Hospital volume, margin status, and long-term survival after pancreaticoduodenectomy for pancreatic adenocarcinoma

An association between hospital surgical volume and short- and long-term outcomes after pancreatic surgery has been demonstrated. Identification of specific factors contributing to this relationship is difficult. In this study, the authors evaluated if margin status can be identified as a measure of surgical quality, affecting overall survival, as a function of hospital pancreaticoduodenectomy volume. A systematic review of the literature was performed. Two models for analysis were created, dividing the 18 studies identified into quartiles and two quantiles based on the average annual hospital pancreatectomy volume. Regression modeling and analysis of variance were used to find an association between hospital volume, margin status, and survival. Increasing hospital volume was associated with a significantly increased negative margin status rate: 55 per cent for low-volume, 72 per cent for medium-volume, 74.3 per cent for high-volume, and 75.7 per cent for very high-volume centers (P = 0.008). The negative margin status rates were 64 per cent and 75.1 per cent for volume centers with less and more than 12 pancreaticoduodenectomies/year, respectively (P = 0.04). Low-volume centers negatively affected both margin positive resection and 5-year survival rates, compared with high-volume centers. Margin status rate after pancreaticoduodenectomy could, therefore, be considered a measure of quality for selection of hospitals dedicated to pancreatic surgery.     

Prolonged in vitro exposure to autoantibodies against CD38 impairs the function and survival of human pancreatic islets

Autoantibodies against CD38 (adenosine-5'-diphosphate[ADP]-ribosyl cyclase/cyclic ADP-ribose hydrolase) have been described in 10-12% of patients with type 2 diabetes. In human islets, anti-CD38 autoantibodies (CD38Abs) acutely stimulate insulin release (IR) and increase the cytosolic calcium concentration ([Ca(2+)](i)). Whether CD38Abs affect human islet cell function and survival upon prolonged in vitro exposure is not known. We cultured human islets for up to 7 days in the presence of sera from 10 patients with type 2 diabetes that had neither CD38Ab- nor [Ca(2+)](i)-mobilizing activity (-/-), sera from 6 patients with type 2 diabetes that was CD38Ab-positive and had [Ca(2+)](i)-mobilizing activity (+/+), or no sera (control). At baseline, +/+ sera caused a significant (P < 0.002) acute stimulation of IR (IR at 3.3 mmol/l glucose was 45 +/- 19, 84 +/- 24, and 34 +/- 12 micro U/ml in control, +/+, and -/- sera, respectively; the corresponding IR at 16.7 mmol/l glucose was 72 +/- 25, 204 +/- 56, and 80 +/- 32 micro U/ml). At 3 days, IR at 3.3 mmol/l glucose was 42 +/- 18, 27 +/- 11, and 43 +/- 24 micro U/ml (P = 0.0003) for control, +/+, and -/- sera, respectively, whereas at 16.7 mmol/l glucose, it was 95 +/- 76, 45 +/- 35, and 76 +/- 42 micro U/ml, respectively. After 7 days of exposure, the corresponding IR at 3.3 mmol/l glucose was 40 +/- 11, 28 +/- 12, and 35 +/- 15 micro U/ml, respectively, whereas at 16.7 mmol/l glucose it was 79 +/- 39, 39 +/- 17, and 62 +/- 39 micro U/ml. At both 3 and 7 days, IR still increased when switching from 3.3 to 16.7 mmol/l glucose (P < 0.0003), and incubation with +/+ sera induced a significant decrease in the insulin response (P < 0.002). At 7 days, the number of dead cells (as evaluated by an enzyme-linked immunosorbent assay technique) differed significantly between control (1.2 +/- 0.3 OD units) cells, islets exposed to -/- sera (1.4 +/- 0.1), and islets coincubated with +/+ sera (1.9 +/- 0.4, P < 0.01). We conclude that prolonged exposure of human islets to sera positive for the presence of CD38Abs with [Ca(2+)](i)-mobilizing activity impairs beta-cell function and viability in cultured human pancreatic islets.     

Preoperative reduction of spondylolisthesis

The treatment of SL, especially in some cases, is mostly surgical. This lesion can be considered an extremely localised kyphosis (only two vertebrae) or a localized (sub-)luxation: at most hearetically pre-operative reduction should represent the first stage of the treatment, also because reduction makes further surgery easier and enables us to obtain the best results. After a glance at the various surgical techniques that have been used in the past, we describe our method of preoperative reduction in case of severe SL, an improvement of Scaglietti's original technique. According to the parameters taken into consideration, spondylolisthesis (SL) of the 4th and, above all, the 5th lumber vertebrae can be considered, especially in severe cases, as kyphosis or displacement (or even dislocation in the case of ptosis). In SL-kyphosis the antero posterior axes of the contiguous vertebral bodies are no longer parallel but tend to over-impose one to the other anteriorly forming an open posterior angle of varying degrees. It is an extremely short kyphosis (only two vertebrae) but from all points of view, even therapeutic, it reflects the characteristics of all types of vertebral kyphosis. SL-subluxation or SL-luxation (ptosis) is characterized by the respectively partial or total loss of normal alignment between the vertebrae involved. This can be explained by the fact that nearly all those who have dealt with the problem of treating SL, especially of L5, always ask themselves beforehand if it is possible and/or opportune to eliminate or improve the condition before surgery. In other words the question of reduction (pre or intraoperative, partial or total) of more or less severe L5 SL is always considered by all authors, even if their conclusions are often in disagreement.     

Acute Appendicitis: Still a Surgical Disease? Results from a Propensity Score-Based Outcome Analysis of Conservative Versus Surgical Management from a Prospective Database

Objective

The aim of the present study was to compare the outcomes of conservative versus surgical treatment for acute appendicitis.

Background

Although acute appendicitis is a common disease, great debate exists regarding the appropriate management of patients. Conservative treatment has shown positive results in several RCTs, eliciting questions about indications to surgery, therapeutic appropriateness and ethical conduct.

Methods

Data were prospectively collected; a Propensity Score-based matching method was implemented in order to reduce bias arising from characteristics of the patients; a proportion of patients (69 in total) were excluded to obtain two comparable groups of study (1a). Main outcomes of the study were: failure rate, in-hospital length of stay (at first admission and cumulative), post-discharge absence from work. Within the medical group, failure was defined as the necessity for appendectomy after conservative treatment, while it was identified with complications and negative appendectomy within the surgical group (Failure 1). In parallel, an additional definition of failure was proposed (Failure 2) and excluded negative appendectomy from the reasons for failure within the surgical group (5b).

Results

The failure rate for the conservative treatment resulted to be inferior, as compared to the surgical treatment (16.5 vs. 28.4%, OR 0.523 p = 0.019), considering negative appendectomy as a reason for failure. When excluding negative appendectomy from the definition of failure, medical and surgical treatment appeared to perform equally (failure rate: 16.5 vs. 18.3%, OR 1.014 p = 0.965). Patients managed conservatively showed to have a shorter length of stay at first admission than the patients who underwent appendectomy (3.11 vs. 4.11 days, β = ?0.628 days, p < 0.0001). A lower number of lost work days after discharge resulted from a conservative approach (6 vs. 14.64 days, β = ?8.7 days, p < 0.0001).

Conclusions

Considering each outcome as part of a wide-angle analysis, the conservative management of acute appendicitis resulted to be safe and effective in the selected group of patients. In terms of failure rate, the medical treatment resulted to perform as effectively as surgical treatment, if negative appendectomy was excluded from failure, or better, when negative appendectomy was included in the definition of failure. A diminished length of stay during the first admission and a reduced number of lost work days were evident with a conservative approach. The comparison between medical and surgical treatment for acute appendicitis requires a change in perspective, from a spare ‘effectiveness analysis’ to a more thorough ‘appropriateness analysis’: in the present study, the conservative treatment showed to address the clinical requirements in terms of therapeutic appropriateness. Although acute appendicitis is considered a ‘surgical disease’, increasing evidence supports the effectiveness and safety of a conservative approach for selected groups of patients.

     

Interchromosomal effect in sperm of males with translocations: report of 6 cases and review of the literature

Somatic chromosomal abnormalities are frequently found in infertile men, particularly in those with low sperm count and/or seeking intracytoplasmic sperm injection. These abnormalities mostly consist of numerical sex chromosome abnormalities and translocations (Robertsonian or reciprocal). In this study, we searched for the occurrence of non-disjunction of chromosomes not involved in translocations during meiosis, phenomenon called interchromosomal effect (ICE) and first described by Lejeune (1965). Ejaculate samples of two patients carrying a Robertsonian translocation and four a reciprocal translocation patients and four controls (men with a 46,XY karyotype and normal sperm parameters) were studied in dual FISH 7-9, dual FISH 13-21 and triple FISH X-Y-18. A statistically significant increase of disomy X, Y and XY (P = 0.009, P = 0.004, P < 0.001) was found in the Robertsonian der(13;14)(q10;q10) carrier but not in the der(14;21)(q10;q10) carrier compared with controls. Among reciprocal translocation carriers, a significant increase of disomy 21 (P = 0.033) was observed in a sole patient with a t(9;22)(q21;q11.2). The increase of meiotic non-disjunction for chromosome 21 and sex chromosomes is a recurrent event found in other studies. According to our results and published data, the ICE on some specific chromosomes is likely in men carrier of a translocation, although it cannot be excluded that the aneuploidy is related to the oligoasthenoteratozoospermia usually present in these men. Moreover, this phenomenon showed interindividual variations which cannot be predicted. The risk of aneuploidy in sperm of males used for ICSI need to be evaluated. It could be superadded to that of meiotic segregation of the translocation to give a more precise and personalized risk assessment of aneuploidy in the offspring of those men.     

Adjuvant endocrine therapy for perimenopausal women with early breast cancer

Adjuvant treatment with aromatase inhibitors (AIs) improves outcomes in postmenopausal women with hormone-sensitive early breast cancer compared with tamoxifen. However, AIs should not be used in premenopausal women because they can paradoxically increase estrogen secretion and may therefore stimulate tumor progression. In perimenopausal women undergoing treatment for breast cancer, it can be difficult to determine true menopausal status because adjuvant chemotherapy, tamoxifen, and gonadotropin-releasing hormone analogues can induce transient (or permanent) ovarian suppression. How can one determine whether these women are truly postmenopausal and therefore candidates for AI therapy? A panel of experts in the field of endocrine therapy in breast cancer met in Dubrovnik, Croatia, on October 23, 2006, to discuss this clinical dilemma. This report summarizes the conclusions and recommendations that arose from this discussion.     

A new mutation in two siblings with cystinosis presenting with Bartter syndrome

Nephropathic cystinosis is a severe autosomal recessive inherited metabolic disease characterized by accumulation of free cystine in lysosomes. Cystinosis can lead to renal failure and multiorgan impairment. Only five cases of cystinosis with associated Bartter syndrome are reported in the literature, and no genetic evaluation has been reported. We describe two siblings with nephropathic cystinosis presenting with features of Bartter syndrome and their genetic pattern.     

18,X,Y aneuploidies and transmission electron microscopy studies in spermatozoa from five carriers of different reciprocal translocations

We analysed ejaculated spermatozoa from five infertile men with different balanced reciprocal translocations to contribute to the study of meiotic segregation of chromosomes 18, X and Y and also to evaluate sperm morphology by transmission electron microscopy （TEM） analysis. Conventional lymphocyte karyotype analyses highlighted dif- ferent reciprocal balanced translocations： t（12; 13）, t（4;9）, t（X;8）, t（8; 10） and t（3; 16）. Semen analysis was performed by light and TEM. Fluorescence in situ hybridization was performed directly on sperm nuclei using centromeric probes for chromosomes 18, X and Y. The carriers of the balanced reciprocal translocations considered in the present study showed a very similar pattern of sperm pathologies： diffused presence of apoptosis and immaturity. All patients showed meiotic segregation derangements, highlighted by the presence of sperm diploidies and sex chromosome disomies particularly related to the failure of the first meiotic division. However, an increased incidence of chromosome 18 aneuploidy was detected in spermatozoa from t（X;8） and t（8;10） carriers. We have also reported values from sex chromosomes such as t（X;8）, although the X chromosome was involved in translocation. Since patients with reciprocal translocations and spermatogenetic impairment are candidates for intracytoplasmic sperm injection cycles, the study of sperm parameters, and particularly of the level of aneuploidy rates, would provide better information for couples at risk and would contribute to the data in the literature for a better understanding of the effects of chromosomal rearrangement on the whole meiotic process and, in particular, on chromosomes not involved in translocation.     

Reconstruction of the proximal femur with a modular resection prosthesis

Background

Various megaprostheses are currently available for reconstruction of the proximal femur after tumor resection. This study evaluates the survival and complications of a modular megaprosthesis for reconstruction of the proximal femur.

Materials and methods

We studied the medical files of 109 tumor patients (age range 16–86 years) who underwent proximal femoral reconstruction with the MRP^® megaprosthesis from 2002 to 2011. There were 70 patients with metastases, 34 patients with bone sarcomas, and five patients with hematological malignancies; 82 were primary and 27 were revision reconstructions. Mean follow-up was 2.5 years; 31 patients had a minimum five-year follow-up. We evaluated the survival and function of the patients, and the survival and complications of the megaprostheses.

Results

Survival was significantly higher for the patients with bone sarcomas compared to those with metastases and hematological malignancies. Mean MSTS functional score was similar between patients with bone sarcomas and those with hematological malignancies and metastases, and between patients with primary and those with revision reconstructions. Overall survival of the MRP^® megaprostheses was 74 % at 5 and 9 years. Fourteen (13.6 %) major complications occurred at a mean period of 1.4 years (range 3 months to 4.5 years); these included infection (5.8 %), dislocation (3.9 %), local recurrence (2.9 %), and acetabular fracture (1 %).

Conclusion

MRP^® megaprostheses are a valuable reconstruction option after tumor resection of the proximal femur.