Colon cancer: Generalized peritoneal pigmentation - rare sequel of India ink tattooing

Colonoscopic tattooing of colorectal neoplasms with India ink is currently the preferred technique for tumor localization during subsequent laparoscopic resections. It is safe (complications 0.22%) and accurate (90.5 - 97.9%).^1,2,3 Dye spillage occurs in 2.4 – 13 % patients and is usually asymptomatic.⁴

Tattooing may sometimes result in rare findings that cause diagnostic dilemma during surgery.

A 65 year old male presented with history of weight loss, recent onset constipation and bleeding of bright red per rectum for 1 year. His general physical and abdominal examination was unremarkable as was digital rectal examination and proctoscopy.

Colonoscopy revealed large polypoidal sigmoid colon tumor which was tattooed with India ink. Admittedly the tumor in our patient was large and may well have been localized without tattooing also.

Endoscopic biopsy suggested well differentiated adenocarcinoma.  Contrast enhanced abdominal computed tomography scan showed large, non obstructing tumor involving distal sigmoid colon (Figure 1).  

Figure 1: Contrast enhanced abdominal computed tomography scan showing large enhancing tumor in distal sigmoid colon

The patient was planned for laparoscopy assisted radical sigmoid colectomy.  At initial laparoscopy there were dark pigmented macules diffusely present over peritoneal cavity raising suspicion of metastatic malignant melanoma (Figure 2). 

Figure 2: Laparoscopy showing multiple pigmented patches over peritoneum with minimal free fluid

Frozen section from multiple such lesions did not reveal tumor deposits and was proceeded with. Final histopathology staging was pT2N0M0. On Hematoxylin & Eosin (H & E) staining, pigmented lesions were due to black pigment (presumably carbon from India ink) laden macrophages. Negative immunohistochemistry (IHC) for HMB45 & Melan A ruled out melanocytes as causative for pigmentation (Figure 3).

Figure 3: Microphotograph: H & E stain - showing black pigment laden macrophages; IHC HMB45 - negative for melanocytes

 The postulated mechanisms for such findings include intraperitoneal spillage of India ink or via pigment laden macrophages.⁵

Awareness of this entity is important for surgeons to avoid misinterpretation of peritoneal findings at laparoscopy.

References

1.       Nizam R, Siddiqi N, Landas SK, Caplan DS, Holtzapple PG. Colonic tattooing with India ink: Benefits, risks and alternatives. Am J Gastroenterol 1996;91(9):1804-08

2.       Acuna SA, Elmi M, Shah PS, Coburn NG, Quereshi FA. Preoperative localization of colorectal cancer: A systematic review and metanalysis. Surg Endosc 2017;31(6):2366-2379

3.       Cho YB, Lee WY, Yun HR, Lee WS, Yun SH, Chun HK. Tumor localization for laparoscopic colorectal surgery. World J Surg 2007;31(7):1491-5

4.       Trakarnsanga A, Akaraviputh T. Endoscopic tattooing of colorectal lesions: Is it a risk free procedure ? World J Gastrointest Endosc. 2011;3 (12):256-60

5.       Cappell MS, Courtney JT, Amin M. Black macular patches on parietal peritoneum and other extra intestinal sites from intraperitoneal spillage and spread of India ink from preoperative endoscopic tattooing: an endoscopic, surgical, gross pathologic and microscopic study. Dig Dis Sci 2010;55(9):2599-2605

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

Why is pancreatic cancer so aggressive?

The term pancreatic cancer is synonymously used for pancreatic ductal adenocarcinoma (PDAC) - one of the most aggressive of all cancers. Accounting for >80% of pancreatic cancers, PDAC is currently the third leading cause of cancer related deaths in USA and is projected to become second leading cause by 2025. The overall 5-year survival in PDAC for localized cancer (no spread beyond pancreas) is 37%, regional cancer (spread to nearby structures or regional lymph nodes) is 12% and for metastatic cancer (spread to distant parts of body such as liver, lungs of bones) the 5-year survival is 3%.

However, PDAC is not the only type of cancer pancreas and there are several other types of cancers arising from the pancreas. In a recent study using National Cancer Database of USA, survival analysis of different histologic types of pancreatic cancers reported median overall survival of 20.2 months for PDAC. In contrast median survival for cystic mucinous neoplasms with an associated invasive carcinoma was 52.6 months while median survival was not reached for neuroendocrine tumors, with 5-year overall survival rates of 84%¹. For this reason, biological behavior of PDAC is considered to be entirely different and more aggressive in comparison to other malignant pancreatic tumors.

The biological factors responsible for this aggressive nature of PDAC are not fully understood.

This article briefly summarizes some of the proposed mechanisms responsible for aggressive nature of PDAC.

Metastasis (i.e. spread to distant organs such as liver, lung or bone) is the most common cause of death in cancer patients. This holds particularly true for PDAC because most of the patients are diagnosed late with metastasis. The factors that may be responsible for this aggressive nature of PDAC may include

·         Late diagnosis

·         Early metastasis

·         Minimally effective systemic therapy

The proposed time for progression from the initiating event that began pancreatic cancer genesis until development of the cancer clone is an average of 11.7 years. Further it takes an average of 6.8 years for development of metastatic subclones and patients dying an average of 2.7 years later. Unfortunately, most patients with PDAC are diagnosed late towards the end of this 21-year average time span, indicating that the poor prognosis may be due to late diagnosis in the natural history of the disease².

Many studies have proposed that epithelial to mesenchymal transition (EMT) contributes to early dissemination of cancer cells and plays important role in invasion and metastasis of PDAC³. Several EMT inducing transcription factors such as Snail, Twist and Zeb1 have been studied. For the sake of simplicity, the current discussion is restricted to recently proposed Zeb1 factor which controls ability of cells to migrate and survive in early embryonic development. The Zeb 1 is blocked in normal cells but its re-activation in cancer cells leads to early dissemination of cancer cells throughout the body and quick adaptation of these cancer cells to the changing conditions in their new environment.  This leads to easier dissemination of cancer cells and early development of metastases⁴.  

In summary, PDAC is associated with limited survival with current therapies and further improvement in survival is likely to come with advancements either in diagnostic modalities for early detection of cancer or effective systemic therapy i.e. chemotherapy / immunotherapy, against metastases.

References

1.       Pokrzywa CJ, Abbott DE, Matkowskyj KA et al. Natural History and Treatment Trends in Pancreatic Cancer Subtypes. J Gastrointest Surg. 2019

2.       S Yachida and CA Iacobuzio-Donahue. Evolution and dynamics of pancreatic cancer progression. Oncogene 2013

3.       Zheng X, Carstens JL, Kim J et al. EMT program is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature 2015

4.       Krebs AM, Mitschke J, Lasierra Losada M, Schmalhofer O et al. The EMT activator ZEB1 is a key factor for cellular plasticity and promotes metastasis in pancreatic cancer. Nat Cell Biol 2017

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

Solid Pseudopapillary Tumor / Neoplasm: Pitfalls in Management of Cystic tumor of Pancreas

A 13 year girl presented with history of mild upper abdominal pain of 6 years duration. The pain had increased in intensity for 1 month. However there was no history of use of intravenous analgesics or of hospitalization for pain relief. She was evaluated and diagnosed to have pancreatic pseudocyst and an open cystoenterostomy was attempted elsewhere. However operative findings at exploration precluded internal drainage. She had an uneventful recovery and was subsequently referred to higher center for further management.

On examination at our centre, she was found to be thin built with stable vitals. Abdominal examination was unremarkable except for well healed midline laparotomy scar.

All routine hematologic and biochemical investigations were within the prescribed normal range. A contrast enhanced computed tomography (CECT) scan of the abdomen was performed (Figure 1 & 2).

Figure 1.

Figure 1 of abdominal CECT shows a 6 cm tumour of the body and tail of the pancreas with solid and cystic components. 

Figure 2.

Figure 2 reveals an air pocket in the tumour at the site of previous biopsy.

 In view of young female patient with an indolent history and aforementioned image features, a diagnosis of solid pseudopapillary tumour (SPT) was made and distal pancreatectomy with splenectomy performed (Figure 3). Histopathology was confirmatory of SPT.

Our report reiterates that when managing cystic lesions of pancreas, a careful evaluation of history, biochemical investigations and imaging is essential to differentiate pseudocyst from cystic tumors. In most instances, the latter can be easily identified by an absence of documented episode of acute pancreatitis and cross sectional imaging depicting thick walled multilocular lesion with septae or solid components. Cyst fluid analysis (preferably endoscopic ultrasound guided) may be helpful when doubt exists in diagnosis. The features indicative of PC include high amylase content, inflammatory cytology and tumor markers (CEA, CA19-9, CA 72-4) within the specified normal range.¹

First described by Frantz in 1959, SPT of the pancreas is a rare neoplasm comprising of 1-2% of all pancreatic tumors.² This entity is encountered almost exclusively in young females in their second or third decade with male to female ratio of 1 is to 9. The tumor may be asymptomatic or associated with vague symptoms such as abdominal pain/discomfort, nausea or loss of appetite. Consequently SPTs often attain large size (3-16cms) by the time a diagnosis is made. At imaging, the characteristic CECT features include a large heterogeneous mass with solid and cystic components and areas of hyperattenuation representing hemorrhage.

With an increased understanding of the biological behavior [low malignant potential (15%) and excellent long-term prognosis in patients with metastatic disease the surgical management of SPTs has evolved over the last decade. The essence of management of primary tumor is on organ preservation. For the tumors in the pancreatic head, pylorus preserving pancreaticoduodenectomy and for the body and tail tumors into a spleen preserving distal pancreatectomy are acceptable procedures. However in patients with large tumors, spleen preservation may not always be feasible. Central resections for body tumors should only be performed at high volume centers. Due to a low incidence of lymph node involvement (<2%) a formal lymphadenectomy is not indicated. The currently available evidence supports metastectomy with 1 cm margin for liver metastases and debulking for peritoneal deposits. Overall 5-year survival is as high as 100% in patients undergoing surgical resection.³ Extended survival is still possible even with extensive disease with debulking surgery.

References

1.       Brugge WR, Lauwers GY, Sahani D, Fernandezdel,Castillo C, Warshaw AL. Cystic neoplasms of the pancreas. N Engl J Med 2004, 351:1218-26

2.       Frantz VK. Papillary tumors of the pancreas: Benign or malignant? Tumors of the pancreas. In: Atlas of Tumor Pathology, Section 7, Fascicles 27 and 28.Washington, DC, USA: Armed Forces Institute of Pathology, 1959:32-3.

3.       de Castro S. M. M, Singhal D, Aronson DC, Busch OR,TM van Gulik, Obertop H, D Gouma et al. Management of Solid-pseudopapillary Neoplasms of the Pancreas: a Comparison with Standard Pancreatic Neoplasms. World J Surg. 2007; 31(5): 1130–1135

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

Tumors of Appendix: Issues in the management of Mucocele of the appendix

Background
Mucocele of the appendix (0.2 – 0.3% of appendectomy specimens) is a morphologic descriptive term for obstructive dilatation of the appendix by intraluminal accumulation of mucoid material.^1,2 As such MA is not a pathologic diagnosis and can arise from various non neoplastic, benign neoplastic or malignant conditions. The clinical importance of MA arises from the fact that it is the primary cause of pseudomyxoma peritonei (PP). Curative surgery for MA mandates R0 resection without iatrogenic peritoneal spillage of mucinous material.³

The MA is often a postoperative diagnosis and most of the current literature therefore provides management options primarily based on histopathological diagnosis (such as adenoma or mucinous adenocarcinoma) following appendectomy. With this strategy many patients particularly those with malignant mucinous tumors need completion second surgery. Additionally there is risk of mucin spillage and chance of cure compromised.

In present times due to an increased awareness and easy access to abdominal contrast enhanced computed tomography (CECT), a diagnosis of MA prior to surgery is more likely. We share our experience in managing one such patient.

Brief case presentation

A 61 year old non smoker, gentleman presented with complaints of colicky pain abdomen of 20 days duration. Abdominal examination was unremarkable except for mild tenderness in right iliac fossa. On abdominal CECT, there was mural calcification in MA and no other abdominal malignancy was detected (Figure 1). 

Figure 1. CECT abdomen

Patient had an elevated CEA (6.3ng/ml). Further work up with colonoscopy did not reveal any synchronous colorectal malignancy.  In view of the elevated CEA levels and that with existing medical literature it is very difficult to differentiate benign from malignant mucocele of the appendix preoperatively he was advised laparoscopic ileo-cecal resection with extracorporeal ileo-ascending anastomosis (Figure 2). He had an uneventful postoperative period and was discharged from the hospital on postoperative period 7.

Figure 2. Surgery specimen - displaying mucocele of the appendix

The CEA levels returned to normal (<3 ng/ml) on 7^th postoperative day and was discharged from the hospital on POD7. The biopsy revealed benign cystadenoma and tumor mucosa stained positive for CEA on immunohistochemistry.

Issues in the management of preoperatively diagnosed - Localized mucocele appendix (MA)

1.      Are there any indicators for malignancy? What is the role of CECT and elevated carcinoma embryonic antigen (CEA)?

The current multidetector CECT scans have accuracy in excess of 85% for definitive diagnosis of MA.⁴ The differentiation of benign from malignant etiology however remains difficult. Imaging features such as soft tissue thickening (internal soft tissue attenuation nodularity) and irregular walls contour (as opposed to smooth) are reported to be significantly associated with malignant lesions.² The radiological features not predictive of malignancy include: dimensions of short diameter of mucocele, presence of calcification, maximal wall thickness and internal septations.² The experience with other modalities such as positron emission tomography is very limited. Abdominal CECT therefore may be regarded as the imaging modality of choice for diagnosis and treatment planning.

CEA levels may be elevated in patients with benign cystadenoma and high values are not necessarily indicative of malignancy. These may return to normal after surgical resection. Similar findings have been reported in few other reports also. ⁵

A thorough evaluation to rule out synchronous colorectal and other malignancies is indicated in all patients with MA irrespective of the CEA levels.^6,7

2.      What should be the extent of surgery?

All medically fit patients with MA should be planned for R0 resection without spillage of mucinous material (https://jamanetwork.com/journals/jamasurgery/article-abstract/2601315).³ At surgery a thorough evaluation of peritoneal cavity is performed to rule out any evidence of peritoneal dissemination. In those with localized MA, the extent of surgery is guided by findings on abdominal CECT – likely malignancy and anatomical extent of disease. The patients with likelihood of malignancy should be advised to undergo oncologic right hemicolectomy.^6,7

 For those with involvement of appendicular base, simple appendectomy in all likelihood would result in margin positive resection and mucin spillage. Hence appropriate surgery for such patients is ileocecal resection .³ Remaining patients with distal MA likely due to benign on abdominal CECT scan may undertake appendectomy (without mucin spillage) with excision of mesoappendix. In case of doubt pertaining to the anatomic extent of disease or malignancy, right hemicolectomy and not appendectomy should be the preferred option.

3.      Is MIS a safe option in presence of MA?

An 'open' surgical approach is preferred by many due to possibility of rupture of mucocele during laparoscopic manipulation. All patients in the present study underwent laparoscopic ileocecal resection with extracorporeal anastomosis (no tumor rupture). The guiding principle was 'no touch' technique whereby MA was not directly grasped by surgical instruments. Many recent publications have also demonstrated MIS to be a safe surgical option for MA.^8,9

The strength of our strategy is that it is likely to provide a potentially curative resection and avoid completion second surgery in vast majority of this subgroup of patients. We appreciate that no imaging modality is infallible and few patients deemed benign on abdominal CECT may have malignant disease on final histopathology. They are managed as per existing protocols for postoperatively diagnosed MA.

References:

1.      Dhage-Ivatury Shubhada, Sugarbaker Paul H. Update on the surgical approach to mucocele of the appendix. J Am Coll Surg. 2006;202(4):680-684.
https://www.journalacs.org/article/S1072-7515(05)01859-4/abstract

2.      Wang H, Chen YQ, Wei R, Wang QB, Song B, Wang CY, Zhang B. Appendiceal mucocele: a diagnostic dilemma in differentiating malignant from benign lesions with CT. AJR. 2013;201(4):W590-595.
https://www.ajronline.org/doi/full/10.2214/AJR.12.9260

3.      Vashistha N, Aggarwal B, Singhal D. Incidentaloma in the right iliac fossa. JAMA Surg. 2017;152(4):405-406.
https://jamanetwork.com/journals/jamasurgery/article-abstract/2601315

4.      Crichlow L, Jaffe BM, Bellows CF. Image of the month. Low-grade appendiceal mucinous neoplasm. Arch Surg 2012; 147(8):781-2.
https://jamanetwork.com/journals/jamasurgery/fullarticle/1351831

5.      McFarlane MEC, Plummer JM, Bonadie K. Mucinous cystadenoma of the appendix presenting with an elevated carcinoembryonic antigen (CEA): report of two cases and review of the literature. Int J Surg Case Rep. 2013;4(10):886-888.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785880/

6.      Nitecki SS, Wolff BG, Schlinkert R, Sarr MG. The natural history of surgically treated primary adenocarcinoma of the appendix. Ann Surg. 1994;219:51-57.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1243090/

7.      Stocchi L, Wolff BG, Larson DR, Harrington JR.Surgical treatment of appendiceal mucocele. Arch Surg. 2003;138:585-590.
https://jamanetwork.com/journals/jamasurgery/fullarticle/394931

8.      Rangarajan M, Palanivelu C, Kavalakat AJ, Parthsarthi R. Laparoscopic appendicectomy for mucocele of the appendix. Indian J Gastroenterol. 2006;25:256-257.
https://www.ncbi.nlm.nih.gov/pubmed/17090846

9.      Park KJ, Choi HJ, Kim SH. Laparoscopic approach to mucocele of appendiceal mucinous cystadenoma: feasibility and short-term outcomes in 24 consecutive cases. Surg Endosc. 2015;29(11):3179-3183.
https://link.springer.com/article/10.1007%2Fs00464-014-4050-4

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

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