Surgery for intrahepatic cholangiocarcinoma (IHC)

A male patient in seventh decade presented to emergency with obstructed umbilical hernia that got spontaneously reduced. He was well controlled diabetic on Injection insulin. There was history of heavy tobacco use for over 3 decades. During work up for elective laparoscopic umbilical hernia repair, abdominal CT scan was performed which revealed a large mass lesion in left hepatic lobe. A subsequent triple phase contrast enhanced MRI scan showed 7 x 5 cm lesion in segment 2, 3 & 4 of the liver that showed initial rim enhancement and then progressive and centripetal enhancement after the administration of intravenous contrast material with associated capsular retraction (Figure 1).

Figure 1. Triple phase MR scan of liver

Based on characteristic MRI scan findings, a diagnosis of IHC was made.

Diagnostic work up was completed by HRCT chest and estimation of tumor markers – serum CA 19-9, CEA and AFP all of which were in specified normal range.

At laparotomy, the liver was non cirrhotic and there was a large tumor in segment 2, 3, & 4.  Anatomic left hepatectomy with designated lymph node dissection was performed(Figure 2). The postoperative period was uncomplicated and the patient was discharged on 7^th day after surgery. The biopsy was confirmatory for IHC (small duct type) pT2N0.

Figure 3. Left hepatectomy specimen

Intrahepatic Cholangiocarcinoma

Arising from bile duct epithelium proximal to second order biliary radicals, IHC is the second most primary hepatic cancer after hepatocellular carcinoma.¹ Tumors arising from within hepatic parenchyma and secondarily involving extrahepatic biliary tree are classifies as IHC (c.f. hilar cholangiocarcinoma which arises from main hepatic ducts or hepatic confluence).¹

The incidence of IHC is increasing worldwide.² A recent systematic review of 57 studies (4756 patients) reported that median age of IHC patients ranged from 49-67 years and 57% were males.³ Another large retrospective single centre study reported that heavy tobacco use and diabetes mellitus were particularly prevalent in these patients.¹

Presentation: Intrahepatic cholangiocarcinoma is usually asymptomatic with majority of tumors being diagnosed during investigations for non specific symptoms such as weight loss, fatigue or abdominal pain or unrelated abdominal conditions. Some patients though would be diagnosed with tumor related symptoms e.g. jaundice.⁴

Imaging: On triple phase contrast enhanced abdominal CT scan, IHC shows early arterial peripheral enhancement with gradual filling towards the centre of the lesion.^{1, 4} At MRI , IHC are generally hypointense on T1-weighted images and hyperintense on T2 – weighted images. Other characteristic features have already been described.

Tumor markers: Preoperative CA 19-9 is raised in about 90% patients. Preoperative tumor marker levels of CA 19-9 and CEA have been shown to have prognostic value. In a recent study of 588 patients, 5 year overall (54.5%) survival was significantly better among patients with low CA 19-9 and CEA.⁵

Surgery: All medically fit patients with IHC localized to the liver are candidates for surgery which entails major hepatectomy and lymphadenectomy.  A recent multicenter study has reported that patients who underwent liver resection with lymphadenectomy had better 3 & 5 year survival and disease free survival compared to patients who underwent liver resection without lymphadenectomy. ⁶

Resection margin: Liver resection with 'wide' resection margin of at ≥ 10 mm is shown to be associated with favourable outcomes particularly in patients with node negative disease and for mass forming type of IHC.⁷

Lymphadenectomy: The Liver Cancer Surgery Group of Japan proposed that 3 group of lymph nodes as draining nodes for IHC ⁸

Group 1 – Nodes in hepatoduodenal ligament. When the tumor is located in left lobe, lesser curvature nodes are included in group 1

Group 2 – Nodes along common hepatic artery, left gastric artery, celiac trunk and on posterior surface of pancreatic

Group 3 – Para aortic nodes

In HPB centres in Japan, group 1 & 2 lymph nodes are commonly dissected.  A recent study has reported that the rate of lymph node metastasis (LNM) was high across all T categories and that 1 in 5 patients with T1 disease have LNM.⁹  

 For optimal staging 8^th edition of AJCC recommends to harvest at least 6 locoregional nodes

Expanding boundaries of resection: Portal vein embolization (PVE) is indicated for safe liver resection if the remnant liver volume is likely to less than 30-40%. ALPPS may be a valuable adjunct to achieve R0 resection in locally advanced IHC where remnant liver volume remains inadequate after PVE. A multicenter study involving 102 patients with advanced IHC suggests that ALPPS should be restricted to patients with single lesions and sufficient future liver remnant at stage II operation (FLR2) to get most oncological benefit. ¹⁰

Current status of Liver transplantation: For most centres, liver transplantation is contraindicated for patients with IHC in a cirrhotic liver. However a recent multicenter study reported a 5 year actuarial survival rate of 65% in cirrhotic patients with very early IHC defined as ≤ 2 cm.^11,

A recent systematic review of 57 studies (4756 patients) reported that the median survival was 28 (range 9 – 53) months and overall survival was 30% (5-56%). Adverse prognostic factors included large tumor size, multiple tumors, LNM and vascular invasion.³

References

1.       Endo I, Gonen M, Yopp A et al. Intrahepatic  Cholangiocarcinoma.  Ann Surg 2008;248: 84-96

2.       Mazzaferro V, Gorgen V, Roayaie S. Liver resection and transplantation for intrahepatic cholangiocarcinoma. J Hepatol;2020:72:364-77

3.       Mavros MN, Economopoulos KP, Alexiou VG et al. Treatment and prognosis for patients with intrahepatic cholangiocarcinoma: Systematic review and meta –analysis. JAMA Surg; 149:565-74

4.       Umberto Cillo, Constatino Fondevilla, Matteo Donadon et al. Surgery for cholangiocarcinoma. Liver Int; 143:143-55

5.       Moro A, Mehta R, Sahara K et al. The impact of preoperative CA 19-9 and CEA on outcomes of patients with intrahepatic cholangiocarcinoma. Ann Surg Oncol 2020 doi: 10/1245/s10434-020-08350-8

6.       Yoh T, Cauchy F, Le Roy B et al. Prognostic value of lymphadenectomy for long term outcomes in node negative intrahepatic cholangiocarcinoma: A multicentre study. Surgery 2019;166(6):975-982

7.       Watanabe Y, Matsuyama Y, Izumi N et al. Effect of surgical margin width after R0 resection after intrahepatic cholangiocarcinoma: A nationwide survey of liver cancer study group of Japan. Surgery 2020 doi 10.1016/j.surg.2019.12.009

8.       Uenishi T, Yamamoto T, Takemura S et al. Surgical treatment for intrahepatic cholangiocarcinoma. Clin J Gastroenterol; 7:87-93

9.       Zhang XF, Chakedis J, Bagante F et al. Trends in use of lymphadenectomy in surgery with curative intent for intrahepatic cholangiocarcinoma. Br J Surg 2018; 105:857-866.

10.   Li J, Moustafa M, Lineckar M et al. ALPPS for locally advanced intrahepatic cholangiocarcinoma: Did aggressive surgery lead to oncological benefit? An international multicentre study. Ann Surg Oncol 2020doi: 10.1245/s10434-019-08192-z

11.   Sapisochin G, Facciuto M, Rubbia‐Brandt L, et al. Liver transplantation for "very early" intrahepatic cholangiocarcinoma: international retrospective study supporting a prospective assessment. Hepatology. 2016;64:1178–1188

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

Gallbladder Cancer: Dilemmas faced during day-to-day clinical practice

Mucinous Cystic Neoplasm (MCN) of Pancreas

A woman in her 8^th decade presented with 2 months history of dull aching pain in the upper abdomen.  She was in good health and there was no serious comorbidity though she had hypertension that was well controlled on medication. Her physical examination was unremarkable except for obesity (BMI 31kg/m²). An initial abdominal ultrasound done elsewhere was suggestive of large cystic lesion in the body of pancreas.

The patient was further investigated with contrast enhanced abdominal magnetic resonance imaging (MRI) of the abdomen which showed a well defined, large (> 5 cm) unilocular cystic lesion with thick enhancing capsule located centrally in the body of pancreas. There was no duct – cyst communication (Figure 1 & 2).

Figure 1

Figure 2

A diagnosis of mucinous cystic neoplasm (MCN) was made. A subsequent endoscopic ultrasound revealed a large multiseptated cyst with solid components in the pancreatic body raising the possibility of mucinous cystadenocarcinoma. The cyst fluid CEA was 47788 IU.

In view of large, centrally placed lesion, a hybrid procedure i.e. laparoscopy assisted lateral to medial mobilization of pancreas and spleen with open transection of the pancreas was proceeded with. The postoperative period was uncomplicated.

At histopathology there was 7x5 cm MCN with low grade dysplasia.

The patient is well 3 years after surgery

Discussion

1.       Pseudocyst or MCN

2.       Surgery for MCN

These are sequentially discussed below:

1.       Pseudocyst or MCN: Prior to any intervention for cystic tumors of the pancreas, pseudocyst needs to be conclusively ruled out. In patients where doubt persists after all investigative modalities have been utilized it is best to follow the surgical dictum ‘it is better to resect a pseudocyst than to drain a cystic tumor’. The salient features for differentiating MCN and  pseudocyst are summarized in table 1

Table 1. Pseudocyst versus MCN¹

Parameter	MCN	Pseudocyst
History of acute pancreatitis	Absent. (c.f. 10% patient may present with acute pancreatitis)2,3	Present
Contrast MRI with MRCP	Cyst wall enhancing Main pancreatic duct – cyst communication absent (Figure 3)	Cyst wall nonenhancing Main pancreatic duct – cyst communication present (Figure 4)
EUS guided cyst fluid aspiration	Cyst fluid amylase – CEA  +++	Cyst fluid +++ CEA -

 

Figure 3. Main pancreatic duct – cyst communication absent

Figure 4. Main pancreatic duct – cyst communication present

2. Mucinous cystic neoplasms are characterized by presence of ovarian stroma and lack of communication with main pancreatic duct.² They occur most frequently in women (95%), in distal pancreas (97%) and are always a single lesion.³ The risk of malignancy is reported to be 17%.² The clinical and imaging parameters associated with malignancy include older age, presence of mural nodules and cyst diameter of ≥ 60 mm.²

Resection should be considered in all patients with MCN.² This is most commonly in the form of distal pancreatectomy. In low risk MCN (≤ 4 cm, no mural nodules) non radical resections are appropriate

References

1.       Singhal D, Kakodkar R, Sud R et al. Issues in management of pancreatic pseudocysts. JOP 2006;7(5):502-7

2.       Crippa S, Salvia R, Warshaw AL et al. Mucinous cystic neoplasm of the pancreas is not an aggressive entity: lessons from 163 resected patients. Ann Surg 2008;247(4):571-9

3.       Farrell JJ, Castillo F. Pancreatic cystic neoplasms: management and unanswered questions Gastroenterology 2013;144:1303-15

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

Surgery for Cancer of Pancreas during COVID - 19 Pandemic

Surgery For Colorectal Cancers During COVID-19 Pandemic at SGE, Max Hosp...

Surgery for colorectal cancer (CRC) with first presentation as bowel obstruction

According to international statistics, colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and second in females.¹ However in India lies, the incidence is lower as compared in Europe and North America. According to ICMR consensus document on management of CRC (2014), colon cancer ranks as 8^th and rectal cancer as 9^th among men and amongst women colon cancer ranks 9^th while cancer rectum does not figure in top 10 cancers.

First presentation of CRC as emergency – obstruction, perforation or bleeding is not uncommon. Malignant large bowel obstruction is reported in 8-13% patients with CRC In Western studies.^2,3 Another multicentre study from UK involving 286591 patients over a 15 year period (1997 – 2012) reported  that 24.3% (69718 patients) needed emergency for CRC and all cause 30 and 90 day mortality was significantly higher in patients undergoing emergency surgery as compared to elective surgery.⁴

 Management of such patients is particularly challenging as they are often elderly with significant comorbidity and histopathologic diagnosis may not be unavailable. At surgery large bowel may be hugely distended and complex resections may be required.

In the following sections, we briefly discuss the management CRC presenting as emergency through a representative case series of patients wherein the first presentation was obstruction or perforation.

Case study 1

An elderly woman in her 5^th decade presented with acute intestinal obstruction. Her contrast enhanced abdominal computed tomography (CT) scan showed mass lesion in cecum – ascending colon (Figure 1).

Figure 1. Carcinoma right colon with acute

Intestinal obstruction

She underwent right hemicolectomy with primary anastomosis and had an uneventful recovery. The biopsy was suggestive of adenocarcinoma T3N1. She was stared on adjuvant chemotherapy after 3 weeks and is currently well 4 years after surgery.

Case study 2

An elderly woman in her 8^th decade presented with 6 months history of weight loss and progressive constipation that for last 4 days had progressed to obstipation. There was no major comorbid illness and prior to obstipation she was managing her daily activities. Her abdominal CT scan revealed obstructing lesion in rectosigmoid region with closed loop obstruction. There were multiple colorectal liver metastases in segment 2 & 3 (Figure 2 & 3).

Figure 2. Abdominal CT scan with distended left colon and CLM

Figure 3. Abdominal CT scan showing closed obstruction of large bowel

At surgery, the whole of whole of large bowel was massively distended but the cecum was viable. Anterior resection with ascending colostomy was done. She opted for colostomy closure 8 weeks later but declined further chemotherapy. Following this second surgery she was restored to good quality of life and passed away 16 months later.

Case study 3

An elderly male with history of weight loss and progressive constipation presented to emergency room. He was a known diabetic and had undergone coronary bypass 1 year ago had low ejection fraction (35%). Abdominal CT scan is provided in Figure 4. The total white blood cell count was 39,000 mm³

Figure 4. Closed loop obstruction of large bowel with hugely distended cecum

At surgery, there was an obstructing mass lesion in sigmoid colon with infiltration of dome of urinary bladder. The cecum appeared gangrenous. A subtotal colectomy with partial cystectomy was performed. Reconstruction was by an ileorectal anastomosis with diverting loop ileostomy. He had an uneventful postoperative recovery and was discharged on 8^th postoperative day. The biopsy reported adenocarcinoma sigmoid colon T4N1 with all clear surgical margins. The ileostomy was successfully reversed 8 weeks later.

Discussion

A US study (1991 – 2005) involving 1004 patients ≥65 years with stage IV colon cancer reported that obstruction occurred a median of 7.4 months after colon cancer diagnosis and median survival after obstruction was approximately 2.5 months.⁵ Risk factors for presentation with obstruction included proximal location, high grade tumor, mucinous histological type and nodal stage N2.³ Another study from Australia has reported that emergency patients had 5 year survival rate of 39. 2% compared to 64.7% for elective patients (p< 0.0001) and they also had significantly more advanced Dukes C & D tumors. Also both emergency Dukes B and C groups had significantly more T4 cases.⁶

The current treatment options for MLBO include:

1.    Endoscopic stenting with self expanding metallic stent (SEMS) placement

Endoscopic stenting with SEMS can be used as a palliative therapy in patients with unresectable primary or metastatic disease. For patients with malignant large bowel obstruction where a curative surgery is deemed feasible SEMS is used as a bridge to definitive surgery thereby avoiding risks of emergency surgery, higher chances of primary anastomosis  and avoiding permanent stomas in 30-40% patients.^7.8 However SEMS placement may result in perforation rates ranging between 6.9 – 7.7%.^8,9

2.    Surgery: This may be done as one, two or 3 stage procedure:

-          Single stage procedure: Oncologic resection + primary anastomosis.

This is generally acceptable for obstructing carcinoma on the right side and in select patients on left side in the form of subtotal colectomy with ileorectal anastomosis.

-          Two stage – (i) Oncologic resection with anastomosis + proximal diverting stoma (ii) stoma closure

-          Three stage – (i) Proximal diverting stoma (ii) oncologic resection of the tumor(iii) stoma closure

The choice of treatment depends on the usual combination of patient factors (e.g. age, comorbidity, hemodynamic stability, patient preference etc), tumor factors (stage, location, degree of obstruction – partial or complete, condition of the proximal bowel e.g. bowel dilatation, viability of cecum) and available local expertise.

Hence for optimal immediate and oncological outcomes such patients should always be managed by surgical teams experienced in GI oncosurgery as well as emergency GI surgery.

References

1.      Torre LA¹, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics 2012. CA Cancer J Clin. 2015 Mar;65(2):87-108

2.      Jeanin E. van Hooft, Joyce V. Veld, 2, Dirk Arnold et al. Self-expandable metal stents for obstructing colonic and extracolonic cancer: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2020. Endoscopy

3.      Winner M, Mooney SJ, Hershman DL et al. Incidence and predictors of bowel obstruction in elderly patients with stage IV colon cancer. JAMA Surg 2013;148(8):715-22

4.      Askari A, Nachiappan S, Currie A et al. Who requires emergency surgery for colorectal cancer and can national screening programs reduce this need. Int J Surg 2017;42:60-68  

5.      Winner M, Mooney SJ, Hershman DL et al. Management and outcome of bowel obstruction in patients with stage IV colon cancer. Dis Colon Rectum. 2013 Jul; 56(7): 834–843.

6.      Wong SK¹, Jalaludin BB, Morgan MJ. Tumor pathology and long term survival in emergency colorerectal cancer. Dis Colon Rectum. 2008 Feb;51(2):223-30

7.      Hsu J, Sevak S. Malignant large bowel obstruction. Dis Colon Rectum 2019; 62: 1028–1032

8.      Amelung FJ, Borstlap WAA, Consten ECJ et al. Propensity score-matched analysis of oncological outcome between stent as bridge to surgery and emergency resection in patients with malignant left-sided colonic obstruction. Br J Surg 2019;106:1075-1086

9.      Tan CJ, Dasari BV, Gardiner K Systematic review and meta-analysis of randomized clinical trials of self-expanding metallic stents as a bridge to surgery versus emergency surgery for malignant left-sided large bowel obstruction. Br J Surg 2012;99:469-76

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

Primary hepatic neuroendocrine tumor (NET) or metastatic ileal NET – that is the question

A 65 year old male presented with recurrent epigastric pain, loose stools, flushing of face and breathing difficulty for 1 year. He had undergone right hepatectomy elsewhere for primary hepatic neuroendocrine tumor (NET) 12 years ago. His hematologic and biochemical investigations were within normal range except for raised urine 5 Hydroxyindolacetic acid (HIAA) levels (309 ng/24 hours).

Abdominal contrast enhanced computed tomography studies for liver (triple phase study) and bowel (enterography) were performed. Figure 1 A shows peripheral hyper enhancing lesion in hepatic segment III. Previous right hepatectomy with hypertrophy of remnant liver is noted. There was a markedly enhancing intraluminal polypoidal mass in the ileum (Figure 1 B).

Figure 1. Contrast enhanced computed tomography scan of abdomen

The patient underwent liver mestastatectomy with segmental bowel resection. The 'cut open section' of the resected small bowel revealed a stenosing tumor and a large draining lymph node (Figure 2). Histopathology revealed a well differentiated, intermediate grade NET (WHO; G2). Cytoreductive surgery together with initiation of long acting octreotide analogue resulted in symptomatic control of carcinoid syndrome.

 Figure 2. Segemental ileal resection showing small tumor with large mesenteric lymph node

Primary hepatic NETs are exceedingly rare and such diagnosis should be made only after a thorough clinical and radiological evaluation to exclude an elusive primary elsewhere (usually in the small intestine).¹ Primary ileal NET are often detected late and long term follow up therefore is essential. This is the most likely scenario in the present case also. A revised diagnosis of primary ileal NET with liver metastasis and carcinoid syndrome thus was made.

Aggressive surgery in metastatic NET in the form of removal of small bowel primary together with involved draining lymph nodes is reported to provide significant reduction in tumor related symptoms and improves survival. 

For liver secondaries, even a 70 % cytoreduction by means of parenchyma sparing debulking has been reported to improve progression free and overall survival.² Liver transplantation may be offered to select patients with: well-differentiated NET (Ki-67 <10 %), age <55 years, absence of extrahepatic disease, primary tumor removed before transplantation, stable disease for at least 6 months before LT, and <50% liver involvement.³

 References

1. Fenwick SW, Wyatt JI, Toogood GJ, Lodge JP. Hepatic resection and transplantation for primary carcinoid tumors of the liver. Ann Surg 2004;239(2):210-219.

2. Maxwell JE, Sherman SK, O'Dorisio TM, Bellizzi AM, Howe JR. Liver directed surgery of neuroendocrine metastases: what is the optimal strategy? Surgery 2016;159(1):320-333.

3. Rossi RE, Burroughs AK, Caplin ME. Liver transplantation for unresectable neuroendocrine tumor liver metastases. Ann Surg Oncol 2014;21(7):2398-405.

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