Three GB-NEC patients, with two female cases and one male case, were admitted into our hospital (Table 1). Two patients complained upper quadrant pain, and one of them showed right upper quadrant tenderness during physical examination. Another one was admitted to our hospital due to an incidental finding of gallbladder occupation during a routine health checkup. No patient complained jaundice, weight loss, or carcinoid syndrome-related symptoms including diarrhea, edema, flushing and wheezing. The preoperative levels of cancer antigen 199 (CA-199) and carcinoembryonic antigen (CEA) for all patients were normal. All patients underwent ultrasonography, and showed space-occupying lesions of gallbladder wall. Contrast-enhanced computed tomography (CT) examination was performed for three patients, and demonstrated local wall thickening of the gallbladder (Fig. 1). In addition, two patients had gallbladder stones and one patient showed focal liver parenchymal invasion. None of the three patients' preoperative imaging examination revealed lymph nodes (LNs) metastases. Based on these findings, all three patients were diagnosed as gallbladder tumor preoperatively and failed to define the pathological type, and they were scheduled to undergo laparoscopic treatment. Wedge resection of gallbladder bed (≥ 2 cm) was performed for two patients without liver parenchymal invasion or vascular inflow involvement. For another patient with liver parenchymal invasion, the segment Ⅳb/V resection was performed. The surgically removed specimen of all patients were diagnosed as poorly differentiated gallbladder malignancy based on intraoperative histological examination. Thus, they all underwent laparoscopic radical cholecystectomy, and D2 lymph nodes dissection, including the LNs around gallbladder, extrahepatic bile duct, hepatoduodenal ligament plus peri-pancreatic head area, inter-aortocaval area and celiac axis area, was performed for all three patients (Fig. 2). The margin of cystic duct was sent to frozen section as well and all cases showed negative margin of cystic duct. According to postoperative pathological report, all patients were diagnosed as poorly differentiated GB-NEC with clear resection margins, and TNM stage were ⅢA (T3N0M0), ⅢB (T3N1M0) and ⅣB (T3N2M0), respectively. Chromogranin A (CgA) and synaptophysin (Syn) were positive in all cases. Ki-67 index ranged from 50–80%, and mitotic count ranged from 4 to 40.
Table 1
Clinical features of three gallbladder neuroendocrine carcinoma cases.
No. | 1 | 2 | 3 |
Sex | Female | Female | Male |
Age (years) | 37 | 44 | 84 |
BMI | 26.57 | 19.53 | 17.70 |
Clinical manifestation | | | |
Right upper quadrant pain | Yes | Yes | No |
Weight loss | No | No | No |
Jaundice | No | No | No |
Diarrhea | No | No | No |
Flushing | No | No | No |
Gallbladder stone | Yes | Yes | No |
Pathological results | | | |
Tumor size (cm) | 4.3 × 3.5 × 2.1 | 5.5 × 3.0 × 2.0 | 5.0 × 4.0 × 4.0 |
TNM grade | ⅣB (T3N2M0) | ⅢA (T3N0M0) | ⅢB (T3N1M0) |
Ki-67 (%) | 80 | 50 | 65 |
Mitotic rate (mitoses/2 mm2) | 40 | 40 | 4 |
Cystic duct margin | Negative | Negative | Negative |
Immunohistochemistry | | | |
CgA | Positive | Positive | Positive |
Syn | Positive | Positive | Positive |
No. number, BMI body mass index, CgA chromogranin A, Syn synaptophysin. |
No patient encountered postoperative bleeding, bile leakage, abdominal abscess, gastrointestinal fistulas or pulmonary complication (Table 2). No patients underwent re-operation during postoperative stay. The average days of oral diet recovery, drainage tubes removal and postoperative hospital stay were 2.0 days, 9.3 days and 11.7 days, respectively. One patient underwent chemotherapies with two cycles of etoposide plus cisplatin, and presented with liver and bile duct recurrence at 2.3 months after surgery, with the overall survival of 4.6 months. One patient underwent chemotherapies with seven cycles of etoposide plus cisplatin, and presented with liver, LNs, and bile duct recurrence at 3.3 months after surgery with the overall survival of 16.8 months. Another patient did not receive postoperative chemotherapy due to his poor general condition and presented with liver metastasis at 3.0 months after surgery. As of the last follow-up, he is still alive with the overall survival of 8.5 months.
Table 2
Postoperative outcomes of three gallbladder neuroendocrine carcinoma cases.
No. | Postoperative complications | Oral diet recovery (days) | Drainage tubes removal (days) | Postoperative hospital stays (days) | Chemotherapy | Recurrent sites | Tumor-free survival time (months) | Overall survival time (months) |
1 | No | 3 | 15 | 16 | Yes | Liver, Bile duct | 3.3 | 4.6 |
2 | No | 2 | 7 | 8 | Yes | Liver, Bile duct, LNs | 2.3 | 16.8 |
3 | No | 1 | 6 | 11 | No | Liver | 3.0 | 8.5 |
No. number, LNs lymph nodes.