The Prognostic Implications of Immune Classification Using IDO1 Expression in Extrahepatic Bile Duct Carcinoma

Background: Indoleamine 2, 3-dioxygenase 1 (IDO1) is an immunomodulatory enzyme that catalyzes the degradation of tryptophan to kynurenine (Kyn) and induces immune tolerance in tumour cells. The effects of IDO1 on extrahepatic bile duct carcinoma (EHBDC) are poorly understood. This study aimed to investigate the expression and prognostic significance of IDO1 in EHBDC. Methods: An immunohistochemical microarray analysis of IDO1 expression was performed for 77 surgically resected cases of EHBDC, and the results were compared with various clinicopathologic variables including survival data. CD8+ tumour infiltrating lymphocytes (TILs) were also investigated to elucidate their relationship with IDO1 expression and prognosis through a combination analysis with IDO1 expression. Results: IDO1 was highly expressed in 25 of 76 (32.9%) cases. High expression of IDO1 was associated with decreased numbers of CD8+ TILs (P=0.008), a higher pN category (P=0.007), an advanced overall stage (P=0.001), and frequent recurrence (P=0.018). When IDO1 expression was further stratified with CD8+ TIL state, the IDO1high /CD8low subgroup showed the worst prognosis in terms of overall survival (P = 0.025, Cox risk ratio = 2.168) and disease-free survival (P = 0.015, Cox risk ratio = 2.460) in a multivariate analysis. Conclusions: Our study confirmed that high IDO1 expression was correlated with a decreased number of CD8+ TILs and associated with a poor prognosis. As IDO1 may be a new target of immunotherapy applications, IDO1/CD8+ TIL subgrouping can be a useful prognostic prediction tool in the patients with EHBDC.

The New Era of Immunotherapy in Bile Duct Cancer Management

Bile duct carcinoma or well known as cholangiocarcinoma (CCA) is the second most common of primary liver malignancy after hepatocellular carcinoma (HCC). Although cholangiocarcinoma is a rare cancer, it has an aggressive feature with very poor prognosis. The epidemiological profile of cholangiocarcinoma varies widely across the world, which is reflecting the exposure of different risk factors, such as chronic inflammatory disease of the biliary tract, specific infectious disease, and congenital malformation. Diagnosis of CCA is quite challenging. CCA is generally asymptomatic in the early stages. Therefore, the management of this malignancy is often delayed due to late diagnosed, where the metastasis has already present or even when it is causing bile duct obstruction. Treatment for CCA is often difficult and should be managed in the tertiary referral hospital with a multidisciplinary team approach. Surgical treatment with complete resection could be benefit only for patient with early stage of the disease. Other treatment modalities as adjuvant therapy are also have been developed to improve survival of the patient, such as chemotherapy, radiotherapy, molecular targeted therapy, targeting angiogenesis and EGFR, and immunotherapy. Recently, immunotherapy has also been developed as a new cancer treatment option and showed a promising result. Whether immunotherapy can be useful for treatment biliary malignancy is still controversial. Hence, a lot of studies is still required to confirm the preliminary findings.

Intraductal Papillary Adenocarcinoma Of The Bile Duct With Associated Invasive Neuroendocrine Component: Case Report

Casestudy Intraductal papillary neoplasm of the bile duct (IPNB) is a variant of bile duct carcinoma that is characterized by intraductal growth and better outcomes compared with common cholangiocarcinoma. IPNBs are mainly found in patients from Far Eastern countries, where hepatolithiasis and clonorchiasis are endemic. Approximately 40%-80% of IPNBs are associated with invasive carcinoma. The invasive carcinomas are most often tubular or mucinous type. Invasive neuroendocrine component has not been previously described. We present a case of 69 year-old African American male who presented with worsening abdominal pain and jaundice over few months. Computed tomography showed 4 cm mass near the porta hepatis with massive ductal dilatation. A fine needle aspiration of the mass was performed and a diagnosis of adenocarcinoma was made. Subsequently, the patient underwent Right Trisegmentectomy. Conclusion Histologic sections revealed intraductal papillary neoplasm in the bile duct lumina. The papillae were lined by columnar epithelial cells with delicate fibrovascular cores. The tumor cell nuclei were slightly elongated, hyperchromatic and basally located without significant multilayering. The cytoplasm was eosinophilic with occasional intestinal differentiation. Frank invasion of the stalk and underlying periductular tissues was identified. Interestingly; the invasive component had different cytological features than the intraductal component, it was composed of small to medium sized cells with granular cytoplasm. The nuclei were uniform and round with “salt and pepper” chromatin. The invasive component stained positively for the neuroendocrine markers (Synaptophysin, Chromogranin and CD56), whereas the intraductal component stained positively for CK7, CK20 and CDX2 and negative for neuroendocrine markers. Three years later, a recurrent tumor was found in the left lobe on imaging. Biopsy of the lesion showed metastatic neuroendocrine carcinoma. The intraductal papillary neoplasm with invasive neuroendocrine component is very unusual tumor, we think more studies are warranted to best evaluate the treatment options and the prognosis of such neoplasms.

Precision Liver Resection: Three-Dimensional Reconstruction Combined with Fluorescence Laparoscopic Imaging

Liver surgery has entered the era of precision surgery. Therefore, how to optimize the resection of lesions and reduce the unnecessary time of liver ischemia and hypoxia have become the focus. A total of 11 patients who underwent fluorescence laparoscopic liver mass resection and preoperative three-dimensional (3D) reconstruction between August 2018 and July 2020 were evaluated. Liver cirrhosis occurred in 3 patients. The mean intraoperative blood loss was 166.8 ± 105.7 mL. The average length of the operation time was 152.0 ± 45.3 minutes. The average intraoperative hilar occlusion time was 9.3 minutes (except for hilar cholangiocarcinoma). The liver function of all patients, except patients with hilar bile duct carcinoma, returned to the preoperative level at 72 hours, and no serious complications occurred. 3D reconstruction combined with fluorescence laparoscopic imaging is safe and effective for precision liver resection.