Ioannis T. Konstantinidis

Combined Ablation and Resection (CARe) as an Effective Parenchymal Sparing Treatment for Extensive Colorectal Liver Metastases

Background Combined intra-operative ablation and resection (CARe) is proposed to treat extensive colorectal liver metastases (CLM). This multicenter study was conducted to evaluate overall survival (OS), local recurrence-free survival (LRFS), hepatic recurrence-free survival (HRFS) and progression-free survival (PFS), to identify factors associated with survival, and to report complications. Materials and Methods Four centers combined retropectively their clinical experiences regarding CLM treated by CARe. CLM characteristics, pre- and post-operative chemotherapy regimens, surgical procedures, complications and survivals were analyzed. Results Of the 288 patients who received CARe, 210 (73%) had synchronous and 255 (88%) had bilateral CLM. Twenty-two patients (8%) had extrahepatic disease. Median follow-up was 3.17 years (95%CI 2.83–4.08). Median OS was 3.33 years (95%CI 3.08–4.17) and 5-year OS was 37% (95%CI 29–45). One- and 5-year LRFS from ablated lesions were 87.9% (95%CI 83.3–91.2) and 78.0% (95%CI 71–83), respectively. Median HRFS and PFS were 14 months (95%CI 11–18) and 9 months (95%CI 8–11), respectively. One hundred patients experienced complications: 29 grade I, 68 grade II–III–IV, and three deaths. In the multivariate models adjusted for center, the occurrence of complications was confirmed as a major independent factor associated with 3-year OS (HR 1.80; P = 0.008). Five-year OS was 25.6% (95%CI 14.9–37.6) for patients with complications and 45% (95%CI 33.3–53.4) for patients without. Conclusions Recent strategies facing advanced CLM include non-anatomic resections, portal-induced hypertrophy of the future remnant liver and aggressive medical preoperative treatments. CARe has the qualities of an approach that allows effective tumor clearance while maintaining good tolerance for the patient.

Insulin-Like Growth Factor 1 Receptor (IGF1R) Expression and Survival in Operable Squamous-Cell Laryngeal Cancer

Introduction Prognosis of patients with operable laryngeal cancer is highly variable and therefore potent prognostic biomarkers are warranted. The insulin-like growth factor receptor (IGFR) signaling pathway plays a critical role in laryngeal carcinogenesis and progression. Patients and Methods We identified all patients with localized TNM stage I–III laryngeal cancer managed with potentially curative surgery between 1985 and 2008. Immunohistochemical (IHC) expression of IGF1R-alpha, IGF1R-beta and IGF2R was evaluated using the immunoreactive score (IRS) and mRNA levels of important effectors of the IGFR pathway were assessed, including IGF1R, IGF-binding protein 3 (IGFBP3), suppressor of cytokine signaling 2 (SOCS2) and members of the MAP-kinase (MAP2K1, MAPK9) and phosphatidyl-inositol-3 kinase (PIK3CA, PIK3R1) families. Cox-regression models were applied to assess the predictive value of biomarkers on disease-free survival (DFS) and overall survival (OS). Results Among 289 eligible patients, 95.2% were current or ex smokers, 75.4% were alcohol abusers, 15.6% had node-positive disease and 32.2% had received post-operative irradiation. After a median follow-up of 74.5 months, median DFS was 94.5 months and median OS was 106.3 months. Using the median IRS as the pre-defined cut-off, patients whose tumors had increased IGF1R-alpha cytoplasm or membrane expression experienced marginally shorter DFS and significantly shorter OS compared to those whose tumors had low IGF1R-alpha expression (91.1 vs 106.2 months, p = 0.0538 and 100.3 vs 118.6 months, p = 0.0157, respectively). Increased mRNA levels of MAPK9 were associated with prolonged DFS (p = 0.0655) and OS (p = 0.0344). In multivariate analysis, IGF1R-alpha overexpression was associated with a 46.6% increase in the probability for relapse (p = 0.0374). Independent predictors for poor OS included node-positive disease (HR = 2.569, p<0.0001), subglottic/transglottic localization (HR = 1.756, p = 0.0438) and IGF1R-alpha protein overexpression (HR = 1.475, p = 0.0504). Conclusion IGF1R-alpha protein overexpression may serve as an independent predictor of relapse and survival in operable laryngeal cancer. Prospective evaluation of the IGF1R-alpha prognostic utility is warranted.

Unresectable intrahepatic cholangiocarcinoma: Systemic plus hepatic arterial infusion chemotherapy is associated with longer survival in comparison with systemic chemotherapy alone.

Intrahepatic cholangiocarcinoma (ICC) is associated with poor survival. This study compared the outcomes of patients with unresectable ICC treated with hepatic arterial infusion (HAI) plus systemic chemotherapy (SYS) with the outcomes of patients treated with SYS alone.

Predicting recurrence patterns after resection of hepatocellular cancer.

BACKGROUND The reliable prediction of hepatocellular carcinoma (HCC) recurrence patterns potentially allows for the prioritization of patients for liver resection (LR) or transplantation. OBJECTIVES The aim of this study was to analyse clinicopathological factors and preoperative Milan criteria (MC) status in predicting patterns of HCC recurrence. METHODS During 1992-2012, 320 patients undergoing LR for HCC were categorized preoperatively as being within or beyond the MC, as were recurrences. RESULTS After a median follow-up of 47 months, 183 patients developed recurrence, giving a 5-year cumulative incidence of recurrence of 62.5%. Patients with preoperative disease within the MC had better survival outcomes than those with preoperative disease beyond the MC (median survival: 102 months versus 45 months; P < 0.001). Overall, 31% of patients had preoperative disease within the MC and 69% had preoperative disease beyond the MC. Estimated rates of recurrence-free survival at 5 years were 61.8% for all patients and 53.8% for patients with initial beyond-MC status. Independent factors for recurrence beyond-MC status included preoperative disease beyond the MC, the presence of microsatellite or multiple tumours and lymphovascular invasion (all: P < 0.001). A clinical risk score was used to predict survival and the likelihood of recurrence beyond the MC; patients with scores of 0, 1, 2 and 3 had 5- year incidence of recurring beyond-MC of 9.0%, 29.5%, 48.8% and 75.4%, respectively (P < 0.0001). CONCLUSIONS Regardless of initial MC status, at 5 years the majority of patients remained disease-free or experienced recurrence within the MC after LR, and thus were potentially eligible for salvage transplantation (ST). Incorporating clinicopathological parameters into the MC allows for better risk stratification, which improves the selection of patients for ST and identifies patients in need of closer surveillance.

Pancreas and liver resection in Jehovah's Witness patients: feasible and safe.

BACKGROUND Jehovahs Witness (JW) patients undergoing liver or pancreas surgery represent a challenging ethical and medical problem, with few reports about their optimal management. STUDY DESIGN To analyze the perioperative outcomes of JW patients submitted to hepatic or pancreatic resection, clinicopathologic data of JW patients who underwent surgical exploration for a hepatic or pancreatic tumor between March 1996 and July 2011 were reviewed retrospectively. RESULTS Clinicopathologic data of 27 patients, 28 explorations, and 25 resections were included. Median age was 58 years (range 28 to 75 years) and 20 patients were female. Three patients were explored and deemed unresectable. Fifteen hepatic resections (9 segmentectomy or bi/trisegmentectomy, 6 hemi-hepatectomy or extended hepatectomy) and 10 pancreatic resections (6 pancreaticoduodenectomy, 4 distal pancreatectomy/splenectomy) were reviewed; additional organs were resected in 5 patients (2 gastrectomy, 1 colectomy, 1 nephrectomy, 1 adrenalectomy, 1 salpingoophorectomy). Median estimated blood loss for the hepatectomies was 400 mL (range 100 to 1,500 mL) and for the pancreatectomies was 400 mL (range 250 to 1,800 mL). Six patients received preoperative erythropoietin; hemodilution was used in 9 patients and 3 had Cell Saver-generated autotransfusions. Median preoperative hemoglobin was 12.5 g/dL (range 9.5 to 14.4 g/dL) and median postoperative hemoglobin was 10.4 g/dL (range 9 to 12.4 g/dL). In-hospital mortality was 0%. One patient required re-exploration for decreasing hemoglobin and refusal of transfusion; a total of 11 complications developed in 7 other patients (5 wound infection/breakdown, 1 urinary tract infection, 1 ileus, 1 nausea/vomiting, 1 lymphedema, 1 ascites, and 1 ARDS). Median hospital stay was 7 days (range 4 to 23 days). CONCLUSIONS Pancreatic and liver resection can be done safely in selected JW patients who refuse blood products by using a variety of blood-conservation techniques to help spare red cell mass.

MicroRNA-203 predicts human survival after resection of colorectal liver metastasis

Background Resection of colorectal liver metastasis (CRLM) can be curative. Predicting which patients may benefit from resection, however, remains challenging. Some microRNAs (miRNAs) become deregulated in cancers and contribute to cancer progression. We hypothesized that miRNA expression can serve as a prognostic marker of survival after CRLM resection. Results MiR-203 was significantly overexpressed in tumors of short-term survivors compared to long-term survivors. R1/R2 margin status and high clinical risk score (CRS) were also significantly associated with short-term survival (both p = 0.001). After adjusting for these variables, higher miR-203 expression remained an independent predictor of shorter survival (p = 0.010). In the serum cohort, high CRS and KRAS mutation were significantly associated with short-term survival (p = 0.005 and p = 0.026, respectively). After adjusting for CRS and KRAS status, short-term survivors were found to have significantly higher miR-203 levels (p = 0.016 and p = 0.033, respectively). Materials and Methods We employed next-generation sequencing of small-RNAs to profile miRNAs in solid tumors obtained from 38 patients who underwent hepatectomy for CRLM. To validate, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed on 91 tumor samples and 46 preoperative serum samples. Conclusions After CRLM resection, short-term survivors exhibited significantly higher miR-203 levels relative to long-term survivors. MiR-203 may serve as a prognostic biomarker and its prognostic capacity warrants further investigation.