Med Oncol (2011) 28:140–150 DOI 10.1007/s12032-010-9421-7
CASE REPORT
A patient of situs ambiguus with pancreatic head cancer successfully treated with gemcitabine and erlotinib Po-Chou Lin • Jiun-I Lai • Cheng-Hwai Tzeng Wei-Shu Wang
•
Received: 22 December 2009 / Accepted: 6 January 2010 / Published online: 22 January 2010 Ó Springer Science+Business Media, LLC 2010
Abstract We report a case of a 66-year-old Taiwanese female patient with situs ambiguus diagnosed of pancreatic head cancer. She was treated with gemcitabine and erlotinib and remained in stable disease on follow-up imaging studies. Situs ambiguus is a rare disease and reports of such patients with cancer have rarely been reported in the literature. Our case illustrates that standard chemotherapy in this group of patients may be undergone with promising results. Keywords Erlotinib
Pancreatic cancer Situs ambiguus
Case report A 66-year-old female patient with the past history of hyperthyroidism and type 2 diabetes mellitus was diag-
Po-Chou Lin and Jiun-I Lai are co-first authors of this article. They contribute equally to this work. P.-C. Lin J.-I. Lai C.-H. Tzeng W.-S. Wang National Yang-Ming University School of Medicine, Taiwan, Republic of China P.-C. Lin J.-I. Lai C.-H. Tzeng Division of Hematology & Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China P.-C. Lin J.-I. Lai W.-S. Wang (&) Department of Medicine, National Yang-Ming University Hospital, No. 152, Xin-Min Road, Yi-lan, Taiwan, Republic of China e-mail:
[email protected]
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nosed as having situs ambiguus (or situs ambiguous) incidentally around the age of 20. She came to our hospital due to progressive postprandial pain in February 2009. A series of imaging studies revealed total mirror reversal of the abdominal organs and a 4.5 9 4.0 cm soft tissue mass at the pancreatic head, with encasement of splenic vessels. Midline liver with hepatomegaly and polysplenism was present. Laboratory exams revealed elevated liver and biliary enzymes, normal pancreatic enzymes, and mild anemia. A screening for hepatitis B and hepatitis C was negative for active or previous infection (Table 1). Tumor markers screening showed elevated carcinoembryonic antigen (CEA) (9.65 ng/ml), CA-125 (107 U/ml), and CA19-9 (3694 u/ml) levels, with normal alpha fetoprotein level. Under the impression of pancreas head tumor with biliary tract compression related obstructive jaundice, endoscopic retrograde cholangiopancreatography (ERCP) was performed in plans of dilation of obstruction and prevention of further exacerbation of liver enzymes, but the procedure was failed due to technical difficulties. Percutaneous transhepatic drainage of the gallbladder (PTGBD) was done instead, and liver enzymes decreased subsequently. She received one course of chemotherapy with gemcitabine 1460 mg and was started on oral erlotinib (150 mg daily). She was then discharged uneventfully and continued on erlotinib use. Till now, she received at least two abdominal computed tomography (CT) follow-up images in April 2009 and July 2009. The follow-up abdominal CT revealed stable disease with no interval change of both the pancreatic and hepatic lesions in these images. Whole-body bone scan done in May 2009 revealed no osseous metastasis. The CA19-9 tumor markers were 3694 (February 2009), 3319 (April 2009) and 3003 (June 2009), respectively. Moreover, the patient was clinically well with no jaundice or other overt symptoms.
Med Oncol (2011) 28:140–150
141
Table 1 Laboratory values on initial presentation Values
Normal range
Albumin
3.4
3.7–5.3 g/dl
Calcium
9.1
8.4–10.6 mg/dl
BUN/Cr.
7/0.7
7–20/0.5–1.2 mg/dl
T/D. Bili
1.59/1.28
0.2–1.6 mg/dl
Alk-P
721
10–100 u/l
LDH
162
95–213 u/l
ALT/AST
297/136
0–40/5–45 u/l
CK
19
24–120 u/l
AFP
10.89
\20 ng/ml
CEA
9.65
\6.00
CA-125 CA-199
107 3694
\35 \35
BUN blood urea nitrogen, Cr. creatinine, Alk-p Alkaline-P, LDH lactate dehydrogenase, T/D.Bili total bilirubin/direct bilirubin, AFP alpha fetal protein, CK creatine kinase
Discussion Situs ambiguous or situs ambiguus (with the latter spelling more correct, but the former spelling more common), or heterotaxy, is a rare condition when the cardia and visceral organs are malpositioned and without mirror imaging from conventional anatomy [1]. The proper nomenclature has been proposed by the pediatric cardiology society recently that denotes heterotaxy as an abnormality in which there are components of situs solitus (normal lie of cardiac apex) and situs inversus (mirror
image of situs solitus) in the same person [2, 3]. Due to the frequency of accompanying cardiac and splenic malpositions with situs ambiguus, the presentation of the cardiac and apex and the morphology of the spleen are crucial in describing the disease [4]. In our patient, the cardiac presentation was levocardia with the apex pointing anterolaterally. The spleen was in the right upper quadrant, while the liver, stomach, and pancreatic head lied to the left side. Bridging liver and polysplenism were present, compatible with a cardinal feature of sinus ambiguous. No other cardiac abnormalities or ciliary disorders could be found. No medical condition arose due to the situs ambiguus in the patient’s lifetime until the onset of this pancreatic cancer episode. Situs ambiguus is often accompanied by splenic abnormalities and other lifespan-limiting major structural malformations. While asplenia patients are usually male, those with polysplenia are predominantly female and tend to have less severe associated cardiac defects [5, 6]. This woman had no obvious spleen structure abnormality on abdomen CT scan. Conventional EKG (Fig. 1) was normal, and conventional chest X-ray showed normal cardiac position with a right side gas bubble demonstrating stomach at the right of midline (Fig. 2). Together with abdomen CT images (Figs. 3, 4, 5), we can confirm situs ambiguus in this patient. Due to the extreme rarity of the disease, very few reports exist of malignancy in patients with situs ambiguus [2, 7–12]. There is a trend of malignancies to occur mostly in the abdominal cavity, in liver, kidney or the
Fig. 1 The electrocardiogram (EKG) of this woman revealed normal sinus rhythm
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Med Oncol (2011) 28:140–150
Fig. 4 This is another section of the arterial phase contrast materialenhanced abdominal CT scan, which was the same series as Fig. 3. A 4.5 9 4.0 cm soft tissue density at the pancreatic head (arrows) was seen
Fig. 2 Chest X-ray of this patient: Heart at left side and stomach gas at right side
Fig. 5 This is the follow-up CT scan done on July 29, 2009. There is a soft tissue density measured about 4 cm at pancreatic head encasing SMA, SMV, and splenic vein (arrows), which showed no significant interval change compared with the image of the previous CT scan done on February 18, 2009. The high-density foreign material (arrow heads) was the percutaneous transhepatic gallbladder drainage tube. (SMA: superior mesenteric artery; SMV: superior mesenteric vein) Fig. 3 Abdomen CT of this patient. This image is a transverse section of the arterial phase contrast material-enhanced abdominal CT scan, which was obtained before any treatment. It shows centrally situated liver with hepatomegaly (long arrows), inverted visceral organ including right-sided stomach (short arrows) and spleen (arrow heads), and left-sided aorta (asterisk)
pancreatobiliary system [7], but whether a causal relationship exists is in question, due to the low prevalence of the disease. No genetic relationship was found [7]. Several
123
Table 2 Treatments of patients with situs inversus and with situs ambiguous
Number of cases
SI
SA
Total
27
9
36
27
8
35
6
1*
7
Treatment Operation Chemotherapy
SI situs inversus, SA situs ambiguus, * our case
Med Oncol (2011) 28:140–150 Table 3 Types of malignancies in patients with situs inversus and with situs ambiguous
SI situs inversus, SA situs ambiguous, OP operation, C/T chemotherapy, NA not available
143
Type of cancer
Case numbers
SI/SA
OP/C/T 6/0
Renal cell
6
3/3
Gastric adenocarcinoma
5
5/0
5/1
Hepatocellular
5
5/0
5/2
Colorectal adenocarcinoma
4
3/1
4/0
Esophageal (squamous or adenocarcinoma)
4
3/1
4/0
Biliary
3
2/1
3/0
Bladder (transitional cell)
2
1/1
1/0
Lymphoma
1
1/0
1/1
Ovarian embryonal cell cancer
2
2/0
2/2
Lung cancer
2
2/0
1/0
Pancreatic adenocarcinoma
3
1/2
2/1
Periampullary
1
0/1
1/0
Cervical
1
1/0
1/0
Thyroid (follicular)
1
1/0
1/1
Breast adenocarcinoma Meningioma
1 1
0/1 0/1
NA NA
Basal cell (skin)
1
0/1
NA
Squamous cell carcinoma (unknown primary)
1
0/1
NA
30/14
37/8
Total
44
(NA:4)
Table 4 Illustration of multiple primary malignancies patients with situs inversus and situs ambiguous Type of cancer
Age Sex
SI SA Treatment Operation
Survival
References
She was well 32 months after the operation.
[28]
She was well 10 months postoperatively but recurrence
[40]
Chemotherapy
Combined hepatocellular and cholangiocellular carcinoma
69
Female 1
Transcatheter arterial embolization ? (44 days after TAE) Resection of the postero-superior segment
Hepatocellular carcinoma and early signet ring cell gastric carcinoma
66
Female 1
Left hepatic lobectomy for HCC combined with B–I gastrectomy for stomach cancer
Synchronous double cancer originating from the stomach and rectum (gastric cancer was diagnosed as papillary adenocarcinoma and rectal cancer, as moderately differentiated adenocarcinoma)
71
Female 1
Total gastrectomy for gastric cancer and lowanterior resection of the rectum for rectal cancer
NA.
[41]
Subtotal colectomy
NA
[7]
Stage I adenocarcinoma of the 59 sigmoid colon ? bladder (transitional cell) cancer ? benign meningioma of the frontal lobe ? basal cell carcinoma of the right cheek ? moderately differentiated squamous cell carcinoma of unknown primary affecting a cervical lymph node ? stage I invasive ductal carcinoma of the right breast
Female
1
Hepatic arterial infusional chemotherapy
SI situs inversus, SA situs ambiguous, NA not available
123
123 Female
Female
20
17
58
62
54
68
68
69/54
33
Embryonal cell carcinoma of the ovary
Embryonal carcinoma of the ovary
Adenocarcinoma of the transverse colon
Renal cell adenocarcinoma in a horseshoe kidney
Renal cell carcinoma
Lung squamous cell carcinoma
Adenocarcinoma of the distal common bile duct
Gastric malignant disease
Pancreatic adenocarcinoma
Female
Male/female
Female
Male
Female
Female
Female
Male
37
Hepatocellular carcinoma
Sex
Age
Type of cancer
1
1
1
1
1
1
1
1
1
1
SI
SA
Surgical resection with cholecystojejunostomy and jejunojejunostomy
Total gastrectomy
Surgical resection
Surgical resection
Uncomplicated right radical nephrectomy and lymph node dissection
Right-sided nephrectomy and resection of the isthmus containing the tumor
‘‘Left’’ hemicolectomy with lymph nodal dissection followed by ileo-colic anastomosis
1. A large left ovarian tumor was resected with the left fallopian tube 2. hysterectomy and excision of the remaining fallopian tube and ovary on the right side
Left salpingooophorectomy
Left hepatic artery ligation
Operation
Treatment
Table 5 Illustration of malignancies patients with situs inversus and situs ambiguous
Melphalan: poor response
1. Monthly courses of melphalan (March 1981– September 1982) 2. combination of bleomycin, vinblastine ?? and cisplatinum
(Adjuvant) 5-fluorouracil 250 mg per day, and 600 mg of 5-FU and 3.0 g of the protein-bound polysaccharide preparation, termed PS-K, were also given daily orally
Chemotherapy
She received interferon intramuscularly and 5220 rads of external beam radiotherapy to the right renal fossa
Other
NA
NA
The patient died 18 months later
NA
Died in the fifth postoperative month
NA
NA
Loss to follow-up
Complete remission
Died of recurrent neoplastic disease of the liver about 18 months
Survival
[25]
[24]
[23]
[22]
[21]
[20]
[19]
[17]
[16, 18]
[15]
References
144 Med Oncol (2011) 28:140–150
82
55
69
82
59
30
46
76
51
72
Renal cell carcinoma
Follicular thyroid carcinoma
Combined hepatocellular and cholangiocellular carcinoma
Grade III/III muscleinvasive transitional cell carcinoma of the bladder
Esophageal carcinoma (squamous cell carcinoma)
Esophageal carcinoma (Barrett’s ADK)
Uterine cervical cancer stage Ib
Early gastric cancer (welldifferentiated tubular adenocarcinoma)
Malignant lymphoma of the stomach of the diffuse large cell type
Ascending colon cancer with liver metastasis (welldifferentiated adenocarcinoma)
Age
Type of cancer
Table 5 continued
Female
Female
Male
Female
Male
Male
Male
Female
Female
Female
Sex
1
1
1
1
1
1
1
1
1
1
SI
SA
A resection of the cecum and ascending colon, a resection of the posterior upper segment of the liver, and a cholecystectomy were performed
First, a cholecystectomy was done, followed by total gastrectomy with dissection of the lymph nodes (D2) and splenectomy, and finally, Roux-en-Y reconstruction
Laparoscope-assisted distal gastrectomy
Radical hysterectomy
Subtotal transthoracic esophagectomy by the Ivor Lewis procedure
Radical cystectomy, bilateral pelvic lymph node dissection, and ileal loop urinary diversion Subtotal transthoracic esophagectomy with gastroplasty and cervical esogastric anastomosis
Transcatheter arterial embolization ? (44 days after TAE) Resection of the postero-superior segment
Total thyroidectomy
Left radical nephrectomy
Operation
Treatment
CHOP regimen (cyclophosphamide 1200 mg, adriamycin 50 mg, vincristine 80 mg, and prednisone 65 mg) 1 month postoperatively, which was given three times
(Adjuvant) 150 mCi of 131I, and a further dose of 100 mCi of 131I was administered six months later
Chemotherapy
1.8 Gy doses of irradiation (total 36 Gy) were delivered to the area of the inverted Y in the abdomen
Other
NA
NA
NA
NA
NA
NA
NA
NA.
Complete remission
NA
Survival
[34]
[33]
[32]
[31]
[30]
[30]
[29]
[28]
[27]
[26]
References
Med Oncol (2011) 28:140–150 145
123
Age
76
57
70
68
66
66
Type of cancer
Proximal bile duct carcinoma (papillary adenocarcinoma)
Esophageal cancer
Hepatocellular carcinoma
Non-small cell carcinoma of the left lung
Hepatocellular carcinoma
Hepatocellular carcinoma and early signet ring cell gastric carcinoma
Table 5 continued
123 Female
Male
Male
Female
Male
Female
Sex
1
1
1
1
1
1
SI
SA
Left hepatic lobectomy for HCC combined with B–I gastrectomy for stomach cancer
Abdominal angiography demonstrated two large tumor stains, and transcatheter arterial embolization was performed with emulsion of epirubicin hydrochloride and lipiodol injected from the right and left hepatic artery
NA
Partial hepatectomy and transarterial embolization
Laparoscopic gastric mobilization and thoracoscopic esophagectomy
She underwent endoscopic sphincterotomy and lithotomy for choledocholithiasis, laparoscopic cholecystectomy for cholecystolithiasis, right hepatic lobectomy, caudate lobectomy, and extrahepatic bile duct resection for papillary adenocarcinoma of the proximal bile duct
Operation
Treatment
Hepatic arterial infusional chemotherapy
NA
Chemotherapy
NA
Other
She was well 10 months postoperatively but recurrence
NA
NA
NA.
NA
The patient died 7 months after the operation
Survival
[40]
[39]
[38]
[37]
[36]
[35]
References
146 Med Oncol (2011) 28:140–150
49
52
39
58
44
Renal adenocarcinoma in the left kidney with distant metastasis to the lung
Esophageal (leiomyoma)
Renal cell carcinoma
Adenocarcinoma of the ampulla
Female
Male
Female
Male
Male
Female
53
Renal adenocarcinoma in the right kidney
Female
71
Synchronous double cancer originating from the stomach and rectum (gastric cancer was diagnosed as papillary adenocarcinoma and rectal cancer as moderately differentiated adenocarcinoma) The carcinoma of the head of the pancreas, with duodenal infiltration
Sex
Age
Type of cancer
Table 5 continued
1
SI
1
1
1
1
1
1
SA
After these anatomic variations of the mesenteric vessels were clearly delineated, a pylorus-preserving pancreaticoduodenectomy was performed with an end-to-side pancreaticojejunostomy, an end-to-side cboledochojejunostomy, and an end-to-side duodenojejunostomy
Left radical nephrectomy
They resected only the distal 10–12 cm of esophagus and replaced it by drawing the gastric fundus into the chest
Transcatheter embolization of the left renal artery
Right nephrectomy
Total pancreatectomy and dissection of the regional lymph nodes with end-toend gastro-jejunostomy and end-to-side hepaticojejunostomy in Roux-enY fashion was performed
Total gastrectomy for gastric cancer and lowanterior resection of the rectum for rectal cancer
Operation
Treatment Chemotherapy
Other
NA
Died 10 weeks postoperatively
NA.
NA
NA
NA
NA
Survival
[43]
[11]
[42]
[9]
[9]
[8]
[41]
References
Med Oncol (2011) 28:140–150 147
123
123
57
59
66
Peripheral papillary cholangiocarcinoma with hilar extension
Stage I adenocarcinoma of the sigmoid colon ? bladder (transitional cell) cancer ? benign meningioma of the frontal lobe ? basal cell carcinoma of the right cheek ? moderately differentiated squamous cell carcinoma of unknown primary affecting a cervical lymph node ? stage I invasive ductal carcinoma of the right breast
Pancreatic head adenocarcinoma with SMA, SMV, and CBD encasement and liver metastasis Female
Female
Female
Sex
SI
1
1
1
SA
Subtotal colectomy
Resection of segments 4 to 8 extended to the common bile duct with lymphadenectomy and reconstruction by hepaticojejunostomy
Operation
Treatment
SI situs inversus, SA situs ambiguous, NA not available, ‘‘a’’ means our case
Age
Type of cancer
Table 5 continued
Gemcitabine and Erlotinib
Chemotherapy
Other
The patient is now under chemotherapy with no signs of recurrence
NA
No signs of recurrence at 18-month followup
Survival
a
[7]
[12]
References
148 Med Oncol (2011) 28:140–150
Med Oncol (2011) 28:140–150
cases underwent surgery [2, 7, 8, 11, 12], but in our case, the patient received medical treatment only and is in stable status. We searched PubMed database from 1980 to 2009 for similar cases [5–7, 9, 10; Table 5). All the cases were illustrated in Tables 2 and 5. There were 36 cases of cancer in patients with SI and SA, 27 cases of SI, and 9 cases of SA (Table 3). Among these cases, most of them underwent surgical intervention and 6 cases received adjuvant chemotherapy. Our case was the only case that underwent chemotherapy without surgical treatment. We also found 4 cases of SA or SI with multiple primary malignancies, and these cases were illustrated in Table 4. The median survival rate of untreated pancreatic cancer patients is reported as 4–6 months [13]. Our patient received erlotinib and gemcitabine from February 2009 till now and is in stable disease. Current advanced pancreas cancer chemotherapy treatment includes cisplatin ?5-FU and gemcitabine [14]. This case was the first situs ambiguus patient with pancreas cancer who received erlotinib and gemcitabine and may serve as reference for further physician treatment. In summary, we report a case of situs ambiguus with pancreatic cancer treated with erlotinib and gemcitabine. Very few cases exist reporting situs ambiguus with cancer, and surgery remains the primary therapeutic option, if feasible. Our cases illustrate that situs ambiguus with coexisting malignancy can be treated with similar regimens as that of situs solitus with erlotinib and gemcitabine, an effective regimen.
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