Prognostic Value of KRAS Mutations in Relation to PDL1 Expression and Immunotherapy Treatment in Adenocarcinoma and Squamous Cell Carcinoma Patients: A Greek Cohort Study.

BACKGROUND: Factors that could predict which patients will benefit from Immune Checkpoint Inhibitors (ICIs) are not fully understood. This study aimed to investigate the prognostic value of KRAS biomarker in patients with advanced non-small cell lung cancer (NSCLC) in relation to clinical characteristics, treatment response and PDL1 expression. PATIENTS AND METHODS: The study included 100 patients with NSCLC who received immunotherapy with or without chemotherapy as 1st line treatment. In biopsy samples, the PDL1 biomarker expression rate and somatic mutations of KRAS gene were determined. RESULTS: The mean age of the patients was 67 ± 8 years. Patients were all male and 66% were found with adenocarcinoma whereas 34% with squamous cell carcinoma. The KRAS G12C mutation was found with the highest percentage (73%). In the Kaplan-Meier survival analysis, patients with PDL1 > 49% in combination with a negative KRAS result had a median overall survival of 40 months compared to patients with a positive KRAS result (9 months, p < 0.05). In addition, patients diagnosed with adenocarcinoma, PDL1 < 49% and negative KRAS result had a median overall survival of 39 months compared to patients with a positive result (28 months, p < 0.05). CONCLUSIONS: Our study suggests that the presence of KRAS mutations in advanced NSCLC patients has a poor prognostic value, regardless of their PDL1 expression values, after receiving immunotherapy as first-line treatment.

Follicular Cholangitis: A Rare Cause of Benign Biliary Stricture.

Introduction: The differential diagnosis of focal biliary strictures comprises both malignant and benign conditions. We report a rare case of follicular cholangitis presenting with segmental stricture of the left hepatic duct. Case description: An asymptomatic 59-year-old male with no past medical history presented with dilation of the left intrahepatic bile ducts revealed as an incidental finding on an abdominal ultrasound. Blood examinations showed only a slightly elevated γ-glutamyl transferase (γGT) value, while carbohydrate antigen 19-9 (Ca 19-9) and serum immunoglobulin G4 (IgG4) were within normal range. Abdominal computed tomography and magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP) scans revealed a high grade focal intrahepatic stricture of the left hepatic duct (FIHS type III) with proximal dilatation. Given that a diagnosis of cholangiocarcinoma could not be ruled out, the patient was referred for a left hepatectomy with regional lymph node dissection. Histological analysis showed a lymphoplasmacytic infiltration of the left hepatic duct with fibrosis and follicle formations in the submucosa, findings consistent with follicular cholangitis. The postoperative course was uneventful and there is no evidence of recurrence 8 months after the surgery. Discussion: The clinical and imaging presentation of follicular cholangitis is very similar to cholangiocarcinoma, rendering it a challenging diagnosis preoperatively. Conclusion: The approach to these cases should be primarily surgical. Even though it is very rare -- our report is the 13th case reported worldwide -- follicular cholangitis should be included in the differential diagnosis of focal biliary strictures. LEARNING POINTS: The differential diagnosis of biliary strictures comprises malignancies, like cholangiocarcinoma, as well as benign conditions.It is very challenging to distinguish between malignant and benign biliary strictures preoperatively, so the most reliable treatment approach to these cases is often surgical.Follicular cholangitis is a very rare condition and more data is needed to better understand disease pathophysiology, management, recurrence rates, and possible alternatives to surgery.

Pancreatic cystic neoplasms: Adherence to management recommendations and associated endosonographic cyst characteristics.

BACKGROUND: The purpose of this study is to assess patients' compliance to recommendations after evaluation of pancreatic cystic neoplasm (PCN) with EUS and investigate how the presence of "worrisome" characteristics including cyst's size, main pancreatic duct dilation and presence of mural nodules might affect the adherence rates of management recommendations. METHODS: We performed a retrospective cohort study of patients at a private tertiary hospital who were referred for evaluation with EUS over a 5-year period (2015-2019), after the diagnosis of pancreatic cystic neoplasm during radiological imaging. RESULTS: We included 111 patients (mean age 64.1 years, SD = 13.9) with PCN. After the EUS examination, 16 patients were referred for surgical resection, 4 patients needed no further follow up and 91 patients were recommended to follow imaging surveillance. In total, 70 (63.1%) subjects adhered to surveillance recommendations. In the group of subjects who adhered to surveillance, cyst size ≥3cm was found in 27 (38.6%) patients, main pancreatic duct diameter ≥5mm in 12 (17.1%) subjects and only 3 (4.3%) pancreatic cysts demonstrated mural nodules. However, none of the aforementioned cystic "worrisome features" was significantly correlated with increased adherence to follow up (p = 0.709, P = 0.642 and P = 0.630, respectively). CONCLUSIONS: Although the majority of patients with PCN adhered to given recommendations after EUS examination, the number of noncompliant subjects was noticeable. The presence of cystic "worrisome" features did not correlate with an increased compliance rate to suggested management plan. Further prospective studies are needed to elucidate the factors that may enhance patients' adherence.