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<<< < Предыдущая 1 2 3 4 5 6 7 8 9 1011 / 2611 12 13 14 15 16 17 18 19 20 21 22 23 24 25 > Следующая >>>

Figure8.7 • MRI demonstrating planes of the right

pelvic side-wall: mesorectal plane (A), ureteric plane (B) and bony plane lateral to internal iliac vessels (C).

Sacrectomy

Resection of the sacrum at S3 or below has acceptable morbidity and established oncological and functional benet.

S1 and S2 involvement is challenging due to the need

for pelvic reconstruction and stabilisation as well as the resulting sensory and motor neurological deficit (the procedure involves ligation of the cauda equina and freeing the sacrum with sacrifice of sacral nerve roots below the level of resection). A recent series reporting on high sacrectomy with preservation of S1 and avoidance of pelvic stabilisation procedures has demonstrated an R0 resection rate of over 70% with a major complication rate of 43%.20 Not surprisingly, patients undergoing high sacrectomy had a higher rate of postoperative neurological (motor and sensory) deficit and neuropathic bladder dysfunction. Otherwise there was minimal increased morbidity with the high sacrectomy. New techniques such as unilateral sacral compartment

Advanced and recurrent colorectal cancer

excision also offer the prospect of high sacral resection without the need for pelvic stabilisation, but more data on these are awaited.

Perineal reconstruction

This may be required due to the size of the defect and impaired wound healing after previous chemoradiotherapy. Omentoplasty to the pelvis should be attempted where possible. Biological mesh reconstruction of the pelvic floor has been described for ELAPE; however, it is usually not appropriate in exenterative surgery due to the size of the defect and the fact that it also requires a flap of skin for closure. Pedicled flaps are most commonly used and include:

• Rectus abdominis myocutaneous flaps (unilateral with reconstruction of the abdominal harvest site often using mesh).

• Gracilis myocutaneous flaps (bilateral as they offer the least coverage).

• Gluteal myocutaneous rotational or advancement flaps (usually both sides).

• Inferior gluteal artery perforator flap (usually both sides).

Where pedicled flaps are not an option, free flaps can be considered. The decision should be made with a plastic surgeon, and tailored to patient factors (comorbidity, tissue quality and perfusion) as well as previous surgery (abdominal and perineal incisions).12 Vaginal reconstruction can be achieved and intercourse is feasible after this.

Colorectal peritoneal metastases (CRPM)

CRPM (Fig.8.8) can present synchronously (10.3% of primary right colon cancers, 6.2% of left colon cancers, and 27% of rectal cancers) metachronously (20% of colorectal cancers).

5,6

and

Figure8.8 • CRPM involving the omentum (A) and recto-uterine pouch of Douglas (B).

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Chapter 8

100

123456789

At risk HIPEC Standard

Systemic chemotherapy and palliative support used to be the mainstay of treatment, with surgery restricted to relieving obstruction. In the past decade, however, compelling data on outcomes from cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) from several specialist centres have emerged.24 These studies have shown a median survival of 63months and a 5-year survival of 51% is achievable with CRS/ HIPEC, compared to 24months and 13% for matched patients receiving systemic chemotherapy alone (Fig.8.9).

CRS/HIPEC is now a recommended treatment for

selected cases of CRPM.

CRS/HIPEC

This is an established treatment for peritoneal tumours (appendix neoplasms and pseudomyxoma peritonei [PMP]). PMP is a rare syndrome that arises from a low-grade appendiceal mucinous neoplasm (LAMN) that perforates, with leakage of mucin and cells into the peritoneal cavity, resulting in abdominal distension and organ compression.26 The principle is to remove all visible tumour followed by administration of HIPEC using a cytotoxic drug with depth of penetration of approximately 3 mm. Hyperthermia itself also has a direct cytotoxic effect, probably through

formation of heat shock proteins.27 Figure 8.10 shows the ‘Coliseum’ technique (see also Video 1).

CRS can include peritonectomy, omentectomy, umbilectomy, excision of falciform ligament and ligamentum teres, cholecystectomy and any other required visceral resections. These may include segmental small- and/or large-bowel resections, splenectomy, total abdominal hysterectomy, bilateral salpingo-oophoerctomy and gastrectomy. HIPEC at 42 degrees is administered for 60–90 minutes with either mitomycin C or oxaloplatin and intravenous 5FU. (See Video 2 for an outline of the CRS procedure.)

Scoring systems

There are currently two main systems used to stratify outcomes from CRS/HIPEC, namely the Peritoneal Cancer Index (PCI) Sugarbaker, and the Completeness of Cytoreduction (CC) score developed by Sugarbaker.

PCI is an intraoperative score accounting for both size and distribution of lesions (Fig.8.11). Thirteen regions are each given a score of 0–3 based on lesion size, with final score ranging from 0 to 39. A higher PCI is associated with poorer short- and long-term outcomes.

CC score is calculated at the end of the operation. CC = 0 indicates no residual disease, CC = 1 indicates nodules less than 2.5 mm in size remained, CC = 2 indicates nodules between 2.5 mm and 2.5 cm, and CC = 3 indicates that nodules over 2.5 cm remained.

Overall survival (%)

Time (years)

HIPEC Standard

48 46 35 28 20 16 63 48 36 24 13 9621

Figure8.9 • Overall survival of group receiving CRS/HIPEC (labelled ‘HIPEC’) versus those on systemic chemotherapy

(labelled ‘Standard’).

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Figure8.10 • Open ‘Coliseum’ technique for HIPEC

with temperature probes (A), circulating intraperitoneal chemotherapy solution (B), HIPEC circulation and delivery system (C) and HIPEC inflow and outflow ports (D).

Patient Selection

In England, CRS/HIPEC is a procedure that remains restricted to specialised units. Specialist peritoneal tumour MDTs in these centres take into account the patient’s full treatment history, tumour type and biology, previous chemotherapy, prior surgery and future options. Patients are carefully selected and counselled for surgery. Laparoscopy plays a role in some cases (see Video 3 for a diagnostic laparoscopy for CRPM). Annually audited results demonstrate a major morbidity rate of less than 30% and mortality of less than 1%.

Colorectal liver metastases

Certain ‘technical criteria’ have to be fulfilled in order for liver metastases to be considered

Advanced and recurrent colorectal cancer

resectable, as outlined in Table 8.1. In a proportion of patients resection is made possible through portal vein embolisation, twostage hepatectomy or hepatectomy combined with ablation. The finding that despite being technically resectable, approximately half of patients develop widespread systemic disease within 3 years, has led to ‘oncological criteria’ that should also be considered when selecting patients (Table8.1).

If a patient fulls these criteria to undergo surgical resection, there is the option of either upfront surgery or perioperative (pre- and postoperative) chemotherapy. The best available data from the EPOC study are not conclusive on whether perioperative chemotherapy improves outcome. The study reported a 5-year OS rate of 51% (95% CI 45–58) in the perioperative chemotherapy group versus 48% (95% CI 40–55) in the surgery-only group.29 It would therefore not be unreasonable to consider upfront surgery for easily technically resectable liver metastases with favourable oncological criteria, but choose perioperative chemotherapy for patients with favourable technical criteria, but unfavourable oncological criteria as outlined in Table8.1. Data from the EPOC group also suggest that perioperative chemotherapy should comprise 3months chemotherapy before surgery and 3months’ chemotherapy post-surgery with FOLFOX or alternatively capecitabine with oxaliplatin – CAPOX.

Two further groups of patients with colorectal

liver metastases should be considered.

The first is patients with primary colorectal

tumours and synchronous liver metastases. In these patients consideration should be given to synchronous versus staged resections, although the former is generally reserved for small isolated lesions. Ultimately the combined morbidity of both procedures needs to be considered. In the case of staged resections, surgery for the primary tumour and liver metastases does not necessarily need to be interrupted with systemic chemotherapy.30 Ultimately these decisions need to be taken in consultation with a hepatobiliary MDT.

The second is patients with unresectable colorectal

liver metastases in whom systemic chemotherapy renders the disease resectable. This has led to the introduction of the concept of ‘conversion chemotherapy’ into clinical practice. It is an area where data on long-term outcome from surgery after conversion versus continuation of chemotherapy are required.

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Chapter 8

Peritoneal Cancer Index

Regions Lesion size Lesion size score

Central

Right upper

Epigastrium

Left upper

Left flank

Left lower

Pelvis

Right lower

Right flank

Upper jejunum

Lower jejunum

Upper ileum

Lower ileum

PCI

LS 0

No tumour seen

LS 1

Tumour up to 0.5 cm

LS2

Tumour up to 5.0 cm

LS 3

Tumour > 5.0 cm or confluence

Figure8.11 • Peritoneal Cancer Index (PCI).

Table8.1 • Technical and oncological criteria considered in surgery for colorectal liver metastases

Technical criteria Oncological criteria

1. R0 resection possible 1. 5 or fewer lesions

2. Maintenance of 30% of future liver remnant (FLR) or a remnant liver-to-body-weight ratio >0.5 (e.g. >350 g of liver per 70 kg patient)

3. R0 resection possible only with complex procedures (portal vein embolisation, two-stage hepatectomy or hepatectomy combined with ablation).

2. Presence (or suspicion) of extrahepatic disease

3. The resectability of extrahepatic disease

4. Evidence of tumour progression

Key points

• Advanced and recurrent colorectal cancers should be managed in specialist centres with the

required multidisciplinary teams.

• Histological confirmation, biomarker (extended RAS, BRAF) and DNA mismatch repair testing should

be undertaken at the outset where possible.

• CT thorax, abdomen and pelvis with oral and intravenous contrast and MRI for pelvic tumours is the

minimal recommendation for staging advanced and recurrent colorectal cancers.

• Radiotherapy should be considered for patients with locally advanced and recurrent rectal cancer

prior to surgery.

• Locally advanced and recurrent rectal cancers require surgery beyond the TME plane through

exenterative surgery that must be tailored to the patient.

• Sacrectomy should be undertaken in units with the required expertise and access to spinal

orthopaedic or neurosurgeons.

• Perineal reconstruction should be planned with a plastic surgeon and the type of flap used tailored to

the patient.

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Advanced and recurrent colorectal cancer

• CRS/HIPEC is an established treatment for CRPM and is undertaken in specialist centres in the UK

with the required decision-making and operative experience.

• All units treating advanced and recurrent colorectal cancer should collect, audit and present their

long-term outcome data.

• Treatment of liver metastases should be planned with a specialist hepatobiliary MDT and based on

both technical and oncological criteria.

Recommended videos:

1. HIPEC: the ‘Coliseum’ technique – https://youtu.be/

UB4Lxypd0Kw

2. Cytoreductive surgery procedure – https://youtu.

be/_WT8grwjzoQ

3. Diagnostic laparoscopy for CRPM – https://youtu.

be/aEHgQubDKNw

Full references available at http://expertconsult.

inkling.com

Key references

15. McCarthy K, Pearson K, Fulton R, et al. Preoperative chemoradiation for non-metastatic locally advanced rectal cancer. The Cochrane Database of systematic reviews 2012 Dec 12;12:. CD008368.

PMID: 23235660.

A meta-analysis of six randomised controlled trials comparing the efficacy of preoperative chemoradiation to radiotherapy alone before surgery in the treatment of T3–4, node-positive (locally advanced) rectal cancer. While there was no difference in overall survival, chemoradiotherapy was significantly associated with less local recurrence.

25. Elias D, Lefevre JH, Chevalier J, et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol 2009;27:681–5. PMID: 19103728.

A case-control study comparing the long-term survival of matched groups of patients with isolated and resectable peritoneal metastases from colorectal cancer treated with systemic chemotherapy including oxaliplatin or irinotecan versus cytoreductive surgery with hyperthermic intraperitoneal chemotherapy and systemic chemotherapy. Patients with isolated, resectable peritoneal cancer achieved a median survival of 24 months with modern chemotherapies, but only surgical cytoreduction plus HIPEC was able to prolong median survival to 63months, with a 5-year survival rate of 51%.

29. Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): longterm results of a randomised, controlled, phase 3 trial. Lancet Oncol 2013;14:1208–15. PMID:

24120480.

A randomised controlled trial that found no difference in overall survival with the addition of perioperative chemotherapy with FOLFOX4 compared with surgery alone for patients with resectable liver metastases from colorectal cancer.

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Anal cancer

David J. Humes John H. Scholefield

Introduction

Anal cancer is rare, accounting for approximately 2–4% of large bowel malignancies; however, there is some evidence that its incidence is increasing. Most anal cancers arise from the squamous epithelium of the anal margin or anal canal, although a few arise from anal glands and ducts.

Traditionally, the anal region is divided into the anal canal and the anal margin or verge. The natural history, demography and surgical management of anal cancer differ between these areas. There is controversy regarding the exact definition of the anal canal. Anatomists see it as lying between the dentate line and the anal verge, whereas surgically it is defined as lying between the anorectal ring and the anal verge. For pathologists, the canal has been defined as corresponding to the longitudinal extent of the internal anal sphincter. The canal above the dentate line is lined by rectal mucosa, except for a small zone immediately above the dentate line called the transitional or junctional zone. Inferiorly, the canal is covered by stratified squamous epithelium. Further confusion relates to the definition of the anal canal and anal margin as sites for cancer. The anal margin is variously described as the visible area external to the anal verge, or as the area below the dentate line. Anal margin tumours are said to be within a 5-cm radius of the anal orifice. This argument has become less important as surgery plays a lesser role in treatment, but reports of surgical results from past decades are confused by this variation in definition.

Over 80% of anal cancers are of squamous origin, arising from the squamous epithelium of the anal

canal and perianal area; 10% are adenocarcinomas arising from the glandular mucosa of the upper anal canal, the anal glands and ducts. A very rare and particularly aggressive tumour is anal melanoma. Lymphomas and sarcomas of the anus are even less common but have increased in incidence in recent years, particularly among patients with human immunodeficiency virus (HIV) infection. There has also been a rise in the incidence of other anal epidermoid tumours among patients with HIV.

Epidermoid tumours

Aetiology and pathogenesis

Anal squamous carcinomas are relatively uncommon tumours; there are just over 1300 cases of anal cancer diagnosed each year in the United Kingdom (UK).1 Based on these figures, each consultant colorectal surgeon might expect to see one or two anal cancers every year or so. However, anal cancers are probably under-reported, since some anal canal tumours are misclassified as rectal tumours and some perianal tumours as squamous carcinomas of the skin.

A recent study using English data from the National

Cancer Data Repository reported an incidence of

0.73 and 1.13 per 100 000 population, respectively, for men and women from 2006 to 2010. These figures represented a 69% and 126% increase in incidence when compared to rates from1990 to1994.2 This increase in incidence has also been confirmed in studies in the USA using data from

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Anal cancer

the Surveillance, Epidemiology and End Results (SEER) Program, in France using cancer registry data and in Norway.

3–5

The median age at diagnosis is 60 years. There is wide geographical variation in the incidence of anal cancers around the world. Areas with a high incidence of anal cancer usually also have a high incidence of cervical, vulval and penile tumours (reflecting the common aetiological agent – papillomaviruses).

The increasing incidence of HIV infection has resulted in a rise in the incidence of anal cancer; this has been seen particularly in areas such as San Francisco, with a large homosexual population, reportedly seeing a large increase but part of this increase in recent times may be due to detection of more in situ lesions among men who have been targeted for screening.6 Daling et al.7 identified risk factors for the development of squamous cell carcinoma of the anus: a history of receptive anal intercourse in males increased the relative risk of developing anal cancer by 33 times compared with controls with colon cancer, and a history of genital warts also increased the relative risk of developing anal cancer (27-fold in men and 22-fold in women). This reflects the likely aetiological link to human papillomaviruses in anal squamous cell carcinoma.

The incidence of anal cancer is increasing in

both males and females with a greater increase in

females.

Epidemiological and molecular biological data have shown an association with human papillomavirus (HPV) type 16 DNA, and less commonly types 18, 31 and 33 and their DNA was consistently found to be integrated into the genome in cervical, vulval and penile squamous cell carcinomas. The same HPV DNA types have also been identified in a similar proportion of anal squamous cell carcinomas.

There are more than 60 types of HPV (a DNA virus), capable of causing a wide variety of lesions in squamous epithelium. Common warts can be found on the hands and feet of children and young adults, and are caused by the relatively infectious but otherwise innocuous HPV types 1 and 2. Anogenital papillomaviruses are less infective than HPV types 1 and 2 and are exclusively sexually transmitted. The epidemiology of genital papillomavirus infection is poorly understood, largely due to the social and moral taboos surrounding sexually transmissible infections. Anogenital papillomavirus-associated lesions range from condylomas through intraepithelial neoplasias to invasive carcinomas. The most common HPV types causing genital warts are types 6 and 11, which may also be isolated from

low-grade intraepithelial neoplasia. HPV types 16, 18, 31 and 33 are much less commonly associated with genital condylomas but are more commonly found in high-grade intraepithelial neoplasias and invasive carcinomas, with the most frequently isolated being HPV 16 (84%) and the next most frequent HPV18.9 Once one area of the anogenital epithelium is infected, spread of papillomavirus infection throughout the rest of the anogenital area probably follows, but remains occult in the majority of individuals. Although there is a commonly held belief that anal cancer occurs only in individuals who practise anal intercourse, this is unfounded.

Anal and genital papillomavirus-associated lesions may be identied clinically either by naked eye inspection or with high-resolution anoscopy with the application of acetic acid to the epithelium, resulting in an ‘aceto-white’ lesion. This technique permits targeted biopsy of a lesion, but histological examination remains the diagnostic standard. The natural history of anal papillomavirus infection and intraepithelial neoplasia is in large part dependent on the infecting viral type and on the host immune state. In immunocompetent individuals the risk of malignant conversion from AIN III to invasive cancer is around 10% over 10years, but in HIV patients the risk is nearer 30% in 10years.

Premalignant lesions

Anogenital intraepithelial neoplasia of the

cervix (CIN), vulva (VIN), vagina (VAIN) and anus (AIN) is graded from I to III, according to the number of thirds of epithelial depth that appear dysplastic on histological section. Thus, in grade III the cells of the whole thickness of the epithelium appear dysplastic, being synonymous with carcinoma in situ.

High-grade anal intraepithelial (AIN III) lesions

may be characterised by hyperkeratosis or changes in the pigmentation of the epithelium. Thus, carcinoma in situ may appear white, red or brown, the pigmentation commonly being irregular. The lesions may be flat or raised, but ulceration is suggestive of invasive disease. It is important that any suspicious area is biopsied and examined histologically. The terms ‘Bowen's disease of the anus’ and ‘leucoplakia’ are best avoided as they are confusing and convey no specific information, the malignant potential of leucoplakia being very uncertain.

At present, multifocal genital intraepithelial

neoplasia represents a difficult clinical problem, which may be further complicated by the occurrence of synchronous or metachronous AIN.

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Chapter 9

Histological types

Included within the category of epidermoid tumours are squamous cell, basaloid (or cloacogenic) carcino mas and muco-epidermoid cancers. The different morphological types of anal cancer do not appear to have different prognoses. Tumours arising at the anal margin tend to be well differentiated and keratinising, occurring more in men, whereas those arising in the canal are more commonly poorly differentiated and are commoner in women. Basaloid tumours arise in the transitional zone around the dentate line and form 30–50% of all anal canal tumours.

Patterns of spread

Anal canal cancer spreads locally, mainly in a cephalad direction, so that the tumour may appear to have arisen in the rectum. The tumour also spreads outwards into the anal sphincters and into the rectovaginal septum, perineal body, scrotum or vagina in more advanced cases (Fig. 9.1). Lymph node metastases occur frequently, especially in tumours of the anal canal. Spread occurs initially to the perirectal group of nodes and thereafter to inguinal, haemorrhoidal and lateral pelvic lymph nodes. The frequency of nodal involvement is related to the size of the primary tumour together with its depth of penetration. Approximately 14% of patients will present with inguinal lymph node involvement, but this rises to approximately 30% when the primary tumour is greater than 5 cm in diameter. Only 50% of enlarged nodes at presentation will subsequently be shown to contain tumour. Synchronously involved nodes carry a particularly poor prognosis, whereas when metachronous spread develops the salvage rate is much higher.

Haematogenous spread tends to occur late and is usually associated with advanced local disease. The principal sites of metastases are the liver, lung, paraaortic nodes and bones. However, metastases have been described in the kidneys, adrenals and brain.

Clinical presentation

The predominant symptoms of epidermoid anal cancer are pain and bleeding, which are present in about 50% of cases. The presence of a mass is noted by a minority of patients, around 25%. Pruritus and discharge occur in a similar proportion. Advanced tumours may involve the sphincter mechanism, causing faecal incontinence. Invasion of the posterior vaginal wall may cause a fistula.

Cancer of the anal margin usually has the appearance of a malignant ulcer, with a raised, everted, indurated edge. Lesions within the canal may not be visible, though extensive lesions spread to the anal verge, or can extend via the ischiorectal fossa to the skin of the buttock. Digital examination of the anal canal is usually painful, and may reveal the distortion produced by the tumour. Since anal cancer tends to spread upwards, there may be involvement of the distal rectum, giving the impression that the lesion has arisen there. Involvement of the perirectal lymph nodes may be palpable on digital examination. If the tumour has extended into the sphincter muscles, the characteristic induration of a spreading malignancy may be felt around the anal canal.

Patients should be assessed for other risk factors such as HIV and all patients should be considered for testing and referred to an HIV clinic if found to be positive. Female patients should also have a referral for cervical cancer screening if not up to date.

Figure9.1 • Locally advanced anal cancer involving the anal canal, perianal skin, perineal skin and base of scrotum.

Treatment with chemo-irradiation failed to control the disease and the patient underwent a salvage abdominoperineal excision.

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Although up to one-third of patients will have inguinal lymph nodes that are enlarged, biopsy will conrm metastatic spread in only 50% of these; the rest are due to secondary infection. Biopsy or ne-needle aspiration is recommended to conrm involvement of the groin nodes if radical block dissection is contemplated.12 Distant spread is unusual in anal cancer, so hepatomegaly, though it must be looked for, is very uncommon. Frequently, other benign perianal conditions will exist in association with anal cancer, such as stulas, condylomas or leucoplakia.

Investigation

The most important investigation in the management of anal cancer is a detailed clinical examination under anaesthetic. Examination under anaesthesia permits optimum assessment of the tumour in terms of size, involvement of adjacent structures and nodal involvement, and also provides the best opportunity to obtain a biopsy for histological confirmation.

All patients should be staged with magnetic

resonance imaging (MRI) of the pelvis and computed tomography (CT) of the chest, abdomen and pelvis. The MRI allows locoregional staging whilst the CT stages for metastatic disease. The use of 18 F-FDG positron emission tomography (PET)/ CT has been suggested for staging. It may help with planning of radiotherapy and improve assessment of locoregional lymph node involvement.13 However, it is not currently mandated in all cases as part of the European or US National Comprehensive Cancer Network (NCCN) guidelines as it has not been fully assessed.12 Endoanal ultrasound has been suggested but may only be useful in small tumours as more information is usually available from MRI, particularly on spread beyond the anal canal.

Enlarged inguinal lymph nodes can be chara-

cterised by clinical and radiological features as to whether they may be reactive or metastatic. In cases where there is doubt, fine-needle aspiration can be performed, although this may not be required in those who have had a PET/CT that shows avid uptake. Serum tumour markers are unhelpful as they do not provide reliable information.

Clinical staging

No one system of staging for anal tumours has been adopted universally. However, the current 7th edition of the American Joint Committee on Cancer (AJCC) and Union for International Cancer Control (UICC) staging is the most widely used and follows the TNM classification (Table9.1).

Anal cancer

Table9.1 • AJCC TNM staging of anal cancer, 7th

edition

T stage N stage M stage

T1 – <2 cm N1 – Mesorectal

nodes

T2 – >2 to 5 cm N2 –Unilateral

internal iliac or

M0 – No metastasis

M1 – Distant metastasis

inguinal nodes

T3 – > 5 cm N3 – Perirectal

and inguinal lymph nodes or bilateral internal iliac and/ or inguinal lymph nodes

T4 – Invasion into adjacent organs (e.g. vagina, urethra)

Treatment

Historical

Traditionally, anal cancer was treated as a ‘surgical’ disease. Anal canal tumours were treated by radical abdominoperineal excision and colostomy, whereas anal margin lesions were treated by local excision. Over the past 30 years, non-surgical radical treatments, i.e. radiotherapy with or without chemotherapy, have taken over as primary treatments of choice in most cases.

Abdominoperineal excision (APE) for anal canal cancer differs little from the procedure used for rectal cancer, but particular care is taken to clear the space below the pelvic floor. Around 20% of cases are incurable surgically at presentation.

Around 75% of cancers at the anal margin have been treated in the past by local excision. The rationale for this was based on the perception that margin lesions rarely metastasise, though this has not always been confirmed by prolonged follow-up.

Current

The current standard of care for anal cancer is chemoradiotherapy with 50.4 Gy radiotherapy in 28 daily fractions with mitomycin C and 5FU in all cases except those where local excision is complete or there are contraindications to radiotherapy. This achieves equivalent survival rates to surgery but with the advantage of stoma avoidance in the majority of

12,14,15

cases.

Radiation-alone therapy

The initial treatment for anal cancer was radiotherapy because the mortality and morbidity of surgical

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Chapter 9

100

Probability of local failure (%)

treatment of anal carcinoma were unacceptable. By the 1930s, however, it was recognised that the low-voltage radiotherapy used frequently produced severe radionecrosis. As surgery became safer, APE for invading lesions, and local excision for small growths, became the standard treatment for the next four decades.

The development in the 1950s of equipment that could deliver high-energy irradiation by the cobalt source generator or, more recently, by linear accelerators, enabled radiotherapists to deliver higher penetrating doses to deeper placed structures with less superficial scatter of energy. Radiation damage to surrounding tissues was consequently reduced while simultaneously delivering an enhanced tumouricidal effect.

Chemo-irradiation therapy (combined modality therapy)

Combined modality therapy for anal cancer was championed by Norman Nigro. Nigro chose to use 5-fluorouracil (5FU) and mitomycin C empirically as a preoperative regimen aimed at improving the results of radical surgery.16 The radiotherapy then consisted of 30 Gy of external beam irradiation over a period of 3 weeks. A bolus of mitomycin C was given on the first day of treatment, and 5FU was delivered in a synchronous continuous 4-day infusion during the first week of radiotherapy. After completion of radiotherapy, a further infusion of 5FU was administered and patients later proceeded to APE. It was evident to Nigro that the majority had quite

dramatic tumour shrinkage: in his 1974 publication the tumour was reported to have disappeared completely in all three patients. No tumour was found in the surgical specimen in either of the patients who underwent APE; the third refused surgery.

A variety of similar techniques have subsequently been described. With wider experience, it became clear that higher doses of radiotherapy (45–60 Gy) could be applied, usually split into two courses to minimise morbidity; however, recent RCT results have now shown no need to have a break in radiotherapy treatment.

All the reported series describe excellent results, but there was a debate about whether chemotherapy added any advantage over radiotherapy alone.

The UK Coordinating Committee on Cancer Research (UKCCCR ACT I) compared chemo-irradiation with radiotherapy alone in a randomised multicentre study.15 This study randomised 585 patients. The trial showed that combined modality therapy gave superior local control of disease compared with radiotherapy alone. Only 36% of patients receiving combined therapy had ‘local failure’ compared with 59% of those receiving radiotherapy alone. Although there was no significant overall survival advantage for either treatment regimen, the risk of death from anal cancer was significantly less in the group receiving combined modality therapy (Fig.9.2). As a result of this trial it seems that the standard treatment for anal squamous carcinoma should be a combination of radiotherapy and intravenous 5FU with mitomycin, which remains the gold standard.

Cause-specific survival (%)

At risk: 285 238 173 113 67 32 15 283 240 163 99 65 42 18

Figure9.2 • (a) Deaths from anal cancer. Number of events: radiotherapy (RT) 105, combined modality therapy (CMT)

77 (RR = 0.71, 95% CI 0.53–0.95, P = 0.02). Number at risk = number alive. (b) UKCCCR Anal Cancer Trial: risk of local failure (T1–2 and N0). Panel (a): UKCCCR Anal Cancer Trial Working Party. Lancet 1996;348:1055, Figure5. With permission from Elsevier. Panel (b): Northover J, Meadows A, Ryan C etal., on behalf of UKCCCR Anal Cancer Trial Working Party. Lancet 1996;349:206. With permission from Elsevier.

100

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Year from randomisation

CMT

Radiotherapy

RT alone (61/121) Chemotherapy + RT (28/106)

1235

Year from randomisation

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Соседние файлы в папке Библиотека им академика М.И. Перельмана

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31.08.202632 Мб0Книга_904_Библиотеки_им_академика_М_И_Перельмана.pdf
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31.08.202632 Мб0Книга_905_Библиотеки_им_академика_М_И_Перельмана.pdf
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31.08.202632 Мб0Книга_907_Библиотеки_им_академика_М_И_Перельмана.pdf
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31.08.202632 Мб0Книга_908_Библиотеки_им_академика_М_И_Перельмана.pdf
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31.08.202632 Мб0Книга_909_Библиотеки_им_академика_М_И_Перельмана.pdf
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31.08.202632 Мб0Книга_911_Библиотеки_им_академика_М_И_Перельмана.pdf
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31.08.202632 Мб0Книга_912_Библиотеки_им_академика_М_И_Перельмана.pdf
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31.08.202632 Мб0Книга_917_Библиотеки_им_академика_М_И_Перельмана.pdf
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31.08.202632 Мб0Книга_918_Библиотеки_им_академика_М_И_Перельмана.pdf
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31.08.202631 Мб0Книга_920_Библиотеки_им_академика_М_И_Перельмана.pdf
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31.08.202631 Мб0Книга_921_Библиотеки_им_академика_М_И_Перельмана.pdf