Combination immunohistochemistry for CK5/6, p63, GATA6, and HNF4a predicts clinical outcome in treatment-naïve pancreatic ductal adenocarcinoma.

Although sequence-based studies show that basal-like features lead to worse prognosis and chemotherapy-resistance compared to the classical subtype in advanced pancreatic ductal adenocarcinoma (PDAC), a surrogate biomarker distinguishing between these subtypes in routine diagnostic practice remains to be identified. We aimed to evaluate the utility of immunohistochemistry (IHC) expression subtypes generated by unsupervised hierarchical clustering based on staining scores of four markers (CK5/6, p63, GATA6, HNF4a) applied to endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) materials. EUS-FNAB materials taken from 190 treatment-naïve advanced PDAC patients were analyzed, and three IHC patterns were established (Classical, Transitional, and Basal-like pattern). Basal-like pattern (high co-expression of CK5/6 and p63 with low expression of GATA6 and HNF4a) was significantly associated with squamous differentiation histology (p < 0.001) and demonstrated the worst overall survival among our cohort (p = 0.004). IHC expression subtype (Transitional, Basal vs Classical) was an independent poor prognosticator in multivariate analysis [HR 1.58 (95% CI 1.01-2.38), p = 0.047]. Furthermore, CK5/6 expression was an independent poor prognostic factor in histological glandular type PDAC [HR 2.82 (95% CI 1.31-6.08), p = 0.008]. Our results suggest that IHC expression patterns successfully predict molecular features indicative of the Basal-like subgroup in advanced PDAC. These results provide the basis for appropriate stratification for therapeutic selection and prognostic estimation of advanced PDAC in a simplified manner.

A Prospective Study of Neoadjuvant Gemcitabine Plus Nab-paclitaxel in Patients with Borderline-resectable Pancreatic Cancer.

Objectives Neoadjuvant therapy followed by radical resection improves the borderline-resectable pancreatic cancer (BRPC) prognosis; however, the optimal therapeutic regimen remains unclear. Gemcitabine plus nab-paclitaxel (GnP) showed a high anti-tumor effect in primary lesions in a prospective study for metastatic disease. However, evidence concerning its feasibility is still lacking in patients with BRPC. We therefore evaluated the tolerability of neoadjuvant GnP (NAC-GnP) for BRPC. Methods This single-center prospective study evaluated 10 patients with BRPC who were treated with two cycles of NAC-GnP. The primary endpoint was feasibility for NAC-GnP. Treatment feasibility was defined as a successful outcome in at least eight patients. Results Ten patients who had BRPC in contact with the celiac artery (n=5), superior mesenteric artery (n=3), or hepatic artery (n=2) were enrolled. The median age was 75 (range, 40-82) years old. Grade 3 anorexia and grade 2 pneumonia occurred in one patient each, so treatment was feasible in eight patients. The median primary tumor reduction and response rates were 33% (range, 0-68%) and 60%, respectively. Six of eight patients who had abnormal CA19-9 levels at the time of enrolment showed a decrease in CA19-9 levels, with a median decrease of 72%. Five patients underwent radical resection, including R0 resection in four. Postoperative grade IIIa Clavien-Dindo complications occurred in one patient (upper gastrointestinal bleeding and pancreatic fistula). Conclusion Two-cycle NAC-GnP is a feasible treatment for patients with BRPC. Further studies on NAC-GnP in patients with BRPC are warranted.

Successful treatment of mediastinal pancreatic pseudocyst and pancreatic pleural effusion with endoscopic pancreatic duct drainage: A case report.

An 81-year-old man with chronic pancreatitis was being treated with a protease inhibitor. He developed an acute exacerbation of chronic pancreatitis and dyspnea. Contrast-enhanced computed tomography showed disruption of the main pancreatic duct, a cystic lesion connecting the mediastinum to the main pancreatic duct, and left pleural effusion. We diagnosed a pancreatic pseudocyst, mediastinal pancreatic pseudocyst, and pancreatic pleural effusion. Endoscopic retrograde pancreatography showed leakage of contrast medium from the pancreatic body; furthermore, a cystic cavity extending to the mediastinum through a pancreatic duct fistula was visualized. An endoscopic transpapillary nasopancreatic drainage tube was placed in the cystic cavity. Computed tomography showed that the mediastinal pseudocyst and pleural effusion had disappeared. Endoscopic transpapillary pancreatic duct drainage may be useful when a connection between the main pancreatic duct and a mediastinal pseudocyst is confirmed by imaging.

Effectiveness of introducing a 20-gauge core biopsy needle with a core trap in EUS-FNA/B for diagnosing pancreatic cancer.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is a standard method for pathological diagnosis of pancreatic solid lesions. The EchoTip ProCore 20G® (PC20), a 20-gauge biopsy needle with a forward-bevel core trap, has been available in Japan since 2015. METHODS: We compared the efficacy of the PC20 with that of the EchoTip ProCore 22G® (PC22) and Acquire 22G® (AC22) in EUS-FNA/B for diagnosing pancreatic cancer. This retrospective study included 191 patients with pancreatic cancer who underwent EUS-FNA/B using the PC20, PC22, or AC22 at our facility from April 2013 to October 2019. We investigated the patients' clinical characteristics and the diagnostic accuracy and safety of each needle. RESULTS: A sufficient stroke length of puncture was secured in all patients. The maximum length under EUS was shorter with the AC22 (22.1 ± 2.2 mm) than PC20 (30.6 ± 0.7 mm, p < 0.01) and PC22 (30.3 ± 0.8 mm, p < 0.01). The histological accuracy was 96.4% with the PC20 but only 58.8% with the PC22 (adjusted p (p-adj) < 0.0001) and 75.0% with the AC22 (p-adj = 0.06). The diagnostic accuracy of the combination of histology and cytology was 96.4% with the PC20, while it was 72.1% with the PC22 (p-adj < 0.0001) and 91.7% with the AC22 (p-adj > 0.99). One patient (0.9%) in the PC20 group developed mild pancreatitis, but no adverse events occurred with the other needles. CONCLUSIONS: The PC20 showed better diagnostic capability than the PC22. The diagnostic efficacy was similar between the PC20 and AC22. The high histological accuracy of the PC20 could be advantageous for lesions in which histological assessment is critical.

Utilization of a new technology of 3D biliary CT for ERCP-related procedures: a case report.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is still performed using two-dimensional (2D) X-ray images. The success rate and risk of complications are considered operator-dependent. We explored performing an ERCP-related procedure with 3D-computed tomography (CT) biliary imaging for preoperative simulation and intraoperative reference in a patient with malignant biliary obstruction. CASE PRESENTATION: The patient was a 66-year-old man who underwent rectal resection and postoperative chemotherapy for rectal cancer. A liver metastasis caused obstructive jaundice and acute cholangitis, necessitating emergency hospitalization. A 3.5 cm mass in the hilar region of the biliary tree caused type IV biliary obstruction according to the Bismuth-Corlette classification of hilar cholangiocarcinoma. ERCP and biliary drainage were performed repeatedly, but had no effect. Given that selective bile duct drainage had proven extremely difficult with the conventional procedures, three-dimensional (3D) images were created from preoperative CT image data using a 3D image reconstruction system (SYNAPSE VINCENT version 5, FUJIFILM Corporation, Tokyo, Japan). Using the 3D images for preoperative planning and intraoperative reference, biliary drainage and stent placement were successfully performed without complications. Postoperatively, the patient had no further cholangitis or need for stent replacement up to his death. CONCLUSIONS: We report the first case of an ERCP-related procedure with 3D biliary imaging for preoperative simulation and intraoperative reference in a patient with malignant biliary obstruction. The 3D image reconstruction is useful for preoperative planning and could contribute to an increased success rate, decreased complications, a shorter operation time, and reduced radiation exposure to the operator.

Pharmacokinetic-pharmacodynamic comparison of ceftriaxone regimens in acute cholangitis.

The most important factors determining the prognosis of patients with acute cholangitis (AC) are prompt biliary drainage and appropriate choice of antibiotics. This study was performed to evaluate whether dividing the number of doses based on the PK-PD theory contributes to better clinical outcome in the management of acute cholangitis. We measured ceftriaxone levels in blood and bile in 21 cases diagnosed with moderate-to-severe AC. Eleven cases were administered 2 g of ceftriaxone once-daily (group A) and 10 cases were given 1 g of ceftriaxone twice-daily (group B). The theoretical effect of ceftriaxone was evaluated by pharmacokinetic-pharmacodynamic (PK-PD) parameters. Clinical efficacy was evaluated by body temperature, white blood cell count and serum levels of C-reactive protein. Minimum level of ceftriaxone in serum (in mg/L) in groups A and B at 24 h after the first dose was 9.1 and 9.2, whereas that in bile was 2.9 and 2.5, respectively. The minimum inhibitory concentration (MIC) of ceftriaxone for all isolated bacteria was below the minimum serum and biliary concentration of ceftriaxone 24 h after the first administration (except for Enterococcus species). The MIC for isolated bacterial strains was <16 mg/L, which is the PK-PD breakpoint for ceftriaxone at 2 g/day. Both regimens showed clinical efficacy and did not contradict the effect predicted based on PK-PD.