Background
Liver resection is a potentially curative approach for hepatocellular carcinoma (HCC). Laparoscopic liver resections may reduce complication rates, especially in patients with cirrhosis. ...The aim of this study was to compare the results of laparoscopic liver resection with those of open liver resection for HCC.
Methods
Patients with cirrhosis who underwent minor liver resections for HCC from 2006 to 2013 were identified retrospectively from a prospective database according to the technique adopted (laparoscopic or open). Short‐ and long‐term outcomes were compared between the two groups before and after 1 : 1 propensity score matching.
Results
A total of 269 patients were considered: 226 who underwent open liver resection and 43 who had a laparoscopic procedure. The two groups differed at baseline in terms of median age, sex, performance status, tumour location and type of resection. After propensity score matching, two comparable groups of 43 patients each were obtained. Intraoperative bleeding, margin clearance and operative mortality were similar in the two groups, whereas complication rates were lower (49 versus 19 per cent in open versus laparoscopic groups respectively; P = 0·004) and median hospital stay was shorter (8 versus 5 days; P < 0·001) in the laparoscopic group. On multivariable logistic regression analysis, the only independent factor that reduced the risk of postoperative complications was the use of laparoscopy (odds ratio 0·12, 95 per cent c.i. 0·03 to 0·55; P = 0·006). Median overall survival was 57·8 months in the open group and 48·8 months in the laparoscopic group (P = 0·802). Median disease‐free survival was 31·7 and 25·5 months respectively (P = 0·990).
Conclusion
In comparison with the open approach, laparoscopic minor liver resections for HCC improved short‐term outcomes, with similar survival results.
Laparoscopic is better
The urban heat island (UHI) of Milan (Italy) was analyzed by means of an Energy Balance Model calibrated for four different sites representative of an urban park, the UHI plateau and the UHI peak of ...the selected town. The model was driven by weather stations data and parameterized as a function of land use, urban morphology, human activities and soil hydrology. A run of the model on the 1981–2014 period was carried out on four hourly datasets. Results provided useful statistics of energy balance terms and the climate risk of extreme thermal events (sensible heat fraction of the total turbulent flux H% exceeding specific thresholds). Results for summer (June–August trimester) show that the mitigation of climate risk of high values of H% given by the urban park is more effective for June than for July and August. We also discuss the relevance of enhanced soil water reservoirs in urban green areas to improve the mitigating effect of urban vegetation on UHI by both the substitution of sensible heat fluxes with latent heat ones and the increase of the shading effect of tree canopies.
Display omitted
•A surface energy balance (SEB) was applied to model the urban heat island of Milan•Three different levels of UHI impact were considered (urban park, urban plateau, urban peak)•Three different levels of green management were considered•The maximum mitigation of UHI was provided by tree shade but irrigation is also effective.•The SEB approach provide support to evaluate the effect of wide set alternative urban design and green management options.
The use of home parenteral nutrition (HPN) in incurable cancer patients is extremely varied across different countries and institutions. In order to assess the clinical impact implied, we previously ...conducted a survey of incurable cancer patients receiving HPN, which shows that survival was markedly affected by Karnofsky performance status (KPS), tumor spread, Glasgow prognostic score (GPS) and tumor site. The aim of this study was to develop a nomogram incorporating the above factors for survival prediction.
We gathered a series of 579 patients, all receiving HPN, which was randomly split into a training and a testing sample. Using Cox proportional hazard regression modeling, a nomogram was built in the training sample, in order to estimate median survival or survival probability at 3 and 6 months according to individual patient characteristics. The nomogram performance was then verified in the testing sample.
In the training sample, median survival was 3.2 (95% CI 3.0–3.7) months. GPS, KPS, tumor site and spread were confirmed to be significant prognostic factors. A significant interaction was also shown between the site and spread while weight loss (WL), adjusted for body mass index, failed to provide any substantial prognostic contribution. In the testing sample, nomogram performance was good in terms of calibration and discreet regarding discrimination.
With the growing availability of new oncological treatments and their tendency to transform the trajectory of the advanced cancer into a chronic condition characterized by progressive WL and poor nutrients intake, an increasing number of patients are expected to receive HPN. In such a setting, tools for predicting the survival outcome may play a role toward personalized medicine and for investigating novel experimental therapies. Our proposed nomogram is a step forward in this direction but needs to be made stronger in order to definitely have clinical utility.
Breast cancer is one of the most prevalent and devastating malignant diseases in women worldwide. Fortunately, while breast cancer incidence is still increasing, its death rate is declining. This is ...mainly due to early diagnosis and potent therapies such as blockade of estrogen receptor- or of ErbB2 (HER2-neu) membrane receptor signaling.In recent years, the PI3K/AKT/mTOR pathway, which transmits signals from the cell membrane into the nucleus and activates multiple oncogenic programs, has been found to play a crucial role in the regulation of breast cancer cell growth. This pathway is densely interconnected with a multitude of other important regulatory systems for glucose-,lipid- and amino acid-metabolism, for energy balance, and for autophagy. It has been found that PI3K/AKT/mTOR signaling modulates estrogen receptor function. Using transverse and feedback regulatory loops the PI3K/AKT/mTOR cascade can communicate with concurrent and with upstream systems. Thus, PI3K/AKT/mTOR is a crucial element within a complicated signaling network. This pathway is hyperactive in more than 70% of breast tumors. Hence, the protein kinases located along this route represent very attractive and promising drug targets for breast cancer therapy. Currently, numerous small molecular drugs that inhibit PI3K, AKT and/or mTOR are being developed in preclinical and clinical models of breast cancer. Some of these compounds are highly selective blocking only one particular kinase complex, whereas others interfere with two (mTORC1+mTORC2) or even three effectors (PI3K+mTORC1+mTORC2) of the pathway. Due to the many interactions with other regulatory systems, silencing of the pathway can cause unexpected results. Therefore, detailed preclinical and clinical evaluation of these compounds as single drugs and in combination is required to achieve optimal results with maximal clinical benefit and acceptable toxicity. Also, reliable biomarkers for the identification of patient subsets that will maximally benefit from PI3K/AKT/mTOR inhibition need to be developed. Thus, selective silencing of PI3K/AKT/mTOR signaling represents a promising approach for breast cancer and might prove useful when combined with other drugs. Here we review the current preclinical and clinical data and compare the potential benefits of multi- versus single-targeting PI3K/AKT/mTOR drugs.
Data on preoperative chemotherapy in resectable oral cavity cancer are conflicting. We present the long-term results of a randomized trial of induction chemotherapy in resectable oral cavity cancer.
...A randomized, parallel, multicentre trial evaluated the impact of three cycles of cisplatin 100 mg/m2 and fluorouracil 1000 mg/m2 (120-h infusion administered every 21 days) in stage T2–T4, N0–N2, previously untreated patients with advanced disease. Control group received upfront surgery. Postoperative radiation was offered to both arms when pathologic risk features were identified. The co-primary end points were the occurrence of locoregional or distant tumour relapse, and death.
Among the 198 enrolled patients, with a median follow-up of 11.5 years, there was no difference in the incidence of locoregional relapse between chemotherapy and control group (P = 0.6337), nor in distant metastasis development (P = 0.1527). There was also no difference between groups in overall survival (P = 0.3402). Patients with a pathological complete response (pCR) had higher probability of survival than those without (10-year OS: 76.2% versus 41.3%, P = 0.0004). Late toxicities in patients with a minimum follow-up of 60 months (42 in each group) were similar between arms, except from fibrosis (cumulative incidence 40% versus 22% in chemotherapy arm) and grade 2 dysphagia (14% versus 5%).
Long-term follow-up of this randomized trial confirmed the absence of survival benefit with preoperative chemotherapy in oral cavity cancer. Late toxicity was similar in the two arms except for fibrosis and dysphagia, which were less in the chemotherapy arm. The survival benefit for patients achieving a pCR was maintained.
Context
Although consensus guidelines recommend dopamine agonists (DAs) as the first-line approach in prolactinomas, some patients may opt instead for upfront surgery, with the goal of minimizing the ...need for continuation of DAs over the long term. While this approach can be recommended in selected patients with a microprolactinoma, the indication for upfront surgery in macroprolactinomas remains controversial, with limited long-term data in large cohorts. We aimed at elucidating whether first-line surgery is equally safe and effective for patients with micro- or macroprolactinomas not extending beyond the median carotid line (i.e., Knosp grade ≤ 1).
Methodology
Retrospective study of patients with prolactinomas Knosp grade ≤ 1 treated with upfront surgery. The primary endpoint was patients’ dependence on DAs at last follow-up. The secondary endpoint was postoperative complications. Independent risk factors for long-term dependence on DAs were analyzed.
Results
A microadenoma was noted in 45 patients (52%) and a macroadenoma in 41 (48%), with 17 (20%) harboring a Knosp grade 1 prolactinoma. Median follow-up was 80 months. First-line surgery resulted in long-term remission in 31 patients (72%) with a microprolactinoma and in 18 patients (45%) with a macroprolactinoma (
p
= 0.02). DA therapy was ultimately required in 11 patients (24%) with microadenomas vs. 20 (49%) with macroadenomas (
p
= 0.03). As for the latter, DA was required in 13 patients (76%) with Knosp grade 1 macroadenomas vs. 7 patients (29%) with Knosp grade 0 macroadenomas (p = 0.004). There was no mortality, and morbidity was minimal. Knosp grade 1 prolactinomas (OR 7.3, 95% CI 1.4–37.7,
p
= 0.02) but not adenoma size (i.e., macroprolactinomas) were an independent predictor of long-term dependence on DAs.
Conclusions
First-line surgery in patients with microprolactinomas or macroprolactinomas Knosp grade 0 resulted in a good chance of non-dependency on DA therapy. However, in patients with prolactinomas Knosp grade 1, first-line surgery cannot be recommended, as adjuvant DA therapy after surgery is required in the majority of them over the long term.
Selection criteria and benefit of liver transplantation for hepatic metastases from neuroendocrine tumors (NETs) remain uncertain. Eighty‐eight consecutive patients with metastatic NETs eligible for ...liver transplantation according to Milan‐NET criteria were offered transplant (n = 42) versus nontransplant options (n = 46) depending on list dynamics, patient disposition, and age. Tumor burden between groups did not differ. Transplant patients were younger (40.5 vs. 55.5 years; p < 0.001). Long‐term outcomes were compared after matching between groups made on multiple Cox models adjusted for propensity score built on logistic models. Survival benefit was the difference in mean survival between transplant versus nontransplant options. No patients were lost or died without recurrence. Median follow‐up was 122 months. The transplant group showed a significant advantage over nontransplant strategies at 5 and 10 years in survival (97.2% and 88.8% vs. 50.9% and 22.4%, respectively; p < 0.001) and time‐to‐progression (13.1% and 13.1% vs. 83.5% and 89%; p < 0.001). After adjustment for propensity score, survival advantage of the transplant group was significant (hazard ratio = 7.4; 95% confidence interval (CI): 2.4–23.0; p = 0.001). Adjusted transplant‐related survival benefit was 6.82 months (95% CI: 1.10–12.54; p = 0.019) and 38.43 months (95% CI: 21.41–55.45; p < 0.001) at 5 and 10 years, respectively. Liver transplantation for metastatic NETs under restrictive criteria provides excellent long‐term outcome. Transplant‐related survival benefit increases over time and maximizes after 10 years.
This comparative study from Milan establishes restrictive criteria for patient selection in cases of liver metastases from neuroendocrine tumors and demonstrates a significant 10‐year survival benefit of liver transplantation that justifies the use of donated organs for this rare indication. See Trotter's editorial on page 2775.
The efficacy and safety of a combination of chemotherapeutic agent compared with single-agent chemotherapy in the second-line setting of advanced urothelial carcinoma (UC) are unclear. We aimed to ...study the survival impact of single-agent compared with doublet chemotherapy as second-line chemotherapy of advanced UC.
Literature was searched for studies including single-agent or doublet chemotherapy in the second-line setting after platinum-based chemotherapy. Random-effects models were used to pool trial-level data according to treatment arm, including median progression-free survival (PFS), overall survival (OS), objective response rate (ORR) probability, and grade 3–4 toxicity. Univariable and multivariable analyses, including sensitivity analyses, were carried out, adjusting for the percent of patients with ECOG performance status ≥1 and hepatic metastases.
Forty-six arms of trials including 1910 patients were selected: 22 arms with single agent (n = 1202) and 24 arms with doublets (n = 708). The pooled ORR with single agents was 14.2% 95% confidence interval (CI) 11.1–17.9 versus 31.9% 95% CI 27.3–36.9 with doublet chemotherapy. Pooled median PFS was 2.69 and 4.05 months, respectively. The pooled median OS was 6.98 and 8.50 months, respectively. Multivariably, the odds ratio for ORR and the pooled median difference of PFS were statistically significant (P < 0.001 and P = 0.002) whereas the median difference in OS was not (P = 0.284). When including single-agent vinflunine or taxanes only, differences were significant only for ORR (P < 0.001) favoring doublet chemotherapy. No statistically significant differences in grade 3–4 toxicity were seen between the two groups.
Despite significant improvements in ORR and PFS, doublet regimens did not extend OS compared with single agents for the second-line chemotherapy of UC. Prospective trials are necessary to elucidate the role of combination chemotherapy, with or without targeted agents, in the salvage setting. Currently, improvements in this field should be pursued considering single-agent chemotherapy as the foundation for new more active combinations.
To report on a prospective, investigator-driven, phase II study on lapatinib in epidermal growth factor receptor (EGFR)-positive advanced chordoma patients.
From December 2009 to January 2012, 18 ...advanced progressing chordoma patients entered this study (median age: 61 years; disease extent: metastatic 72% and locally advanced 28%). Epidermal growth factor receptor (EGFR) expression and activation were evaluated by immunohistochemistry and/or phospho-arrays, real-time polimerase chain reaction, fluorescence immunostaining. Fluorescence in situ hybridization analysis was also carried out. Patients received lapatinib 1500 mg/day (mean dose intensity = 1282 mg/day), until progression or toxicity. The primary study end point was response rate (RR) as per Choi criteria. Secondary end points were RR by Response Evaluation Criteria in Solid Tumor (RECIST), overall survival, progression-free survival (PFS) and clinical benefit rate (CBR; RECIST complete response + partial response (PR) + stable disease (SD) ≥ 6 months).
All patients were evaluable for response. Six (33.3%) patients had PR and 7 (38.9%) SD, as their best Choi responses, corresponding to RECIST SD in all cases. Median PFS by Choi was 6 interquartile (IQ) range 3–8 months. Median PFS by RECIST was 8 (IQ range 4–12) months, with a 22% CBR.
This phase II study showed a modest antitumor activity of lapatinib in chordoma. The clinical exploitation of EGFR targeting in chordoma needs to be further investigated, both clinically and preclinically. Clinical trial Registration No: EU Clinical Trials Register trial no. 2009-014456-29.
•Development of the mathematical model of a triple-screw pump.•Idler screws without a dedicated support determine complex friction phenomena.•Experimental assessment of volumetric and mechanical ...performances.•Maximum global efficiency achieved equal to 70%•8.2% efficiency improvement on ICE cooling application compared to centrifugal pump.
Internal Combustion Engine (ICE) cooling system is receiving a new technological interest for the influence it has on primary harmful and CO2 emissions reduction. Improvements on pump efficiency are requested to reduce its required energy during real on-the-road operation. Present technology always considers centrifugal pumps whose efficiency is highly dependent on rotational speed: consequently, pumps designed to have a very high efficiency at design point, show poor performances during usual operation, wasting energy.
This study aims to assess the screws pumps potentiality to substitute the traditional centrifugal pumps for engine cooling. The main advantage is that positive displacement pumps have an efficiency ideally non-dependent on rotational speed, flow rate and head delivered, so having requirements that can fit more the engine cooling features.
A novel comprehensive zero-dimensional mathematical model has been formulated to predict the performances of triple-screw pumps, in terms of volumetric, indicated and mechanical efficiency as a function of main operating conditions of the pump. A wide experimental activity has been done, resulting in a good agreement with predictions in spite of the manufacture of the pump, which privileges a low-cost solution as it is requested for the specific sectors of application. The model, once experimentally validated, demonstrates a high validity as virtual platform for a model-based design, thus offering the possibility to include design aspects particularly suitable for engine cooling systems. At last, by simulating the World Harmonized Transient Cycle on an F1C IVECO 3l engine, the triple-screw pump shows an average efficiency about 8% greater than that of the centrifugal pump, leading to an energy saving equal to 18.5%. This result leads the way to the use of screws pumps also in the engine cooling system of an on-the-road vehicle, which could represent a new potential application, never considered before.
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