whipple

CASE PRESENTATION:

Dr.Amra FarrukhPG.T SU.I

Pt,s Profile

NAME maqsooda AGE 65 years MARITAL STATUS married ADDRESS hazroo tehsil Attock MOA ER DATE 06/10/10

PRESENTING COMPLAINTS

Yellowish discoloration of the eyes and body for 1.5 months

Pain RHC and epigastrium for last 3 days

HOPI

-Yellowish discoloration of eyes and body

-Progresive worsening of discoloration

-Clay color stools and dark colored urine

-Itching on body and pain RHC

-Significant weight loss

PAST HISTORY

No significant surgical or medical history

DRUG HISTORY

Unremarkable

PERSONAL HISTOR Married No children

Non smoker non addict FAMILY HISTORY Insignificant

SYSTEMIC REVIEW

CVS No c\o SOB,chest pain,pedal edema.CNS No complaints.RESP. No c/o chest pain SOB,or cough.GIT. H/o clay coloured stools,anorexia,jaundice No c/o melena or haemetemesis.

GPE

-Pulse 85/min -B.P 110/70 mmHg

-TEMP afebrile -R/R 14/min -yellowish discoloration of body -Patient was jaundiced

Systemic Examination:

CVS Unremarkable.CNS Intact.RESP. Normal vesicular breathing.GIT. No visible pulsations,scar marks. Soft abdomen,minimally tender in RHC No mass or swelling palpable Shifting dullness,fluid thrill absent

Provisional Diagnosis:

Obstructive Jaundice Malignancy Gall stones

Investigations:

BCP Hb 10g\dl TLC 10,000 Plt 346

PT/APTT Normal

Conti..............

RFT,s WNLRBS WNLLFT,s Total billi 23mg/dl Alt 113 IU/l Alk Po4 1140 U/l

ULTRASOUND ABDOMEN

Grossly distended G.B

Wall thickness 3 mm

CBD 9 mm

C.T Scan

Ill defined hypodense lesion with differential post contrast enhancement in periampullary region

SIZE : 2x2x1 cm Laterally indenting the 2nd part of duoidenum

Postero medially compressing the IVC.Anteriorly it is interfaced with gut loops

C.T Scan

CONCLUSION: Enhancing peri ampullary lesion with grossly distended CBD,gall bladder and intrahepatic cholestasis is suggestive of peri

ampullay carcinoma.

Final Diagnosis:

PERI AMPULLARY CARCINOMA

Pancreatoduodenectomy (Whipple procedure)

19/10/2010Peri ampullary mass not involving blood vessels and

adjacent structures.Grossly distended CBD and G.B.

Lymph node around hepatic artery just proximal to gastroduodenal artery.

Lymph node enlarged in the mesentry of jejunum.

Anastamosis

Pancreatico jejunalCholedochojejunal

Gasstro jejunalFeeding jejunostomy

Post op course:

Pt remained vitally stableNo blood transfusion needed

Abdomen remained softFeeding started on 2nd day

Post op labs:

DATE Hb TLC Total Billi. Alk.Po4

19.10.2010 9.1 11.2 17.0 -

22.10.2010 10.0 13.6 12.1 -

24.10.2010 10.8 10.4 8.6 -

25.10.2010 12.1 12.4 10.3 -

27.10.2010 11.3 10.4 8.8 -

28.10.2010 11.4 9.9 8.4 -

29.10.2010 10.7 9.8 9 -

30.10.2010 10.5 9.4 9 -

Histopathology

Ampulla of Vater3.5x3.5x1 cm

AdenocarcinomaPoorly differentiated

PT3 invading underlying pancreas

Conti.............

Lymph nodes recovered 7L.N involved Nil

Circumferential margin involved

Immunohistochemistry:

CK7 +veCEA +veCA19-9 -ve

Discharge and Followup

LITERATURE REVIEWAMPULLARY CARCINOMA

Ampuula of Vater:

The ampulla of Vater, also known as the hepatopancreatic ampulla, is formed by the union of the pancreatic duct and the common bile duct.

The ampulla is specifically located at the major duodenal papilla.The Ampulla of Vater is an important landmark, halfway along the

second part of the duodenum.It marks the anatomical transition from foregut to midgut (and hence

the point where the celiac trunk stops supplying the gut and the superior mesenteric artery takes over).

Periampullary Region:The periampullary region is anatomically complex,

Represents the junction of 3 different epithelia.

-pancreatic ducts

- bile ducts

- duodenal mucosa.

Grossly, carcinomas originating in the ampulla of Vater can arise from 1 of 4 epithelial types:

(1) terminal common bile duct,

(2) duodenal mucosa, (3) pancreatic duct, or (4) ampulla of Vater

AMPULLARY CARCINOMA

Carcinoma of the ampulla of Vater is a rare malignant tumor arising within 2 cm of the distal end of the common bile duct, where it passes through the wall of the duodenum and ampullary papilla.

EPIDEMIOLOGY:

Carcinoma of the ampulla of Vater is an uncommon tumor.

Ampullary cancer now accounts for approximately 0.5% of all gastrointestinal tract malignancies.

The incidence has been increasing since 1973 at an annual percentage rate of 9%.

Ampullary cancer accounts for some 7% of peripancreatic tumors

ETIOLOGY:

The etiology of the disease is poorly understood.

Patients with ··familial adenomatous polyposis (FAP) have an increased risk of both benign and malignant ampullary tumors.

As many as 50-90% of patients with FAP develop duodenal adenomas, predominantly concentrated on or around the major papilla.

K-ras mutations may be a factor.

Microsatellite instability is associated with a better prognosis. Chromosome 17p and 18q loss of heterozygosity are associated with ampullary carcinoma

PATHOPHYSIOLOGY

Distinguishing between true ampullary cancers and periampullary tumors is critical to understanding the biology of these lesions.

Each type of mucosa produces a different pattern of mucus secretions. sulphomucins and

Sialomucins;

In general, ampullary cancers produce sialomucins, whereas periampullary tumors secrete sulfated mucins. These researchers demonstrated that ampullary tumors secreting sialomucins had a better prognosis (100% vs 27% 5-y survival rate.

Other investigators have confirmed the prognostic power of the pattern of mucin secretion.

TUMOR MARKERS:

Immunohistochemical stains for expressions of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, Ki-67, and p53 have been studied for prognostic power.

In a series of 45 patients, expression of CA 19-9 labeling intensity and apical localization both were statistically significant predictors of poor prognosis.

The 5-year survival rates were markedly different between tumors that expressed CA 19-9 and those that did not (36% vs 100%)

CEA expression also might be a marker for prognosis, but it is much weaker.

Ki-67 and p53 were not demonstrated to have an effect on outcome.

Imaging Investigations:

C.T SCAN:Increased targetlike enhancement of the papilla is likely to represent a

benign condition such as papillitis. whereas an enhancing polypoid mass or focal asymmetric or irregular

thickening with prolonged enhancement in the ampulla of Vater indicates a malignant condition such as ampullary or periampullary carcinoma

Laparoscopy/Laparoscopic USG

Previously been shown to be an effective tool in the staging of pancreatic and ampullary carcinomas.

Being more predictive of resectability than abdominal computed tomography.

With the combined use of CT scanning and LUS, unresectable disease is found in 35–54% of patients

British Journal of Cancer (20200606) 94, 213–217. doi:10.1038/sj.bjc.6602919Published online 24 January 2006

Evaluation of EUS versus CT scan for stagingof ampullary cancer.

EUS is an accurate diagnostic test and exhibits a high level of agreement with surgical pathology.

(GastrointestEndosc 2009;

Gastroenterology. 1992 Jan;102(1):188-99.Staging of pancreatic and ampullary carcinoma by endoscopic ultrasonography. Comparison with conventional sonography, computed tomography, and angiography

In a prospective study, endoscopic ultrasonography was compared with transabdominal ultrasonography, computed tomography, and angiography in 60 consecutive patients with pancreatic and ampullary cancer .

The diagnostic value of these imaging procedures in determining local resectability was assessed

endoscopic ultrasonography was significantly superior to abdominal ultrasonography and computed tomography in determining tumor size and extent and lymph node metastases of pancreatic and ampullary cancer.

Furthermore, involvement of the portal venous system as judged by histopathology or surgical exploration was correctly assessed by endoscopic ultrasonography in 95%, whereas angiography (85%), computed tomography (75%) and abdominal ultrasonography (55%) were less sensitive

Staging of Ampullary cancer

Martin proposed a 4-stage system, as follows:

Stage I - Vegetating tumor limited to the epithelium with no involvement of the sphincter of Oddi Stage II - Tumor localized in the duodenal submucosa without involvement of the duodenal muscularis propria but possible involvement of the sphincter of Oddi Stage III - Tumor of the duodenal muscularis propria Stage IV - Tumor of the periduodenal area or pancreas, with proximal or distal lymph node involvement

The currently accepted American Joint Committee on Cancer staging system for ampullary carcinoma emphasizes the importance of pancreatic invasion and lymph node metastases.

Size has little impact on tumor stage

TNM Staging

Primary tumor

TX – Primary tumor cannot be assessed T0 – No evidence of primary tumor Tis – Carcinoma in situ T1 – Tumor limited to ampulla of Vater T2 – Tumor invades duodenal wall T3 – Tumor invades less than 2 cm into pancreas T4 – Tumor invades more than 2 cm into pancreas or other organs

Conti.............

Regional lymph nodes NX – Regional lymph nodes cannot be assessed N0 – No regional lymph node metastases N1 – Lymph node metastasesDistant metastases MX – Presence of distant metastases cannot be assessed M0 – No distant metastases M1 – Distant metastases

STAGING:

Stage T N M

Stage 0 Tis N0 M0

Stage I T1 N0 M0

Stage II T2-3 N0 M0

Stage III T1-3 N1 M0

Stage IV T4 N0-1 M0

… T1-4 N0-1 M1

Defination of vascular involvement assesed by C.T Scanning.

Grade of Defination Resect.D Hypodense tumor is inseperable from

adjacent vessels,point of contact forms a concavity against the vessel or partially encircles the vessels.

E Hypodense tumor encircles adjacent vessels, no fat plane is identifiable b/w tumor and vessels.

F Tumor occludes the vessels.

Defination of vascular involvement assessed by C.T scanning


Grade of DefinationResectabilityA Fat plane seperates the tumor from

adjacent vessels.B Normal parenchyma seperates the

hypodense tumor from adjacent vesselsC Hypodense tumor is inseperable from

adjacent vessels and point of contact forms a convexity against the vessel.

C.T grading for vascular involvement

This grading system examines the relationship between the tumour and the major vessels

-superior mesenteric vein

-portal vein

-superior mesenteric artery

-hepatic artery

Patients with grade A to D tumours are considered potentially resectable.

while those with grade E or F tumours are invariably not resectable.

In addition a grade O was added to this grading system for those patients with pancreatic and biliary duct dilatation without the presence of a pancreatic mass .

Options for Ampullary cancer.

The standard surgical approach is pancreaticoduodenal resection (Whipple procedure).

The procedure involves en bloc resection of the gastric antrum and duodenum; a segment of the first portion of the jejunum, gallbladder, and distal common bile duct; the head and often the neck of the pancreas; and adjacent regional lymph nodes

PancreaticodudenectomyLocal excisionPalliative

Prognosis of Whipple in Peri-Ampullary C\A Study Annals of surgThe tumor-specific 10-year actuarial survival rates were

- Pancreatic 5%

-Ampullary 25%

- Distal bile duct 21%

-Duodenal 59%

Among patients with periampullary adenocarcinoma treated by pancreaticoduodenectomy, those with duodenal adenocarcinoma are most likely to survive long term.

Five-year survival is less likely for patients with ampullary, distal bile duct, and pancreatic primaries, in declining order

Prognosis of Whipple for Ampullary CancerResults after radical resection of ampullary of Vater carcinoma have been improving.

During the past decade, 5-year survival rates have ranged from 20-61%, averaging higher than 35%.

The reported mortality rates from this operation are decreasing

Local Excision for Ampullary cancer

Because of the mortality and morbidity associated with pancreaticoduodenectomy, physicians have been interested in performing local excisions of cancers of the ampulla of Vater to avoid a major resection.

Transduodenal excision of ampullary tumors has been proposed as an intermediate option between radical resection and palliative bypass for high-risk patients.

Some have argued that this approach is simpler, is better tolerated, and might provide a comparable cure rate (mortality rate 8-13%, 5-y survival rate 0-43%).

This approach generally has been reserved for poor operative candidates (eg, elderly patients, those with other comorbid conditions) with favorable tumors (generally <2 cm, polypoid). Unfortunately, this approach compromises local control

Whipple and Local resection

The 5-year survival rate reported after Whipple's resection for ampullary cancer varies from 22% to 55%..

On the other hand, pancreaticoduodenectomy has been reported to result in morbidity of 43% and mortality of 11%.

This fact has led to interest in local resection of ampullary tumors.

After local resection, it has been reported that the mortality rate reaches 7.1% and the 5-year survival rate 35%

Int Semin Surg Oncol. 2005; 2: 16.

Published online 2005 August 30

Although there are many case reports and a few series on the treatment of ampullary neoplasms by local ampullary resection, the criteria used to decide when local excision is suitable for certain patients are controversial, and not well addressed.

Indications of Local excision

Bottger et al stated that the indications for local excision should be that

-The tumor is completely removed (R0),

-Limited to the ampulla of Vater (pT1),

-Not poorly differentiated and

-With no venous/lymphatic infiltration in patients with

ASAgrade IV, regardless of their age



Study: comparison of whipple and local excision

From 1990 to 1999, 205 pts diagnosed with periampullary C/A.

32 of these patients that proved to have carcinoma of the ampulla of Vater, and underwent surgical treatment.

Pancreaticoduodenectomy was the first choice as the type of surgical treatment.

Local resection was the preferable treatment when the ampullary lesion was less than 2 cm in diameter, the pre-operative biopsy showed a pT1 cancer or adenoma of the ampulla of Vater and/or the patient's concomitant medical illness or age contraindicated a major operation such as Whipple's procedure.



Study: Comparison of whipple and local excisionSurvival after local resection has been reported to be 40% to 50% at 5 years.

This figure is comparable to 37.5% to 62.7% 5-year survival rate reported in pancreaticoduodenectomy series.


Published online 2005 August 30.

Technique of local Excision:

-The abdomen is explored through a subcostal or midline incision. -After a Kocher maneuver for the mobilization of the second part of

the duodenum, the latter is opened by a 4–5 cm "antimesenteric" longitudinal incision.

- Stay sutures are placed in the duodenal wall circumferentially. -Bile and pancreatic duct are canulated with a Fogarty catheter. -Then, the normal duodenal mucosa surrounding the ampullary tumor

is injected with saline containing 1 to 100,000 epinephrine

Conti..............

Once the identification of the ducts had been accomplished, a circumferential resection of duodenal mucosa to a depth necessary to excise the tumor is undertaken.

Margins of 1 cm are obtained in all directions beyond the gross border of the lesion, in order to obtain free margins resection.

Because bile and pancreatic ducts were transected a reconstruction procedure is essential to ensure adequate billiary and pancreatic drainage and to repair the transduodenal defect.

Reconstruction is accomplished by approximating the common walls of the pancreatic and bile ducts that eventually are sutured together on the duodenal wall

Conti...............

-The ducts are probed with billiary dilators to ensure appropriate size. -A diameter of 6 to 8 mm for the bile duct and 4 to 5 mm for the

pancreatic duct are obtained, assuming that scarring will reduce these diameters by 50%.

- After the establishment of an adequate duct patency the duodenotomy is closed transversely.

OPERATIVE FINDINGS:sch

Findings contraindicating resection

Liver metastases (any size)

Celiac lymph node involvement

Peritoneal implants

Invasion of transverse mesocolon

Hepatic hilar lymph node involvement

Findings not contraindicating resection

Invasion at duodenum or distal stomach

Involved peripancreatic lymph nodes

Involved lymph nodes along the porta hepatis that can

be swept down with the specimen

Unresectable Disease.

If metastatic disease or unresectable local vascular invasion is detected during staging then jaundice can be palliated by endoscopic or radiological biliary stenting.

survival is similar following surgical bypass or biliary stenting for the relief of jaundice and this is comparable with the findings of a meta-analysis of three randomised control trials.

For patients with unresectable disease, the presence of distant metastases or advanced local disease may alter the palliative options.

.


Unresectable Disease

For patients with unresectable disease, endoscopic stenting to achieve biliary decompression is an appropriate palliative procedure.

No established answer exists to the question of further therapy.

Very little has been published on adjuvant treatment for locally advanced and advanced ampullary carcinoma.

Confining one's approach to relief of symptoms is reasonable.

Biliary-enteric bypass to palliate unresectable pancreatic cancer. (Reproduced with permission from Bell, Rikkers, Mulholland (eds): Atlas of Pancreatic Surgery, 1st ed. Philadelphia: Lippincott, Williams & Wilkins, 1996.)

Radiotherapy

Pancreaticoduodenectomy is the procedure of choice for patients with resectable disease

but local recurrence plagues all surgical series, particularly when the pancreas has been invaded or lymph node metastases are discovered.

In fact, whether major resection impacts survival in the setting of disease spread to the lymph nodes remains unclear.

Postoperative irradiation of at least 45 Gy with 5-FU as a radiosensitizer is a reasonable treatment and reduces local recurrence.

Cisplatin Plus Gemcitabine Improves Survival of Patients with Advanced Ampullary cancer.

Compared to gemcitabine alone, the chemotherapy combination of cisplatin and gemcitabine improved overall survival of patients with locally advanced or metastatic ampullary cancer.

The drugs were given by intravenous infusion for 12 weeks and patients’ tumors were then evaluated by imaging.

The combination chemotherapy also improved progression-free survival.CONCLUSION: While there has been no single standard of care for advanced

ampullary cancer. This is the closest we have to a gold standard. Physicians can now feel confident they are practicing evidence-based

medicine in recommending this combination to their patients

National cancer institute-clinical trial results-posted 5/11/2010

Prognostic Factors for Survival

Survival after surgical resection is related to

-The extent of local invasion of the primary lesion

-Lymph node involvement

-Vascular invasion

-Perineural invasion

-Cellular differentiation

-Uninvolved surgical margins.

Even a single lymph node with evidence of metastatic carcinoma portends a poor outcome with surgery alone.

Factors influencing long term survivalLong-term survival was independently influenced by

-The depth of tumor infiltration and

-Lymph node metastasis

World J Surg. 2007 Jan;31(1):137-43; discussion 144-6

Pancreatobiliary versus intestinal histologic type of differentiation

By definition "periampullary", originate from ampullary, duodenal, biliary, or ductal pancreatic epithelium.

Typically, periampullary adenocarcinomas have either intestinal or pancreatobiliary type of differentiation.

The aim of the study was to determine whether the histologic type of differentiation is an independent prognostic factor in periampullary adenocarcinoma.

CONCLUSION: Pancreatobiliary versus intestinal type of differentiation independently predicts poor prognosis after pancreaticoduodenectomy for periampullary adenocarcinoma.

BMC Cancer. 2008 Jun 11;8:170

Lymph Node Ratio as prognostic factorCONCLUSIONS: Not the lymph node involvement per se but especially the LN ratio is an independent prognostic factor after resection of pancreatic cancers.

In our series, the LN ratio was even the strongest predictor of survival.

The routine estimation of the LN ratio may be helpful not only for the individual prediction of prognosis but also for the indication of adjuvant therapy

J Gastrointest Surg. 2009 Jul;13(7):1337-44. Epub 2009 May 6

Portal vein Resection.

In view of the close anatomical proximity between the head of the pancreas and the portal/superior mesenteric vein confluence, it is logical for surgeons to seek to expand the pool of patients who may benefit from pancreaticoduodenectomy by undertaking en bloc resection of the vein

However portal vein resection is controversial.

Due tothe small proportion of patients who undergo portal vein resection, it is difficult to construct a suitably designed randomised trial to address this question.

Under these circumstances, surgeons will continue to base their practice on summative evidence from case series.

Pancreaticoduodenectomy for Peri-Ampullary Malignancy: The Case for Portal Vein Resection

2009 by the Annals of The Royal College of Surgeons of England

The current literature suggests the addition of a venous resection does not cause an increase in morbidity and mortality over a standar pancreaticoduodenectomy.

Importantly, the data indicate that portal vein resection can lead to similar survival outcomes in same-stage tumours.

Currently, there is no randomised control trial or metaanalysis assessing the potential benefit of the addition of venous resection to pancreaticoduodenectomy.

However, there are numerous large case series and a systematic review supporting venous resection

Conti...............

Yekebas et al recently reported on 585 patients undergoing pancreaticoduodenectomy between 1994 and 2005 and compared patients

undergoing venous resection with those undergoing a standard pancreaticoduodenectomy on an intentionto- treat analysis.

They found comparable median survival rates (15 months versus 16 months; P = 0.086) with no difference in peri-operative morbidity and mortality.

Concluded that venous resection at the time of pancreaticoduodenectomy can be offered with similar morbidity and mortality.

Options for portal vein reconstruction

Various methods are currently used for portal vein reconstruction. -Adequate mobilisation of the liver and small bowel . -Various conduits for reconstruction. -Bovine pericardium -Autologous saphenous -Internal jugular vein or -Left renal vein. when the venous involvement is over 3 cm, hepatic mobilisation and use a

left renal vein graft, preferring this conduit since it is autologous and located in the same operating field.

Conclusion

All surgeons undertaking pancreaticoduodenectomy should be able to undertake venous resection and reconstruction since, occasionally, the

requirement for thismay be unexpected.

Despite the lack of randomised control trials, large series from major pancreatic centres demonstrate that, when venous resection is

performed, it can be done safely and appears to give similar survival.

THANK YOU

whipple

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