Abstract
Background/Aim: Operable peritoneal dissemination from distal cholangiocarcinoma after pancreaticoduodenectomy is rare. Furthermore, peritoneal dissemination mimicking liver metastasis has scarcely been reported. Case Report: An 81-year-old woman received pancreaticoduodenectomy for distal cholangiocarcinoma. She was diagnosed with stage IIA (T3a N0 M0) and received curative resection. She did not receive adjuvant chemotherapy. As a result of the examination in our department, she showed two tumors, 20 mm and 8 mm in segments 7/8 and 7, respectively, in the subphrenic liver surface four and half years after the initial pancreaticoduo-denectomy. The larger tumor was slow-growing, and cystic degeneration was inside. Plain computed tomography imaging revealed an isodense tumor with a marginal high ring and weak early enhancement, and prolonged peripheral enhancement was recognized at the marginal portion. Magnetic resonance imaging showed a heterogeneous mass with peripheral hypointensity ring that may be caused by fibrous tissue. Although the smaller tumor was diagnosed only after admission, it presented similar imaging findings to the larger tumor. The preoperative diagnosis was suspected to be liver metastases from DCC or inflammatory pseudotumor. Laparoscopic partial liver resection with diaphragm dissection was performed for both tumors. Pathologically, the tumors were diagnosed as peritoneal dissemination from distal cholangiocarcinoma. In the disseminated cancer cells, the expression of Ki67 was decreased, which was suspected to be one of the reasons for the long recurrence-free interval. The patient is doing well without any recurrence three months after the second operation. Conclusion: Laparoscopic surgery can provide excellent results for diagnosing and treating unknown subphrenic tumors.
Distal cholangiocarcinoma (DCC) is a relatively uncommon malignancy known to occur more frequently in Japan than in Western countries, and pancreaticoduodenectomy (PD) is the only chance for a cure (1-3). A meta-analysis (2), which involved 2,063 patients with DCC, showed significant prognostic factors following surgery: Negative perineural invasion [risk ratio (RR), 0.51], negative lymph node metastasis (RR, 0.51), positive resection margin status (RR, 2.11), and not-well-differentiated adenocarcinoma (RR, 1.77). Postoperative adjuvant chemotherapy is not an obvious prognostic factor for DCC after surgery.
The Surveillance, Epidemiology, and End Results database, which contained 4,061 patients with extrahepatic bile tract malignancies, showed the following results (4). The metastatic sites (with the occurrence rates) in patients with DCC after PD included the liver (11.9%), distant lymph nodes (3.0%), lung (2.7%), bone (1.5%), and brain (0.2%). These rates were lower than those in patients with perihilar bile duct and gallbladder carcinomas. Similarly, a Japanese multicenter study demonstrated a high recurrence rate after curative PD for DCC (5). More than half of patients with DCC experienced recurrence, usually within 5 years, and the estimated cumulative 5-year recurrence rate was 54.3%. Independent predictors of recurrence-free survival were perineural invasion, pancreatic invasion, and lymph node metastasis. The initial locoregional and distant recurrence rates were 14.1% and 43.2%, respectively. Distant metastasis occurred in the liver (23.7%), peritoneum (9.3%), retroperitoneal lymph node (6.4%), and lung or mediastinum (3.3%). The median survival after recurrence was poor, only eight months, even after receiving chemotherapy.
Liver metastasis is the most frequently observed distant metastasis after PD for DCC. Conversely, peritoneal dissemination is not frequently observed and is usually diagnosed as one of the multiple-site metastases early after PD (4, 5). Preoperative percutaneous transhepatic biliary drainage (PTBD) for obstructive jaundice is a risk factor for peritoneal dissemination (6). Some reports described peritoneal dissemination under the diaphragm mimicking liver metastasis (7-9). In such cases, the signs exert pressure on the liver surface on computed tomography (CT), called “scalloping” (9).
In this report, we present a case with peritoneal dissemination mimicking liver metastases from DCC four years after the initial surgery that was successfully treated with laparoscopic hepatectomy with dissection of the diaphragm.
Case Report
An 81-year-old woman was referred to our hospital to treat a liver tumor. Four and a half years ago, the patient underwent subtotal stomach preserving pancreaticoduodenectomy for DCC at the referral hospital. The histopathology findings showed a 25×20 mm papillary adenocarcinoma of the inferior bile duct without lymph node metastasis, pancreatic invasion, and perineural invasion. The postoperative staging indicated pathological stage IIA (T3a N0 M0) with R0 resection. The patient was followed up without postoperative adjuvant chemotherapy. Four years after the surgery, a solitary liver tumor, 20 mm in diameter, was detected in segments 7/8. The tumor had higher marginal density than the surrounding liver tissue on plain CT and was slightly ringed enhanced. Imaging findings were atypical for the suspicion of liver malignancy; therefore, the patient was followed up every 3 months. After 6 months, the tumor remained the same size but did not disappear. She presented with no symptoms on admission. Her nutrition status was fair; however, her body mass index was low: 18.3. The patient had diabetes mellitus without medication and progressive fatty liver. Hepatitis B virus surface antigen and hepatitis C virus antibody were negative. The levels of tumor markers were within the normal range, including carcinoembryonic antigen, carbohydrate antigen 19-9, and alpha-fetoprotein. As a result of the examination after admission, she had two liver tumors with maximal diameters of 20 mm and 8 mm, respectively, in segments 7/8 and 7. The images of the two tumors were similar; therefore, the pictures of the former tumor are demonstrated. Plain CT imaging revealed an isodense tumor with a marginal high ring (Figure 1A). The tumor showed weak early enhancement and prolonged peripheral enhancement (Figure 1B and C). As the background liver showed fatty changes, the tumors became distinct lesions. Coronal contrast-enhanced CT (Figure 1D) showed a lens-shaped lesion immediately below the diaphragm without an obvious “beak sign” in its contact surface with the liver. There were no other intraabdominal masses or fluid collection. Gadolinium ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging revealed a ring-like heterogeneous mass without fat content in the chemical-shift images (Figure 2). The dorsal portion of the tumor showed T1 hyperintensity and T2 hypointensity with a lack of signal loss at fat-suppressed T1-weighted image, indicative of hemorrhagic or colloidal contents. During the hepatobiliary phase, the ventral area showed low signal intensity, suggesting the absence of functioning hepatocytes.
Contrast-enhanced computed tomography imaging. Axial non-contrast-enhanced CT (A) shows a ring-like mass with peripheral hyper- and central iso-attenuation relative to the adjacent fatty liver parenchyma. Axial contrast-enhanced CT images during the arterial (B) and delayed (C) phases demonstrate mild peripheral enhancement without delayed washout. In the axial plane, this lesion appears to be located in liver segments 7/8 with a clear boundary. Coronal contrast-enhanced CT (D) depicts the lens-shaped lesion located immediately below the diaphragm. Coronal contrast-enhanced CT (D) depicts the lens-shaped lesion located immediately below the diaphragm.
Gadolinium ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance (MR) imaging. Axial T1- (A) and T2-weighted (B) MR images show a ring-like heterogeneous mass (arrows) with peripheral hypointensity relative to the adjacent liver parenchyma. The diffusion-weighted image (C) depicts the lesion as a heterogeneous hyperintensity mass. The dorsal portion (arrowheads) shows T1 hyper- and T2 hypointensity with a lack of signal loss on the fat-suppressed T1-weighted image (D). The ventral area shows low signal intensity in gadoxetic acid-enhanced images during the hepatobiliary phase (E). The coronal hepatobiliary phase image demonstrates the lesion located immediately below the diaphragm, which cannot be identified as an intrahepatic or extrahepatic lesion (F).
The preoperative suspected diagnosis of this tumor was liver metastases from DCC or an inflammatory pseudotumor due to a history of bile duct–jejunal anastomosis. Therefore, laparoscopic surgery was performed for both pathological diagnosis and curative treatment. Laparoscopic observation revealed two extrahepatic tumors with suspicious diaphragm invasion (Figure 3A and B). Laparoscopic partial liver resection and partial diaphragm resection were performed for both tumors. The resected specimens were whitish elastic hard tumors, and the tumors in segments 7/8 contained a thick liquid (Figure 3C). Adenocarcinoma components were observed outside the liver and were surrounded by circular fibrous tissue (Figure 3D). Furthermore, no liver infiltration was observed, indicating that the adenocarcinoma lesion was a disseminated lesion of DCC. The detailed pathological findings are listed in Figure 4. Both the primary and metastatic tumors showed well to moderately differentiated adenocarcinoma and were positive for CK19 and CA19-9 by immunohistochemical staining. Interestingly, CK7 expression was deleted, and the expression of CA19-9 and Ki67 was decreased in metastatic cancer cells. Ki67 labeling indices decreased from 95% to 40% in the primary and metastatic lesions. CA125 was negative for both lesions. The patient was discharged on postoperative day 8 and has been closely followed without adjuvant therapy. She is doing well without recurrence 3 months after the second operation.
Laparoscopic, macroscopic, and microscopic findings of the tumors. The tumor was located between the diaphragm and liver parenchyma (A). Some invasion or adhesion was expected. First, laparoscopic partial resection of the diaphragm was performed (B). Left and right resected specimens were obtained from the tumors in segments 7/8 and 7, respectively (C). The former was a whitish tumor with liquid degeneration, and the latter was a whitish solid tumor. The pathology of the marginal parts of the metastatic lesion is shown using hematoxylin and eosin staining (D). Additionally, adenocarcinoma components were observed outside the liver with ringed fibrous tissue, and liquid necrosis was obtained inside the tumor.
Pathological findings of the primary and metastatic lesions. Both lesions were positive for CK19 and CA19-9, markers for cholangiocarcinoma. CK7 expression was not detectable in cancer cells of the metastatic lesion. The expression of CA19-9 and Ki67 was also decreased in metastatic cancer cells. CA125 was negative for both the primary and metastatic lesions. HE: Hematoxylin and eosin; CK19: cytokeratin-19; CA19-9: carbohydrate antigen 19-9; CK7: cytokeratin-7; Ki67: Ki67 antigen; CA125: carbohydrate antigen 125.
Discussion
After the PD operation in another hospital, our patient showed the pathological findings of well-differentiated adenocarcinoma without perineural invasion, pancreas invasion, and lymph node metastasis and underwent curative resection with free margins. Although the patient was expected to be a long-term recurrence-free survivor, she showed two subdiaphragmatic tumors mimicking liver metastases four years after the initial surgery. Laparoscopically, the tumors showed distinct extrahepatic growth with diaphragmatic invasion. The two tumors were laparoscopically resected and finally diagnosed as peritoneal dissemination of DCC.
Postoperative peritoneal dissemination rates in patients with DCC are not so high: 9.3% in the Japanese literature and unlisted in Western literature (4, 5). In Western countries, the frequency of peritoneal dissemination is expected to be lower than that of other distant metastases, including the liver, distant lymph nodes, lung, bone, and brain. Interestingly, the two tumors were both located on the subdiaphragmatic liver surface. No other intraabdominal tumors were detected. A few metastases from the ovary, gallbladder, and colorectum that appear suspiciously in the liver can be located under the diaphragm and become buried in the liver parenchyma (7-9). Pathologically, adenocarcinoma components were observed outside the liver parenchyma without invasion. Preoperative PTBD is a risk factor for peritoneal dissemination (6); however, this patient was treated with endoscopic nasal biliary drainage. Besides, intraoperative bile leakage in the abdominal cavity was not observed.
By immunohistochemical examination, Ki67 labeling index decreased from 95% to 40% in the primary and metastatic lesions. The disease-free interval was rather long, approximately four years, possibly because of the decreased expression of Ki67 (10). Additionally, CK7 expression was not detected, and expression of CA19-9 were decreased. Chemotherapy and radiotherapy might cause such transformations (11); however, our patient never received such treatments during the observation period. Adjuvant chemotherapy has been recommended for primary DCC (12); however, the advantage of adjuvant chemotherapy is unclear after resection of recurrent lesions. Therefore, the patient was closely followed every three months without chemotherapy.
In our patient, distinguishing intraabdominal dissemination beneath the diaphragm from liver metastases using any diagnostic modalities is challenging, even retrospectively. Percutaneous tumor biopsy should be avoided for superficial liver tumors to prevent tumor cell seeding (13). However, we can diagnose suspicious peritoneal dissemination under laparoscopic observation and obtain the final pathological diagnosis from an entirely resected specimen. Therefore, laparoscopic surgery is strongly recommended as a less-invasive diagnostic tool for unknown subphrenic tumors to achieve detailed pathological examination. Furthermore, distinguishing malignant tumors from benign ones is crucial because of the possibility of different therapeutic strategies (13).
In conclusion, our patient demonstrated rare peritoneal dissemination from DCC limited to the subdiaphragmatic liver surface four years after the initial PD. Therefore, less-invasive laparoscopic surgery is strongly recommended for correct diagnosis with complete removal of the tumors.
Footnotes
Authors’ Contributions
KY, TB, and HO designed and drafted the manuscript. KK, KM, EO, TM, HM, FM, TM, and TI collected data and assisted in preparing the manuscript. YN analyzed the radiological findings, and RY and YK investigated the pathological findings.
Conflicts of Interest
The Authors declare no conflicts of interest in relation to this study.
- Received January 16, 2023.
- Revision received January 30, 2023.
- Accepted January 31, 2023.
- Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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