Droplet digital polymerase chain reaction detection of KRAS mutations in pancreatic FNA samples: Technical and practical aspects for routine clinical implementation.

BACKGROUND: Pancreatic adenocarcinoma (PDAC) is associated with a 5-year survival rate of less than 6%, and current treatments have limited efficacy. The diagnosis of PDAC is mainly based on a cytologic analysis of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) samples. However, the collected specimens may prove noncontributory in a significant number of cases, delaying patient management and treatment. The combination of EUS-FNA sample examination and KRAS mutation detection can improve the sensitivity for diagnosis. In this context, the material used for molecular analysis may condition performance. METHODS: The authors prospectively compared the performance of cytologic analysis combined with a KRAS droplet digital polymerase chain reaction (ddPCR) assay for PDAC diagnosis using either conventional formalin-fixed, paraffin-embedded cytologic samples or needle-rinsing fluids. RESULTS: Molecular testing of formalin-fixed, paraffin-embedded cytologic samples was easier to set up, but the authors observed that the treatment of preanalytic samples, in particular the fixation process, drastically reduced ddPCR sensitivity, increasing the risk of false-negative results. Conversely, the analysis of dedicated, fresh needle-rinsing fluid samples appeared to be ideal for ddPCR analysis; it had greater sensitivity and was easily to implement in clinical use. In particular, fluid collection by the endoscopist, transportation to the laboratory, and subsequent freezing did not affect DNA quantity or quality. Moreover, the addition of KRAS mutation detection to cytologic examination improved diagnosis performance, regardless of the source of the sample. CONCLUSIONS: Considering all of these aspects, the authors propose the use of an integrated flowchart for the KRAS molecular testing of EUS-FNA samples in clinical routine.

Long-term outcomes after surgical resection of pancreatic metastases from renal Clear-cell carcinoma.

BACKGROUND: Clear-cell renal cell carcinoma frequently metastasizes to the pancreas (PMRCC). The management of such metastases remains controversial due to their frequent multifocality and indolent evolution. METHODS: This study describes the surgical management of these lesions and their long-term oncological outcomes. The study included patients who underwent pancreatic resection of PMRCC at Bordeaux University Hospital between June 2005 and March 2022. Morbidity and mortality were assessed at 90 days. Overall survival (OS) and disease-free (DFS) survival were assessed at 5 years. RESULTS: Forty-two patients underwent pancreatic resection for PMRCC, including 18 (42.8 %) total pancreatectomies. The median time from nephrectomy to the diagnosis of PMRCC was 121 (range: 6-400) months. Lesions were multiple in 19/42 (45.2 %) patients. Ten (23.8 %) patients suffered a severe complication (Dindo-Clavien classification ≥ IIIA by D90), including one patient who died postoperatively. The median follow-up was 76 months. The R0 rate was 100 %. The OS and DFS rates were 92.8 % and 29.6 %, respectively, at 5 years. CONCLUSION: Pancreatic resection for PMRCC provides long-term oncological control despite a high recurrence rate.

Total Versus Subtotal Gastrectomy for Distal Gastric Poorly Cohesive Carcinoma.

BACKGROUND: Gastric poorly cohesive carcinoma (PCC) in advanced stages has a poor prognosis. Total gastrectomy (TG) remains the common treatment for distal gastric PCC, but subtotal gastrectomy (SG) may improve quality of life without compromising outcomes. Currently, no clear recommendation on the best surgical strategy for distal PCC is available. This study aimed to compare overall survival (OS) and disease-free survival (DFS) at 5 years for patients with antropyloric PCC treated by total versus subtotal gastrectomy. METHODS: A large retrospective European multicenter cohort study analyzed 2131 patients treated for gastric cancer between 2007 and 2017 by members of the French Association of Surgery (AFC). The study compared a group of patients who underwent TG with a group who underwent SG for antropyloric PCC. The primary outcomes were 5 year OS and DFS. RESULTS: The study enrolled 269 patients: 140 (52.0%) in the TG group and 129 (48.0%) in the SG group. The baseline characteristics and pTNM stage were similar between the two groups. According to Dindo-Claven classification, the patients treated with TG had more postoperative complications than the patients treated with SG (p < 0.001): grades I to IIIa (77.1% vs 59.5%) and grades IIIb to IVb (14.4% vs 9.0%). No difference in 5-year OS was observed between TG (53.8%; 95 % confidence interval [CI], 43.2-63.3%) and SG (53.0%; 95% CI, 41.4-63.3%) (hazard ratio [HR], 0.94; 95% CI, 0.68-1.29). The same was observed for 5-year DFS: TG (46.0%; 95% CI, 35.9-55.5%) versus SG (45.3%; 95% CI, 34.3-55.6%) (HR, 0.97; 95% CI, 0.70-1.34). CONCLUSIONS: At 5 years, SG was not associated with worse OS and DFS than TG for distal PCC. Surgical morbidity was higher after TG. Subtotal gastrectomy is a valuable option for distal PCC gastric cancer.

Feasibility study of a Response Surveillance Program in locally advanced mid and low rectal cancer to increase organ preservation.

BACKGROUND: Assessment of tumor response in rectal cancer after neoadjuvant treatment by MRI (Tumour Regression Grade, TRG 1-5) is well standardized. The overall timing and method of defining complete response (cCR) remain controversial. The aim of this work was to evaluate the feasibility of a defined Response Surveillance Program (RSP) to increase organ preservation for locally advanced rectal cancer after neoadjuvant treatment. METHODS: A standardized program of clinical (CR), radiological (RR) and metabolic (MR) assessment of tumor response is defined over a 6 month period from completion of NACRT with formal assessment performed every 2 months (M). Patients with TRG1-3 at M2 and TRG1-2 at M4 continue in the program up to M6 assessment. Patients managed with this protocol from 2016 to 2020 were analyzed. The primary endpoint was rectal preservation rate. Secondary endpoints included disease-free survival and overall survival at 3 years. RESULT: 314 potentially suitable patients were enrolled in the RSP and 50 patients completed the six month program and were successfully enrolled into watch and wait. Fourteen (28%) were T2 tumor stage, 27 (54%) T3 and nine (18%) were T4. During watch and wait, patients with locoregional recurrence (n = 11) were treated with local excision (n = 3), endocavitary radiotherapy (n = 1), TME (n = 5) and APR (n = 2). With a median follow-up of 32 months, the rectal preservation rate was 88%, with a 3-year disease-free survival of 67% and an overall survival of 98%. CONCLUSION: This study validates the feasibility of the practical implementation of a Response Surveillance Program to increase organ preservation rates without compromising oncological outcomes in rectal cancer.

Laparoscopic fundoplication for para-oesophageal hernia repair improves respiratory function in patients with dyspnoea: a prospective cohort study.

BACKGROUND: Dyspnoea in patients with a para-oesophageal hernia (PEH) occurs in 7% to 32% of cases and is very disabling, especially in elderly patients, and its origin is not well defined. The present study aims to assess the impact of PEH repair on dyspnoea and respiratory function. METHODS: From January 2019 to May 2021, all consecutive patients scheduled for PEH repair presenting with a modified Medical Research Council (mMRC) score ≥ 2 for dyspnoea were included. Before and 2 months after surgery, dyspnoea was assessed by both the dyspnoea visual analogue scale (DVAS) and the mMRC scale, as well as pulmonary function tests (PFTs) by plethysmography. RESULTS: All 43 patients that were included had pre- and postoperative dyspnoea assessments and PFTs. Median age was 70 years (range 63-73.5 years), 37 (86%) participants were women, median percentage of the intrathoracic stomach was 59.9% (range 44.2-83.0%), and median length of hospital stay was 3 days (range 3-4 days). After surgery, the DVAS decreased statistically significant (5.6 [4.7-6.7] vs. 3.0 [2.3-4.4], p < 0.001), and 37 (86%) patients had a clinically significant decrease in mMRC score. Absolute forced expiratory volume in one second (FEV1), total lung capacity, and forced vital capacity also statistically significantly increased after surgery by an average of 11.2% (SD 17.9), 5.0% (SD 13.9), and 10.7% (SD 14.6), respectively. Furthermore, from the subgroup analysis, it was identified that patients with a lower preoperative FEV1 were more likely to have improvement in it after surgery. No correlation was found between improvement in dyspnoea and FEV1. There was no correlation between the percentage of intrathoracic stomach and dyspnoea or improvement in PFT parameters. CONCLUSION: PEH repair improves dyspnoea and FEV1 in a statistically significant manner in a population of patients presenting with dyspnoea. Patients with a low preoperative FEV1 are more likely to have improvement in it after surgery.