The sentinel node biopsy in early gastric cancer: a preliminary study

Background and aims Sentinel node biopsy is currently used in surgery of malignant melanoma and breast cancer. The feasibility of sentinel node mapping in gastrointestinal cancers and its diagnostic sensitivity is unclear. It could be of particular value in the management of early gastric cancer in which radical D2 lymphadenectomy may be unnecessary. Materials and methods From January 2004 to June 2005, ten patients with preoperative diagnosis of early gastric cancer and no nodal involvement (cT1N0) were submitted to sentinel node biopsy using the dual mapping procedure with endoscopic blue dye and ^99mTc radio colloid injection. All the patients underwent standard radical gastrectomy and D2 lymphadenectomy. The resected nodes were evaluated by routine (hematoxylin–eosin) histopathological examination; the sentinel (blue or hot) nodes, in addition, were evaluated with immunohistochemistry for cytokeratin. Results The detection rate of this procedure was 100%. The preliminary results and perspectives for feasibility of sentinel node biopsy and its accuracy in predicting the nodal status in early gastric cancer are discussed.     

A new bioabsorbable sleeve for lung staple-line reinforcement (FOREseal™): report of a three-center phase II clinical trial

Objective: To investigate on the feasibility, safety, and effectiveness of a new bioabsorbable material for lung staple-line reinforcement. Methods: This prospective open trial included 66 patients (mean age of 56 ± 17 years) who underwent various types of lung resection using staplers with knitted calcium alginate sleeves for buttressing (FOREseal™, Laboratoires Brothier, Nanterre, France) at three academic centers: 29 lobectomies, 22 emphysema surgeries, 15 wedge resections or lung biopsies. Intraoperative air leakage was assessed at a mean respiratory peak pressure of 30 cmH₂O, and rated as grade 1, 2, or 3. Persistent air leakage in the postoperative course, as well as any relevant event, was assessed daily. The follow-up period was of 6 months. Results: No technical problem linked to the device occurred. Hemostasis of the cutting edges was completed in all patients. Fifty-six percent of the patients had no intraoperative air leak and 27.3% had grade 1 leaks. Mean postoperative air leaks and thoracic drainage times were 1.9 ± 2.3 days and 6 ± 5.3 days, respectively. In-hospital mortality was nil. There was no empyema. Mean hospital stay was 9.1 ± 6.6 days. At follow-up, one patient underwent lung transplantation, and pathology of the explanted specimen showed the absence of device-related foreign-body inflammation. One patient complained from metalloptysis, and another one, with a metastatic invasive aspergillosis, developed an infectious recurrence that required reoperation. Conclusions: FOREseal is an ergonomic, safe, and promising new material instead of nonabsorbable materials and xenomaterials for staple-line reinforcement. A randomized comparative study is now in progress.     

Lymphadenopathies in patients with renal cell carcinoma: clinical and pathological predictors of pathologically confirmed lymph node invasion

Introduction

In renal cell carcinoma (RCC), lymph node status at preoperative imaging is affected by a non-negligible false-positive rate. We aimed to investigate which factors are related to a concordance between clinical suspicion and pathological confirmation of lymph node invasion (LNI).

Methods

At a single tertiary care institution, 2954 RCC patients underwent either partial or radical nephrectomy. For the aim of the study, only clinically positive lymph node cases were included (cN1). Statistical analyses assessed the concordance between preoperative and pathological nodal status.

Results

Preoperative axial CT scans revealed 424 (14.4 %) patients showing at least one enlarged lymph node suspected for LNI (cN1). All lymphadenopathies were removed at surgery, and LNI was pathologically confirmed (pN1) in 122 patients (28.8 %). When focusing the analyses on clinical characteristics (variables known before surgery), metastases at diagnosis [OR 3.0 (95 %1.9–4.8), p < 0.001] and tumor size [OR 1.1 (95 % 1.1–1.2), p < 0.001] were the two most informative predictors of concordance between clinical and pathological nodal status. Concordance was also more likely in patients with papillary type II tumors (55.6 %) relative to papillary type I (38.1 %), clear cell (27.7 %) and chromophobe (8.3 %) tumors. At multivariable analyses, none of the considered blood markers resulted to be independently associated with LNI.

Conclusions

Roughly 70 % of patients showing a suspected lymph node preoperatively do not show LNI at the final pathological report. Among patients with clinically positive nodes, clinical tumor size and metastases at diagnosis represent the most informative and independent predictors of confirmed LNI at final pathology.

     

Expandable intramedullary nailing and platelet rich plasma to treat long bone non-unions

Background  Roentgenographic and functional outcomes of expandable self locking intramedullary nailing and platelet rich plasma (PRP) gel in the treatment of long bone non-unions are reported. Materials and methods  Twenty-two patients suffering from atrophic diaphyseal long bone non-unions were enrolled in the study. Patients were treated with removal of pre-existing hardware, decortication of non-union fragments, and fixation of pseudoarthrosis with expandable intramedullary nailing (Fixion™, Disc’O Tech, Tel Aviv, Israel). At surgery, PRP was placed in the pseudoarthrosis rim. Results  The thirteen-month follow-up showed 91% (20/22 patients) of patients attaining bony union. The average time to union was 21.5 weeks. No infection, neurovascular complication, rotational malalignment, or limb shortening >4 mm were observed. The healing rate of non-unions was comparable to that observed in previous studies but with a lower complication frequency. Conclusions  The combined use of self locking intramedullary nailing and PRP in the management of atrophic diaphyseal long bone non-unions seems to produce comparable results with less complications than previously reported. Further data are warranted to investigate the single contribution of PRP gel and Fixion nail.     

Natural history of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a slowly growing tumor, whose natural history is not completely known. Since the hepatocarcinogenetic process may evolve for years in a stepwise fashion from premalignant to overt HCC, detection of early, better treatable tumors is made possible by surveillance of patients at risk. A 6-month interval surveillance with ultrasound is considered cost-effective, generally leading to the identification of a single < 3 cm tumor in 50-70% of the patients at risk. For greater than 2 cm tumors, demonstration of arterial hypervascularization of the node by sonovue US, triphasic spiral CT or MRI is diagnostic for HCC. The diagnosis of a less than 2 cm in diameter tumor may be more difficult due to the risk of false negative diagnoses with contrast imaging technique (50% of the cases) caused by immature arterial vascularization of the small nodules. Prognosis largely depends on the evolutionary stage at which HCC is detected, i.e. a size and number of HCC nodes, vascular invasiveness and degree of liver impairment. The multinodular pattern of HCC, representing one third of all early cancers, heralds poor prognosis, especially for patients not fitting the Milan criteria for liver transplantation. The best prognosis is for a single, less than 5 cm node in compensated cirrhosis without vascular invasion, since this tumor is amenable to both liver transplantation and hepatic resection which may confer long-term survival Better survivals of cirrhotic patients with a recently identified tumors reflect the application of accurate criteria for tumor staging and stringent criteria for curative treatments. However, ageing of the patients, deterioration of liver function during surveillance, occurrence of multinodular tumors and limited access to liver transplantation may hamper surveillance programs effectiveness.     

Iron indices and vitamin D receptor polymorphisms in hemodialysis patients

Cardiovascular disease caused by accelerated atherosclerosis is the major determinant of morbidity and mortality in chronic kidney disease patients. Vitamin D and its analogs provide survival benefit for hemodialysis (HD) patients. Vitamin D exerts its effects through the vitamin D receptor (VDR) that is coded for by a gene showing several polymorphisms that, in turn, are associated with a variety of diseases and differential responses to vitamin D. In this study, we evaluated the association between 4 VDR polymorphisms (ie, those identified by the restriction enzymes BsmI, ApaI, TaqI, and FokI) and iron indices (serum iron, transferrin, transferrin saturation, and ferritin) in 88 hemodialysis patients routinely treated with vitamin D. The absence or presence of the BsmI, ApaI, TaqI, and FokI restriction sites were denominated B and b, A and a, T and t, F and f, respectively. Our results show that in HD patients with transferrin saturation <20%, the F allele was more frequent than in HD patients with transferrin saturation >20% (P = .03). This relationship may provide a link between VDR alleles and iron and nutritional markers, which are highly predictive variables of cardiovascular morbidity and mortality in hemodialysis patients.     

Quantitative evaluation of background parenchymal enhancement (BPE) on breast MRI. A feasibility study with a semi-automatic and automatic software compared to observer-based scores

Objective:

To evaluate quantitative measurements of background parenchymal enhancement (BPE) on breast MRI and compare them with observer-based scores.

Methods:

BPE of 48 patients (mean age: 48 years; age range: 36–66 years) referred to 3.0-T breast MRI between 2012 and 2014 was evaluated independently and blindly to each other by two radiologists. BPE was estimated qualitatively with the standard Breast Imaging Reporting and Data System (BI-RADS) scale and quantitatively with a semi-automatic and an automatic software interface. To assess intrareader agreement, MRIs were re-read after a 4-month interval by the same two readers. The Pearson correlation coefficient (r) and the Bland–Altman method were used to compare the methods used to estimate BPE. p-value <0.05 was considered significant.

Results:

The mean value of BPE with the semi-automatic software evaluated by each reader was 14% (range: 2–79%) for Reader 1 and 16% (range: 1–61%) for Reader 2 (p > 0.05). Mean values of BPE percentages for the automatic software were 17.5 ± 13.1 (p > 0.05 vs semi-automatic). The automatic software was unable to produce BPE values for 2 of 48 (4%) patients. With BI-RADS, interreader and intrareader values were κ = 0.70 [95% confidence interval (CI) 0.49–0.91] and κ = 0.69 (95% CI 0.46–0.93), respectively. With semi-automated software, interreader and intrareader values were κ = 0.81 (95% CI 0.59–0.99) and κ = 0.85 (95% CI 0.43–0.99), respectively. BI-RADS scores correlated with the automatic (r = 0.55, p < 0.001) and semi-automatic scores (r = 0.60, p < 0.001). Automatic scores correlated with the semi-automatic scores (r = 0.77, p < 0.001). The mean percentage difference between automatic and semi-automatic scores was 3.5% (95% CI 1.5–5.2).

Conclusion:

BPE quantitative evaluation is feasible with both semi-automatic and automatic software and correlates with radiologists'' estimation.

Advances in knowledge:

Computerized BPE quantitative evaluation is feasible with both semi-automatic and automatic software. Computerized BPE quantitative scores correlate with radiologists'' estimation.     

Gene transfer of constitutively active Akt markedly improves human islet transplant outcomes in diabetic severe combined immunodeficient mice

Akt is an important intracellular mediator of beta-cell growth and survival in rodents. However, whether constitutive activation of Akt in human beta-cells enhances the survival and function of transplanted islets is unknown. In the current study, we examined the efficacy of constitutive activation of Akt in improving human islet transplant outcomes using a marginal mass model in diabetic severe combined immunodeficient (SCID) mice. Human islets transduced with adenoviruses encoding constitutively active Akt1 (Adv-CA-Akt) displayed increased total and phosphorylated Akt and Akt kinase activity compared with control islets. Expression of CA-Akt in human islets induced a significant increase in beta-cell replication and a significant decrease in beta-cell death induced by serum and glucose deprivation or chronic hyperglycemia. Two control groups of islets (1,500 uninfected or adenovirus LacZ [Adv-LacZ]-transduced human islet equivalents [IEQs]) transplanted under the kidney capsule of streptozotocin-induced diabetic SCID mice were insufficient to correct hyperglycemia. Importantly and in marked contrast to these controls, 1,500 Adv-CA-Akt-transduced IEQs were capable of restoring euglycemia in diabetic SCID mice. Moreover, blood glucose normalization persisted for at least 6 months. Human plasma insulin at day 54 after transplant was 10-fold higher in Adv-CA-Akt islet recipients (2.4 +/- 0.4 ng/ml) compared with those receiving Adv-LacZ islets (0.25 +/- 0.08 ng/ml) (P < 0.05). In summary, expression of CA-Akt in human islets improves islet transplant outcomes in a subcapsular renal graft model in SCID mice. Akt is an attractive target for future strategies aimed at reducing the number of islets required for successful islet transplantation in humans.     

Skeletonized bilateral internal mammary arteries for non-elective surgical revascularization in unstable angina.

OBJECTIVE: The aim of this study was to evaluate the feasibility, safety and outcome of skeletonized bilateral internal mammary arteries (BIMA) in patients with unstable angina (UA) undergoing non-elective myocardial revascularization. METHODS: Between January 1997 and December 2003, 758 patients, mean age 62+/-12 years, underwent non-elective coronary artery bypass grafting (CABG) for unstable angina. Two hundred and five (27%) were operated emergently and 503 (73%) urgently. BIMA were employed in 320 (42%) patients (Group B) and isolated left IMA and/or saphenous vein grafts in the remaining 438 (58%) patients (Group M). RESULTS: In-hospital mortality (B = 5.9% and M = 5.3%), and perioperative myocardial infarction (B = 2.2%; M = 1.96%) were similar between the two groups (P = ns). Actuarial survival at 1, 3 and 7 years was 98.7, 97.5 and 96.2% in B and 99, 94.3 and 88.4% in M (P < 0.05 at 7 years follow-up). At 7 years follow-up, the event-free cardiac survival (92 vs. 87%, P = 0.021), angina-free survival (98.6 vs. 94%, P = 0.039), reoperation-free cardiac survival (98 vs. 95%, P = 0.04) and infarct-free cardiac survival (98.7 vs. 96%, P = 0.05) were better in Group B. Multivariate analysis identified age > 65 years (P = 0.02), LVEF < 35% (P = 0.01), > 1 ischemic irreversible area (P = 0.03) as independent predictors for late deaths, while the use of the LIMA (P=0.006) and both mammary arteries (P=0.001) decreased the risk of late deaths. CONCLUSIONS: The use of BIMA in non-elective CABG for UA is safe and effective. Mid-term outcome, however, are superior with improved freedom from cardiac death, from coronary reintervention and from myocardial infarction.