Frailty Increases Morbidity and Mortality in Patients Undergoing Oncological Liver Resections: A Systematic Review and Meta-analysis.

BACKGROUND: Considered to reflect a patients' biological age, frailty is a new syndrome shown to predict surgical outcomes in elderly patients. In view of the increasing age at which patients are proposed oncological liver surgery and the morbidity associated with it, we attempted to perform a systematic review and meta-analysis to compare morbidity and mortality between frail and nonfrail patients after liver resections. METHODS: The study was registered with PROSPERO. A systematic search of PubMed and EMBASE databases was performed for all comparative studies examining surgical outcomes after liver resections between frail and nonfrail patients. RESULTS: Ten studies were included based on the selection criteria with a total of 71,102 patients, split into two groups: frail (n = 17,167) and the control group (n = 53,928). There were more elderly patients with a lower preoperative albumin level in the frail group (p = 0.02, p = 0.001). Frail patients showed higher rates of morbidity with more major complications and a higher incidence of postoperative liver failure (p < 0.001). Mortality (p < 0.001) and readmission rate (p = 0.021) also was higher in frail patients. CONCLUSIONS: Frailty seems to be a solid predictive risk factor of morbidity and mortality after liver surgery and should be considered a selection criterion for liver surgery in at-risk patients.

Laparoscopic versus open resection of primary colorectal cancers and synchronous liver metastasis: a systematic review and meta-analysis.

PURPOSE: Combined resection of primary colorectal cancer and associated liver metastases is increasingly common. This study compares peri-operative and oncological outcomes according to surgical approach. METHODS: The study was registered with PROSPERO. A systematic search was performed for all comparative studies describing outcomes in patients that underwent laparoscopic versus open simultaneous resection of colorectal primary tumours and liver metastases. Data was extracted and analysed using a random effects model via Rev Man 5.3 RESULTS: Twenty studies were included with a total of 2168 patients. A laparoscopic approach was performed in 620 patients and an open approach in 872. There was no difference in the groups for BMI (mean difference: 0.04, 95% CI: 0.63-0.70, p = 0.91), number of difficult liver segments (mean difference: 0.64, 95% CI:0.33-1.23, p = 0.18) or major liver resections (mean difference: 0.96, 95% CI: 0.69-1.35, p = 0.83). There were fewer liver lesions per operation in the laparoscopic group (mean difference 0.46, 95% CI: 0.13-0.79, p = 0.007). Laparoscopic surgery was associated with shorter length of stay (p < 0.00001) and less overall postoperative complications (p = 0.0002). There were similar R0 resection rates (p = 0.15) but less disease recurrence in the laparoscopic group (mean difference: 0.57, 95% CI:0.44-0.75, p < 0.0001). CONCLUSION: Synchronous laparoscopic resection of primary colorectal cancers and liver metastases is a feasible approach in selected patients and does not demonstrate inferior peri-operative or oncological outcomes.

Evaluation of Changes in Circulating Cell-Free DNA as an Early Predictor of Response to Chemoradiation in Rectal Cancer-A Pilot Study.

Background and Objectives: The objective of this study was to investigate quantitative changes in cell-free DNA (cfDNA) found in the bloodstream of patients with locally advanced rectal cancer who received neoadjuvant long-course chemoradiation, assuming a change in DNA fragments release during therapeutic stress. Materials and Methods: This was a prospective observational study that involved 49 patients who had three distinct pathologies requiring neoadjuvant chemoradiation: 18 patients with breast cancer, 18 patients with cervical cancer, and 13 patients with rectal cancer. Both breast cancer and cervical cancer patients were used as a control groups. Breast cancer patients were used as a control group as irradiation targeted healthy tissue after the tumor resection (R0), while cervical cancer patients were used as a control group to evaluate the effect of chemoradiation regarding cfDNA in a different setting (squamous cell carcinomas) and a different tumor burden. Rectal cancer patients were the study group, and were prospectively evaluated for a correlation between fragmentation of cfDNA and late response to chemoradiation. Blood samples were collected before the initiation of treatment and after the fifth radiation dose delivery. cfDNA was quantified in peripheral blood and compared with the patients' clinicopathological characteristics and tumor volume. Conclusion: Thirteen patients with locally advanced rectal cancer (T3/T4/N+/M0) were included in the study, and all of them had their samples analyzed. Eight were male (61.54%) and five were female (38.46%), with an average age of 70.85 years. Most of the patients had cT3 (53.85%) or cT4 (46.15%) tumors, and 92.31% had positive lymph nodes (N2-3). Of the thirteen patients, only six underwent surgery, and one of them achieved a pathological complete response (pCR). The mean size of the tumor was 122.60 mm3 [35.33-662.60 mm3]. No significant correlation was found between cfDNA, tumor volume, and tumor regression grade. cfDNA does not seem to predict response to neoadjuvant chemoradiotherapy and it is not correlated to tumor volume or tumor regression grade.

Splenectomy Does Not Increase Early Morbidity in Patients Undergoing Total Gastrectomy: A Case-Control Study with Propensity Score Analysis.

AIM: In gastric cancer (GC), D2 lymph node dissection is, alongside negative-margins gastrectomy, of paramount importance. There is a debate between Western and Eastern scientific communities concerning the risk-benefit balance with respect to splenectomy, as Western countries are inclined to perform spleen-preserving gastrectomy due to an increased risk for postoperative complications. In Eastern countries (such as Japan) this is not the case. Our study aimed to determine whether or not spleen-sacrificing total gastrectomy for GC was associated with a higher rate of early postoperative morbidity or mortality. METHOD: We performed a retrospective case-control study in which we included patients who underwent total gastrectomy with D2 lymphadenectomy for GC (stages I-III) with curative intent, in a single high-volume tertiary oncologic centre. We divided the cases into two groups: spleenpreserving (SP) and spleen-sacrificing (SS) and evaluated the early complications rate following surgery. Afterwards, we performed propensity score matching (PSM) and analysis of the two groups. Results: We included 74 patients, 29 in the SS group and 45 in the SP group. Fifteen cases (20.2%) developed early postoperative complications and the complication rate was 53% (n=8) in the SS group and 46% (n=7) in the SP group. The overall 30-day mortality rate was 2.7%. Conclusions: Splenectomy is not associated with increased early morbidity following total gastrectomy with D2 lymphadenectomy if performed by an experienced surgeon.

Predictive and Prognostic Role of Neutrophil to Lymphocyte Ratio in Rectal Cancer: A Case Control Study with Propensity Score Analysis.

Background: Neutrophil to lymphocyte ratio (NLR) is promoted as a marker reflecting the antitumoral inflammatory response. Herein, we aim to assess whether NLR at the time of diagnosis can predict response to neoadjuvant therapy and long-term survival in a matched cohort of rectal cancer patients. Methods: This is a case control study on rectal cancer patients who underwent standard oncological treatment and had NLR sampled at each stage. ROC curve was used to establish the cut off value of NLR at diagnosis. Two groups (high and low NLR) were compared. Kaplan Meier overall and disease-free survival (DFS) analysis was done comparatively between two groups of patients: low and high NLR. Pearson and Log Rank tests were used to establish statistical significance. Propensity score matching (PSM) was performed, and all variables were compared again on the matched subgroups. Results: One hundred patients were included and 54 were compared again after PSM. NLR at diagnosis did not correlate with tumor regression grade (p=0.77). High NLR at diagnosis (NLR 2.58) was not found to be significantly associated with worse overall survival (p=0.096) or DFS (p=0.128). Similar results were achieved after PSM, except when stage III subgroups were compared, where higher NLR was associated with worse DFS (p=0.04), while results for OS were borderline (p=0.05). Conclusions: Overall, a pretherapeutic high NLR ( 2.58) was not found to predict survival or response do neoadjuvant therapy in patients with rectal cancer. However, a higher NLR may be associated with worse outcomes in advanced colorectal cancer.

Impact of Quilting Sutures on Surgical Outcomes After Mastectomy: A Systematic Review and Meta-Analysis.

BACKGROUND: Seroma after mastectomy and/or axillary lymph node dissection (ALND) is among the most common issue surgeons have to face in the early postoperative management of breast cancer. Using quilting sutures (QS) to aid in tissue approximation and decrease dead space is proposed as a simple technique to reduce seroma rate. We aimed to perform a systematic review, and analyse, in a meta-analytical model, the role of QS in improving wound outcomes and decrease volume, duration of drainage, and length of stay in hospital. METHODS: The study was registered with PROSPERO. A systematic search of the PubMed, EMBASE, and SCOPUS databases was performed for all comparative studies examining surgical outcomes in patients who underwent QS versus conventional closure (CC) after mastectomy ± ALND. RESULTS: Twenty-one studies with a total of 3473 patients (1736 in the study group and 1737 in the control group) were included based on the selection criteria. The study group showed significantly lower rates of seroma (p < 0.00001), total volume of drainage (p < 0.0001), days to drain removal (p < 0.00001), and length of stay (p < 0.00001) compared with the control group, while wound complication rates (surgical site infection, flap necrosis, hematoma, skin dimpling) were comparable between the two groups. CONCLUSIONS: QS are a reliable intraoperative technique that decrease seroma formation, volume of postoperative drainage, duration of drainage and length of hospital stay, and should be considered in mastectomies with or without ALND.

TECHNICAL DIFFICULTIES AND PROCEDURAL COMPLICATIONS IN CLOSING MALIGNANT ESOPHAGEAL-RESPIRATORY FISTULAS.

The aim of the study was to outline technical difficulties and procedural complications of using partially covered esophageal self-expandable metal stents (SEMSs) in malignant esophageal respiratory fistulas (ERFs) as a palliative treatment option. In this study, 150 patients with malignant dysphagia underwent treatment with SEMSs. A total of 36 ERFs were detected through endoscopic or clinical assessment. Complete fistula sealing with SEMSs was possible in 35 of the 36 patients. The majority of fistulas were diagnosed in male patients with advanced esophageal cancer. All of them presented with prolonged dysphagia and cachexia. Stent migration or tumoral overgrowth was identified in 6 cases with recurrent dysphagia, and required a second stent insertion. SEMSs were highly efficient in 98% of the patients studied with ERFs, with successfully sealed ERFs after the first attempt, with an overall median survival rate of 92 days. The technique of esophageal SEMS placement is simple and can be rapidly mastered. Patients with ERFs have a respiratory shunt that makes intubation difficult and is often avoided. Restoring oral feeding increased the patient quality of life. SEMS placement is generally safe, but has few associated postoperative complications.

Quality assessment of surgery for colorectal cancer: Where do we stand?

Quality assurance in surgery has been one of the most important topics of debate among colorectal surgeons in the past decade. It has produced new surgical standards that led in part to the impressive oncological outcomes we see in many units today. Total mesorectal excision, complete mesocolic excision (CME), and the Japanese D3 lymphadenectomy are now benchmark techniques embraced by many surgeons and widely recommended by surgical societies. However, there are still ongoing discrepancies in outcomes largely based on surgeon performance. This is one of the main reasons why many countries have shifted colorectal cancer surgery only to high volume centers. Defining markers of surgical quality is thus a perquisite to ensure that standards and oncological outcomes are met at an institutional level. With the evolution of CME surgery, various quality markers have been described, mostly based on measurements on the surgical specimen and lymph node yield, while others have proposed radiological markers (i.e. arterial stumps) measured on postoperative scans as part of the routine cancer follow-up. There is no ideal marker; however, taken together and assembled into a new score or set of criteria may become a future point of reference for reporting outcomes of colorectal cancer surgery in research studies and defining subspecialization requirements both at an individual and hospital level.

Age, blood tests and comorbidities and AIMS65 risk scores outperform Glasgow-Blatchford and pre-endoscopic Rockall score in patients with upper gastrointestinal bleeding.

BACKGROUND: Upper gastrointestinal (GI) bleeding is a life-threatening condition with high mortality rates. AIM: To compare the performance of pre-endoscopic risk scores in predicting the following primary outcomes: In-hospital mortality, intervention (endoscopic or surgical) and length of admission (≥ 7 d). METHODS: We performed a retrospective analysis of 363 patients presenting with upper GI bleeding from December 2020 to January 2021. We calculated and compared the area under the receiver operating characteristics curves (AUROCs) of Glasgow-Blatchford score (GBS), pre-endoscopic Rockall score (PERS), albumin, international normalized ratio, altered mental status, systolic blood pressure, age older than 65 (AIMS65) and age, blood tests and comorbidities (ABC), including their optimal cut-off in variceal and non-variceal upper GI bleeding cohorts. We subsequently analyzed through a logistic binary regression model, if addition of lactate increased the score performance. RESULTS: All scores had discriminative ability in predicting in-hospital mortality irrespective of study group. AIMS65 score had the best performance in the variceal bleeding group (AUROC = 0.772; P < 0.001), and ABC score (AUROC = 0.775; P < 0.001) in the non-variceal bleeding group. However, ABC score, at a cut-off value of 5.5, was the best predictor (AUROC = 0.770, P = 0.001) of in-hospital mortality in both populations. PERS score was a good predictor for endoscopic treatment (AUC = 0.604; P = 0.046) in the variceal population, while GBS score, (AUROC = 0.722; P = 0.024), outperformed the other scores in predicting surgical intervention. Addition of lactate to AIMS65 score, increases by 5-fold the probability of in-hospital mortality (P < 0.05) and by 12-fold if added to GBS score (P < 0.003). No score proved to be a good predictor for length of admission. CONCLUSION: ABC score is the most accurate in predicting in-hospital mortality in both mixed and non-variceal bleeding population. PERS and GBS should be used to determine need for endoscopic and surgical intervention, respectively. Lactate can be used as an additional tool to risk scores for predicting in-hospital mortality.

Targeted Cancer Therapy via pH-Functionalized Nanoparticles: A Scoping Review of Methods and Outcomes.

(1) Background: In recent years, several studies have described various and heterogenous methods to sensitize nanoparticles (NPs) to pH changes; therefore, in this current scoping review, we aimed to map current protocols for pH functionalization of NPs and analyze the outcomes of drug-loaded pH-functionalized NPs (pH-NPs) when delivered in vivo in tumoral tissue. (2) Methods: A systematic search of the PubMed database was performed for all published studies relating to in vivo models of anti-tumor drug delivery via pH-responsive NPs. Data on the type of NPs, the pH sensitization method, the in vivo model, the tumor cell line, the type and name of drug for targeted therapy, the type of in vivo imaging, and the method of delivery and outcomes were extracted in a separate database. (3) Results: One hundred and twenty eligible manuscripts were included. Interestingly, 45.8% of studies (n = 55) used polymers to construct nanoparticles, while others used other types, i.e., mesoporous silica (n = 15), metal (n = 8), lipids (n = 12), etc. The mean acidic pH value used in the current literature is 5.7. When exposed to in vitro acidic environment, without exception, pH-NPs released drugs inversely proportional to the pH value. pH-NPs showed an increase in tumor regression compared to controls, suggesting better targeted drug release. (4) Conclusions: pH-NPs were shown to improve drug delivery and enhance antitumoral effects in various experimental malignant cell lines.

Postoperative Quality Assessment Score Can Select Patients with High Risk for Locoregional Recurrence in Colon Cancer.

BACKGROUND: Monitoring surgical quality has been shown to reduce locoregional recurrence (LRR). We previously showed that the arterial stump length (ASL) after complete mesocolic excision (CME) is a reproducible quality instrument and correlates with the lymph-node (LN) yield. We hypothesized that generating an LRR prediction score by integrating the ASL would predict the risk of LRR after suboptimal surgery. METHODS: 502 patients with curative resections for stage I-III colon cancer were divided in two groups (CME vs. non-CME) and compared in terms of surgical data, ASL-derived parameters, pathological parameters, LRR and LRR-free survival. A prediction score was generated to stratify patients at high risk for LRR. RESULTS: The ASL showed significantly higher values (50.77 mm ± 28.5 mm) with LRR vs. (45.59 mm ± 28.1 mm) without LRR (p < 0.001). Kaplan-Meier survival analysis showed a significant increase in LRR-free survival at 5.58 years when CME was performed (Group A: 81%), in contrast to non-CME surgery (Group B: 67.2%). CONCLUSIONS: The prediction score placed 76.6% of patients with LRR in the high-risk category, with a strong predictive value. Patients with long vascular stumps and positive nodes could benefit from second surgery to complete the mesocolic excision.

Preoperative warm-up using a virtual reality simulator.

BACKGROUND AND OBJECTIVES: All modern surgical procedures require a high level of cognitive and psychomotor skills achieved using different training methods, but could be influenced by fatigue and other psychological factors. We evaluated the effect of warm-up exercises on operative laparoscopic performances. METHODS: The surgical team operated on a consecutive series of 20 patients with gallstones. Patients were randomly allocated in 2 groups: group A to be operated on without warm-up exercises and group B to be operated on after a short-term warm-up. All the patients were operated on by the same surgical team. The full-time records of the operation were analyzed by 2 independent reviewers. A modified simplified Global Rating Score (GRS) was used to assess the surgical procedures. A training module using the Lap Mentor simulator was designed for the warm-up. RESULTS: Better performances were noted by both observers in group B only regarding "Respect for tissue" scores (3.75 0.16 vs 4.43 0.20, P=.021 and 3.87 0.22 vs 4.57 0.20, P=.041) achieving significant or marginally significant differences for all categories; GRS scores for "time and motion" and "overall impression" tend to be better after warm-up, but differences failed to reach statistical significance in our series. CONCLUSION: Surgeons, even the most experienced in laparoscopic surgery, can increase specific psychomotor skills associated with a laparoscopic environment by doing simple exercises on a virtual reality simulator, just before an operation. These improvements are reflected in more accurate handling of tissue during laparoscopic cholecystectomy.

Hair EDX Analysis-A Promising Tool for Micronutrient Status Evaluation of Patients with IBD?

Micronutrient deficiencies can arise in various conditions, including inflammatory bowel diseases (IBD), and diagnosing these deficiencies can be challenging in the absence of specific clinical signs. The aim of this study was to evaluate the status of various trace elements hair concentration in IBD patients compared to a healthy control group and to identify potential correlations between the micronutrient status and relevant parameters related to disease activity. The concentrations of iron, magnesium, calcium, zinc, copper, manganese, selenium and sulfur in the hair of 37 IBD patients with prior diagnosed IBD (12 Crohn's disease and 25 ulcerative colitis) and 31 healthy controls were evaluated by Energy Dispersive X-Ray spectroscopy (EDX). Significant differences in hair concentration profile of studied trace elements were identified for IBD patients compared to healthy controls. A significantly decreased hair concentration of iron, magnesium, calcium and selenium and a significantly increased sulfur hair concentration were observed in IBD patients at the time of evaluation. A decreased hair calcium concentration (r = -0.772, p = 0.003) and an increased sulfur concentration (r = 0.585, p = 0.046) were significantly correlated with disease activity. Conclusion: Hair mineral and trace elements evaluation may contribute to a proper evaluation of their status in IBD patients and improving the management of nutritional status of IBD patients.

Adrenal schwannoma.

BACKGROUND: Adrenal schwannomas are very rare tumors that are difficult to diagnose preoperatively. We report the case of a left adrenal schwannoma incidentally discovered in a 55-year-old man during a postoperative checkup for a cutaneous malignant melanoma. METHODS: The biological evaluation was unremarkable, and the radiological examination revealed the adrenal mass that was first considered a metastatic lesion. Adrenalectomy was performed by the laparoscopic approach. RESULTS: The postoperative course was uneventful. Histological examination established the correct diagnosis of schwannoma, which was also confirmed by immunohistochemical staining. CONCLUSIONS: A nonsecreting adrenal mass can be easily misjudged, especially in the context of a recently operated on malignancy. Unilateral adrenal metastasis needs pathological confirmation, as it can dramatically affect prognosis. Unusual tumors of the adrenal gland may be found incidentally, and a malignant context will generate difficulties in establishing the right management. Complete laparoscopic excision is the treatment of choice whenever feasible and will also clarify pathology.

Leptin and adiponectin dynamics at patients with rectal neoplasm - Gender differences.

BACKGROUND: Numerous studies associate adipokines with colorectal malignancy, but few data deal with patients suffering exclusively of rectal carcinoma (RC). AIMS: We evaluated leptin and adiponectin levels in RC patients compared to healthy population and their dynamics after surgery. MATERIAL AND METHODS: Serum leptin and adiponectin were evaluated before surgery in 59 RC consecutive patients (38 males and 21 females), and in age and weight matched healthy controls. Measurements were repeated at 24, 72 hours and 7 days after surgery. RESULTS: Adipokine levels were higher in women. Controls had higher leptin (32.±4.34 vs 9.51±1.73 ng/ml in women and 11±2.66 vs 2.54±0.39 ng/ml in men, p = 0.00048 and 0.0032) and lower adiponectin (9±0.64 vs 11.85±1.02 µg/ml in women and 7.39±0.51 vs 8.5±0.62 µg/ml in men, p = 0.017 and 0.019) than RC patients. Surgery caused an increase of leptin from 5.11±0.8 to 18.7±2.42 ng/ml, p = 6.85 x 10¨8, and a decrease of adiponectin from 9.71±0.58 to 7.87±0.47 µg/ml, p = 1.4 x 10¨10 for all RC patients and returned thereafter to the initial range at 7 days. Adipokines were correlated with body weight (BW). The significance of correlation persisted after surgery only in males, but disappeared in females. Adipokines were not modified by tumor position, presurgical chemoradiotherapy or surgical technique. Women with RC experiencing weight loss had higher adiponectin than women without weight modifications (p<0.05 at all time points). CONCLUSIONS: Adipokine levels of patients with RC differ from the healthy population, possibly reflecting an adaptation to disease. Adipokine modifications after surgery may be related to acute surgical stress. Whether leptin and adiponectin directly interact is not clear. Women have higher adipokine levels, more so after significant weight loss, but the strength of their correlation with BW decreases after surgery. These data suggest gender differences in the adipokine profile of RC patients which may find clinical applications.

Post-operative computed tomography scan - reliable tool for quality assessment of complete mesocolic excision.

BACKGROUND: Quality control in colon cancer surgery is an ongoing debate ever since standardization proved to be highly efficient in improving survival in rectal cancer. Complete mesocolic excision (CME) is widely acclaimed as the new gold-standard in colon cancer resections, thus it is imperative to establish quality criteria of CME in order to make it easily understood and verified by surgeons worldwide. One simple and reproducible tool could be the measurement of arterial stumps postoperatively and a straightforward way to test its reliability is to test it in a comparative study between CME and non-CME surgery. AIM: To validate arterial stump measurement as a surgical quality tool by comparing CME with conventional radical colectomies. METHODS: This was a retrospective study, carried out on a prospective database. We collected data from two groups of patients, divided according to standard CME with D2 central vascular ligation (group A) and non-standardized surgery (group B). The two groups were compared with regard to the arterial stump length after right- and left-sided colectomies for colon cancer. The actual stump lengths of the ileocolic artery (ICA) and inferior mesenteric artery (IMA) were compared with their theoretical best D2 position of predicted ligation levels (D2PLLs) for calculating the potential for improvement. Measurements on follow-up computed tomography scans were carried out by three observers. Pathological data were recorded (specimen length, lymph node yield) and correlated with stump length. RESULTS: We analysed 58 colectomies. The stump lengths (mean ± SD) in group A were 16.97 ± 4.77 mm for ICA and 31.70 ± 15.71 mm for IMA, whereas group B had 49.93 ± 20.29 mm for ICA and 67.24 ± 28.71 mm for IMA. Shorter lengths were obtained in group A, by a mean difference of 35.66 mm (χ 2 = 27.38, P < 0.001), which was significant for all types of colectomies. Except for a 5.85 ± 4.71 mm difference for right colectomies, all the ligations from group A significantly reached their potential height (0.26 ± 12.18 mm from D2PLL; χ 2 = 0.005, P = 0.944). Apart from three left colectomies, group B failed to reach D2PLL, by a mean difference of 32.14 ± 26.15 mm (χ 2 = 21.77, P < 0.001). The calculated improvement potentials were significantly shorter in group A than in group B, by a mean of 31.88 mm (χ 2 = 22.13, P < 0.001). The large spread of results in group B showed that there is significant variability (P = 0.004) when compared to standard surgery. Significant correlations were found between stump length, specimen length and number of lymph nodes (P = 0.018 and P = 0.008 respectively). No statistical difference was found between observers' measurements (P = 0.866). CONCLUSION: Arterial stump monitoring is a significant step in defining surgical quality, as longer stumps contain residual mesocolic tissue and correlate with major prognostic factors.

Tumor-facing hepatocytes significantly contribute to mild hyperthermia-induced targeting of rat liver metastasis by PLGA-NPs.

The effect of mild hyperthermia (MHT) on nanoparticle (NP) accumulation in rat model liver metastasis and the contribution of neoplastic and non-neoplastic cells were characterized. CdSe/ZnS QD-doped poly(lactic-co-glycolic acid) (PLGA) NPs (155 ±â€¯10 nm) were delivered via the ileocolic vein to metastatic livers 15 min after localized MW irradiation (1 min, 41 °C) or in normothermia (37 °C, NT). Quantitative analysis of tissue sections by confocal fluorescence microscopy 1 h after NP injection showed no NP tumor accumulation in NT. On the contrary, MHT increased NP association with tumor, compared to normal tissue. Counterstaining of specific markers showed that the MHT effect is due to an increased NP endocytosis not only by tumor cells, but also by hepatocytes at the growing tumor edge and, to a minor extent, by tumor-associated macrophages. High-NP capturing hepatocytes, close to the tumor, may be a relevant phenomenon in MHT-induced increased targeting of NPs to liver metastasis, influencing their therapeutic efficacy.

New experimental model for single liver lobe hyperthermia in small animals using non-directional microwaves.

PURPOSE: Our aim was to develop a new experimental model for in vivo hyperthermia using non-directional microwaves, applicable to small experimental animals. We present an affordable approach for targeted microwave heat delivery to an isolated liver lobe in rat, which allows rapid, precise and stable tissue temperature control. MATERIALS AND METHODS: A new experimental model is proposed. We used a commercial available magnetron generating 2450 MHz, with 4.4V and 14A in the filament and 4500V anodic voltage. Modifications were required in order to adjust tissue heating such as to prevent overheating and to allow for fine adjustments according to real-time target temperature. The heating is controlled using a virtual instrument application implemented in LabView® and responds to 0.1° C variations in the target. Ten healthy adult male Wistar rats, weighing 250-270 g were used in this study. The middle liver lobe was the target for controlled heating, while the rest of the living animal was protected. RESULTS: In vivo microwave delivery using our experimental setting is safe for the animals. Target tissue temperature rises from 30°C to 40°C with 3.375°C / second (R2 = 0.9551), while the increment is lower it the next two intervals (40-42°C and 42-44°C) with 0.291°C/ s (R2 = 0.9337) and 0.136°C/ s (R2 = 0.7894) respectively, when testing in sequences. After reaching the desired temperature, controlled microwave delivery insures a very stable temperature during the experiments. CONCLUSIONS: We have developed an inexpensive and easy to manufacture system for targeted hyperthermia using non-directional microwave radiation. This system allows for fine and stable temperature adjustments within the target tissue and is ideal for experimental models testing below or above threshold hyperthermia.

Postoperative survival in advanced gastric cancer.

We assessed the postoperative survival in 143 consecutive patients with advanced gastric cancer. Police databases represented a very powerful research tool and allowed a response rate of 94.4%. Mean postoperative survival was 10 months - irrespective of stage - with 52.6% and 30.3% survival rates at 6 months and 12 months respectively. Long-term survival cannot be really commented with only 11 % of patients alive after 24 months. Statistical analysis demonstrated a lack of prognostic significance of tumour stage (except for stage 4), as well as lymph node spread. No real benefit in survival was evident for palliative resection in locally advanced gastric cancer. We were not able to prove a significant benefit of more extensive (D2) lymph node dissection. The only proven prognostic factor in our study appeared to be the oncologic quality of resection. Survival was significantly longer in R1 (no macroscopic residual tumor) cases vs. R2 macroscopic residual tumour cases (p<0.05), but no difference could be found between R2 (macroscopic residual tumor) cases and non-resectable cases.