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Purpose: Pancreatic adenosquamous carcinoma (PASC) is a subtype of pancreatic cancer with a poorer prognosis than pancreatic ductal carcinoma (PDAC). The pathogenesis of this histological subtype has not been fully explained due to its rarity. Methods: Of the 245 patients who underwent pancreatic resection for pancreatic cancer, six (2.3%) were diagnosed with PASC. They were retrospectively allocated to Group A (≥ 50% adenocarcinoma components) or Group S (≥ 50% squamous cell carcinoma components). Results: The six patients with PASC were all males between the ages of 63 and 77 years, with tumors of 12 to 52 mm in diameter. Tumors were located in the pancreatic head (n = 2) and the pancreatic tail (n = 4). Relative to Group A, all three patients in Group S had larger tumors diameters, ≥ 40 mm with invasion to other organs. Cancer-specific survival of Group S was worse than that of the PDAC group (median survival, 1.5 years vs. 4.1 years). All patients in Group A were alive at the end of follow-up. Recurrence-free survival of Group S was inferior to that of the PDAC group (median survival, 0.2 years vs. 1.8 years; Group A, not defined). Immunohistochemistry revealed the MIB-1 positivity rate in squamous cell carcinoma regions was 1.8 times higher than that in adenocarcinoma regions in the same specimens. Conclusion: In PASC patients, an increased proportion of squamous cell carcinoma components was associated with aggressive behavior and a worse prognosis. This was due to the high MIB-1 positivity rate of squamous cell carcinoma components. [ABSTRACT FROM AUTHOR]

Pancreatic adenosquamous carcinoma (PASC) is a rare subtype of pancreatic cancer (PC), with no established consensus on the optimal treatment for postoperative liver metastasis recurrence. We report a case of a 48-year-old male patient who underwent radical surgery and was pathologically diagnosed with microsatellite instability-high (MSI-H) PASC. The patient experienced liver metastasis recurrence following single-agent gemcitabine adjuvant chemotherapy. After one session of transarterial chemoembolization (TACE) with oxaliplatin, fluorouracil, and epirubicin, followed by six cycles of adjuvant chemotherapy with gemcitabine and nab-paclitaxel combined with sintilimab immunotherapy and bevacizumab targeted therapy, complete pathological regression of the liver metastasis was achieved. The patient has now reached a 24-month survival period and continues to be monitored at our center. This case illustrates the promise of the proposed treatment regimen, highlighting the significant potential of multimodality strategies in managing metastatic recurrence of MSI-H PASC.

Summary: Pancreatic cancer is associated with an oncogenic KRAS mutation in approximately 90% of cases. However, a non-negligible proportion of pancreatic cancer cases harbor wild-type KRAS (KRAS-WT). This study establishes genetically engineered mouse models that develop spontaneous pancreatic cancer in the context of KRAS-WT. The Trp53loxP/loxP;Smad4loxP/loxP;Pdx1-Cre (PPSSC) mouse model harbors KRAS-WT and loss of Trp53/Smad4. The Trp53loxP/loxP;Tgfbr2loxP/loxP;Pdx1-Cre (PPTTC) mouse model harbors KRAS-WT and loss of Trp53/Tgfbr2. We identify that either Trp53/Smad4 loss or Trp53/Tgfbr2 loss can induce spontaneous pancreatic tumor formation in the absence of an oncogenic KRAS mutation. The Trp53/Smad4 loss and Trp53/Tgfbr2 loss mouse models exhibit distinct pancreatic tumor histological features, as compared to oncogenic KRAS-driven mouse models. Furthermore, KRAS-WT pancreatic tumors with Trp53/Smad4 loss reveal unique histological features of pancreatic adenosquamous carcinoma (PASC). Single-cell RNA sequencing (scRNA-seq) analysis reveals the distinct tumor immune microenvironment landscape of KRAS-WT (PPSSC) pancreatic tumors as compared with that of oncogenic KRAS-driven pancreatic tumors.

A female in her 60s with vague abdominal symptoms was found to have a pancreatic mass in her CT scan. A core needle biopsy done endoscopically demonstrated a poorly differentiated adenocarcinoma. The patient completed nine cycles of neoadjuvant systemic mFOLFIRINOX. Repeat staging demonstrated a partial radiographic response. She underwent an open pylorus-preserving pancreatoduodenectomy with segmental superior mesenteric vein resection with primary reconstruction (ISGPS Type 3). The final pathology demonstrated a poorly differentiated adenosquamous carcinoma, R1 margin status. The case report demonstrates the effect of mFOLFIRINOX on pancreatic adenosquamous (PASC) carcinoma with a review of the microscopic pictures following the neoadjuvant therapy. It can be postulated that glandular component being the major component in a PASC has a good response to mFOLFIRINOX like that seen in pancreatic ductal adenocarcinoma with some presumed effect on the squamous component as well. From the above case report, we are proposing that mFOLFIRINOX can be an effective chemotherapy regime in the management of PASC. [ABSTRACT FROM AUTHOR]

Abstract Background The incidence and mortality of pancreatic adenosquamous carcinoma (PASC) have received little attention. The goal of our study was to explore the overall epidemiological trend of PASC at the population level. Methods The Surveillance, Epidemiology, and End Results database was used to collect the incidence, incidence‐based (IB) mortality, and patient details for PASC from 2000 to 2017. The Joinpoint regression tool was used to examine the trends in incidence and IB mortality. The Kaplan–Meier approach was used for survival analysis. Univariate and multivariate Cox regression analyses were used to determine the independent prognostic factors. Results We included 815 patients with PASC in the study. The incidence of PASC continuously increased from 2000 to 2017, with an annual percentage change (APC) of 3.9% (95% CI: 2.2%–5.7%, p

Background: The incidence and mortality of pancreatic adenosquamous carcinoma (PASC) have received little attention. The goal of our study was to explore the overall epidemiological trend of PASC at the population level. Methods: The Surveillance, Epidemiology, and End Results database was used to collect the incidence, incidence‐based (IB) mortality, and patient details for PASC from 2000 to 2017. The Joinpoint regression tool was used to examine the trends in incidence and IB mortality. The Kaplan–Meier approach was used for survival analysis. Univariate and multivariate Cox regression analyses were used to determine the independent prognostic factors. Results: We included 815 patients with PASC in the study. The incidence of PASC continuously increased from 2000 to 2017, with an annual percentage change (APC) of 3.9% (95% CI: 2.2%–5.7%, p < 0.05). IB mortality also increased continuously, with an APC of 5.0% (95% CI: 2.5%–7.6%, p < 0.05). Multivariate Cox regression analysis revealed that age, treatment, regional lymph node involvement, and tumor size were independent prognostic factors. Nomograms were created for PASC to predict 1‐ and 2‐year survival probabilities, respectively. Conclusions: The incidence and IB mortality of PASC had a sustained and rapid increase, indicating that the preventive and treatment measures for PASC were not ideal. We must identify the significance of this condition as soon as possible, and commit greater attention and resources to PASC research. [ABSTRACT FROM AUTHOR]

Pancreatic adenosquamous carcinoma (PASC) is a rare pathological subtype of pancreatic cancer (PC), with a worse prognosis than pancreatic ductal adenocarcinoma (PDAC). Due to its rarity, our knowledge of PASC and its biological characteristics are limited. In this review, we provide an overview of the histogenesis, genetic features, diagnosis, treatment, and prognosis of PASC, as well as pancreatic squamous cell carcinoma (PSCC). The information provided here may help to clarify our understanding of PASC and provide useful avenues for further research on this disease. [ABSTRACT FROM AUTHOR]

Pancreatic adenosquamous carcinoma (PASC) is a rare variant of pancreatic ductal adenocarcinoma (PDAC). The usual treatment for metastatic or recurrent PASC is systemic chemotherapy in accordance with the PDAC treatment strategy. This study aimed to investigate the efficacy of chemotherapy, especially the benefit of recent combination therapies, in patients with metastatic or recurrent PASC. We conducted a multicenter retrospective analysis of 116 patients with metastatic or recurrent PASC treated with first-line chemotherapy between April 2001 and December 2017 at 24 Japanese institutions. Combination chemotherapies included gemcitabine + nab-paclitaxel (GnP, n = 28), fluorouracil/leucovorin + irinotecan + oxaliplatin (FFX, n = 10), gemcitabine + S-1 (GS, n = 10), and others (n = 9). Monotherapies included gemcitabine (n = 51) and S-1 (n = 8). The median overall survival (OS) was 6.5, 7.3, and 4.3 months for the whole cohort, the combination therapy group, and the monotherapy group, respectively. Multivariate analysis indicated that combination therapy showed a better trend in OS than monotherapy (hazard ratio = 0.68; 95% confidence interval, 0.38–1.20). GnP or FFX were selected in 58.7% of patients after FFX was approved in Japan, and revealed a median OS, median progression-free survival, and objective response rate of 7.3 months, 2.8 months, and 26.9% in GnP and 7.2 months, 2.3 months, and 20.0% in FFX respectively. This study suggests that combination therapy may be more effective than monotherapy. GnP and FFX showed similar and clinically meaningful efficacy for patients with metastatic or recurrent PASC. [ABSTRACT FROM AUTHOR]

Purpose: Pancreatic adenosquamous carcinoma (PASC) is a subtype of pancreatic cancer with a poorer prognosis than pancreatic ductal carcinoma (PDAC). The pathogenesis of this histological subtype has not been fully explained due to its rarity., Methods: Of the 245 patients who underwent pancreatic resection for pancreatic cancer, six (2.3%) were diagnosed with PASC. They were retrospectively allocated to Group A (≥ 50% adenocarcinoma components) or Group S (≥ 50% squamous cell carcinoma components)., Results: The six patients with PASC were all males between the ages of 63 and 77 years, with tumors of 12 to 52 mm in diameter. Tumors were located in the pancreatic head (n = 2) and the pancreatic tail (n = 4). Relative to Group A, all three patients in Group S had larger tumors diameters, ≥ 40 mm with invasion to other organs. Cancer-specific survival of Group S was worse than that of the PDAC group (median survival, 1.5 years vs. 4.1 years). All patients in Group A were alive at the end of follow-up. Recurrence-free survival of Group S was inferior to that of the PDAC group (median survival, 0.2 years vs. 1.8 years; Group A, not defined). Immunohistochemistry revealed the MIB-1 positivity rate in squamous cell carcinoma regions was 1.8 times higher than that in adenocarcinoma regions in the same specimens., Conclusion: In PASC patients, an increased proportion of squamous cell carcinoma components was associated with aggressive behavior and a worse prognosis. This was due to the high MIB-1 positivity rate of squamous cell carcinoma components., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pancreatic adenosquamous carcinoma (ASPC) is a rare subtype of pancreatic cancer with lethal malignancy, and few studies have focused on the heterogeneity of ASPC. Here, we performed a single-cell sequencing procedure on pancreatic tumor tissue from an ASPC patient and a patient with high-grade intraductal papillary mucinous neoplasm (IPMN). Through the combined analysis of single-cell sequencing data from five pancreatic ductal adenocarcinoma (PDAC) patients, one IPMN patient, and one ASPC patient in a public database, we identified 11 main types of cells, including macrophages, B cells, cancer stem cells, ductal cells, fibroblasts, endo/stellate cells, neutrophils, acinar cells, T cells, natural killer (NK) cells, dendritic cells, and mast cells. Then, the different characteristics and differentiation paths of the immune microenvironment among IPMN, ASPC, and PDAC in macrophages, T cells, and cancer-associated fibroblasts (CAFs) were identified through multiple bioinformatics analyses. Two novel special cancer-associated fibroblasts were identified as nCAFs and imCAFs. Then, cancer cells in duct cells were identified using the infercnv software. Two ASPC-specific subgroups of cancer cells with squamous cell features were identified. Finally, the identified specific CAFs and cancer cells were mapped to TCGA-PAAD cohort through the cibersoftx software. All of these identified subgroups were calculated to have a significant prognostic value in pancreatic cancer patients. These findings will promote the clinical application of single-cell sequencing data of pancreatic cancer and deepen our understanding of ASPC. [ABSTRACT FROM AUTHOR]

Background: Pancreatic adenosquamous carcinoma (PASC) is a heterogeneous group of primary pancreatic cancers characterized by the coexistence of both glandular and squamous differentiation. The aim of this study was to develop nomograms to predict survival outcomes in patients with PASC. Methods: In this retrospective study, data on PASC, including clinicopathological characteristics, treatments, and survival outcomes, were collected from the SEER database between 2000 and 2018. The primary endpoints were overall survival (OS) and cancer-specific survival (CSS). The eligible patients were randomly divided into development cohort and validation cohort in a 7:3 ratio. The nomograms for prediction of OS and CSS were constructed by the development cohort using a LASSO-Cox regression model, respectively. Besides the model performance was internally and externally validated by examining the discrimination, calibration, and clinical utility. Results: A total of 632 consecutive patients who had been diagnosed with PASC were identified and randomly divided into development (n = 444) and validation (n = 188) cohorts. In the development cohort, the estimated median OS was 7.0 months (95% CI: 6.19–7.82) and the median CSS was 7.0 months (95% CI: 6.15–7.85). In the validation cohort, the estimated median OS was 6.0 months (95% CI: 4.46–7.54) and the median CSS was 7.0 months (95% CI: 6.25–7.75). LASSO-penalized COX regression analysis identified 8 independent predictors in the OS prediction model and 9 independent risk factors in the CSS prediction model: age at diagnosis, gender, year of diagnosis, tumor location, grade, stage, size, lymph node metastasis, combined metastasis, surgery, radiation, and chemotherapy. The Harrell C index and time-dependent AUCs manifested satisfactory discriminative capabilities of the models. Calibration plots showed that both models were well calibrated. Furthermore, decision curves indicated good utility of the nomograms for decision-making. Conclusion: Nomogram-based models to evaluate personalized OS and CSS in patients with PASC were developed and well validated. These easy-to-use tools will be useful methods to calculate individualized estimate of survival, assist in risk stratification, and aid clinical decision-making. [ABSTRACT FROM AUTHOR]

Abstract Background Pancreatic adenosquamous carcinoma has a poor prognosis, with limited prospective trial data to guide optimal treatment. The potential impact of drug metabolism on the treatment response of patients with pancreatic adenosquamous carcinoma is largely unknown. Case presentation We describe the case of a 51 year old woman with pancreatic adenosquamous carcinoma who, following surgical resection, experienced early disease relapse during adjuvant gemcitabine therapy. Paradoxically, this was followed by an exceptional response to capecitabine therapy lasting 34.6 months. Strong expression of cytidine deaminase was detected within the tumour. Conclusions This case study demonstrates that early relapse during adjuvant chemotherapy for pancreatic adenosquamous carcinoma may be compatible with a subsequent exceptional response to second line chemotherapy, an important observation given the poor overall prognosis of patients with adenosquamous carcinoma. Cytidine deaminase is predicted to inactivate gemcitabine and, conversely, catalyze capecitabine activation. We discuss strong intra-tumoural expression of cytidine deaminase as a potential mechanism to explain this patient’s disparate responses to gemcitabine and capecitabine therapy, and highlight the benefit that may be gained from considering similar determinants of response to chemotherapy in clinical practice.

BackgroundPancreatic adenosquamous carcinoma (PASC) is a heterogeneous group of primary pancreatic cancers characterized by the coexistence of both glandular and squamous differentiation. The aim of this study was to develop nomograms to predict survival outcomes in patients with PASC.MethodsIn this retrospective study, data on PASC, including clinicopathological characteristics, treatments, and survival outcomes, were collected from the SEER database between 2000 and 2018. The primary endpoints were overall survival (OS) and cancer-specific survival (CSS). The eligible patients were randomly divided into development cohort and validation cohort in a 7:3 ratio. The nomograms for prediction of OS and CSS were constructed by the development cohort using a LASSO-Cox regression model, respectively. Besides the model performance was internally and externally validated by examining the discrimination, calibration, and clinical utility.ResultsA total of 632 consecutive patients who had been diagnosed with PASC were identified and randomly divided into development (n = 444) and validation (n = 188) cohorts. In the development cohort, the estimated median OS was 7.0 months (95% CI: 6.19–7.82) and the median CSS was 7.0 months (95% CI: 6.15–7.85). In the validation cohort, the estimated median OS was 6.0 months (95% CI: 4.46–7.54) and the median CSS was 7.0 months (95% CI: 6.25–7.75). LASSO-penalized COX regression analysis identified 8 independent predictors in the OS prediction model and 9 independent risk factors in the CSS prediction model: age at diagnosis, gender, year of diagnosis, tumor location, grade, stage, size, lymph node metastasis, combined metastasis, surgery, radiation, and chemotherapy. The Harrell C index and time-dependent AUCs manifested satisfactory discriminative capabilities of the models. Calibration plots showed that both models were well calibrated. Furthermore, decision curves indicated good utility of the nomograms for decision-making.ConclusionNomogram-based models to evaluate personalized OS and CSS in patients with PASC were developed and well validated. These easy-to-use tools will be useful methods to calculate individualized estimate of survival, assist in risk stratification, and aid clinical decision-making.

Pancreatic cancer is associated with an oncogenic KRAS mutation in approximately 90% of cases. However, a non-negligible proportion of pancreatic cancer cases harbor wild-type KRAS (KRAS-WT). This study establishes genetically engineered mouse models that develop spontaneous pancreatic cancer in the context of KRAS-WT. The Trp53 loxP/loxP ;Smad4 loxP/loxP ;Pdx1-Cre (PPSSC) mouse model harbors KRAS-WT and loss of Trp53/Smad4. The Trp53 loxP/loxP ;Tgfbr2 loxP/loxP ;Pdx1-Cre (PPTTC) mouse model harbors KRAS-WT and loss of Trp53/Tgfbr2. We identify that either Trp53/Smad4 loss or Trp53/Tgfbr2 loss can induce spontaneous pancreatic tumor formation in the absence of an oncogenic KRAS mutation. The Trp53/Smad4 loss and Trp53/Tgfbr2 loss mouse models exhibit distinct pancreatic tumor histological features, as compared to oncogenic KRAS-driven mouse models. Furthermore, KRAS-WT pancreatic tumors with Trp53/Smad4 loss reveal unique histological features of pancreatic adenosquamous carcinoma (PASC). Single-cell RNA sequencing (scRNA-seq) analysis reveals the distinct tumor immune microenvironment landscape of KRAS-WT (PPSSC) pancreatic tumors as compared with that of oncogenic KRAS-driven pancreatic tumors., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

To assess the ability of the ring-enhancing sign and focal necrosis to diagnose adenosquamous carcinoma (ASqC), a variant of pancreatic ductal adenocarcinoma (PDAC), on MRI and CT. The following features of ASqC and conventional PDAC were evaluated on CT and MRI: tumor size, location, margins, borders (non-exophytic, exophytic), and T1 signal intensity. Two readers, blinded to histopathology results, rated their confidence in detecting ring-enhancement and focal necrosis (FN) on a 5-point Likert scale on both MRI and CT. Inter-reader agreement was assessed with Cohen's kappa (k). A total of 24 patients were included: eight patients with treatment naïve and histologically proven ASqC (six women, mean age: 63, range: 40–75) and 16 patients with PDAC (eight women, mean age: 67, range: 47–83). Statistically significant differences between ASqC and PDAC were seen in tumor size, location, presence of FN, and ring enhancement (p = 0.01–0.037). The readers were more confident in depicting the key differentiating feature ring-enhancement in ASqC on MRI compared to CT (confidence 1.71 ± 0.49 vs. 0.88 ± 0.35, p = 0.017) with moderate inter-reader agreement (k = 0.46 and 0.5, respectively). FN showed substantial inter-reader agreement on MR and moderate agreement on CT (k = 0.67 and 0.5, respectively). Compared to CT, MRI depicts ring-enhancement in ASqC with greater reader confidence and FN in ASqC with higher inter-reader agreement. The concurrent presence of these two imaging features should raise high suspicion for ASqC. • MRI depicts ring-enhancement with higher reader confidence when compared to CT. • There is greater inter-reader agreement in detecting the presence of focal necrosis on MRI relative to CT. • The presence of ring-enhancement and focal necrosis raises suspicion for pancreatic adenosquamous carcinoma. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Pancreatic cancer is one of the most lethal malignancies worldwide. Pancreatic adenosquamous carcinoma (PASC) is a rare histological type of pancreatic carcinoma with a poor prognosis. The median survival time after diagnosis is less than one year. It is believed that the pathogenesis of PASC is different from pancreatic adenocarcinoma. In this study, we tried to reveal the intrinsic gene mutations associated with PASC through whole exome sequencing. METHODS: Both cancerous and paracancerous tissues were collected from 12 pathologically diagnosed PASC patients. Their clinical characteristics were collected, and patient survival information was obtained through follow-up. The correlations between the mutations and clinical characteristics were analysed. RESULTS: Germline mutations were identified in MAP3K1 (9 cases), PDE4DIP (7), BCR (7), ALK (6), USP6 (5), AR (4), HLA-A (4), SPEN (4), KMT2D (3), NUTM2B (3), ZFHX3 (3), and MN1 (3), while somatic mutations were found in TP53 (5), KRAS (3), HRNR (3), and OBSCN (3). Peripheral tissue invasion was associated with somatic mutations in KRAS (P = 0.0339). Additionally, there were significant correlations between lymphatic metastasis and germline mutations in USP6 (P = 0.0228) and somatic mutations in OBSCN and HRNR (P = 0.0339). CONCLUSION: In conclusion, susceptibility genes including MAP3K1, PDE4DIP, and BCR are frequently found to be mutated in the germlines of PASC patients. Somatic mutations in KRAS, OBSCN, and HRNR and germline mutations in USP6 are related to tumour invasion and metastasis, reinforcing the necessity of translating these potential biomarkers into clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: To investigate 18F-FDG PET/CT feature of pancreatic adenosquamous carcinoma (PASC) in contrast with conventional pancreatic ductal adenocarcinoma (PDAC), and its correlation with pathological findings. Patients and methods: Patients with PASC or PDAC confirmed by surgical pathology, who underwent FDG PET/CT scanning before surgical resection, were retrospectively studied. PASC group and conventional PDAC group included 13 and 104 patients, respectively. Delayed phase of PET/CT scanning was performed in 12 patients with PASC and 99 with PDAC. Maximum standardized value (SUVmax) was measured, and the mean retention index (RI) was calculated by ([PET120min SUVmax]–[PET 60min SUVmax]) ÷ PET 60min SUVmax × 100%. Results: On PET/CT, all lesions of PASC group showed intense FDG uptake, and the SUVmax were significantly higher than the lesions of conventional PDAC group both on the early [10.43 ± 5.10 (4.37–24.00) vs. 7.31 ± 3.86 (1.93–21.08), P = 0.011] and delayed phase [13.29 ± 6.04 (5.72–28.16) vs. 8.84 ± 5.14 (1.92–27.58), P = 0.005]. On the delayed phase, all lesions of PASC group had increased SUVmax with positive RI value (27.04% ± 8.87%, 7.14–39.27%). For conventional PDAC group, 81 lesions had increased SUVmax with positive RI value (27.25% ± 19.10%, 1.09–104.49%), while eighteen (18.18%) lesions of PDAC group had slightly decreased SUVmax, and their RI value were negative (− 11.35% ± 13.50%, − 43.17 to − 0.14%). The proliferative index (Ki-67) of lesions of PASC group was positively correlated with both the early (P = 0.034, r = 0.671) and delayed SUVmax (P = 0.019, r = 0.721). The RI value of lesions with adjacent organ invasion in PASC group was significantly higher than those without invasion (33.25% ± 4.92% vs. 20.83% ± 7.49%, P = 0.007). Conclusion: PASC has more intense FDG uptake than conventional PDAC both on early and delayed phase. RI value of PASC was positive. Negative RI value may be helpful for differentiating PDAC from PASC. SUVmax and RI value may be helpful for prediction of its malignancy and invasion. [ABSTRACT FROM AUTHOR]

Background: Pancreatic adenosquamous carcinoma has a poor prognosis, with limited prospective trial data to guide optimal treatment. The potential impact of drug metabolism on the treatment response of patients with pancreatic adenosquamous carcinoma is largely unknown.Case Presentation: We describe the case of a 51 year old woman with pancreatic adenosquamous carcinoma who, following surgical resection, experienced early disease relapse during adjuvant gemcitabine therapy. Paradoxically, this was followed by an exceptional response to capecitabine therapy lasting 34.6 months. Strong expression of cytidine deaminase was detected within the tumour.Conclusions: This case study demonstrates that early relapse during adjuvant chemotherapy for pancreatic adenosquamous carcinoma may be compatible with a subsequent exceptional response to second line chemotherapy, an important observation given the poor overall prognosis of patients with adenosquamous carcinoma. Cytidine deaminase is predicted to inactivate gemcitabine and, conversely, catalyze capecitabine activation. We discuss strong intra-tumoural expression of cytidine deaminase as a potential mechanism to explain this patient's disparate responses to gemcitabine and capecitabine therapy, and highlight the benefit that may be gained from considering similar determinants of response to chemotherapy in clinical practice. [ABSTRACT FROM AUTHOR]

Highlights • These showed positive PD-L1 expression in the squamous cell carcinoma component, and the TPS indicated a high expression. • In contrast, only one case (3%) was positive for PD-L1 in PDACs. • On the other hand, PD-L1 expression in EUS-FNA samples was seldom observed. • PD-L1/PD-1 pathway inhibition may be a treatment strategy for PASC, although the expression in the whole tumor was low. Abstract Aim We examined the programmed death-ligand 1 (PD-L1) expression in surgically resected pancreatic adenosquamous carcinoma (PASC) samples. Furthermore, the detection rate was also assessed using biopsy cases obtained from endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Methods Fifteen cases of PASC (six resected and nine EUS-FNA biopsied) from the Kurume University Hospital between 2009 and 2016 were used for the evaluation of PD-L1 expression. As a control group, 34 cases of pancreatic ductal adenocarcinomas (PDACs) were selected. To compare the positivity and intensity of PD-L1, two types of clones (SP263, E1L3N) were examined for immunostaining. Only the membrane expression of PD-L1 was regarded as positive. The PD-L1 expressions in the squamous cell carcinoma component (SCc), adenocarcinoma component (ACc), and immune cells were assessed separately. The ratio of PD-L1 expression was calculated by counting the positive tumor cells, and tumor proportion score (TPS) was applied (TPS; Null < 1%, low expression; 1 ≤ TPS ≤ 49% and high expression; ≥ 50%). Results PD-L1 expression was observed in five surgical PASC samples (83%). This shows that SCc presented a high expression in these cases. However, the overall TPS indicated a low expression. In contrast, only one case (3%) was positive for PD-L1 in PDACs, and the TPS indicated a low expression. No differences in PD-L1 expression were observed between the two clones, SP263 and E1L3N. High PD-L1 expression in the EUS-FNA sample was found in only one case (11%). Discussion Although assessment using the tumor cells of PASC samples obtained from EUS-FNA was difficult, this study suggests the selective expression of PD-L1 in the SCc of PASC. Furthermore, it was considered that immune checkpoint inhibitors could provide therapeutic effects selectively on the SCc for the entire range of TPSs, though the PD-L1 expression was low. [ABSTRACT FROM AUTHOR]

Background/objectives: Pancreatic adenosquamous carcinoma (PASC) is a rare variant of pancreatic ductal adenocarcinoma (PDAC). The usual treatment for metastatic or recurrent PASC is systemic chemotherapy in accordance with the PDAC treatment strategy. This study aimed to investigate the efficacy of chemotherapy, especially the benefit of recent combination therapies, in patients with metastatic or recurrent PASC., Methods: We conducted a multicenter retrospective analysis of 116 patients with metastatic or recurrent PASC treated with first-line chemotherapy between April 2001 and December 2017 at 24 Japanese institutions., Results: Combination chemotherapies included gemcitabine + nab-paclitaxel (GnP, n = 28), fluorouracil/leucovorin + irinotecan + oxaliplatin (FFX, n = 10), gemcitabine + S-1 (GS, n = 10), and others (n = 9). Monotherapies included gemcitabine (n = 51) and S-1 (n = 8). The median overall survival (OS) was 6.5, 7.3, and 4.3 months for the whole cohort, the combination therapy group, and the monotherapy group, respectively. Multivariate analysis indicated that combination therapy showed a better trend in OS than monotherapy (hazard ratio = 0.68; 95% confidence interval, 0.38-1.20). GnP or FFX were selected in 58.7% of patients after FFX was approved in Japan, and revealed a median OS, median progression-free survival, and objective response rate of 7.3 months, 2.8 months, and 26.9% in GnP and 7.2 months, 2.3 months, and 20.0% in FFX respectively., Conclusions: This study suggests that combination therapy may be more effective than monotherapy. GnP and FFX showed similar and clinically meaningful efficacy for patients with metastatic or recurrent PASC., (Copyright © 2022 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Pancreatic adenosquamous carcinoma (ASPC) is a rare subtype of pancreatic cancer with lethal malignancy, and few studies have focused on the heterogeneity of ASPC. Here, we performed a single-cell sequencing procedure on pancreatic tumor tissue from an ASPC patient and a patient with high-grade intraductal papillary mucinous neoplasm (IPMN). Through the combined analysis of single-cell sequencing data from five pancreatic ductal adenocarcinoma (PDAC) patients, one IPMN patient, and one ASPC patient in a public database, we identified 11 main types of cells, including macrophages, B cells, cancer stem cells, ductal cells, fibroblasts, endo/stellate cells, neutrophils, acinar cells, T cells, natural killer (NK) cells, dendritic cells, and mast cells. Then, the different characteristics and differentiation paths of the immune microenvironment among IPMN, ASPC, and PDAC in macrophages, T cells, and cancer-associated fibroblasts (CAFs) were identified through multiple bioinformatics analyses. Two novel special cancer-associated fibroblasts were identified as nCAFs and imCAFs. Then, cancer cells in duct cells were identified using the infercnv software. Two ASPC-specific subgroups of cancer cells with squamous cell features were identified. Finally, the identified specific CAFs and cancer cells were mapped to TCGA-PAAD cohort through the cibersoftx software. All of these identified subgroups were calculated to have a significant prognostic value in pancreatic cancer patients. These findings will promote the clinical application of single-cell sequencing data of pancreatic cancer and deepen our understanding of ASPC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Wu, Pan, Wang, Wang, He, Zhang, Cui, Song, Li, Shi, Huang and Xu.)

Summary: Pancreatic adenosquamous carcinoma is a rare morphological variant of pancreatic adenocarcinoma with an especially poor prognosis. The purpose of this study is to identify clinicopathologic features associated with prognosis, assess whether the percentage of squamous differentiation in pancreatic adenosquamous carcinoma is associated with an inferior prognosis, and examine the impact of adjuvant chemoradiation therapy on overall survival. Forty-five (1.2%) of 3651 patients who underwent pancreatic resection at the Johns Hopkins Hospital, Baltimore, MD, between 1986 and 2007 were identified with adenocarcinoma of the pancreas with any squamous differentiation. All pathologic specimens were re-reviewed. Statistical analyses were performed on the 38 patients amenable to adjuvant chemoradiation therapy for whom clinical outcome data could be obtained. Median age was 68 years (61% male). Sixty-one percent underwent pancreaticoduodenectomy. Median tumor size was 5.0 cm. Seventy-six percent of carcinomas were node positive, 37% were margin-positive resections, and 68% had 30% or more squamous differentiation. Median overall survival of the pancreatic adenosquamous carcinoma cohort was 10.9 months (range, 2.1-140.6 months; 95% confidence interval, 8.2-12.5 months). Adjuvant chemoradiation therapy was associated with superior overall survival in patients with pancreatic adenosquamous carcinoma (P = .005). Adjuvant chemoradiation therapy was associated with improved survival in patients with tumors 3 cm or larger and vascular or perineural invasion (P = .02, .03, .02, respectively). The proportion of squamous differentiation was not associated with median overall survival (<30% versus ≥30%, P = .82). Survival after pancreatic resection of pancreatic adenosquamous carcinoma is poor. Treatment with adjuvant chemoradiation therapy is associated with improved survival. The proportion of squamous differentiation in resected pancreatic adenosquamous carcinoma specimens does not appear to impact overall survival. [Copyright &y& Elsevier]

A 51-year-old woman with an unresectable pancreatic tumor that was histologically diagnosed as an adenosquamous carcinoma underwent chemoradiotherapy with 5-fluourouracil (FU) and low-dose cisplatin (low-dose FP). Because we recognized a partial response to the chemoradiotherapy, we subsequently administered combined chemotherapy with S-1 and cisplatin. After one course of this combined chemotherapy, the tumor was further reduced in size and became difficult to discern on abdominal computed tomography (CT). We have continued to administer the S-1 and cisplatin combined chemotherapy, and the patient is still alive. After 20 months of treatment, the tumor has not recurred (as assessed by abdominal CT). Additionally, we have not seen elevation of tumor markers. This report presents the successful use of chemoradiotherapy with low-dose FP and additional combined chemotherapy with S-1 and cisplatin for unresectable pancreatic adenosquamous carcinoma. [ABSTRACT FROM AUTHOR]