Cancer of distal duodenum: Whipple's procedure or pancreas preserving distal duodenectomy (PPDD)?

The cancer of duodenum is a rare but aggressive disease and radical surgery to achieve complete tumor excision is the only potentially curative treatment. Due to rarity, these tumors are often grouped either with periampullary or small bowel cancers and therefore available literature for their management is limited.

Traditionally pancreatoduodenectomy or Whipple's procedure is the recommended surgical procedure for duodenal cancers. Whipple's procedure is a complex procedure and still carries a mortality of up to 5% and morbidity in the range of 30-50% at well endowed centers. Moreover for non-ampullary duodenal cancers the risks associated with Whipple's procedure are reported to be higher due to risk factors including non dilated pancreatic duct & soft pancreas.

As per the recent NCCN guidelines while the preferred treatment for duodenal cancers is Whipple's procedure however in select patients limited segmentectomy with regional lymphadenectomy is an acceptable alternative. We present one such patient recently managed by our team.

Case presentation

A 57 years gentleman with a recent history (May 2019) of coronary artery bypass graft (CABG) and aortic valve replacement (AVR) presented in emergency room with massive upper GI bleed in August 2019. He also had history of recurrent vomiting of 20-25 days duration and also loss of weight of approx 15 kg over 2 months following cardiac surgery. Following initial resuscitation in ICU and discontinuation of anti-platelet & anti-coagulation medications, an urgent upper GI endoscopy was performed. On endoscopy except for bleeding from stricture in fourth part of duodenum, rest of the upper GI tract was normal (Figure 1). 

Figure 1. Upper GI endoscopy - bleed from stricture duodenum

Bleeding was controlled with injection sclerotherapy and the biopsy from the lesion was reported as tubulo-villous adenoma with high grade dysplasia. A subsequent CECT whole abdomen was suggestive of circumferential duodenum wall thickening in third part of duodenum (Figure 2). 

Figure 2. CECT abdomen displaying circumferential wall thickening in III part of duodenum (white arrows) & additional findings of horse shoe kidney (asterisk )

The tumor markers CEA (1.31) & Ca 19.9 (0.8) were within normal range and colonoscopic examination did not reveal any abnormality. After thorough work up and discontinuation of anticoagulants 12 hours prior he was taken up for surgery.

In our patient because of recent CABG and AVR surgery, early resumption of anticoagulants & anti-platelet medications was warranted. Hence PPDD was an obvious alternative especially because tumor was confined to the wall of duodenum and distally located (III & IV part of duodenum).

At surgery there was stricture in III & IV part of duodenum and enlarged regional lymph nodes. A PPDD with 5 cm proximal and 10 cm distal margin along with regional lymphadenectomy was performed.  A side to side duodeno-jejunal anastomosis (second part of duodenum & proximal jejunum) and feeding jejunostomy was fashioned. In post operative period injection Enoxaparin (0.6 mg sc BD) was re-started on post operative day (POD) 1 and subsequently anti-platelet medications were added on POD 4. Except for delayed gastric emptying his postoperative period was uneventful. Histopathology reported well differentiated adenocarcinoma of duodenum and tumour was invading muscularis propria & focally into subserosa (pT3). No lympho-vacular emboli or perineural spread was seen. All 17 lymph nodes and surgical margins (proximal, distal and radial) were free from tumour.

Discussion

Primary adenocarcinoma of the duodenum is an uncommon neoplasm but the prognosis is better in comparison to cancer of pancreas or distal bile duct.

Because of the soft pancreatic texture and small size pancreatic duct, the rate of pancreatic fistula following Whipple's procedure for non-ampullary duodenal cancers is reported to be in the range of 28.9 – 32.5% which is almost double in comparison to Whipple's procedure for all other pathologies.^1,2

There are conflicting reports on the extent of surgery for duodenal cancers. Some advocate PD for all duodenal cancers regardless of location while others support segmental resection (PPDD) for distal duodenal cancers if margin negative resection is feasible.

In one of the early study from Johns Hopkins Hospital, significant 5 year overall survival advantage with PD (69%)  was reported in comparison to PPDD (0%).³ However several subsequent studies have not supported these results in favour of PD. A study from Mayo Clinic reported comparable overall survival between the groups of patients undergoing PD or PPDD for duodenal cancer. The 5 year survival estimate in PPDD group was 52% and in PD group was 42 % (p=0.50).⁴ A study of SEER database involving 1611 patients' also reported that PD does not impact 5 year survival (37.6%) compared with segmental resection (41.3 %) for duodenal cancers (p > 0.05).⁵ In a recent systematic review of largest collective number of patients (n = 1728) authors concluded that aggressive surgical approach to achieve complete tumor excision should be pursued and PPDD should be considered if tumor invasion is confined to duodenal wall especially for distal duodenal tumors.⁶

In summary, PPDD is an acceptable alternative to Whipple's procedure for non ampullary duodenal cancers particularly in high risk cases.

 References

1.       Le CHA, Shingler G, Mowbray NG et al. Surgical outcomes for duodenal adenoma and adenocarcinoma: a multicentre study in Australia and the United Kingdom. ANZ J Surg. 2018;88:E157-E161. Doi:10.1111/ans.13873

https://onlinelibrary.wiley.com/doi/abs/10.1111/ans.13873

2.       Shamali A, McCrudden R, Bhandari P et al. Pancreaticoduodenectomy for nonampullary duodenal lesions: indications and results. Eur J Gastroenterol Hepatol. 2016;28(12):1388-1393

https://journals.lww.com/eurojgh/Abstract/2016/12000/Pancreaticoduodenectomy_for_nonampullary_duodenal.6.aspx

3.       Sohn TA, Lillemoe KD, Cameron JL et al. Adenocarcinoma of the duodenum: factors influencing long-term survival. J Gastrointest Surg. 1998;2(1):79-87  

https://www.ncbi.nlm.nih.gov/pubmed/9841972

4.       Onkendi EO, Boostrom SY, Sarr MG et al. 15-year experience with surgical treatment of duodenal carcinoma: a comparison of periampullary and extra-ampullary duodenal carcinomas. J Gastrointest Surg. 2012;16(4):682-691

https://www.surgonc.org/wp-content/uploads/2019/03/National-Video-Conference-Jan-2017-Article-6.pdf

5.       Cloyd JM, Norton JA, Visser BC et al. Does the extent of resection impact survival for duodenal adenocarcinoma? Analysis of 1,611 cases. Ann Surg Oncol. 2015;22(2):573-580

https://link.springer.com/article/10.1245%2Fs10434-014-4020-z

6.       Debang Li, Xiaoying Si, Tao Wan et al. Outcomes of surgical resection for primary duodenal adenocarcinoma: A systematic review. Asian J Surg. 2019;42(1):46-52

https://www.sciencedirect.com/science/article/pii/S1015958418300216

Suggested for further reading:

https://www.healthline.com/health/duodenal-cancer

https://www.medicalnewstoday.com/articles/324309.php

Authors:

Dr Nitin Vashistha, MS, FIAGES, FACS

Dr Dinesh Singhal, MS, FACS, DNB (Surg Gastro)

Department of Surgical Gastroenterology,
Max Super Speciality Hospital, Saket, New Delhi, India
E mail: gi.cancer.india@gmail.com

www.gicancerindia.com

Ascites following Whipple's procedure (Pancreatoduodenectomy)

Quiz

A 67 year non alcoholic, non smoker lady presented with dull ache in the right upper quadrant of abdomen and a progressive abdominal mass of 10 years duration. She denied any history of vomiting, weight loss or any major comorbidity.  There was no icterus or peripheral lymphadenopathy. Abdominal examination revealed a large firm mass with bosselated surface in right hypochondrium extending into the right lumbar region. 

The initial investigations were within normal range except for deranged liver functions (total bilirubin 1.5 mg/dL, aspartate transaminase 75 U/L, alanine transaminase 87 U/L, alkaline phosphatase 367 U/L, serum albumin 4 gm/L).  Contrast enhanced magnetic resonance imaging (Figure A) showed a large periampullary tumor which was suggestive of nonfunctioning islet /neuroendocrine tumor or duodenal gastrointestinal stromal tumor. 

Figure A.  Large periampullary tumor with central necrosis and peripheral enhancement (Image 1). Atrophic pancreas (arrow - Image 2). Compression of inferior vena cava (Image 3).Common duct with proximal biliary dilatation (arrow head - Image 4). 

The patient underwent standard pancreatoduodenectomy (PD) with an uneventful recovery. The histopathology was suggestive of spindle cell tumor arising from the duodenal wall (CD 117 positive; mitotic activity < 2 / 50 high power field).

Three months after surgery she developed low appetite, loss of weight, pedal edema and abdominal distension. On investigations by the primary physician there was ascites for which 'no cause was detected'.  Six months after PD, the patient was readmitted with icterus, progressive pedal edema and ascites. Her initial work up investigations:

-          Total bilirubin 4.9mg/dL, liver enzymes - within normal limits, serum proteins 5.8 gm/L; 

           serum albumin 1.6 gm/L

-          Serum lipid profile (mg/dL): triglycerides 150; cholesterol 70; HDL 14; LDL 26; VLDL 30,

-          Urine proteins nil.

-          Ascitic fluid: Clear, straw colored; cell count- 50/mm³ (all lymphocytes); Proteins 1.1g/dL  Albumin 0.3 g/dL, Sugar 105mg/dL; Amylase 37 IU/L; Triglycerides 30 mg/dL

Subsequently, contrast enhanced abdominal computed tomography (CECT) scan was done (Figure B).

Figure B. Abdominal contrast enhanced computed tomography scan (image 1 & 2)

What is the diagnosis?

1.       Peritoneal carcinomatosis

2.       Portal vein thrombosis

3.       Chylous ascites

4.       Post PD non alcoholic steatohepatitis  (NASH)

Answer

4. Post PD non alcoholic steatohepatitis

This seemingly complex clinical problem has a simple solution- estimation of serum albumin - ascites gradient (SAAG) and close look at abdominal CECT (Figure B). On readmission our patient had high SAAG ascites.  This ruled out options 1 & 3 - peritoneal carcinomatosis (PC) and chylous ascites (CA). There are other features against these two diagnoses as well. A potentially serious complication of PD, CA is milky fluid with triglyceride content of ≥ 110 mg / dL from drain/ drain site/ wound after 3^rd postoperative day.¹ In our patient,  onset of ascites was delayed, it was straw colored & with triglyceride content of 30 mg/dL.  A large periampullary tumor with long, indolent history, absence of jaundice and imaging features of an expansive growth pattern, pushing rather than invading major vascular structures is likely to be benign (Figure A). This is well supported by PD specimen surgical pathology report of benign gastrointestinal stromal tumor of the duodenum (CD 117 positive; mitotic activity < 2 / 50 per high power field). Therefore PC is also ruled out

Of the remaining two options with high SAAG ascites, a well opacified portal and splenic vein (Figure B, image 2) on abdominal CECT excluded portal vein thrombosis (option 2) as well. Other notable findings of interest in this image include post PD pancreato-jejunal anastomosis, biliary-enteric anastomosis and an atrophic pancreas.

In our patient, initial plain images of abdominal CT scan show ascites with the liver having extremely low attenuation when compared to the spleen (Figure B, Image 1) highly suggestive of NAFLD.  This was confirmed by Hounsfield units (HU) measurement (liver with a mean of - 3.25 HU when compared to spleen 52 HU with Liver -to- spleen attenuation ratio of - 0.0625, Figure C). In addition she had loss of weight, low serum albumin and cholesterol - regarded as characteristic of post PD NASH.²  In contradistinction conventional NASH presents with obesity and hyperlipidemia.² The final diagnosis therefore is post PD NASH (option 4).

Figure C. Liver & spleen attenuation values on unenhanced abdominal computed tomography image

Following PD, NAFLD is recognized in up to 37% patients of which 10 % may progress to NASH.³ Low remnant pancreatic volume and resulting pancreatic exocrine insufficiency are some of the proposed risk factors. Management is primarily supportive and the mainstay of therapy includes high protein calorie diet, pancreatic enzyme replacement and diuretics. 

References

1.       Van der Gaag NA, Verhaar AC, Haverkort EB, Busch OR, van Gulik TM, Gouma DJ. Chylous ascites after pancreaticoduodenectomy: introduction of a grading system. J Am Coll Surg;207:751-7

2.       Tanaka N, Horiuchi A, Yokoyama T, Kaneko G, Horigome N, Yamura T et al. Clinical characteristics of de novo nonalcoholic fatty liver disease following pancreaticoduodenectomy. J Gastroenterol 2011;46:758-68

3.       Kato H, Isaji S, Azumi Y, Kishiwada M, Hamada T, Mizuno S et al. Development of nonalcoholic fatty liver disease(NAFLD) and nonalcoholic steatohepatitis (NASH) after pancreaticoduodenectomy: proposal of a postoperative NAFLD scoring system. J Hepatobiliary Pancreat Sci 2010;17:296-304

Authors:

Dr Nitin Vashistha, MS, FIAGES, FACS

Dr Dinesh Singhal, MS, FACS, DNB (Surg Gastro)

Department of Surgical Gastroenterology,
Max Super Speciality Hospital, Saket, New Delhi, India
E mail: gi.cancer.india@gmail.com

www.gicancerindia.com