluated the methodological quality and risk of bias of the included studies according to Cochrane standards.

Main results

We included six randomised controlled trials with a total of 465 patients. Our critical appraisal revealed vast heterogeneity with respect to methodological quality and outcome parameters. In-hospital mortality (OR 0.49; 95% confidence interval (CI) 0.17 to 1.40; P = 0.18), overall survival (HR 0.84; 95% CI 0.61 to 1.16; P = 0.29) and morbidity showed no significant differences. However, we noted that operating time (MD -68.26 minutes; 95% CI -105.70 to -30.83; P = 0.0004) and intra-operative blood loss (MD -0.76 millilitres; 95% CI -0.96 to -0.56; P < 0.00001) were significantly reduced in the PPW group. All significant results have low quality of evidence based on GRADE criteria.

Authors' conclusions

There is no evidence of relevant differences in mortality, morbidity and survival between the two operations. Given obvious clinical and methodological heterogeneity, future research must be undertaken to perform high-quality randomised controlled trials of complex surgical interventions on the basis of well-defined outcome parameters.

Published Online: 11 MAY 2011

Assessed as up-to-date: 21 FEB 2011

DOI: 10.1002/14651858.CD006053.pub4

Surgical management of disappearing colorectal liver metastases

Background

Owing to expanded surgical indications for colorectal liver metastasis (CRLM) and improved systemic therapy, hepatic surgeons are increasingly faced with the problem of disappearing (no longer visible on imaging) liver metastasis (DLM).

Methods

A review of relevant studies was performed. Studies that reported on DLM associated with preoperative chemotherapy for CRLM were identified, and data were synthesized and tabulated. The PubMed database was searched for relevant articles published between January 2000 and December 2012.

Results

A complete response on imaging does not necessarily equate with a complete clinical or pathological response. Rather, residual macroscopic disease is found in about 25–45 per cent of patients at the time of operation. Even among patients with a complete pathological response, long-term remission occurs in only 20–50 per cent of those treated with systemic therapy. A durable response of DLM is more common following the use of hepatic artery infusion therapy.

Conclusion

Liver resection should include all original sites of disease if possible.

Feed: British Journal of Surgery
Posted on: Friday, August 16, 2013 10:33 PM
Author: D. A. Bischof, B. M. Clary, S. K. Maithel, T. M. Pawlik
Subject: Surgical management of disappearing colorectal liver metastases

Subxiphoid pericardial window to exclude occult cardiac injury after penetrating thoracoabdominal trauma

Background

An occult cardiac injury may be present in patients with an acute abdomen after penetrating thoracoabdominal trauma. This study assessed the use of a subxiphoid pericardial window (SPW) as a diagnostic manoeuvre in this setting.

Methods

This was a retrospective review of a trauma database (2001–2009). Patients presenting with a penetrating thoracoabdominal injury with an acute abdomen, and in whom there was concern about a potential cardiac injury from the site or tract of the injury, were included.

Results

Fifty patients with an indication for emergency laparotomy underwent a SPW for a possible cardiac injury. An occult haemopericardium was present at SPW in 14 patients (28 per cent) mandating, median sternotomy. Nine cardiac injuries (18 per cent) were identified including five tangential injuries and four perforations. The specific complication rate relating to the SPW was 2 per cent.

Conclusion

The SPW is a useful technique at laparotomy to identify cardiac injuries in patients with penetrating thoracoabdominal injuries.

British Journal of Surgery
Posted on: Thursday, August 08, 2013 5:14 PM
Author: M. Hommes, A. J. Nicol, J. van der Stok, I. Kodde, P. H. Navsaria
Subject: Subxiphoid pericardial window to exclude occult cardiac injury after penetrating thoracoabdominal trauma

Systematic review and meta-analysis of population-based mortality from ruptured abdominal aortic aneurysm

Background

A substantial proportion of patients with a ruptured abdominal aortic aneurysm (rAAA) die outside hospital. The objective of this study was to estimate the total mortality, including prehospital deaths, of patients with rAAA.

Methods

This was a systematic review and meta-analysis following the MOOSE guidelines. The Embase, MEDLINE and Cochrane Library databases were searched. All population-based studies reporting both prehospital and in-hospital mortality in patients with rAAA were included. Studies were assessed for methodological quality and heterogeneity, and pooled estimates of mortality from rAAA were calculated using a random-effects model.

Results

From a total of 3667 studies, 24 retrospective cohort studies, published between 1977 and 2012, met the inclusion criteria. The quality of included studies varied, in particular the method of determining prehospital deaths from rAAA. The estimated pooled total mortality rate was 81 (95 per cent confidence interval 78 to 83) per cent. A decline in mortality was observed over time (P = 0·002); the pooled estimate of total mortality in high-quality studies before 1990 was 86 (83 to 89) per cent, compared with 74 (72 to 77) per cent since 1990. Some 32 (27 to 37) per cent of patients with rAAA died before reaching hospital. The in-hospital non-intervention rate was 40 (33 to 47) per cent, which also declined over the years.

Conclusion

The pooled estimate of total mortality from rAAA is very high, although it has declined over the years. Most patients die outside hospital, and there is no surgical intervention in a considerable number of those who survive to reach hospital.

British Journal of Surgery
Posted on: Wednesday, September 04, 2013 7:46 PM
Author: J. J. Reimerink, M. J. van der Laan, M. J. Koelemay, R. Balm, D. A. Legemate
Subject: Systematic review and meta-analysis of population-based mortality from ruptured abdominal aortic aneurysm