What are the types of aero digestive tract fistulas?

Tracheo-oesophageal fistula (TOF)

Broncho- oesophageal fistula (BOF)

Oesophageal-lung parenchyma fistulas (rare)

What are the causes of these fistulas?

• These fistula’s develops either because of direct tumor invasion and subsequent perforation or after radiation, laser therapy, chemotherapy or pre-existing stents (primarily, oesophageal stents), or a combination of these.

• Approximately 77% of MTOF are related to oesophageal cancer, whereas approximately 16% originate from a primary lung neoplasm.

• Other tumours like malignant mediastinal nodal disease, thyroid, laryngeal cancer etc causes MTOF rarely

How common is it?

It develops in approximately 5%–15% of patients with an oesophageal malignancy and in less than 1% of those with bronchogenic carcinoma

What are the symptoms?

Intractable cough and repeated aspirations.

Autopsy data indicate a higher incidence of fistulas, thus suggesting that fistulas are more common in patients than is usually diagnosed.  A history of repeated coughing associated with eating, drinking, or both, with an increase in dysphagia and dyspnea are highly suggestive of a fistula. Endoscopic findings are sometimes inadequate in demonstrating a fistula, in which case a water contrast swallow is required.

Lung abscess is the most frequent and severe complication of oesophageal-lung parenchyma fistulas. In this particular type of aero digestive fistula, stent placement may worsen the infectious problem by impairing natural drainage of the abscess.

In one study, lung abscesses decreased in size, but persisted even after stent placement. Concomitant abscess drainage procedures should thus be considered. Thus, oesophageal stent remains the accepted treatment for oesophageal-lung parenchyma fistulas (with percutaneous drainage of the abscess)

What is the prognosis?

Once a fistula (stage T4) develops, the tumour is incurable. The treatment is palliative to alleviate symptoms. Treatment should be begun immediately after the diagnosis is confirmed since the usual cause of death in these patients is pulmonary sepsis resulting from chronic aspiration through the fistula. In two, large series reports (4, 5), mean patient survival was reported to be 3.1-3.4 months. The usual causes of death are: massive bleeding, pneumonia or malnutrition

What are the treatment options?

Therapy is mainly directed to palliate symptoms and maintain quality of life.

• Unfortunately, at the time of diagnosis, the patient’s performance and disease status usually precludes aggressive palliative surgical therapy (oesophageal bypass using a gastric bypass and cardiostomy)

• Radiation therapy and chemotherapy are generally contraindicated due to the concern regarding fistula enlargement caused by tumor necrosis.

• Oesophageal or tracheobronchial stenting or both is the treatment of choice.

• Gastrostomy: Stenting however achieves better palliation of respiratory symptoms with a better quality of life.

Discuss selection of stent?

Several kinds of covered oesophageal stents are available (i.e., Ultraflex stent, Wallstent, and Z stent). However, there are no randomized or controlled trials to compare the outcomes of any of these stents when used to treat malignant aero digestive fistulas

Discuss the stenting area?

The selection guide for determining the stenting area could be summarized as follows:

• oesophageal stent placement if a patient has a stricture in the oesophagus,

but with no or only mild airway stricture since an oesophageal stent can successfully treat both oesophageal stricture and a fistula;

• airway stent placement if a patient has no or only mild stricture in the oesophagus, or has moderate to severe stricture in the airway, since an oesophageal stent migrates well when oesophageal stricture is absent or mild, and an airway stent can treat an airway stricture; or
• both the airway and oesophageal stent placement when a patient has moderate to severe stricture involving both the oesophagus and the airway, since both the airway and oesophageal stents are necessary to treat a stricture involving both the oesophagus and the airway.
• In case of a high (fistula at 18-20cm from incisor) tracheo-oesophageal fistula –oesophageal stent may be undesirable and a tracheal stent is the better option.

NB: Airway stent is preferred in malignant fistula developing after Ivor Lewis

Oesophagectomy (the replaced stomach or colon shows a large lumen compared

with the lumen of the original oesophagus). The larger lumen makes oesophageal stent migration (and hence uncovering fistula) easier.

Discuss double stenting i.e. both oesophageal and Tracheobronchial stent insertion?

Double stenting appear to provide more benefits than either oesophageal or respiratory stents alone in terms of palliation and safety. Double stenting is definitely indicated when fistula occlusion is not achieved by the oesophageal or airway stent alone. In cases of double stenting, airway stent should be placed first in order to avoid tracheal or bronchial compression secondary to the oesophageal stent.

Mechanical friction between the oesophageal and airway stents may cause pressure necrosis of the interposed tissue between the two stents, thereby possibly resulting in a fatal haemorrhage. Thus, parallel stenting should only be performed after thoroughly reviewing a patient’s clinical indications.

Discuss the success of oesophageal stenting?

• Oesophageal stenting is technically feasible in the majority.

• Oesophageal stent completely seals off the fistula in 60-100% of cases. Incomplete closure of the fistula caused by spillage of material through a gap between the proximal stent margin and the oesophageal wall (‘funnel phenomenon’). This is difficult to manage despite the insertion of additional stents or glue injection to seal the gap. An additional airway stent is usually required. Thus, a contrast swallow is obtained immediately after stent insertion to confirm the sealing of the fistula and subsequently allow a patient to eat a soft diet. If there is persistent leakage through the fistula, resulting from an incomplete stent expansion, a follow-up contrast swallow should be obtained 2-3 days after stent placement in order to confirm stent expansion before food intake is resumed.

• The fistulas may reopen/recur in 0-20% of cases. The reported causes of reopening following stent placement were stent occlusion (caused by tumor overgrowth or in growth, food impaction, or granulation tissue formation), stent migration, and stent covering disruption.

Does stenting have a survival advantage?

A recent study (3) compared treatment of MTEF in three groups:  oesophageal stent group, gastrostomy group and control group (refused both stenting and gastrostomy).

There was no statistical difference in survival time (Average survival time for stent group was 93 days with a range of 44-165 days, gastrostomy group- 62 days, range 41-111 days and control group survival time was 66 days- range 20-119 days).

In two, large series reports (4, 5), mean patient survival was reported to be 3.1-3.4 months. In one of these reports (4), the survival benefit was significant in patients in the stenting group (3.4 months) compared with the gastrostomy group (1.1 months), and the supportive management group (1.3 months).

NB: It is very important to carefully evaluate the airway stenosis with CT scans or

bronchoscopy prior to oesophageal stent placement, since it is possible to develop tracheal compression caused by expanding oesophageal stents. Further, for airway

stenting, reconstructed CT images are very useful for measuring the distance between the fistula and a carina or vocal cord, in the determination optimal stent length.

References:

1.Rodriguez AN, Diaz-Jimenez JP. Malignant respiratory-digestive fistulas. Curr Opin Pulm Med. 2010 Jul;16(4):329-33.

2. Shin JH et al. Interventional management of esophagorespiratory fistula. Korean J Radiol. 2010 Mar-Apr; 11(2):133-40.

3. Hu Y et al. Comparative study of different treatments for malignant tracheoesophageal/bronchoesophageal fistulae. Dis Esophagus. 2009;22(6):526-31.

4. Balazs A, Kupcsulik PK, Galambos Z. Esophagorespiratory fistulas of tumorous origin. Non-operative management of 264 cases in a 20-year period. Eur J Cardiothorac Surg 2008;34:1103-1107

5. Shin JH, Song HY, Ko GY, Lim JO, Yoon HK, Sung KB. Esophagorespiratory fistula: long-term results of palliative treatment with covered expandable metallic stents in 61 patients. Radiology 2004;232:252-259

• The polyp is completely excised by the endoscopist and is submitted in toto for pathological examination.
• Histology- it is possible to accurately determine the depth of invasion, grade of differentiation, and completeness of excision of the carcinoma.
• The cancer is not poorly differentiated.
• There is no vascular or lymphatic involvement.
• The margin of the excision is not involved. Invasion of the stalk of a pedunculated polyp, by itself, is not an unfavorable prognostic finding, as long as the cancer does not extend to the margin of stalk resection.

When all of these low risk criteria are not met, the decision to proceed to surgical resection needs to be individualized, taking into account the age and comorbidity of the patient. Surgical resection is generally recommended for any invasive cancer in a sessile adenoma where the patient is otherwise well.

Cancerous polyp are often described using Haggitt levels.

Cancerous polyps are classified according to Haggitt level:

Level 0- carcinoma in situ

Level 1- submucosa in the head of the polyp

Level 2- submucosa in the neck of the polyp

Level 3- submucosa in the stalk of the polyp

Level 4- submucosa beyond the stalk

Polyps classified as Haggitt level 3 or lower have a less than 1% likelihood of lymph node metastasis and can be treated with polypectomy alone when they meet the following pathologic criteria:

Specimen margins are greater than 2 mm

There is no evidence of lymphovascular invasion and

The tumour is well differentiated.

Haggitt level 4 polyps have a 12-25% risk of lymph node metastasis and should be treated with segmental colectomy.

Reference:

American College of Gastroenterology Guidelines (Archived copy at WebCite)

CUP is a cancer in which a complete diagnostic work-up detects only metastases, but no primary tumour. CUP accounts for 3–5% of all malignancies. Modern investigations identify the primary tumour in 10-20% of patients only. Even in post mortem series, a primary is found in only 50% to 75% of cases. The median survival of patients with the CUP syndrome is 3 to 6 months.

Discuss the diagnostic approach to CUP?

CUPs are by de?nition metastatic tumours. Thus the diagnostic approach should be to de?ne the extent of tumour dissemination and help identify a minority of CUP patients who can expect to bene?t from directed therapy. This must be achieved with a minimum of stress to the patient. It is recommended that all patients with CUP should have:

• Thorough physical examination (including head and neck, rectal, pelvic and breast examination), basic blood and biochemistry survey, urinalysis, faecal occult blood test and CT scan of thorax, abdomen and pelvis.
• Endoscopy should be sign or symptom guided.
• Serum assessment of AFP, HCG and PSA is suggested in male patients to exclude potentially curable extragonadal germ-cell tumour and those amenable to hormone treatment for prostate cancer. Other tumour markers, such as CEA, CA125, CA19-9, or Ca 15-3, are of low specificity and can only be used to follow the course of the illness.
• Mammography or breast MRI is recommended in female patient with axillary adenopathy.
• PET is suggested in patients with head and neck CUP

Discuss the favourable sub groups of CUP?

CUP has a very poor prognosis. However 20-30% of patients with CUP have good prognosis and can have long-term survival or even cure. Identification of these subgroups with favourable prognosis is of vital importance for the therapy of patients with CUP syndrome. The first step is always to test whether a patient has one of these well characterized disease entities and then to plan the treatment accordingly. These CUP subgroups with favourable prognosis are rare. These subgroups are

• Axillary lymph node metastasis of adenocarcinoma in a women
  All should undergo mammography or breast MRI. Immunohistology for hormone status and c-erb2 should be checked. These patients with compatible immunohistology and absence of a breast primary should be treated as breast cancer with lymph node involvement (stage II)
• Papillary carcinomatosis of a serous papillary adenocarcinoma in women-usually originates in the ovary or peritoneum. Ca125 is often increased. Therapy is identical to that of metastatic ovarian carcinoma in stage FIGO III.
• Cervical lymph node metastasis of squamous cell cancer-These patients should undergo CT and/or MRI of the neck. PET is recommended as it may pick up small metabolically active lesions that are not seen on CT or MRI. They should also have a through ENT examination with biopsies of any suspicious lesions. Treatment is as for metastatic ENT tumours with a known primary.
• Inguinal lymph node metastasis of squamous cell carcinoma- a large majority will have a detectable primary site in the genital or anorectal area. So external genitalia should be carefully examined in both sexes. Digital rectal examination and proctoscopy should be performed in both sexes to exclude anorectal lesions. If no primary site is identified, lymphadenectomy with or without postoperative radiation therapy to the inguinal nodal region may result in long-term survival.

Undifferentiated neuroendocrine carcinoma- a platinum/etoposide based regimen as currently used for small cell lung cancer is generally used.

• Poorly differentiated carcinoma with germ cell characteristics- these patients typically have some of the following features;
  • Young males (<50) with retroperitoneal and mediastinal lymph node metastasis.
  • Serum levels of HCG or AFP is markedly elevated.
  • They also have cytogenetic aberrations like presence of 12p chromosomal gain on molecular genetic analysis.

These tumours should be treated like poor prognosis germ cell tumours. The response to chemotherapy is excellent and some are cured

• Solitary metastasis: A PET scan is suggested to rule out any additional unrecognized sites of metastatic disease prior to definitive local therapy. If the metastasis is truly solitary, resection or definitive local radiation therapy is indicated. Local treatment sometimes results in long disease-free intervals.

• They have secretory characteristics and frequently present with hypersecretory syndromes.
• NET is the preferred term rather than carcinoid.

What are the commonest sites of NET?

Appendix (35%), ileum (15%), rectum (10%) and lung (15%)

Discuss the clinical features of NET?

• Primary gut tumours can be asymptomatic but may present with obstructive symptoms (pain, nausea, and vomiting) despite normal radiology.
• Secretory tumours can present with
  • Carcinoid syndrome
    • It is a result of metastases to the liver with the subsequent release of hormones (serotonin, tachykinins, and other vasoactive compounds) directly into the systemic circulation.
    • This syndrome is characterised by flushing, diarrhoea and palpitations. Less commonly wheezing and pellagra may occur as presenting features, with carcinoid heart disease typically not occurring unless the syndrome has been present for some years. Occasionally, similar syndromes can occur when there are no measurable hormones detected in blood or urine.
    • The carcinoid crisis is characterised by profound flushing, bronchospasm, tachycardia, and widely and rapidly fluctuating blood pressure. It is usually precipitated by anaesthetic induction for any operation, intraoperative handling of the tumour, or other invasive therapeutic procedures such as embolisation and radiofrequency ablation.
  • Pancreatic NETs like insulinoma, gastrinoma, glucagonoma, VIPoma and somastatinoma produce relevant secretory symptoms.

Discuss the genetics of NET?

NETs may occur as part of complex familial endocrine cancer syndromes such as MEN1, MEN2 etc although the majority are sporadic isolated tumours. However, it is important to search thoroughly for MEN1, MEN2, and NF1 in all patients with NETs by obtaining a detailed family history, clinical examination, and appropriate biochemical and radiological investigations.

Discuss the diagnosis of NET?

If a patient presents with symptoms suspicious of a gastroenteropancreatic NET: baseline tests should include chromogranin A (CgA) and 5-hydroxy indole acetic acid (5- HIAA). Specific biochemical tests should be requested depending on which syndrome is suspected. The gold standard in diagnosis is detailed histology and this should be obtained whenever possible.

Blood and urine measurements

• 24 h urinary 5-HIAA is usually raised (70% of patients) in midgut carcinoids.
• Plasma CgA- CgA is a large protein which is produced by all cells deriving from the neural crest. The function of CgA is not known but it is produced in very significant quantities by NET cells regardless of their secretory status.
• Gut hormones will be raised in pancreatic NETs.

Currently in UK, the following hormones are normally performed when gut hormones are requested: gastrin, glucagon, somatostatin, PP, VIP and neurotensin. CgA will be performed on the same sample when requested. Blood is taken in a 10ml standard heparin bottle and spun immediately before being frozen and sent to the reference lab.

Imaging
The optimum imaging modality depends on whether it is to be used in detecting disease in a patient suspected of an NET or for assessing the extent of disease in a known case.

• CT scan or endoscopy is useful to locate the primary in case of metastases.
• SSRS (somatostatin receptor scan or octreoscan)-

Neuroendocrine tumours express somatostatin receptors (SSTR) and this has led to the development of radiolabelled somatostatin analogues for diagnostic imaging.
SSRS has a sensitivity of 90% for gut NETs and plays a central role in locating and assessing the primary in gastroenteropancreatic NETs.
However, in patients whose octreoscan is negative and in whom no diagnosis is reached after upper and lower gastrointestinal endoscopy, a triple phase CT scan of the thorax and abdomen is regarded as the investigation of choice.
The diagnostic test of choice to locate secondaries is SSRS. SSRS prior to surgery revised the staging and changed management in 33% in Krenning’s series

Monitoring progression of disease

• Spiral CT scanning, MRI, and ultrasound scans are useful for monitoring lesions.
• Urinary 5-HIAA levels do not accurately correlate with disease progression and response to treatment.
• CgA is a sensitive marker which correlates well with response and relapse.

Discuss staging of NET?
Tumours should be classified according to the recent WHO classification. This places all enteropancreatic NETs into one of four categories, based on a combination of gross and histological features

• Well differentiated endocrine tumour of probable benign behaviour.
• Well differentiated endocrine tumour of uncertain behaviour.
• Well differentiated endocrine carcinoma.
• Poorly differentiated endocrine carcinoma.

There is currently no TNM staging system for these tumours.

Discuss the treatment of NET?

The aim of treatment should be curative where possible but is palliative in the majority of cases. Metastatic disease is a common presentation in patients with NETs; therefore, the aim of treatment is frequently improvement of their quality of life rather than cure. These patients often maintain a good quality of life for a long period despite having metastases.

Discuss the role of surgery in NETs?

This is the only curative treatment for NETs. With carcinoid, if the primary lesion is less than 2 cm in diameter, the incidence of metastasis is low.

a. Incidental carcinoid in appendectomy specimen-

• Right hemicolectomy is indicated if the carcinoid tumour is more than 2 cms in diameter.
• Tumours 1–2 cm or invading the serosal surface may require further resection, particularly if atypical with goblet cell or adenocarcinoid features, or if it is located at the base of the appendix, or if histology shows mesoappendiceal and/or vascular invasion, when a right hemicolectomy with locoregional lymphadenectomy should be considered. Whether or not this is performed, the patient should be followed up for five years.
• If the lesion is less than 1 cm in diameter- no further resection is needed, provided complete resection by appendicectomy has been undertaken. Extended follow up appear unnecessary.

b. Stomach- 3 types of gastric carcinoid

c. Small intestinal carcinoid

Resection of the primary (along with mesenteric lymphadenectomy) is appropriate, even in presence of liver metastases, to delay progression that would otherwise endanger the small bowel.
Nodal metastases cause sclerosis with vascular compromise of the associated small bowel, which can lead to pain, malabsorption, and even death.
Patients, who only after laparotomy and histological examination are discovered to have small intestinal carcinoid, may be candidates for further surgery, notably for extensive
mesenteric lymphadenectomy. Resection of mesenteric metastases may alleviate symptoms dramatically, and possibly prolong survival.

d. Colorectum
Standard resection with locoregional lymphadenectomy is appropriate. Small lesions less than 1 cm in diameter may be considered adequately treated by complete endoscopic removal but the patient will require follow up endoscopy to ensure this has been accomplished.

e. Pancreas
Often the diagnosis is established biochemically prior to surgery, and although preoperative localisation can be difficult, the biochemical diagnosis provides some indication of the site of the tumour. Appropriate resections are done depending on the location of the tumour.

f. Liver
In the presence of liver metastases, ‘‘curative’’ liver resection is possible in approximately 10% of cases if the lesions are confined to one lobe. With bilobar metastases and one very dominant lesion causing symptoms, a debulking operation may be carried out for palliation, particularly if there is resistance to medical therapy.

Discuss the symptom control measures in NETs?

• There are a number of treatment options available for patients displaying symptoms due to hormones/peptides secreted by a secretory tumour.
• Somatostatin analogues- Somatostatin receptors are present in the vast majority (70–95%) of NETs. Somatostatin analogues inhibit the release of various peptide hormones in the gut, pancreas, and pituitary, antagonise growth factor effects on tumour cells, and at very high dosage may induce apoptosis.
  • Octreotide is administered subcutaneously (50–100 mg 2-3 times/day to a maximum daily dose of 1500 mg). Other long acting analogues have been synthesised recently like lanreotide (fortnightly injection), Sandostatin LAR (monthly), and Lanreotide Autogel (also monthly).
  • This lead to symptomatic control in the majority. Few side effects from somatostatin analogues have been reported and they include fat malabsorption, gall stones and gall bladder dysfunction, vitamin A and D malabsorption, headaches, diarrhoea, dizziness, and hypo- and hyperglycaemia.
• Use of PPI in gastrinomas, diazoxide for insulinoma. Additional octreotide is usually not needed in gastrinomas and insulinomas
• VIPomas, Glucagonoma respond to octreotide.

What is the role of chemotherapy?

The role of chemotherapy for NETs is uncertain but is being actively researched. One paper showed that response to chemotherapy in patients with strongly positive carcinoid tumours was of the order of only 10% whereas patients with SSRS negative tumours had a response rate in excess of 70%. The highest response rates with chemotherapy are seen in the poorly differentiated and anaplastic NETs: response rates of 70% or more have been seen with cisplatin and etoposide based combinations.

Discuss any other treatment options?

Targeted radionuclide therapy
This is a useful palliative option for symptomatic patients with inoperable or metastatic tumour. The principle of treatment is only to give radionuclide therapy when there is abnormally increased uptake of the corresponding imaging agent.
The gamma emitting imaging radionuclide is replaced by a beta imaging therapy radionuclide: 131 I-MIBG for 123 I-MIBG, 90Y-octreotide for 111In-octreotate, and 90Y-lanreotide for 111In-lanreotide. Contraindications include pregnancy and breast feeding, myelosuppression, and renal failure (glomerular filtration rate, <40 ml/min). Symptom control is up to 80% and a five year survival rate of 60% has been recorded. Treatment is well tolerated and toxicity limited to temporary myelosuppression 4–6 weeks post therapy

Embolisation of hepatic artery
This procedure is indicated for patients with non-resectable multiple and hormone secreting tumours with the intention of reducing tumour size and hormone output. There are two types of embolisation: particle and chemoembolisation. Particles used include polyvinyl alcohol and gel foam powder. For chemoembolisation, agents such as doxorubicin and cisplatin are used primarily. Contraindications for chemoembolisation include complete portal vein obstruction, liver insufficiency, and biliary reconstruction.

Radiofrequency ablation
This has been used with some effect in stabilising or reducing tumour size but randomised trials are lacking. It may be indicated in patients with inoperable bilobar metastases in whom hepatic artery embolisation has failed. Destroying the largest lesion may not necessarily switch off hormone production. To achieve a reduction in hormone secretion it is necessary to ablate at least 90% of the visible tumour

External beam radiotherapy

Carcinoid tumours are radioresistant. However, it may provide excellent relief of the pain from bone secondaries.

What is the prognosis?

• 5 year survival is 83% following complete surgical resection of the primary tumour and liver metastases if present.
• 5 year survival is 30-70% if curative surgical resection is not feasible.

How do you prevent carcinoid crisis?
When a functioning carcinoid tumour is found before surgery, a potential carcinoid crisis could be prevented by prophylactic administration of octreotide, given by constant intravenous infusion at a dose of 50 mg/h for 12 hours prior to and at least 48 hours after surgery. It is also important to avoid drugs that release histamine or activate the sympathetic nervous system.

Ref

1. British Society of Gastroenterology Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumour

British Society of Gastroenterology Guidelines 2010

British Society of Gastroenterology guidelines for follow up after resection of colorectal cancer

• It is reasonable to offer CT imaging of the liver to asymptomatic patients within 2 years after potentially curative resection.
• Although there is no evidence that colonoscopic follow-up improves survival, it does yield some treatable tumours. It is recommended that a colonoscopy is done 5 years after surgery and thereafter ever y 5 years until the bene?t is outweighed by co -morbidity. Patients found to have adenomas at the time of diagnosis of colorectal cancer or on follow-up surveillance should follow adenoma surveillance guidance, continuing surveillance at least 5-yearly until bene?t is outweighed by co morbidity.

British Society of Gastroenterology guidelines for colorectal cancer screening and surveillance in moderate risk family groups

First degree kinship: Affected relatives who are ?rst-degree relatives of each other AND at least one is a ?rst degree relative of the consultand.

NB- All other FH of CRC: should be reassured and encouraged to avail themselves of population-based screening measures. The low level residual risk over that of the general population should be explained. Furthermore, because the population lifetime risk in the UK is around 1:20, some people without any family history will develop colorectal cancer, and this residual population risk should be made explicit.

American Gastroenterological Association (page 24)

• Usual features- Abdominal pain, Change in bowel habit, Haematochezia or melena, Anaemia without other gastrointestinal symptoms, Weight loss.
  A change in bowel habit is a more common presenting symptom for left-sided cancers. Occult colonic bleeding occurs more often with caecal and ascending colon tumors.
• Unusual features
  Malignant fistula formation into adjacent organs, such as bladder or small bowel. This is most common with caecal or sigmoid carcinomas.
  Streptococcus bovis bacteraemia and Clostridium septicum sepsis can be due to underlying colonic malignancies.

What are synchronous and metachronous cancers?

Synchronous CRCs are defined as two or more distinct primary tumors separated by normal bowel and not due to direct extension or metastasis. It occurs in upto 5 percent of patients with colon cancer.
Metachronous CRCs are defined as non anastomotic new tumors developing at least six months after the initial diagnosis. It occurs in upto 3 percent of patients in the first five years postoperatively.

Discuss the differential diagnosis of CRC?
Rare malignancies other than adenocarcinoma which are primary to the large bowel;

• Disseminated Kaposi’s sarcoma can involve the colon in patients with AIDS, manifested as characteristic violaceous macules or nodules.
• Primary non-Hodgkin’s lymphoma of large bowel most commonly arises in the cecum, right colon, and rectum. It typically appears as a large solitary mass.
• Colonic carcinoid tumors appear as submucosal nodules.

Discuss the staging for CRC?

Duke’s A- Localized to the mucosa and submucosa
Duke’s B- Extending into or through the muscle layer without lymph node involvement
Duke’s C- Lymph node involvement
Duke’s D- Distant metastases

TNM staging

T1 Tumour invades the submucosa

T2 Tumour invades muscularis propria

T3 Tumor invades through the muscularis propria into the subserosa, or into non-peritonealized pericolic or perirectal tissues

T4 Tumor directly invades other organs or structures, and/or perforates visceral peritoneum

N1- Metastasis in 1-3 regional lymph nodes. N2- Metastasis in >= 4 regional lymph nodes

M0- No distant metastasis M1- Distant metastases

What investigations are needed?

• CT scan of chest/abdomen/pelvis for staging
• MRI- useful for staging of rectal cancer. MRI is better at assessing perirectal node involvement.
• PET scans — it may be useful in localizing site of disease recurrence in patients who have a rising serum CEA level and nondiagnostic conventional imaging evaluation. It may also be used to evaluate patients who are thought to be candidates for resection of isolated colorectal cancer liver metastases.
• EUS – helps in assessing depth of invasion and nodal status in rectal cancer. Both transrectal or endorectal ultrasound (EUS) and MRI with endorectal coils can demonstrate the various layers of the rectal wall, but the EUS is less expensive.
• Tumor markers — Carcinoembryonic antigen (CEA) have a low diagnostic ability to detect primary CRC. However serum CEA has prognostic utility in patients with newly diagnosed CRC. Patients with preoperative serum CEA > 5 ng/mL have a worse prognosis, stage for stage, than those with lower levels. American Society of Clinical Oncology (ASCO) guidelines recommend that serum CEA levels be obtained preoperatively in patients with demonstrated colorectal cancer to aid in staging, surgical treatment planning, and in the assessment of prognosis. Elevated CEA levels should normalize following curative resection; if they do not, residual disease should be suspected.

Discuss the treatment of CRC?

Surgery is the only curative modality for localized colon cancer. The goal of colon cancer surgery is complete removal of the tumor along with the major vascular pedicle feeding the affected colonic segment and the lymphatic drainage basin. Regional lymphadenectomy is of prognostic and therapeutic value. At least 12 lymph nodes should be assessed for adequate staging. The 30-day postoperative mortality rate is around 5 %.

There is great variability in the frequency of postoperative bowel movements following a hemicolectomy. Most patients will have a minimal increase in frequency, and some have at least a temporary increase to four or more movements per day. Such patients may benefit from the addition of dietary fiber, and when necessary, an antimotility agent. The remaining colon will often adapt over a four to six month period, gradually returning to a more normal bowel pattern.

Laparoscopic resection is a reasonable option to open colectomy for potentially curative resection of colon cancer. Approximately 20 percent will require conversion to an open approach.

What is the role of adjuvant therapy?

• Node positive cancer- Adjuvant systemic therapy (5-FU based) is routinely used. Such treatment is associated with an approximately 30 percent reduction in the risk of disease recurrence, and a 22 to 32 percent reduction in mortality.
• Node negative cancer- ASCO guidelines suggest that a course of 5-FU-based adjuvant chemotherapy be considered for patients with incomplete sampling of the regional lymph nodes (ie, fewer than 12 nodes in the surgical specimen) or high-risk stage II disease (perforation, T4 lesions, poorly differentiated histology)
• The evidence is inconclusive as to the benefit of adding radiotherapy (RT) to chemotherapy for patients at high risk of local recurrence (ie, those with positive resection margins, perforation of the visceral peritoneum, or invasion of other adjacent organs). It is reasonable to consider RT on a case-by-case basis for such patients.

Discuss the palliative options?

I. Palliation of obstruction

• For unresectable distal obstructing tumors of the sigmoid colon, palliation involves a diverting colostomy and the creation of a mucous fistula with the distal bowel segment. The colostomy diverts the fecal stream and the mucous fistula decompresses the secretions from the distally obstructed bowel.
  Patients with more proximal unresectable colon cancers can usually be bypassed with a side-to-side anastomosis from proximal bowel to a distal segment. This circumvents the obstruction, permitting internal decompression of the obstructed segments while avoiding a colostomy.
• Colorectal self-expanding metal stents (SEMS) can be placed in poor operative candidates. It can be placed under endoscopic guidance with the aid of fluoroscopy. The most common complications are perforation (5%) and stent migration; less commonly, abdominal pain and bleeding.

II. Palliation of bleeding — Unresectable bleeding tumors present difficult situation. The continued presence of the fecal stream contributes to the bleeding process. The bleeding may resolve or improve with a colonic diversion or bypass. If this fails to control the bleeding, external beam RT may be successful.

Discuss the treatment of rectal cancer?

I. Neoadjuvant therapy- Chemoradiotherapy (5-6 week course, 5-FU based) should be considered in

• Patients with distal mobile rectal cancers, not amenable to local excision
• Patients with more proximal rectal tumors that are large, locally invasive, or clinically node-positive (ie, T3/4, N1).
• All patients who undergo neoadjuvant chemoradiotherapy followed by surgery for low-lying rectal cancers should receive postoperative adjuvant 5-FU-based chemotherapy (4 cycles), even if they have no residual tumor in the surgical specimen.

II. Surgery-The number of lymph nodes sampled is an important predictor of outcome. The surgical specimen should contain at least 12 lymph nodes. The criteria for unresectability are not clearly defined. Locally advanced rectal cancer is defined by some to be T3/4 or N1 disease and/or clinically bulky
There are three surgical options for rectal cancer:

• Abdominal perineal resection (APR) — It is the gold standard for surgical therapy of distal rectal cancers. It involves removal of the tumor along with a complete proctectomy. This results in the need for a permanent colostomy.
  Neoadjuvant chemoradiotherapy may facilitate the conversion of a planned APR to a sphincter-sparing LAR by promoting tumour regression. Thus, the preferred approach for patients with T2/T3 low-lying rectal cancers is neoadjuvant chemoradiotherapy that may, in some cases, permit a sphincter-preserving procedure to be performed rather than APR.
• Low anterior resection & colo-anal anastomosis — for rectal cancers involving the upper third of the rectum, as long as the surgeon can obtain a distal margin of at least 2 cm (some say 1cms).
• Local excision- superficially invasive small cancers may be effectively managed with local excision by transanal approach within 10 cm of the anal verge. Minimally invasive endoscopic techniques such as transanal endoscopic microsurgery (TEM) have expanded the possibility of transanal excision to otherwise inaccessible lesions that are within reach of the endoscope (up to 18 cm from the dentate line)

III. Adjuvant therapy

In contrast to colon cancer, in which the failure pattern is predominantly distant metastases, the site of first failure in rectal cancer patients is equally distributed locally (ie, pelvis) and in distant sites (eg, liver, lung). Local recurrence is mainly related to difficulties in obtaining optimal surgical clearance of the radial margin

• Postoperative adjuvant radiation and chemotherapy (5-FU based) should be offered to all patients with transmural or node-positive disease
• For patients with favorable histology T1 rectal cancer, local excision alone suffices. Postoperative irradiation and chemotherapy should follow local excision procedures for patients with unfavorable histology T1 and all T2 tumors.

IV. Locally recurrent rectal cancer

The choice of therapy depends upon prior therapy and the local extent of the recurrence. Surgery or RT may permit successful salvage. Local re-radiation alone may provide palliation, but does not prolong survival

Discuss localization of rectal tumours at endoscopy?

The most reliable landmark is the dentate line, where the squamous mucosa of the anus transitions to the columnar mucosa of the rectum. The dentate line is located in the middle of the anorectal ring, which is comprised of the sphincters (internal and external). These muscles are responsible for fecal continence and usually extends 1 to 3 cm proximal to the dentate line. A tumor has to be located high enough above the top of the anorectal ring to allow for an adequate distal margin if sphincter preservation is to be achieved.

Discuss resection of colorectal cancer liver metastases?

a. Patients with extrahepatic disease that should be considered for liver resection include:

• resectable/ablatable pulmonary metastases
• resectable/ablatable isolated extrahepatic sites—for example, spleen, adrenal, or respectable local recurrence
• local direct extension of liver mets to, for e.g., diaphragm/adrenal that can be resected.

Contraindications to liver resection-

• non-treatable primary tumour;
• widespread pulmonary disease;
• locoregional recurrence;
• peritoneal disease;
• extensive nodal disease, such as retroperitoneal, mediastinal or portal nodes;
• bone or CNS metastases.

b. Normally, colorectal cancer resection & liver resection would not be performed synchronously. Lesions discovered at operation should not be biopsied. Patients with potentially resectable liver disease and who have undergone radical resection of the primary tumour should be considered for liver resection before consideration of chemotherapy. Patients with unfavourable primary pathology such as perforated primary tumour or extensive nodal involvement should be considered for adjuvant chemotherapy prior to liver resection and be restaged at three months.

c. The natural history of metastatic colorectal cancer is variable. Median survival without treatment is less than eight months from presentation but the prognosis is better for those patients with isolated hepatic metastases. However, even in the group of patients with limited metastatic liver disease, survival at five years is exceptional. Several recent large series on resection for colorectal liver metastases have reported five year survival ranging from 25% to 44%, with operative mortality of 0–6.6%.

d. It has been argued that the limiting factor to the number of lesions that can be resected is whether it is technically possible to remove all tumours. Patients with solitary, multiple and bilobar metastatic disease are candidates for liver resection. The surgeon should define the acceptable residual functioning volume, approximately one third of the standard liver volume, or the equivalent of a minimum of two segments

e. Recent data suggest that if lung metastases of colorectal origin are resectable, five year survival following thoracotomy is similar to that observed in patients after resection of colorectal liver metastases.

f. Recurrence may occur in up to 60% of patients (usually in the first 2 years) following liver resection for colorectal metastases with the most common site being in the liver. These may be suitable for re-resection. The reported morbidity and mortality rates and long term survival rates of re-resection are similar to those reported for the original hepatectomy despite the greater technical difficulty of the procedure.

g. Chemotherapy for metastatic colorectal cancer can improve survival and should be considered in all patients not suitable for surgery. NICE now recommend the use of oxaliplatin based regimens as first line therapy for all patients with non-resectable disease. There is no evidence to support ‘‘pretreatment’’ with neoadjuvant chemotherapy in patients with resectable disease.

Ref-

1. British Society of Gastroenterology guidelines for Resection of Colorectal Cancer Liver Metastases

Gallbladder polyps are outgrowths of the gallbladder mucosal wall. They are usually found incidentally on ultrasonography or after cholecystectomy. The majority of these lesions are not neoplastic but are hyperplastic or represent lipid deposits (cholesterolosis). A minority of polyps could be adenomas or inflammatory polyps.

Discuss the clinical features of GB polyps?

Gallbladder polyps can be associated with biliary pain.

Discuss the treatment of GB polyps?

• Patients who have gallbladder polyps and concomitant gallstones should undergo cholecystectomy regardless of the polyp size or symptoms since gallstones are a risk factor for gallbladder cancer in patients with gallbladder polyps.
• Cholecystectomy should also be recommended for patients who have biliary colic.
• Polyps 10 to 20 mm in diameter should be regarded as possibly malignant. Cancer of this size is usually an early stage cancer and laparoscopic cholecystectomy with full thickness dissection is recommended. Polyps less than 10 mm can be followed up by regular USS.
• Lesions larger than 18 to 20 mm are usually malignant and should be resected. Because these lesions may represent advanced cancer, patients should undergo preoperative staging with a CT scan and EUS.

The majority are adenocarcinomas. The majority are found incidentally in patients undergoing exploration for cholelithiasis. Women are affected two to six times more often than men.

What are the risk factors for GBC?

• Gallstone disease — is one of the strongest risk factors for the development of GBC.
• Porcelain gallbladder — is an uncommon manifestation of chronic cholecystitis that is characterized by intramural calcification of the gallbladder wall. It is associated with cholelithiasis in more than 95 percent of cases.
• Gallbladder polyps.

What are the clinical features of GBC?

• Patients with early invasive GBC are most often asymptomatic or have nonspecific symptoms.
• The most common symptoms caused by GBC are jaundice, pain, and fever.
• Patients with GBC may also present with obstructive jaundice by invasion of tumor into the porta hepatis.
• For GBC- loco regional growth predominates. Haematogenous metastases is unusual

Discuss TNM staging of GBC?

T1 Tumour invades the lamina propria (T1a) or muscle layer (T1b)

T2 Tumor invades perimuscular connective tissue; no extension beyond serosa or into liver

T3 Tumor perforates the serosa (visceral peritoneum) or directly invades one adjacent organ or both (extension 2 cm or less into the liver)

T4 Tumor extends more than 2 cm into the liver, and/or into two or more adjacent organs (stomach, duodenum, colon, pancreas, omentum, extrahepatic bile ducts, any involvement of the liver)

N0 No regional lymph node metastasis N1 Regional lymph node metastasis

M0 No distant metastasis M1 Distant metastases

Discuss the treatment of GBC?

Surgery is the only potentially curative therapy. Only T1 or T2 and N1 lesions are resectable.
A logical surgical approach to potentially resectable GBC consists of total removal of the gallbladder, a portion of the underlying liver (generally segments IVb and V), and dissection of the draining regional lymphatics. Simple cholecystectomy may be sufficient for T1 lesions.

What are the contraindications to surgery?

Among the absolute contraindications to surgery are liver or peritoneal metastases, ascites, extensive involvement of the hepatoduodenal ligament, and encasement or occlusion of major vessels.

Discuss the approach to incidental GBC discovered at cholecystectomy?

Current consensus is that patients would undergo a second curative procedure if an unexpected gallbladder cancer is diagnosed postoperatively after cholecystectomy, except for those who are found to have T1 disease. Implantation of the carcinoma at all port sites after laparoscopic removal of an unsuspected cancer is a problem. Even for stage I cancers, the port sites must be excised completely.

What is the role of adjuvant therapy?

No clear evidence that adjuvant therapy provides survival benefit

What are the treatment options for unresectable disease?

Patients with locally advanced unresectable disease are candidates for chemoradiotherapy. The relative merits of systemic chemotherapy versus basic supportive care for patients with locally advanced or metastatic disease remain to be established in controlled trials.

What is the prognosis?

Patients with cancers confined to the mucosa have 5-year survival rates of nearly 100%. Patients with muscular invasion or beyond have a survival of less than 15%.

Cholangiocarcinomas arise from the epithelial cells of the bile ducts. The majority of cholangiocarcinomas (>90 percent) are adenocarcinomas, with squamous cell carcinoma being responsible for most of the remaining cases. Distant metastases are distinctly uncommon in cholangiocarcinoma.

Cholangiocarcinoma may arise in the intrahepatic (least common), perihilar, or distal
(extrahepatic) biliary tree. Bile duct tumors that involve the common hepatic duct bifurcation are referred to as Klatskin tumors regardless of whether they arise from the intrahepatic or extrahepatic portion of the biliary tree.

What is the epidemiology of cholangiocarcinoma?

Cholangiocarcinoma generally presents between 50 and 70 years of age. However, patients with primary sclerosing cholangitis (PSC) and those with choledochal cysts present nearly two decades earlier. The incidence of cholangiocarcinoma is slightly higher in men. This probably reflects the higher incidence of PSC in men.

What are the risk factors for cholangiocarcinoma?

• PSC is the commonest known predisposing factor for cholangiocarcinoma in the UK. It is interesting to note that the risk of developing cholangiocarcinoma is not associated with the duration of PSC.
• Chronic intraductal gall stones.
• Bile duct adenoma and biliary papillomatosis.
• Caroli’s disease (cystic dilatation of ducts)
• Choledochal cysts
• Thorotrast (a radiological agent no longer licensed for use)
• Smoking (increased risk in association with PSC).
• In SE Asia, where the tumour is quite common, the associated risk factors are liver flukes (Opisthorchis viverrini and Clonorchis sinensis) and chronic typhoid carriers.

What are the clinical features of cholangiocarcinoma?

i. Painless obstructive jaundice, abdominal pain and weight loss.
ii. Cholangiocarcinoma is often associated with intermittent rather than steadily progressive jaundice.

Discuss the diagnosis of cholangiocarcinoma?

• USS- Diagnosis should be suspected when ducts are dilated.
• CT- abdominal lymphadenopathy is common in PSC & does not necessarily indicate malignant change.
• Tumour markers- The value of CA 19-9 in patients with suspected cholangiocarcinoma is unclear. CEA and Ca 125 are also raised in cholangiocarcinoma.
• Tissue diagnosis of cholangiocarcinoma is difficult because it is highly desmoplastic tumour composed of a few malignant cholangiocytes within excessive fibrous tissue. Thus cytology is positive in only 1/3rd of cases.
• Positron emission tomography — PET scan permits visualization of cholangiocarcinomas because of the high glucose uptake of bile duct epithelium. Another role for PET is in screening patients with PSC for the presence of cholangiocarcinoma.
• Staging laparoscopy —laparoscopy will identify 25-30% of patients as unresectable who were thought to be operable before laparoscopy. Therefore laparoscopy should be standard before operation.

Discuss the management of cholangiocarcinoma?

Surgery is the only curative treatment for patients with cholangiocarcinoma.

• Distal cholangiocarcinomas are managed by pancreatoduodenectomy as with pancreatic head cancers.
• Intrahepatic cholangiocarcinoma is treated by resection of the involved segments or lobe of the liver.
• Hilar tumours- en bloc resection of the extrahepatic bile ducts and gall bladder, regional lymphadenectomy, and Roux-en-Y hepaticojejunostomy with or without right or left hepatectomy

Criteria for resectability — the traditional guidelines for resectability in US include:

• Absence of nodal metastases or distant liver metastases.
• Absence of invasion of the portal vein or main hepatic artery
• Absence of extrahepatic adjacent organ invasion
• Absence of disseminated disease

However, as a general rule, true resectability is ultimately determined at surgery, particularly with perihilar tumors.

What is the role of preoperative biliary decompression?

This is controversial. Many surgeons proceed directly to laparotomy without preoperative biliary drainage. On the other hand, there is often uncertainty as to resectability as well as the timetable of surgical evaluation and operative management in patients presenting with jaundice. As a practical issue, stents are often placed to alleviate jaundice while these issues are being settled.

What is the role of chemoradiotherapy?

Neoadjuvant or adjuvant chemotherapy or radiotherapy therapy is not shown to be beneficial in patients with cholangiocarcinoma.

What are the palliative treatment options?

• Photodynamic therapy is emerging as an important palliative option for patients with unresectable cholangiocarcinoma.
• Biliary stenting to relieve symptoms. Palliative radiation therapy after biliary bypass or intubation may be beneficial for some patients.
• Patients with unresectable disease can be considered candidates for phase I and II studies of chemotherapeutic agents or biologics.

What is the prognosis?
Surgery for cholangiocarcinoma is usually extensive and have a high operative mortality (5%-10%) and low curability. There is a 9–18% five year survival for proximal bile duct lesions and 20–30% for distal lesions.
Median survival for patients with intrahepatic cholangiocarcinoma without hilar involvement is 18–30 months and 12–24 months with perihilar involvement.

Ref

1. British Society of Gastroenterology Guidelines for the diagnosis and treatment of cholangiocarcinoma: consensus document

Carcinoma of the pancreas has markedly increased in incidence over the past several decades, and ranks as the fifth leading cause of cancer death in the United States.

What are the risk factors for pancreatic cancer?

The major risk factors include chronic pancreatitis, smoking, diabetes mellitus, and hereditary predisposition to pancreatic cancer.

What are the clinical features?

• Pancreatic cancer occurs in the 60–80 year age group. Most patients with pancreatic cancer experience pain, weight loss, or jaundice.
• Dull aching upper abdominal pain radiating through to the back and worsened by eating.
• Weight loss may be associated with anorexia, early satiety, diarrhea, or steatorrhea.
• Jaundice may be painful or painless. Painful jaundice is usually associated with locally unresectable disease.
• The diagnosis of pancreatic cancer should be considered in cases of
  • Idiopathic acute pancreatitis (no gallstones, no alcohol) in patients over 50 years of age.
  • Unexplained diabetes in patients over 50 years of age (no family history, obesity, or steroids).

What are the sites of pancreatic cancer?

Sixty-five per cent of tumours are located within the head, 15% in the body, 10% in the tail and 10% are multifocal. Tumors in the pancreatic body or tail usually present with pain and weight loss, while those in the head of the gland typically present early with steatorrhea, weight loss, and jaundice.

What are the diagnostic tests?

• US abdomen/ CT scan abdomen
• MRI produces similar results to contrast-enhanced multislice CT and is useful for patients who cannot receive intravenous contrast.
• EUS
• Tumour markers- Ca 19-9. Ca 19-9 may be raised in other benign and malignant conditions.
• EUS- guided FNA biopsy is used in patients with resectable tumours. This is less likely to cause intraperitoneal spread of the tumor since the biopsy is obtained through the bowel wall rather than percutaneously.
  When a mass lesion of the pancreas is detected on CT, it is likely to be a malignant process. Attempts to make a tissue diagnosis in such patients are not useful since a benign sample does not exclude the presence of a neighboring malignancy. Thus, surgically fit patients may be operated without attempting to establish a preoperative diagnosis of malignancy. However, it must be recognized that some patients with benign lesions may be subjected to the radical resections.
• Staging laparoscopy may be needed in the case of equivocal findings of locally advanced or metastatic disease on CT scan.

Discuss TNM staging for pancreatic cancer?

T1= Tumor limited to the pancreas, 2 cm or less in greatest dimension
T2= Tumor limited to the pancreas, more than 2 cm in greatest dimension
T3= Tumor extends beyond the pancreas but without involvement of the coeliac axis or SMA
T4= Tumor involves the coeliac axis or the SMA (unresectable primary tumor)

N0- No regional lymph node metastasis N1- Regional lymph node metastasis
M0- No distant metastasis M1- Distant metastasis

Stage I- T1-2, N0 M0
Stage IIA- T3, N0, M0
Stage IIB- T1-3, N1, M0
Stage III- T4, Any N, M0
Stage IV- Any T, Any N, M1

Discuss the differential diagnosis of pancreatic cancer?

• Endocrine tumours and lymphomas can be confused clinically and radiologically with pancreatic carcinoma. The possibility of a clinically silent endocrine tumour should be considered when a mass is identified in the absence of other clinical features characteristic of pancreatic cancer. A tissue diagnosis is thus important in the management of a patient with a mass in the pancreas.
• Focal chronic pancreatitis and autoimmune pancreatitis are the two benign processes most commonly mistaken for pancreatic malignancy on the basis of CT or US. These diagnoses can sometimes be suspected on the basis of history (eg, extreme young age, prolonged ethanol abuse, history of other autoimmune diseases).

Discuss the treatment of pancreatic cancer?

When is surgery indicated in pancreatic cancer?

Only 15 to 20 percent of patients are candidates for curative resection. Disease that is limited to the pancreas and peripancreatic nodes (stage I-IIB disease) is most likely to be cured by radical resection.

What are the types of surgery done?

• Standard pancreaticoduodenectomy — The standard operation for pancreatic cancer within the head or uncinate process of the pancreas is pancreaticoduodenectomy, also called the “Whipple procedure”. The standard Whipple procedure involves removal of the pancreatic head, duodenum, first 15 cm of the jejunum, common bile duct, and gallbladder. A partial gastrectomy is also performed.
• Left sided resection (with splenectomy) is appropriate for localised carcinomas of the body and tail of the pancreas. Involvement of the splenic vein or artery is not in itself a contraindication to such resection. Prognosis is generally worse than pancreatic head tumours.

What are the contraindications for resection?

Contraindications for resection include

• Presence of metastases in the liver, peritoneum, omentum or any extra abdominal site
• Superior mesenteric, coeliac or hepatic artery encasement
• Major venous encasement: > 2cm in length,>50% circumference involvement
• Cirrhosis with portal hypertension
• Uncertain whether distant lymph node metastases influence prognosis

Not a contraindication to surgery

• Lymph node metastases within the operative field or para aortic lymph node involvement
• Venous impingement or minimal invasion of superior mesenteric and hepatic portal veins
• Gastroduodenal artery encasement
• Continuous invasion of duodenum, stomach or colon

What is the surgical morbidity and mortality?

The standard Whipple procedure is associated with a perioperative mortality rate of less than 4 percent.

What is the role of preoperative stenting?
Clearly, patients with pancreatic cancer who are jaundiced at presentation are at risk for associated coagulopathy, malabsorption, and malnutrition.
But, there is little evidence of benefit from routine stenting of jaundiced patients before resection. However, if definitive surgery must be delayed more than 10 days, it is reasonable to obtain internal biliary drainage with a plastic stent.

What is the role of role of adjuvant therapy?

Adjuvant chemotherapy is used after resection of a pancreatic or ampullary neoplasm. Radical resection alone will result in a 5-year survival of only 10% owing to recurrence after surgery. Adjuvant systemic chemotherapy will increase the 5-year survival from 9% to 12% with resection alone to 23% with gemcitabine. Median survival is 10-20 months.

What are the palliative treatment options?

• Treatment of metastatic pancreatic cancer-Single agent gemcitabine remains the standard of care in 2006 for the treatment of patients with advanced pancreatic cancer. Although the objective response rate for patients with measurable disease was only 11 percent, a clinical benefit like improvement in pain and weight loss was observed in 27 percent.
• Pain can be a significant feature of advanced pancreatic cancer. Often, palliation of pain can be successfully achieved by opioid analgesics alone. The results of percutaneous CT-guided or EUS neurolytic coeliac plexus block are disappointing. The main analgesic method is the use of modern oral opiate preparations; neurolytic coeliac plexus block should be considered as complementary in selected cases. Radiation therapy may also significantly alleviate pain due to local invasion of pancreatic cancer.
• Fat maldigestion may also contribute to abdominal pain, bloating and weight loss. Relief of biliary obstruction and pancreatic enzyme supplementation will alleviate these symptoms. Compared with untreated patients, patients with advanced pancreatic cancer who are given pancreatic enzyme supplements enjoy a better quality of life and improved symptom score.
• Palliative stent placement- Metal stents should be used for patients with a good performance status and favourable prognosis (locally advanced primary tumour <3 cm) and plastic ones for those patients with metastases and tumours 3 cm in diameter. The cost of a plastic prosthesis is approximately 3% or 4% of the cost of a self expanding metal prosthesis.

What is the prognosis of pancreatic cancer?

Without active treatment, metastatic pancreatic cancer has a median survival of 3–5 months and 6–10 months for locally advanced disease, which increases to around 11–15 months with resectional surgery

What is the role of surveillance in high risk patients?

Some patients with pancreatic cancer have a family history of the disease. The best surveillance strategy for such patients is unknown. The optimal timing and frequency of screening for pancreatic cancer in individuals at risk is uncertain. The American Gastroenterological Association (AGA) recommends that screening begin at age 35 for those with hereditary pancreatitis, and 10 years before the age at which pancreatic cancer was first diagnosed in individuals with a positive family history. The AGA recommends the use of spiral CT and EUS.

Discuss peri-ampullary cancers?
In about 20% of cases it is not possible to distinguish the tissue of origin of cancers arising in the head of the pancreas, and the term “peri-ampullary cancer” is often applied.

• Periampullary cancers can be broadly considered as those tumours arising out of or within 1 cm of the papilla of Vater and include ampullary, pancreatic, bile duct, and duodenal cancer. There is a high incidence of these tumours in patients with FAP.
• Pancreatic ductal adenocarcinoma must be distinguished from carcinomas of the intrapancreatic bile duct, ampulla of Vater or duodenal mucosa as these tumours have a much better prognosis.

Ref

1. British Society of Gastroenterology Guidelines for the Management of Patients with Pancreatic Cancer, Periampullary and Ampullary carcinomas
2. Ghaneh P et al. Biology and management of pancreatic cancer. Gut. 2007; 56(8):1134-52.