Background
In patients with resectable colorectal liver metastases (CRLM), the role of pre- and postoperative systemic therapy continues to be debated. Previous studies have shown that circulating tumor DNA (ctDNA) analysis, as a marker of minimal residual disease, is a powerful prognostic factor in patients with nonmetastatic colorectal cancer (CRC). Serial analysis of ctDNA in patients with resectable CRLM could inform the optimal use of perioperative chemotherapy. Here, we performed a validation study to confirm the prognostic impact of postoperative ctDNA in resectable CRLM observed in a previous discovery study.
Methods and findings
We prospectively collected plasma samples from patients with resectable CRLM, including presurgical and postsurgical samples, serial samples during any pre- or postoperative chemotherapy, and serial samples in follow-up. Via targeted sequencing of 15 genes commonly mutated in CRC, we identified at least 1 somatic mutation in each patient’s tumor. We then designed a personalized assay to assess 1 mutation in plasma samples using the Safe-SeqS assay. A total of 380 plasma samples from 54 patients recruited from July 2011 to Dec 2014 were included in our analysis. Twenty-three (43%) patients received neoadjuvant chemotherapy, and 42 patients (78%) received adjuvant chemotherapy after surgery. Median follow-up was 51 months (interquartile range, 31 to 60 months). At least 1 somatic mutation was identified in all patients’ tumor tissue. ctDNA was detectable in 46/54 (85%) patients prior to any treatment and 12/49 (24%) patients after surgery. There was a median 40.93-fold (19.10 to 87.73, P < 0.001) decrease in ctDNA mutant allele fraction with neoadjuvant chemotherapy, but ctDNA clearance during neoadjuvant chemotherapy was not associated with a better recurrence-free survival (RFS). Patients with detectable postoperative ctDNA experienced a significantly lower RFS (HR 6.3; 95% CI 2.58 to 15.2; P < 0.001) and overall survival (HR 4.2; 95% CI 1.5 to 11.8; P < 0.001) compared to patients with undetectable ctDNA. For the 11 patients with detectable postoperative ctDNA who had serial ctDNA sampling during adjuvant chemotherapy, ctDNA clearance was observed in 3 patients, 2 of whom remained disease-free. All 8 patients with persistently detectable ctDNA after adjuvant chemotherapy have recurred. End-of-treatment (surgery +/− adjuvant chemotherapy) ctDNA detection was associated with a 5-year RFS of 0% compared to 75.6% for patients with an undetectable end-of-treatment ctDNA (HR 14.9; 95% CI 4.94 to 44.7; P < 0.001). Key limitations of the study include the small sample size and the potential for false-positive findings with multiple hypothesis testing.
Conclusions
We confirmed the prognostic impact of postsurgery and posttreatment ctDNA in patients with resected CRLM. The potential utility of serial ctDNA analysis during adjuvant chemotherapy as an early marker of treatment efficacy was also demonstrated. Further studies are required to define how to optimally integrate ctDNA analyses into decision-making regarding the use and timing of adjuvant therapy for resectable CRLM.
Trial registration
ACTRN12612000345886.
In patients with suppurative or perforated appendicitis, the rate of intra-abdominal abscess is equivalent between groups treated with peritoneal irrigation and suction alone.
Background: Splenectomy is a surgical procedure indicated in a variety of medical conditions including trauma. Postoperatively, there is a lifelong risk of developing overwhelming sepsis from encapsulated bacteria, most commonly due to Streptococcus pneumoniae. Splenic autotransplantation has been proposed as a method to recover splenic function in patients requiring splenectomy with otherwise normal spleens. This paper aims to systematically review the literature to determine the efficacy of spleen autotransplantation.Methods: MEDLINE, PubMed and the Cochrane Library were searched for all studies assessing splenic autotransplantation (January 1947 to July 2018). Data was extracted on study characteristics, outcomes assessed, including spleen scintigraphy results, blood film counts and serum immunoglobulin levels.Results: Data was obtained from 18 primary studies. All papers demonstrated return of regenerated spleen tissue in the majority of their patients (95.3%) on spleen scintigraphy. 90.2% of patients in 12 studies had blood films return to normal following transplantation. Immunoglobulin levels were shown to return to normal in all 12 studies where it was assessed. 3.7% of patients in 11 studies had postoperative complications.1.3% of patients in five studies had postoperative infections in the follow-up period.
Hepatic hemangiomas are the most common benign tumors of the liver. Surgical treatment can be difficult as a result of the high risk of intraoperative hemorrhage. The present study reviewed clinical features of patients with hepatic hemangioma and surgical techniques used in their treatment. Eight patients with giant hepatic hemangiomas underwent hepatectomies at the Asan Medial Center between January 2006 and March 2009. Patient demographic, clinical, and surgical characteristics and outcomes were reviewed retrospectively. Seven females and one male patient underwent hepatectomies during the study period. The median age was 48.5 years (range, 33 to 58 years). Indications for surgical interventions were abdominal pain (62.5%), an abdominal mass (37.5%), Kasabach-Merritt syndrome (25%), and increased hemangioma size (25%). The hemangiomas were usually multiple (87.5%) and bilobar (75%) and had a median size of 14.5 cm (range, 7 to 29 cm). All patients underwent major hepatic resection with early vascular control using the Glissonean pedicle transection method (GPTM), the liver hanging maneuver (LHM), and preparation for total vascular exclusion (TVE). There was no major morbidity or mortality. The minor morbidity rate was 25 per cent with transfusion rate of 37.5 per cent. Early vascular control using the GPTM, the LHM, and preparation for TVE is essential for safe resection of large hepatic hemangiomas.
SAGS score can be used to simply and accurately classify the severity of appendicitis and to independently predict the risk of intra-abdominal collection. It can therefore be used to stratify risk, guide antibiotic therapy, follow-up and standardize the definitions of appendicitis severity for future research.
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