Combination of mutations in genes controlling DNA repair and high mutational load plays a prognostic role in pancreatic ductal adenocarcinoma (PDAC): a retrospective real-life study in Sardinian population.

BACKGROUND: Patients with pancreatic ductal adenocarcinoma (PDCA) carrying impaired mismatch repair mechanisms seem to have an outcome advantage under treatment with conventional chemotherapy, whereas the role for the tumor mutation burden on prognosis is controversial. In this study, we evaluated the prognostic role of the mutated genes involved in genome damage repair in a real-life series of PDAC patients in a hospital-based manner from the main Institution deputed to surgically treat such a disease in North Sardinia. METHODS: A cohort of fifty-five consecutive PDAC patients with potentially resectable/border line resectable PDAC (stage IIB-III) or oligometastatic disease (stage IV) and tumor tissue availability underwent next-generation sequencing (NGS)-based analysis using a panel containing driver oncogenes and tumor suppressor genes as well as genes controlling DNA repair mechanisms. RESULTS: Genes involved in the both genome damage repair (DR) and DNA mismatch repair (MMR) were found mutated in 17 (31%) and 15 (27%) cases, respectively. One fourth of PDAC cases (14/55; 25.5%) carried tumors presenting a combination of mutations in repair genes (DR and MMR) and the highest mutation load rates (MLR-H). After correction for confounders (surgery, adjuvant therapy, stage T, and metastasis), multivariate Cox regression analysis indicated that mutations in DR genes (HR = 3.0126, 95% CI 1.0707 to 8.4764, p = 0.0367) and the MLR (HR = 1.0018, 95%CI 1.0005 to 1.0032, p = 0.009) were significantly related to worse survival. CONCLUSIONS: The combination of mutated repair genes and MLR-H, which is associated with a worse survival in our series of PDAC patients treated with conventional chemotherapy protocols, might become a predictive biomarker of response to immunotherapy in addition to its prognostic role in predicting survival.

Prophylactic central neck lymphadenectomy in high risk patients with T1 or T2 papillary thyroid carcinoma: is it useful?

INTRODUCTION: The aim of this study was to evaluate the role of prophylactic central neck lymph node dissection in high risk patients with T1 or T2 papillary thyroid cancer. MATERIALS AND METHODS: Seventy-three patients who had undergone total thyroidectomy for papillary thyroid cancer smaller than 4cm, without cervical lymphadenopathy and prophylactic central neck lymph node dissection were included. Patients were divided in two groups: low risk patients (group A) and high risk patients (group B). High risk patients were considered those with at least one of the followings: male sex, age ≥ 45 years, and extracapsular or extrathyroid disease. Statistical significant differences in persistent disease, recurrence and complications rates between the two groups were studied. RESULTS: Persistence of the disease was observed in one case in group A (5.9%) and in three cases in group B (5.4%), while thyroid cancer recurrence was registered in zero and two (3.6%) cases respectively. One single case (5.9%) of transitory recurrent laryngeal nerve damage was reported in group A and none in group B, while transitory hypoparathyroidism was observed in 2 (3.6%) patients in group A, and 1 (1.8%) patient in group B. Permanent recurrent laryngeal nerve damage was observed in one patient in group A, while permanent hypoparathyroidism was registered in one case in group B. Logistic regression evidenced that multifocality was the only risk factor significantly related to persistence of disease and recurrence. CONCLUSIONS: Our results suggests that prophylactic central neck lymph node dissection can be safely avoided in patients with T1 or T2 papillary thyroid cancer, except in those with multifocal disease. KEY WORDS: Cancer, Central neck, Cervical, Lymphadenectomy, Lymph nodes, Papillary carcinoma, Thyroid.

Preneoplastic and neoplastic gallbladder lesions occasionally discovered after elective videocholecystectomy for benign disease. A single centre experience and literature review.

INTRODUCTION: In this study we retrospectively reviewed data on 311 consecutive elective cholecystectomies, performed for benign disease (cholelithiasis, cholecystitis) in our institution in the last six years, in order to determine the frequency of unexpected gallbladder pre-neoplastic and neoplastic lesions and analyse their clinical, diagnostic and therapeutic features. MATERIALS AND METHODS: Three hundred eleven consecutive patients underwent elective cholecystectomy for benign gallbladder disease in our Institution from January 2005 to March 2011. Clinical records and histo-pathological reports were reviewed in order to detect occult gallbladder pre-neoplastic and neoplastic lesions and describe the clinical, diagnostic and therapeutic findings. Eight patients were excluded for lacking of important clinical data. RESULTS: Out of 303 patients examined, 26 (8.6%) were found to be affected by a concomitant pre-neoplastic or neoplastic lesion. Ten (3.3%) were found to have a benign lesion, 13 (4.3%) a dysplasia of the gallbladder epithelium and 3 (1%) a gallbladder adenocarcinoma. DISCUSSION: Dysplasia was found in 4,3% of cases and surgery represents the interruption of an eventual malignant evolution. Adenomiomatosis and adenomas represent the most frequent benign occult lesions discovered; surgery is the definitive cure for such lesions. Occult gallbladder adenocarcinoma was detected in 1% of cases in absence of any preoperative clinical or radiological suspect. Cholecystectomy is curative in stage T1a disease, while a re-resection is necessary for more invasive non metastatic disease.