Pancreas · 2003 · 36 citations
Locally Advanced Acinar Cell Carcinoma of the Pancreas Successfully Treated by Capecitabine and Concurrent Radiotherapy: Report of Two Cases
AbstractAcinar cell carcinoma (ACC) is a rare cancer of the exocrine pancreas that comprises about 1% to 2% of all pancreatic nonendocrine carcinomas. 1 Although these tumors often have a bland histologic feature, they are highly malignant and the prognosis is generally poor. 2 Median overall survival (MOS) has been reported to be 18.7 months, with a 68% 1-year survival rate. Even in the cases of resectable ACC of the pancreas, the average disease free-survival is 9 months. 3 Surgical resection is the treatment of choice for early resectable pancreatic ACC. However, most patients with pancreatic ACC present with obvious metastases or unresectable locally advanced disease. At this stage, no adequate treatment strategy has yet been determined. The efficacy of chemotherapy is not well defined. Holen et al. 3,4 reported a poor response rate of about 10% with inhomogeneous regimens containing gemcitabine, fluorouracil (5-FU), leucovorin, mitomycin, cisplatin, cytarabine, irinotecan, doxorubicin, investigational agents, or a combination thereof. Contradictory to that report, other recent reports have described several cases of ACC of the pancreas who achieved a very good response to intra-arterial combination chemotherapy consisting of 5-FU, mitomycin, and cisplatin 4–6 or gemcitabine-based chemoradiotherapy. 7 We present two cases of locally advanced ACC of the pancreas successfully treated with concurrent capecitabine and radiation therapy. These findings may have important implications in establishing the treatment strategy of advanced ACC of the pancreas. CASE REPORTS Patient 1 A 43-year-old woman was admitted in April 2001 because of epigastric pain and a palpable abdominal mass in the epigastrium. She reported having experienced a 5-kg decrease in body weight over 6 months. She had no history of alcohol consumption and was relatively healthy. Physical examination revealed a large mass over the epigastrium. The following laboratory findings were unremarkable: complete blood counts; blood chemistry; amylase and lipase; carcinoembryonic antigen (CEA, 3.2 ng/mL; normal, <6 ng/mL), carbohydrate antigen 19–9 (CA19–9, 10.6 ng/mL; normal, <37 ng/mL), and alpha-fetoprotein (AFP, 2.2 ng/mL; normal, <20 ng/mL). Fasting and postprandial 2-hour glucose level was 137 mg/dL and 246 mg/dL, respectively. Dynamic computed tomography showed a huge, irregularly lobulated mass encircling the splenic artery, the splenic vein and superior mesenteric vein confluence in the pancreatic head and body, and regional lymph node enlargement (Figure 1A). Magnetic resonance (MR) cholangiography and angiography demonstrated that a huge pancreatic mass had compressed the common bile duct and cystic duct (Figure 1B), and the tumor had invaded the proximal portion of the splenic artery and the confluence portion of superior mesenteric vein and splenic vein (Figure 1C). Endoscopy revealed an ulceroinfiltrative mass at the medial wall of the second portion of the duodenum. Endoscopic biopsy and ultrasonography-guided core biopsy were performed. Under light microscopy, the tumors appeared lobular. They were composed of cuboidal cells having round uniform nuclei with small, distinct nucleoli. The cytoplasm was abundant, eosinophilic, and finely granular. The neoplastic cells had grown forming acinar structures characterized by exhibiting peripherally placed nuclei and small apical lumina or had grown as diffuse sheets separated by fibrovascular stroma (Figure 2A). Mitotic figures were occasionally found. Periodic acid-Schiff with prior diastase treatment (D-PAS) demonstrated positive granules in the cytoplasm (Figure 2B). Mucicarmine stain was negative. Immunohistochemical analysis revealed that the cytoplasm was diffusely positive for cytokeratin (AE1/AE3) and vimentin, focally positive for synaptophysin, and negative for chromogranin and carcinoembryonic antigen. Electron microscopy revealed that the tumor cells contained round electron-dense zymogen granules (100–400 nm) in the apical part of the cytoplasm. Therefore, ACC of the pancreas was diagnosed.FIGURE 1.: A: Computed tomography showed a huge mass in pancreatic head and body. B: MR image showed that the tumor compressed the common bile duct and cystic duct. C: Magnetic resonance (MR) angiography demonstrated that the tumor had invaded the proximal portion of the splenic artery and the confluence portion of superior mesenteric vein and splenic vein. D: After concurrent capecitabine-based chemoradiotherapy, the tumor markedly shrank. *The celiac trunk was chosen as an anatomic landmark to compare the tumor area.FIGURE 2.: A: The tumor cells formed acinar structures or diffuse sheets separated by fibrovascular stroma. B: Periodic acid-Schiff stain with prior diastase treatment (D-PAS; original magnification, ×400) revealed positive granules in the cytoplasm. Mucicarmine (M; original magnification, ×400) stain was negative and synaptophysin (S; original magnification, ×400) stain was focally positive.Concurrent chemoradiotherapy was administered with capecitabine 825 mg/m2 twice daily from the first day to the last day of radiotherapy without a rest period, plus a total radiation dose of 6,000 cGy with a fraction of 200 cGy per day, 5 days per week during a period of 6 weeks. Afterward, the patient received capecitabine 1,250 mg/m2 twice daily for 2 weeks followed by a 1-week rest period given as 3-week cycles for 12 cycles. During and after treatment, a marked reduction in tumor size (from 9.3 cm to 2.8 cm at the largest dimension) was observed (Figure 1D). The patient is well and does not have any evidence of disease progression for 21 months from the treatment. He still receives regular follow-up at an outpatient clinic. Patient 2 A 61-year-old male patient was admitted in November 2001 because of epigastric discomfort. He had no history of alcohol consumption and was previously healthy, except for a spine operation due to intervertebral disk herniation 40 years earlier. His father died of pancreatic adenocarcinoma. Physical examination revealed only mild tenderness over the epigastrium. A review of the laboratory studies showed that CEA, CA 19–9, and AFP were within normal range. A computerized tomography of the abdomen was performed with oral and intravenous contrast and thin cuts through the pancreas (Figure 3A). This showed portal vein thrombosis and a mild swelling of the pancreas head without a definite focal lesion. MR cholangiography and angiography revealed a soft tissue mass lesion abutting the head of the pancreas at the hepatoduodenal ligament. The mass showed low signal intensity on both T1- and T2-weighted images and had compressed the common bile duct. Portal vein thrombosis with cavernous transformation was confirmed. Endoscopic retrograde cholangiopancreatography was performed. The middle and distal portion of the common bile duct was compressed by an extrinsic mass and a pancreatogram was normal. Endoscopic ultrasonography performed at the second portion of the duodenum showed an irregularly shaped low echoic mass lesion at the pancreatic head and multiple peripancreatic collateral vessels. An ultrasonography-guided core biopsy was done. Light microscopic examination of the biopsied sample revealed lobules of tumor cells scattered in dense fibrous stroma. Tumor cells were small and polygonal with round, hyperchromatic nuclei of a uniform size. Mitotic figures were easily identified. PAS staining after diastase digestion revealed finely granular cytoplasm. Mucin stain was negative (Figure 4). ACC of the pancreas was diagnosed. Concurrent chemoradiotherapy was administered with capecitabine 825 mg/m2 twice daily without rest period, plus a total radiation dose of 6,000 cGy with a fraction of 200 cGy per day, 5 days per week during a period of 6 weeks. A reduction in tumor size (from 4.3 cm to 2.3 cm at the largest dimension) was observed (Figure 3B). After concurrent chemoradiotherapy, the patient received capecitabine 1,250 mg/m2 twice daily for 2 weeks followed by a 1-week rest period given as 3-week cycles for 12 cycles. At the time of this report, the patient is well without any evidence of disease progression for 15 months.FIGURE 3.: A: Computed tomography showed a mildly swollen pancreas head with the diameter of 4.3 cm. B: After chemoradiation and chemotherapy with capecitabine, the tumor shrank to approximately 2.3 cm at the largest dimension. *The confluence of the left renal vein and the inferior vena cava was chosen as an anatomic landmark to compare the change of tumor area.FIGURE 4.: Tumor cells were small and polygonal with round, hyperchromatic nuclei in uniform size (stain, hematoxylin–eosin; original magnification, ×40, 400). Mitotic figures are easily identified. PAS staining with prior diastase treatment (D-PAS) revealed finely granular cytoplasm. Mucin (M) stain was negative.DISCUSSION ACCs of the pancreas are rare and represent less than 2% of all exocrine tumors of the pancreas. Although these tumors often present a bland histology, they are highly malignant and survival is generally poor. 1,2,8 The overall 1-year survival rate was 68% and 2-year survival was 35%. 3 Fifty percent of the patients in a large series had metastases at the time of presentation. The most common metastatic sites were the liver and regional lymph nodes. The MOS was 14 months for patients with unresectable disease. 4 Although not widely accepted, the patient's age, sex, size of the tumor, stage of the disease, and levels of serum lipase were found to correlate with survival. 2,4 Surgical resection is the treatment of choice for resectable ACC of the pancreas. However, most patients with pancreatic ACC present with obvious metastases or unresectable locally advanced disease, and because of the rare incidence of this tumor, it is not established how to manage such tumors at this stage. In a report by Holen et al., 4 four patients with unresectable disease were treated with concurrent or sequential 5-FU based chemotherapy plus radiotherapy. Two patients achieved partial responses and the others attained stable diseases. A MOS and a median time to treatment failure were 14 months and 4.5 months, respectively. Recently, Chen et al. 7 reported a case of AFP-producing ACC of the pancreas successfully palliated with concurrent gemcitabine-based chemoradiotherapy. Although these may be anecdotal, some patients with locally advanced pancreatic ACC could be long survivors with combination of chemotherapy and radiotherapy. Fluorouracil is the extensively studied single agent available for the treatment of advanced pancreatic cancer. Response rates are usually less than 20%, mainly partial, and of short duration. 9 In addition, 5-FU is a well-established radiosensitizer, with protracted infusion achieving superior efficacy to bolus infusion when combined with radiotherapy. 10 Conventional external beam radiotherapy combined with 5-FU chemotherapy has been shown to improve survival in patients with locally advanced unresectable pancreatic cancer compared with irradiation alone or chemotherapy alone. 11 Capecitabine (Xeloda) is an orally administered fluoropyrimidine carbamate preferentially converted to 5-FU at the tumor site. 12 Treatment with capecitabine offers the possibility of continuous tumor exposure to 5-FU with a convenience of oral administration. A phase II study of capecitabine in patients with metastatic or locally advanced pancreatic cancer showed clinically significant beneficial effects and objective response activity. 13 Preclinical data indicate that radiotherapy enhances the activity of thymidine phosphorylase, an enzyme that is involved in the final enzymatic pathway for the activation of capecitabine, resulting in highly enhanced activity of capecitabine plus radiotherapy. 14 There are few data on the use of concurrent capecitabine and radiotherapy in pancreatic cancer. 15 A phase I study of capecitabine combined with simultaneous radiotherapy has been performed in rectal cancer. This combination demonstrated promising antitumor activity and was relatively well tolerated. The recommended dose of capecitabine for the phase II study was 825 mg/m2 twice daily. 16,17 Based on these preclinical and clinical data, we performed capecitabine-based chemoradiotherapy for two patients with pathologically confirmed locally advanced ACC of the pancreas. Both of them achieved good response to concurrent chemoradiotherapy. The side effects were minimal with only grade 2 nausea and vomiting. Toxicity worse than grade 3 has not been reported. No one developed hand–foot syndrome, which is known to be one of major limiting toxicities of capecitabine. These cases suggest that ACC of the pancreas may be very sensitive to capecitabine and concurrent radiotherapy. At the time of paper preparation, two patients were in good health without evidence of disease progression; progression-free survival was more than 21 months and 15 months, respectively. In conclusion, for a locally advanced pancreatic ACC in which surgery is not feasible, radiotherapy combined with capecitabine may be an effective treatment with minimal toxicity, which could result in increased survival. More experience with a longer follow-up period is needed to establish the benefit of this approach.
https://doi.org/10.1097/00006676-200307000-00019Pancreas · 2020 · 22 citations
Patients With Acinar Cell Carcinoma of the Pancreas After 2005
AbstractOBJECTIVES: Acinar cell carcinoma of the pancreas is a rare tumor with limited data. We aim to evaluate the characteristics, treatments, and outcomes of pancreatic acinar cell carcinoma after 2005. METHODS: We retrospectively reviewed patients with pancreatic acinar cell carcinoma treated in Peking University Cancer Hospital and Institute (2005-2018) and identified cases from Surveillance, Epidemiology, and End Results database (2005-2015). RESULTS: A total of 306 cases in our institute (n = 11) and Surveillance, Epidemiology, and End Results database (n = 295) were identified. The median age was 67 years, and 73.5% were male. The 5-year survival was 36.8% for all patients (median, 27 months). About 37% underwent surgical resection. The 5-year survival was 65.6% for resected patients as compared with 16.9% for unresected ones (P < 0.0001). Among locoregional and metastatic diseases, surgery significantly prolonged survival as well (P = 0.0003). Stage IV patients who received chemotherapy had a better survival than those without it (median, 16 vs 3 months; P = 0.0019). Aging, stage IV, and no surgery were independent predictors of poor overall survival. CONCLUSIONS: For pancreatic acinar cell carcinoma, surgery is a potentially curative treatment contributing to long-term survival and suggested even in advanced diseases. Chemotherapy improved survival for metastatic patients.
https://doi.org/10.1097/mpa.0000000000001573Pancreas · 2019 · 19 citations
Prognostic Factors of Acinar Cell Carcinomas
AbstractOBJECTIVES: Acinar cell carcinoma is a rare tumor of the pancreas. Our current series aimed to assess the clinical and morphological features of pancreatic acinar cell carcinoma and to evaluate the treatment strategies and prognosis. METHODS: This retrospective study was conducted in 3 French referral centers. Clinical data were obtained from medical records, and data about survival were then calculated and compared using statistical analysis. RESULTS: Forty-four patients were included (men, 81.8%; median age, 65.5 years; range, 21-85). Tumors were localized, locally advanced, or metastatic in 48.8%, 14.0%, and 37.2% of cases, respectively. Twenty-nine patients (65.9%) underwent a curative-intent resection (R0, 79.2%). First-line chemotherapy in metastatic patients was heterogeneous but mainly consisted in 5-fluorouracil-based or gemcitabine plus oxaliplatin combinations. Median disease-free survival was 12 months (range, 0-82 months). Median overall survival was 55.5 months; it was 40 months in patients with metastatic tumor compared with 106.5 months (P = 0.1058) in those with a nonmetastatic one. Age older than 60 years and a proliferation index greater than 30% were poor prognostic factors. CONCLUSIONS: In this large series of patients with pancreatic acinar cell carcinoma, the rate of R0 resection and the prognosis of patients appeared to be much better than that of classic ductal adenocarcinomas.
https://doi.org/10.1097/mpa.0000000000001440