Targeting Stem Cells with Hyperthermia: Translational Relevance in Cancer Patients.

BACKGROUND: Tumor recurrences or metastases remain a major hurdle in improving overall cancer survival. In anticancer therapy, some patients inevitably develop chemo-/radiotherapy resistance at some point. Cancer stem cells are the driving force of tumorigenesis, recurrences, and metastases, contributing also to the failure of some cancer treatments. SUMMARY: Emergent evidence suggests that stem cell diseases are at the base of human cancers, and tumor progression and chemo-/radiotherapy resistance may be dependent on just a small subpopulation of cancer stem cells. Hyperthermia can be a strong cancer treatment, especially when combined with radio- or chemotherapy. It is a relatively safe therapy, may kill or weaken tumor cells, and significantly increases the effectiveness of other treatments. However, these mechanisms remain largely unknown. A literature search was performed using PubMed including cited English publications. The search was last conducted in December 2019. Search phrases included "stem cells," "hyperthermia," "cancer," and "therapy." Abstracts, letters, editorials, and expert opinions were not considered for the drafting of the study. Key Message: Our goal was to focus on and to summarize different biological features of cancer stem cells and new therapeutic approaches using hyperthermia and its potential translation to human clinical trials.

Enteral versus parenteral nutrition in the conservative treatment of upper gastrointestinal fistula after surgery: a multicenter, randomized, parallel-group, open-label, phase III study (NUTRILEAK study).

BACKGROUND: Postoperative upper gastrointestinal fistula (PUGIF) is a devastating complication, leading to high mortality (reaching up to 80%), increased length of hospital stay, reduced health-related quality of life and increased health costs. Nutritional support is a key component of therapy in such cases, which is related to the high prevalence of malnutrition. In the prophylactic setting, enteral nutrition (EN) is associated with a shorter hospital stay, a lower incidence of severe infectious complications, lower severity of complications and decreased cost compared to total parenteral nutrition (TPN) following major upper gastrointestinal (GI) surgery. There is little evidence available for the curative setting after fistula occurrence. We hypothesize that EN increases the 30-day fistula closure rate in PUGIF, allowing better health-related quality of life without increasing the morbidity or mortality. METHODS/DESIGN: The NUTRILEAK trial is a multicenter, randomized, parallel-group, open-label phase III trial to assess the efficacy of EN (the experimental group) compared with TPN (the control group) in patients with PUGIF. The primary objective of the study is to compare EN versus TPN in the treatment of PUGIF (after esophagogastric resection including bariatric surgery, duodenojejunal resection or pancreatic resection with digestive tract violation) in terms of the 30-day fistula closure rate. Secondary objectives are to evaluate the 6-month postrandomization fistula closure rate, time of first fistula closure (in days), the medical- and surgical treatment-related complication rate at 6 months after randomization, the fistula-related complication rate at 6 months after randomization, the type and severity of early (30 days after randomization) and late fistula-related complications (over 30 days after randomization), 30-day and 6-month postrandomization mortality rate, nutritional status at day 30, day 60, day 90 and day 180 postrandomization, the mean length of hospital stay, the patient's health-related quality of life (by self-assessment questionnaire), oral feeding time and direct costs of treatment. A total of 321 patients will be enrolled. DISCUSSION: The two nutritional supports are already used in daily practice, but most surgeons are reluctant to use the enteral route in case of PUGIF. This study will be the first randomized trial testing the role of EN versus TPN in PUGIF. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03742752. Registered on 14 November 2018.

Safety of liver resection for hepatocellular carcinoma after sorafenib therapy: a multicenter case-matched study.

BACKGROUND: Liver resection can be considered in some hepatocellular carcinoma (HCC) patients who received sorafenib. The lack of clinical data about safety of resection after sorafenib treatment led us to assess its potential impact on perioperative course in a multicentric study. METHODS: From 2008 to 2011, a total of 23 HCC patients who underwent liver resection after treatment with sorafenib (sorafenib group) were compared with 46 HCC patients (control group) matched for age, gender, underlying liver disease, tumor characteristics and type of resection. Patients received sorafenib for a median duration of 1 (range 0.2-11) months and drug was interrupted at least 7 days before surgery. End points were intraoperative (operative time, vascular clamping, blood loss and transfusion), and postoperative outcomes focusing on recovery of liver function. RESULTS: In the sorafenib group, HCC was developed on F4 cirrhosis in 48 % and the rate of major resection was 44 %. Surgical procedure duration (280 vs. 240 min), transfusion rate (26 vs. 15 %), blood loss (400 vs. 300 mL) and vascular clamping (70 vs. 74 %) were similar in the two groups. Mortality was zero in the sorafenib group and one (2.1 %) in the control group (p = 1.000). The incidence of postoperative complications was 44 % in the sorafenib group and 59 % in the control group (p = 0.307). Recovery of liver function was similar in the two groups in terms of prothrombin time (90 vs. 81 %, p = 0.429) and bilirubin level (16 vs. 24 µmol/L, p = 102) at postoperative day 5. CONCLUSIONS: No adverse effect of preoperative administration of sorafenib was observed during and immediately after liver resection for HCC.

Assessment of water enema computed tomography: an effective imaging technique for the diagnosis of colon cancer: Colon cancer: computed tomography using a water enema.

AIM: The aim of this study was to assess the accuracy of water enema computed tomography (WECT) for the diagnosis of colon cancer. METHODS: A total of 191 patients referred for clinically suspected colon cancer were prospectively evaluated by WECT in a multicenter trial. Examination was contrast enhanced helical CT after colon filling through a rectal tube. For all the cases, final diagnosis was obtained by colonoscopy and/or surgery. CT data were interpreted both locally and at a centralized site by a specialized and general radiologist. RESULTS: Seventy-one patients were diagnosed with colon cancer. Overall, WECT sensitivity and specificity were 98.6 and 95.0%, respectively. Positive and negative predictive values were 92.1 and 99.1%, respectively. In a subgroup of 33 patients with unclean bowel, the sensitivity and specificity of WECT were 95.0 and 92.3%, respectively. The correlation between local radiologists and the specialized radiologist was excellent (Kappa = 0.87) as was the correlation between the general radiologist and the specialist (Kappa = 0.92). CONCLUSION: This prospective analysis demonstrates that WECT is an effective, safe, and simple imaging technique for the diagnosis of colon cancer and can be proposed when a strong clinical suspicion of colon cancer is present, especially in frail patients.

Use of BiClamp decreased the severity of hypocalcemia after total thyroidectomy compared with LigaSure: a prospective study.

BACKGROUND: Postoperative hypocalcemia is the most common complication after thyroidectomy. New surgical devices have been propose to achieve vessel sealing and hemostasis. However, the risk of parathyroid glands damage has not been fully elucidated. This prospective study was designed to evaluate the severity of hypocalcemia after total thyroidectomy by using two different sealing devices. METHODS: Between January 2005 and December 2006, 86 patients underwent total thyroidectomy by using BiClamp (n = 46) or LigaSure (n = 40) devices in our institution. The severity of postoperative hypocalcemia was analyzed. RESULTS: No mortality or recurrent laryngeal nerve palsy was observed. Patients characteristics were similar in both groups. The mean operation time was significantly shorter in the BiClamp group (142 +/- 35 minutes versus 170 +/- 57 minutes, P = 0.023). Eleven patients had symptomatic hypocalcemia. Hypocalcemia (< 2 mmol/l) at postoperative day 1 was more frequent in the LigaSure group than in the BiClamp group (P = 0.034). Significantly more patients in the LigaSure group required oral calcium supplementation than in the BiClamp group (67.5% versus 34.7% respectively; P = 0.002). CONCLUSION: The present prospective study suggests that total thyroidectomy can be performed safely with both surgical devices. However, BiClamp reduced the operative time and the severity of postoperative hypocalcemia.