The majority of malignant tumors in the pancreas are adenocarcinomas. Adenosquamous carcinoma of the pancreas occurs less frequently with an incidence of 3%-4%[ ¹]. These tumors are a malignant epithelial carcinoma of the pancreas and are characterized by the presence of variable proportions of both glandular and squamous components. At least 30% of the neoplasm should be comprised of the squamous component[ ^{1 , 2}]. Recently, several reports have described cases of adenosquamous carcinoma of the pancreas[ ^{3 - 6}]. However, as the number of patients who undergo resection at a single institute is limited, large studies describing the clinicopathological features, therapeutic management and surgical outcome for adenosquamous carcinoma of the pancreas are lacking.

Table 1 lists 39 patients who had undergone surgical resection for adenosquamous carcinoma of the pancreas. Adenosquamous carcinomas have not been associated with any specific clinical syndromes[ ^{2 , 30}]. Each of the 39 patients presented clinical symptoms such as abdominal pain, back pain, painless jaundice, anorexia, and/or body weight loss (data not shown). Accurate preoperative diagnosis of adenosquamous carcinoma of the pancreas is very difficult, because imaging studies have revealed no characteristic features that can facilitate the differentiation of this tumor type from ordinary invasive ductal carcinoma. One study reported that intense Gallium-67 citrate uptake was observed in adenosquamous carcinoma of the pancreas, indicating that Gallium-67 citrate scintigraphy might be useful in detecting these carcinomas[ ¹⁵]. However, more detailed imaging data are required to improve the ability to diagnose this rare disease.

Since adenosquamous carcinomas are uncommon tumors with a poor prognosis, the outcomes associated with various therapeutic interventions are not well defined.

Table 1 lists the tumor location and operative method used in the 39 cases analyzed here. Three main operative methods were performed: pancreaticoduodenectomy (PD) including pylorus-preserving PD (PPPD) in 30 cases (76.9%); distal pancreatectomy (DP) in eight cases (20.5%); and total pancreatectomy (TP) in one case (2.6%). Tumors were located in the head alone in 28 cases (76.9%), in the head and body in two cases, and in the body and/or tail of the pancreas in nine cases (23.1%). Although adenosquamous carcinoma of the pancreas has different clinicopathological features to pancreatic adenocarcinoma, the treatment strategy of patients with adenosquamous carcinoma is dealt with in the same manner as patients with adenocarcinoma. Surgical treatment remains the only curative management option that is seriously considered for adenosquamous carcinoma of the pancreas.

To date, only eight patients have received adjuvant chemotherapy, indicating that postoperative adjuvant chemotherapy is not usually administered to patients with adenosquamous carcinoma of the pancreas (Table 1). Tanaka et al reported that the size of an unresectable adenosquamous carcinoma of the pancreas was reduced by neo-adjuvant chemotherapy consisting of a combination of interferon-α, tumor necrosis factor-α, and 5-fluorouracil[ ¹¹]. However, the patient only survived 7 mo after surgery[ ¹¹]. In this case, although neo-adjuvant chemotherapy might not have contributed to prolonging the patient’s survival, the ability of the chemotherapy to reduce the size of the tumor from one that was unresectable to one that could be resected was confirmed. In the current study, the adjuvant chemotherapy group had a 2- or 3-year cumulative survival rate of 16.7% and a median survival period of 7 mo (Table 2). In comparison, the group who did not receive adjuvant chemotherapy had a 2-year cumulative survival rate of 9.2% and a median survival period of 5 mo ( P = 0.364). Almost all of the patients in the adjuvant chemotherapy group were treated with a 5-fluorouracil-based regimen. Recently, adjuvant chemotherapy using new drug agents has been considered as the standard therapeutic option following resection for pancreatic adenocarcinoma, and several reports suggest that adjuvant chemotherapy with gemcitabine is responsible for a significant increase in patient survival[ ^{31 - 33}]. Postoperative administration of gemcitabine also significantly delayed the development of recurrent disease after complete resection of pancreatic cancer compared with observation alone[ ³⁴]. However, information regarding gemcitabine use in cases with adenosquamous carcinoma of the pancreas is not available as previous reports lack such data. Further investigations examining whether adjuvant chemotherapy using gemcitabine will improve surgical outcome in patients with adenosquamous carcinoma of the pancreas are therefore warranted.

The overall 1-, 2-, and 3-year survival rates after pancreatic resection were 25.5%, 14.0%, and 14.0%, respectively (Figure 1). Table 1 shows operative mortality occurred in two patients during the early 1980s[ ^{7 , 8}]. One patient died of myocardial infarction 2 d after undergoing PD and another died of numerous postoperative complications including electrolyte disturbance from massive abdominal fluid losses, acute renal failure and eventually congestive heart failure 20 d after undergoing PD[ ^{7 , 8}]. Univariate analysis of the different prognostic factors predicted to contribute to patient prognosis showed that tumor location was the only unfavorable prognostic factor. Median survival of patients with a tumor located in the body and/or tail (4 mo) was significantly worse than those with tumors located in the head (8 mo) (Table 2). Prognostic differences based on tumor location may relate to tumor size, as the size of a distal pancreatic tumor (7.3 ± 1.8 cm) was significantly larger than that of a proximal pancreatic tumor (4.7 ± 1.9 cm, P = 0.002). Age, gender, type of operative procedure, and lymph node metastasis were not significant prognostic factors.

Even though curative resection for adenosquamous carcinoma of the pancreas was performed in the 39 patients, prognosis remained poor because systemic metastases in the liver and peritoneal dissemination were the major sites of recurrence (Table 1). In addition, tumor recurrence occurred during the early stages of the postoperative period in a large number of patients. Yamaue et al. reported that it might be preferable not to perform a pancreatic resection if a pancreatic tumor is diagnosed as an adenosquamous carcinoma[ ²²]. Consensus of opinion regarding the surgical indication required for this type of tumor has not been reached yet. Elucidating a surgical treatment strategy based on the appropriate surgical indication is essential for improving the surgical outcome of adenosquamous carcinoma of the pancreas.

The results of this current study indicate that tumor location may be an important factor in determining the appropriate surgical indication. Namely, surgical resection may be better suited for proximal pancreatic tumors than for distal tumors because the proximal location of tumors was the only significant favorable prognostic factor found in this study. Furthermore, exploration of new radiation techniques and chemotherapeutic regimens using new drug agents such as gemcitabine may be required because conventional chemotherapy and radiotherapy treatments did not contribute to survival benefit. The incorporation of novel ‘molecularly targeted’ agents into therapy will also be required to improve surgical outcome.