The importance of margins status after breast conservative surgery and radiotherapy in node positive patients: a follow-up of 10–15 years

Background

Margin status is the main factor determining local recurrence (LR) after wide excision and radiotherapy for breast cancer. The aim of the study is to evaluate if positive margins are as great a risk factor for LR in node-positive as in node-negative patients, since the major risk in the former group is dissemination and whether there is a correlation between nodal status and margins in relation to prognosis.

Methods

773 patients underwent WLE and radiotherapy between 1988 and 1992 and were followed-up (> 10 years) to determine LR rates according to margin and nodal status. Margins were assessed by cavity-shave biopsies and the axilla was staged by sampling or clearance.

Results

461 patients were node negative and 312 node positive. In the node-negative group 415 patients had negative margins and 46 positive: LR after > 10 years was 12 % and 28 % respectively. Among the 312 patients in the node positive group, 267 were margin negative and 45 positive; the LR rate was 12 % and 18 % respectively. In the node negative-group there was a statistically significant difference between the positive and the negative margins with higher relapse rate and lower overall survival (p < 0.001), whereas in the node-positive group the equivalent comparison didn't show any statistical difference.

Conclusion

Although re-excision should be always recommended, in node-negative patients positive margins are associated with a statistically higher LR rate and lower overall survival while in node-positive disease margins might be of less importance in determining prognosis as dissemination is more likely to occur.

     

Clinical prognostic factors for pediatric extra-abdominal desmoid tumor: analyses of 66 patients at a single institution

Background and purpose

Pediatric desmoid tumor (PDT) is rare and has a high local recurrence rate. The purpose of the present study was to analyze clinical risk factors of local recurrence in PDT patients.

Materials and methods

We reviewed clinical data of 66 PDT patients from 2004 to 2015. All patients underwent macroscopically complete resection, and some recurrent tumors were prescribed radiotherapy. Factors such as sex, age at presentation, location, and proximity to nerves or vasculature were analyzed. The local recurrence rate and recurrence-free survival were analyzed with these factors.

Results

All patients in the present study were children and had extra-abdominal tumors. The median follow-up time was 6.6?years. Thirty-six (55%) patients had local recurrence. Age, sex, tumor site, tumor size, and proximity to nerves/vasculature had a significant impact on prognosis in univariate analysis. Radiotherapy decreased the local recurrence rate. In multivariate analysis, younger age, tumor location in buttocks, larger tumor, and proximity to important nerves/vasculature were independent risk factors for poor prognosis.

Conclusions

Favorable therapeutic strategies could be selected according to the preoperative prognostic risk factors. Radiotherapy should be considered for local recurrence of PDT.

     

Phylloides tumor of the breast: a rare neoplasm,though not that innocent

Background

Cystosarcoma phylloides (CP) is an extremely rare form of breast cancer with an unpredictable clinical course. The histological characteristics of this neoplasm have not proved to offer much in the estimation of prognosis of these patients.

Patients and methods

In our clinics, in a time period of 38 years, 22 patients with cystosarcoma phylloides were treated. There were 5 cases of malignancy, 15 cases with benign tumors, and two cases histologically characterized as borderline neoplasia. Metastases were manifested in one patient. All patients were on a 5-year follow-up, except in five cases, one operated three years ago and four operated within the last two years.

Results

16 of 22 patients did not present any signs of local recurrence or metastases. There were three patients that manifested local recurrence and underwent supplementary ongectomy or mastectomy and are free of recurrence ever since. One patient with metastatic CP died.

Conclusion

Independently of its histopathological behavior, CP is a tumor difficult to be treated. Meticulous follow-up is mandatory in order to manage possible recurrence of the neoplasm.

     

Hypoxia enhances the protective effects of placenta-derived mesenchymal stem cells against scar formation through hypoxia-inducible factor-1α

Objectives

To explore the effect of placenta-derived mesenchymal stem cells on scar formation as well as the underlying mechanism.

Results

The isolated placenta-derived mesenchymal stem cells from mice were distributed in the wounded areas of scalded mouse models, attenuated inflammatory responses and decreased the deposition of collagens, thus performing a beneficial effect against scar formation. Hypoxia enhanced the protective effect of placenta-derived mesenchymal stem cells and hypoxia-inducible factor-1α was involved in the protective effect of placenta-derived mesenchymal stem cells in hypoxic condition.

Conclusions

Hypoxia enhanced the protective effect of placenta-derived mesenchymal stem cells through hypoxia-inducible factor-1α and PMSCs may have a potential application in the treatment of wound.

     

Nucleotide binding domain 1 pharmacophore modeling for visualization and analysis of P-glycoprotein–flavonoid molecular interactions

Background

P-glycoprotein (P-gp) is a 170-kDa membrane protein. It provides a barrier function and help to excrete toxins from the body as a transporter. Some bioflavonoids have been shown to block P-gp activity.

Objective

To evaluate the important amino acid residues within nucleotide binding domain 1 (NBD1) of P-gp that play a key role in molecular interactions with flavonoids using structure-based pharmacophore model.

Methods

In the molecular docking with NBD1 models, a putative binding site of flavonoids was proposed and compared with the site for ATP. The binding modes for ligands were achieved using LigandScout to generate the P-gp–flavonoid pharmacophore models.

Results

The binding pocket for flavonoids was investigated and found these inhibitors compete with the ATP for binding site in NBD1 including the NBD1 amino acid residues identified by the in silico techniques to be involved in the hydrogen bonding and van der Waals (hydrophobic) interactions with flavonoids.

Conclusion

These flavonoids occupy with the same binding site of ATP in NBD1 proffering that they may act as an ATP competitive inhibitor.

     

Pseudo current density maps of electrophysiological heart,nerve or brain function and their physical basis

Background

In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.

Methods

The physical basis of these intuitive maps is clarified by means of analytically solvable problems.

Results

Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.

Conclusion

Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.

     

Predicting ovarian cancer recurrence by plasma metabolic profiles before and after surgery

Background

Previous metabolomic studies have revealed that plasma metabolic signatures may predict epithelial ovarian cancer (EOC) recurrence. However, few studies have performed metabolic profiling of pre- and post-operative specimens to investigate EOC prognostic biomarkers.

Objective

The aims of our study were to compare the predictive performance of pre- and post-operative specimens and to create a better model for recurrence by combining biomarkers from both metabolic signatures.

Methods

Thirty-five paired plasma samples were collected from 35 EOC patients before and after surgery. The patients were followed-up until December, 2016 to obtain recurrence information. Metabolomics using rapid resolution liquid chromatography–mass spectrometry was performed to identify metabolic signatures related to EOC recurrence. The support vector machine model was employed to predict EOC recurrence using identified biomarkers.

Results

Global metabolomic profiles distinguished recurrent from non-recurrent EOC using both pre- and post-operative plasma. Ten common significant biomarkers, hydroxyphenyllactic acid, uric acid, creatinine, lysine, 3-(3,5-diiodo-4-hydroxyphenyl) lactate, phosphohydroxypyruvic acid, carnitine, coproporphyrinogen, l-beta-aspartyl-l-glutamic acid and 24,25-hydroxyvitamin D3, were identified as predictive biomarkers for EOC recurrence. The area under the receiver operating characteristic (AUC) values in pre- and post-operative plasma were 0.815 and 0.909, respectively; the AUC value after combining the two sets reached 0.964.

Conclusion

Plasma metabolomic analysis could be used to predict EOC recurrence. While post-operative biomarkers have a predictive advantage over pre-operative biomarkers, combining pre- and post-operative biomarkers showed the best predictive performance and has great potential for predicting recurrent EOC.

     

Optimization of fecal sample preparation for untargeted LC-HRMS based metabolomics

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.

     

Left atrium remodeling predicts late recurrence of paroxysmal atrial fibrillation after second generation cryoballoon ablation

Background

Atrial fibrillation (AF) is the most common arrhythmia worldwide. Nowadays, AF ablation is a valuable treatment option. It has been shown that the left atrium (LA) diameter is a predictor of AF recurrence after cryoballoon ablation (CBA). Since it does not reflect the true LA size, we compared the role of different LA anatomical parameters using echocardiography for the prediction of AF recurrence after CBA.

Methods

We retrospectively included 209 patients (mean age 56.1?±?13.6 years, male 62%) with paroxysmal AF undergoing CBA. A transthoracic echocardiography was performed in all patients.

Results

At a mean follow-up of 16.9?±?6.3 months, AF recurred in 25.4% of the patients. LA anterior - posterior diameter (LAD), LA minimum volume (LAmin) and early AF recurrence were independent predictors of recurrence. Based on receiver operating characteristics, cut – off values for LAD and, LAmin were 41 mm, 23.69 mL, respectively. The negative predictive values for recurrence were 73% and 87.3% respectively. In patients with AF recurrence, a significant proportion (30.2%) showed LA longitudinal remodeling (LA superior – inferior diameter) even though classically measured LAD was normal.

Conclusions

Longitudinal LA remodeling plays an additional role for predicting AF recurrence after CBA, in patients without LAD dilation. Moreover, LAmin had a high negative predictive value and was an independent predictor of AF recurrence. Therefore, a more complete LA anatomical assessment allows a better prediction of AF recurrences after CBA.

     

Crystal structure of <Emphasis Type="Italic">Escherichia coli</Emphasis> protein ybgI,a toroidal structure with a dinuclear metal site

Background

The protein encoded by the gene ybgI was chosen as a target for a structural genomics project emphasizing the relation of protein structure to function.

Results

The structure of the ybgI protein is a toroid composed of six polypeptide chains forming a trimer of dimers. Each polypeptide chain binds two metal ions on the inside of the toroid.

Conclusion

The toroidal structure is comparable to that of some proteins that are involved in DNA metabolism. The di-nuclear metal site could imply that the specific function of this protein is as a hydrolase-oxidase enzyme.

     

Residual bone fragments in tibiofibular joint and postoperative local recurrence: an analysis of 21 cases of proximal fibular giant cell tumour

Background

Currently, there are no known reports on the aetiology of local giant cell tumour (GCT) recurrence in the proximal fibula following en bloc resection. We analysed 21 cases of proximal fibular GCT, focusing on the presence of residual bone in the tibiofibular joint, its causes and its impact on postoperative recurrence.

Methods

We retrospectively analysed 21 cases with proximal fibular GCT occurring between 2000 and 2017.

Results

There were 14 males and 7 females. The average patient age was 25.0 years. Seventeen patients were diagnosed and treated at our facility, while 4 were referred after local recurrence.Six patients presented with residual bone fragments in the tibiofibular joint during their first month of follow-up. Patients with residual bone fragments had a higher local recurrence rate (83.3%) than those without (0%, p?=?0.0003). Upon further analysis, patients with a preoperative Campanacci grade III tumour (p?=?0.0055) and pathological fractures (p?=?0.0109) were at a higher risk of exhibiting postoperative residual bone fragments.

Conclusions

The presence of residual bone fragments in the tibiofibular joint was the main cause of postoperative local recurrence. The presence of residual bone fragments may be related to the preoperative Campanacci grade and pathological fractures. Therefore, close attention should be paid to postoperative follow-up examinations, and if recurrence is suspected, surgical resection should be planned.

     

A lost opportunity for science: journals promote data sharing in metabolomics but do not enforce it

Introduction

Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.

Objectives

(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.

Methods

A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.

Results

Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.

Conclusion

Further efforts are required to improve data sharing in metabolomics.

     

Iridoid and phenylethanoid/phenylpropanoid metabolite profiles of <Emphasis Type="Italic">Scrophularia</Emphasis> and <Emphasis Type="Italic">Verbascum</Emphasis> species used medicinally in North America

Introduction

Botanicals containing iridoid and phenylethanoid/phenylpropanoid glycosides are used worldwide for the treatment of inflammatory musculoskeletal conditions that are primary causes of human years lived with disability, such as arthritis and lower back pain.

Objectives

We report the analysis of candidate anti-inflammatory metabolites of several endemic Scrophularia species and Verbascum thapsus used medicinally by peoples of North America.

Methods

Leaves, stems, and roots were analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and partial least squares-discriminant analysis (PLS-DA) was performed in MetaboAnalyst 3.0 after processing the datasets in Progenesis QI.

Results

Comparison of the datasets revealed significant and differential accumulation of iridoid and phenylethanoid/phenylpropanoid glycosides in the tissues of the endemic Scrophularia species and Verbascum thapsus.

Conclusions

Our investigation identified several species of pharmacological interest as good sources for harpagoside and other important anti-inflammatory metabolites.

     

Corneal Collagen Cross-Linking for the Management of Mycotic Keratitis

Purpose

To evaluate the efficiency of corneal collagen cross-linking (CXL) in addition to topical voriconazole in cases with mycotic keratitis.

Design

Retrospective case series in a tertiary university hospital.

Participants

CXL was performed on 13 patients with mycotic keratitis who presented poor or no response to topical voriconazole treatment.

Methods

The clinical features, symptoms, treatment results and complications were recorded retrospectively. The corneal infection was graded according to the depth of infection into the stroma (from grade 1 to grade 3). The visual analogue scale was used to calculate the pain score before and 2 days after surgery.

Main Outcome Measures

Grade of the corneal infection.

Results

Mean age of 13 patients (6 female and 7 male) was 42.4 ± 17.7 years (20–74 years). Fungus was demonstrated in culture (eight patients) or cytological examination (five patients). Seven of the 13 patients (54%) were healed with topical voriconazole and CXL adjuvant treatment in 26 ± 10 days (15–40 days). The remaining six patients did not respond to CXL treatment; they initially presented with higher grade ulcers. Pre- and post-operative pain score values were 8 ± 0.8 and 3.5 ± 1, respectively (p < 0.05).

Conclusions

The current study suggests that adjunctive CXL treatment is effective in patients with small and superficial mycotic ulcers. These observations require further research by large randomized clinical trials.

     

Pseudomyxoma extraperitonei occurring 35 years after appendicectomy: a case report and review of literature

Background

Pseudomyxoma peritonei is a rare condition consisting of mucinous ascites, most commonly arising from mucinous tumors of the appendix and occasionally from the ovary. Very rarely mucinous implants arise in the retroperitoneum without any intra-peritoneal involvement. This has been termed as pseudomyxoma extraperitonei.

Case presentation

We report a case of a 57 year old man who developed pseudomyxoma extraperitonei, 35 years after undergoing an appendicectomy for a perforated appendix.

Conclusions

Pseudomyxoma extraperitonei has been previously reported, however we report the longest incubation period of 35 years for this condition.

     

Prognostic significance of microvascular invasion in tumor stage for hepatocellular carcinoma

Background

The presence of microvascular invasion (McVI) in hepatocellular carcinoma (HCC) has been proposed as a cause of recurrence and poor survival, although this has not been officially emphasized in staging systems. Thus, we conducted a retrospective study to investigate the prognostic importance of McVI in tumor staging in patients with HCC who underwent hepatic resection.

Methods

A retrospective analysis was performed of patients who underwent hepatic resection for HCC at our center from 1994 to 2012. Patients with HCC were classified into four groups based on the presence of McVI and extent of gross vascular invasion (VI).

Results

The 5-year overall and recurrence-free survival rates of 676 patients were 63.3 and 42.6%, respectively. There was no difference in tumor recurrence or survival rate between patients with HCC and McVI without gross VI and those with gross VI confined to segmental/sectional branches. Multivariate analysis revealed that the extent of VI based on the presence of McVI and gross VI was independently associated with tumor recurrence and overall survival.

Conclusions

McVI was revealed to be an important risk factor similar to gross VI confined to a segmental/sectional branch in patients with HCC who underwent hepatic resection. This finding should be considered when estimating the stage for prognosis.

     

Successful treatment of desmoid tumor of the chest wall with tranilast: a case report

Introduction

Desmoid tumor is characterized by infiltrative growth and local recurrence often occurs after surgery. To reduce the local recurrence rate, adjuvant therapy, such as radiotherapy and pharmacotherapy with cytotoxic agents, anti-estrogen agents and non-steroidal anti-inflammatory drugs, is often applied. In addition, these non-surgical treatments are also performed in patients with unresectable desmoid tumors. We successfully treated a patient with a desmoid tumor with tranilast; an anti-allergic agent.

Case presentation

A 48-year-old Japanese man with a slow-growing desmoid tumor on his chest wall was treated with an oral administration of tranilast (300 mg per day, three times a day). Two years and two months after the commencement of his therapy, the tumor became impalpable. At this time, the oral administration of tranilast was discontinued. Two years after discontinuation of the treatment, a physical examination showed no recurrence of the tumor and he continued in a state of remission. We were successfully able to reduce the size of the tumor and thereafter maintain the reduced size.

Conclusion

Tranilast was clinically effective in our case, and is probably comparable to cytotoxic agents or anti-estrogen agents. Because tranilast has substantially fewer adverse effects than cytotoxic agents, it could be a very useful therapeutic agent for desmoid tumor.

     

Metabolomic profiling of maternal hair suggests rapid development of intrahepatic cholestasis of pregnancy

Introduction

Intrahepatic cholestasis of pregnancy (ICP) is a common maternal liver disease; development can result in devastating consequences, including sudden fetal death and stillbirth. Currently, recognition of ICP only occurs following onset of clinical symptoms.

Objective

Investigate the maternal hair metabolome for predictive biomarkers of ICP.

Methods

The maternal hair metabolome (gestational age of sampling between 17 and 41 weeks) of 38 Chinese women with ICP and 46 pregnant controls was analysed using gas chromatography–mass spectrometry.

Results

Of 105 metabolites detected in hair, none were significantly associated with ICP.

Conclusion

Hair samples represent accumulative environmental exposure over time. Samples collected at the onset of ICP did not reveal any metabolic shifts, suggesting rapid development of the disease.

     

Recurrent Nicolau syndrome associated with subcutaneous glatiramer acetate injection—a case report

Background

Glatiramer acetate is worldwide used as first line treatment in relapsing remitting multiple sclerosis. Local skin reactions associated with glatiramer acetate are common, however, only isolated cases of severe local injection site reactions known as Nicolau Syndrome have been reported so far.

Case presentation

We describe the case of a recurrent Nicolau Syndrome occurred during longstanding glatiramer acetate treatment in a woman with multiple sclerosis. The haemorrhagic patch necrotized and was treated locally as a deep second degree burn with excision of dead skin tissue and was healed. Treatment with glatiramer acetate was definitely suspended.

Conclusions

GA injections can be complicated by isolated or recurrent Nicolau Syndrome, a potentially life-threatening condition of which neurologists should be aware.

     

Quantitative analysis of tetrahydrofolate metabolites from <Emphasis Type="Italic">clostridium autoethanogenum</Emphasis>

Introduction

Quantification of tetrahydrofolates (THFs), important metabolites in the Wood–Ljungdahl pathway (WLP) of acetogens, is challenging given their sensitivity to oxygen.

Objective

To develop a simple anaerobic protocol to enable reliable THFs quantification from bioreactors.

Methods

Anaerobic cultures were mixed with anaerobic acetonitrile for extraction. Targeted LC–MS/MS was used for quantification.

Results

Tetrahydrofolates can only be quantified if sampled anaerobically. THF levels showed a strong correlation to acetyl-CoA, the end product of the WLP.

Conclusion

Our method is useful for relative quantification of THFs across different growth conditions. Absolute quantification of THFs requires the use of labelled standards.