Breast magnetic resonance imaging: are those who need it getting it?

BACKGROUND: Indications for breast magnetic resonance imaging (mri), a very sensitive but less-specific tool for breast investigation, remain controversial, and accessibility is limited. The purposes of our study were to determine the proportion of breast mri exams performed for various clinical indications, to assess the wait times for breast mri, and to create a list of evidence-based indications for breast mri. METHODS: The indications for breast mri exams performed in September 2013 at our academic centre were audited. A multidisciplinary meeting held in May 2014 established a list of evidence-based indications for breast mri, after which, in September 2014 and 2015, breast mri exams were re-audited for clinical indications, and pending requests were calculated. RESULTS: In September 2013, surveillance of women with a prior diagnosis of breast cancer represented 21% of breast mri exams (24 of 113), with preoperative staging representing 18% of exams (20 of 113) and high-risk screening representing 12% (13 of 113). Of pending mri requests, 230 were within the recommended delay period, and 457 exceeded the recommended delay. After elaboration of evidence-based guidelines, repeat audits in September 2014 and September 2015 showed that mri performed for women with a prior breast cancer diagnosis represented 23% (33 of 141) and 7% (10 of 143) of exams respectively, with preoperative staging having declined to 9% (13 of 141) and 11% (16 of 143) of exams, and high-risk screening having increased to 36% (51 of 141) and 46% (66 of 143) of exams. Overall, wait times were improved for all breast mri indications. CONCLUSIONS: Through multidisciplinary discussion, we actualized a list of breast mri indications, prioritized requests more adequately, and improved wait times.

Guidelines on the use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal surface malignancy arising from colorectal or appendiceal neoplasms.

To meet the needs of patients, Canadian surgical and medical oncology leaders in the treatment of peritoneal surface malignancies (psms), together with patient representatives, formed the Canadian HIPEC Collaborative Group (chicg). The group is dedicated to standardizing and improving the treatment of psm in Canada so that access to treatment and, ultimately, the prognosis of Canadian patients with psm are improved. Patients with resectable psm arising from colorectal or appendiceal neoplasms should be reviewed by a multidisciplinary team including surgeons and medical oncologists with experience in treating patients with psm. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy should be offered to appropriately selected patients and performed at experienced centres. The aim of this publication is to present guidelines that we recommend be applied across the country for the treatment of psm.

Screening for BRCA1 and BRCA2 mutations among French-Canadian breast cancer cases attending an outpatient clinic in Montreal.

Study subjects were French-Canadian women with ductal carcinoma in situ (DCIS) or invasive breast cancer (incident or prevalent) who were treated and followed at a single breast cancer clinic affiliated with the Research Center of University of Montreal (CRCHUM), who were either aged less than 50 years at diagnosis or who were 50 years or older and with at least two affected first- or second-degree relatives. Subjects were tested for six founder mutations (three in BRCA1 and three in BRCA2); 1093 eligible cases were tested. Of these, 56 women (5.1%) were mutation carriers, including 43 BRCA2 carriers and 13 BRCA1 carriers. The prevalence of mutations was 5.3% for unselected women aged 50 and less and was 4.6% for familial cases over age 50. The prevalence of mutations was 3.3% for women with DCIS and was 5.3% for women with invasive cancer. It is rational to offer genetic testing to all French-Canadian women diagnosed recently or in the past with either DCIS or invasive breast cancer before age 50 or with familial breast cancer above age 50.

Clinical efficacy of mini-percutaneous nephrolithotomy versus retrograde intrarenal surgery for the management of upper urinary tract calculus (1-2.5 cm) in children ≤10 years of age.

BACKGROUND: With improvements in endoscopic surgery, open surgical procedures for urinary system stones have cleared the path for the use of less invasive treatment modalities in patients with pediatric kidney stone disease. Extracorporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL), and retrograde intrarenal surgery (RIRS) are among the treatment options available. OBJECTIVE: To prospectively evaluate the outcomes of mini-percutaneous nephrolithotomy and retrograde intrarenal surgery (RIRS) for children ≤10 years of age with upper urinary tract calculus (1-2.5 cm). STUDY DESIGN: Sixty pediatric patients with single or multiple renal stones (1-2.5 cm in diameter) were collected prospectively and equally divided into two groups to undergo RIRS or mini-PCNL. The operative and postoperative outcomes of both groups were analyzed. RESULTS: The groups' mean ages and genders were comparable. The mean stone size for the RIRS group was 1.86 cm and 1.69 cm for the PCNL group (P = 0.449). The PCNL group had statistically longer mean fluoroscopy and hospitalization times. The stone-free rates (SFRs) after a single procedure were 27 (90%) in the PCNL group and 25 (83.33%) in the RIRS group (P = 0.706). The UAS was placed in 13 (43.33%) patients in the RIRS group. In the RIRS group, 14 (46.67%) children required preoperative DJ stent application to passively dilate the ureteric orifice. As regard post DJ stenting, 13 (46%) cases applied DJ in the mini PCNL group. major complications were observed in either group. Minor complication (Clavien 1-3) rates were 16.66% and 13.33% for the PCNL and RIRS groups, respectively. There were no differences found between the RIRS and mini-PCNL groups regarding operative time. The mean cost of RIRS was $703.96 and $537.03 for the mini-PCNL. CONCLUSION: According to the results of this study, mini-PCNL and RIRS are effective procedures for treating renal stones in children up to 2.5 cm with comparable success and complication rates. Hospital stay, radiation exposure, and fluoroscopy time are significantly lower in RIRS than in the mini PCNL technique. Although RIRS is effective, a major disadvantage is the greater requirement for JJ stent insertion either before or after the procedure and the consequent need for a second procedure for removal.

Tick-borne encephalitis in Bulgaria, 2009 to 2012.

For the last 60 years, only a few cases of tick-borne encephalitis (TBE) have been detected in Bulgaria. Considering the remarkable increase in TBE morbidity in Europe over the past two decades, we conducted a study of TBE among patients with acute viral meningitis who were hospitalised in Bulgaria during 2009 to 2012. A total of 86 patients with viral meningitis of unknown aetiology during this period were tested. Acute TBE was confirmed in three of these patients. The last TBE case was detected in October 2012; the other two were diagnosed in 2009. To the best of our knowledge, these three patients are the first confirmed TBE cases reported in Bulgaria. The risk of TBE is underestimated in Bulgaria due to the low awareness of medical doctors.

Prostatic artery embolization versus transurethral resection of the prostate in management of benign prostatic hyperplasia.

BACKGROUND: Transurethral resection of the prostate (TURP) is considered the gold standard surgical intervention for prostate size less than 80 g. Prostatic artery embolization (PAE) has been suggested as a minimally invasive interventional radiological procedure in the management of benign prostatic hyperplasia (BPH), especially by using the PErFecTED technique. We aim through our study to evaluate the efficacy and safety of PAE compared with those of monopolar transurethral resection of prostate (M-TURP) and bipolar transurethral resection of prostate (B-TURP) in treating lower urinary tract symptoms (LUTSs) secondary to BPH. METHODS: We randomized 60 patients into 3 equal groups representing M-TURP, B-TURP, and PAE. Patients were followed up at 1 and 6 months postoperatively with regard to the International prostate symptom score (IPSS) score; uroflowmetry; prostate volume by transrectal ultrasound; and postvoid residual urine. RESULTS: The mean operative time was 59, 68, and 89 minutes for the M-TURP group, the B-TURP group, and the PAE group, respectively; only one patient, who represented 5% of the M-TURP group and 1.7% of the whole study population, developed transurethral resection syndrome. Four patients of the PAE group complained of postembolization syndrome, which represented 20% of the cases. Only two patients in our study, both belonging to the PAE group, developed acute urinary retention after catheter removal, representing 10% of the PAE group and 3.33% of the whole study population. The improvement in the IPSS score, the average uroflowmetry (Q-average) score, postvoid residual urine, and prostate volume reduction was noted in all groups, with more statistically significant improvement in each of the M-TURP and the B-TURP groups than in the PAE group. CONCLUSION: PErFecTED technique is a novel way of embolization, with statistically significant improvement for patients complaining of LUTSs due to BPH in terms of improvement of IPSS, uroflowmetry, prostate size, and amount of postvoid residual urine, yet these results are still not comparable with either the results of M-TURP or B-TURP that still show more effective improvement.

Respiratory mechanics and gas exchanges in the early course of COVID-19 ARDS: a hypothesis-generating study.

RATIONALE: COVID-19 ARDS could differ from typical forms of the syndrome. OBJECTIVE: Pulmonary microvascular injury and thrombosis are increasingly reported as constitutive features of COVID-19 respiratory failure. Our aim was to study pulmonary mechanics and gas exchanges in COVID-2019 ARDS patients studied early after initiating protective invasive mechanical ventilation, seeking after corresponding pathophysiological and biological characteristics. METHODS: Between March 22 and March 30, 2020 respiratory mechanics, gas exchanges, circulating endothelial cells (CEC) as markers of endothelial damage, and D-dimers were studied in 22 moderate-to-severe COVID-19 ARDS patients, 1 [1-4] day after intubation (median [IQR]). MEASUREMENTS AND MAIN RESULTS: Thirteen moderate and 9 severe COVID-19 ARDS patients were studied after initiation of high PEEP protective mechanical ventilation. We observed moderately decreased respiratory system compliance: 39.5 [33.1-44.7] mL/cmH2O and end-expiratory lung volume: 2100 [1721-2434] mL. Gas exchanges were characterized by hypercapnia 55 [44-62] mmHg, high physiological dead-space (VD/VT): 75 [69-85.5] % and ventilatory ratio (VR): 2.9 [2.2-3.4]. VD/VT and VR were significantly correlated: r2 = 0.24, p = 0.014. No pulmonary embolism was suspected at the time of measurements. CECs and D-dimers were elevated as compared to normal values: 24 [12-46] cells per mL and 1483 [999-2217] ng/mL, respectively. CONCLUSIONS: We observed early in the course of COVID-19 ARDS high VD/VT in association with biological markers of endothelial damage and thrombosis. High VD/VT can be explained by high PEEP settings and added instrumental dead space, with a possible associated role of COVID-19-triggered pulmonary microvascular endothelial damage and microthrombotic process.

Canadian guidelines on the management of colorectal peritoneal metastases.

Modern management of colorectal cancer (crc) with peritoneal metastasis (pm) is based on a combination of cytoreductive surgery (crs), systemic chemotherapy, and hyperthermic intraperitoneal chemotherapy (hipec). Although the role of hipec has recently been questioned with respect to results from the prodige 7 trial, the role and benefit of a complete crs were confirmed, as observed with a 41-month gain in median survival in that study, and 15% of patients remaining disease-free at 5 years. Still, crc with pm is associated with a poor prognosis, and good patient selection is essential. Many questions about the optimal management approach for such patients remain, but all patients with pm from crc should be referred to, or discussed with, a pm surgical oncologist, because cure is possible. The objective of the present guideline is to offer a practical approach to the management of pm from crc and to reflect on the new practice standards set by recent publications on the topic.

The contribution of founder mutations to early-onset breast cancer in French-Canadian women.

In an ethnically-homogeneous population, it is valuable to identify founder mutations in cancer-predisposing genes. Founder mutations have been found in four breast-cancer-predisposing genes in French-Canadian breast cancer families. The frequencies of the mutant alleles have been measured neither in a large series of unselected breast cancer patients from Quebec, nor in healthy controls. These estimates are necessary to measure their contribution to the hereditary burden of breast cancer in Quebec and to help develop genetic screening policies which are appropriate for the province. We studied 564 French-Canadian women with early-onset invasive breast cancer who were treated at a single Montreal hospital. Patients had been diagnosed at age 50 or less, and were ascertained between 2004 and 2008. We screened all 564 patients for nine founder mutations: four in BRCA1, three in BRCA2 and one each in PALB2 and CHEK2. We also studied 6433 DNA samples from newborn infants from the Quebec City area to estimate the frequency of the nine variant alleles in the French-Canadian population. We identified a mutation in 36 of the 564 breast cancer cases (6.4%) and in 35 of 6443 controls (0.5%). In the breast cancer patients, the majority of mutations were in BRCA2 (54%). However, in the general population (newborn infants), the majority of mutations were in CHEK2 (54%). The odds ratio for breast cancer to age 50, given a BRCA1 mutation, was 10.1 (95% CI: 3.7-28) and given a BRCA2 mutation was 29.5 (95% CI: 12.9-67). The odds ratio for breast cancer to age 50, given a CHEK2 mutation, was 3.6 (95% CI: 1.4-9.1). One-half of the women with a mutation had a first- or second-degree relative diagnosed with breast or ovarian cancer. Thus, it can be concluded that a predisposing mutation in BRCA1, BRCA2, CHEK2 or PALB2 is present in approximately 6% of French-Canadian women with early-onset breast cancer. It is reasonable to offer screening for founder mutations to all French-Canadian women with breast cancer before age 50. The frequency of these mutations in the general population (0.5%) is too low to advocate population-based screening.

Cytoreduction combined with intraperitoneal hyperthermic perfusion chemotherapy in advanced/recurrent ovarian cancer patients: The experience of National Cancer Institute of Milan.

AIMS: We report the effects of cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP) in the treatment of advanced/recurrent epithelial ovarian cancer (EOC) on survival, morbidity and mortality. PATIENTS: Forty EOC patients were studied. Median age was 52.5 years (range: 30-68) and median follow-up 26.1 months (range: 0.3-117.6). Most patients presented advanced disease (stage III/IV). Previous systemic chemotherapy included cisplatin-based, taxol-based or taxol/platinum containing regimens. RESULTS: After the CRS, 33 patients presented no macroscopic residual disease. Five-year overall survival was 15%; the mean overall and progression-free survivals were 41.4 and 23.9 months, respectively. The morbidity, toxicity and mortality rates were 5%, 15% and 0%, respectively. CONCLUSION: Our results suggest that CRS + IPHP merits further evaluation by a formal prospective trial.

Merkel cell carcinoma of the hand: case report and literature review.

We are reporting on a 72-year-old male who was diagnosed with Merkel cell carcinoma on the dorsal aspect of his left index finger. This rare highly aggressive malignancy of the skin has only exceptionally been described on the finger or hand. This case report helps review important findings associated with this rare malignancy and reviews the pertinent literature.

CDX-2 expression in pseudomyxoma peritonei: a clinicopathological study of 42 cases.

AIMS: CDX-2 is a highly sensitive and specific marker of intestinal epithelial cells and their neoplastic counterparts. CDX-2 status in pseudomyxoma peritonei (PMP) has been barely reported. The aim of this study was to investigate the clinicopathological features of 42 cases of PMP with a special emphasis on CDX-2. METHODS AND RESULTS: All patients were treated by cytoreduction. Immunohistochemistry was performed for CDX-2, MUC-2, MUC-5AC, cytokeratin (CK) 7 and CK20. Statistical correlation was evaluated for age, sex, completeness of cytoreduction and histological subtype with overall and progression-free survival (OS and PFS). PMP consisted of 32 cases of disseminated peritoneal adenomucinosis and 10 cases of peritoneal mucinous carcinomatosis. The appendix evaluated in 25 cases showed two mucinous adenocarcinomas and 21 low-grade appendiceal mucinous neoplasms. CDX-2 was diffusely positive in 40 cases, with the remaining two cases being focally positive. All cases demonstrated diffuse reactions to CK20 and MUC-2, and variable reactions to MUC-5AC, while CK7 was variably positive in 38 cases. Five-year OS was 97%. Histological type was significantly correlated with PFS (P=0.02). CONCLUSIONS: CDX-2 is diffusely and strongly positive in PMP. This is a useful marker to confirm an appendiceal origin of PMP, particularly when used in conjunction with CK7, CK20, MUC-2 and MUC-5AC.

Novel genomic insertion-- deletion in MLH1: possible mechanistic role for non-homologous end-joining DNA repair.

Hereditary non-polyposis colorectal cancer (HNPCC) is an inherited cancer syndrome caused by a defect in the mismatch repair pathway. The majority of HNPCC mutations have been detected in MLH1 and MSH2. Most reported mutations are substitutions, small insertions and deletions, but standard methods of mutation analysis do not detect large rearrangements. It is now established that large deletions, insertions and rearrangements account for a significant proportion of MLH1 and MSH2 mutations. We report an unusual rearrangement resulting in the deletion of exons 6, 7 and 8 of MLH1, with the retention of part of intron 6 and insertions of two nucleotides each flanking the retained sequence. The 349-bp-retained sequence is made up of two closely spaced Alu sequences. The mutation was initially detected by protein truncation test and cDNA sequencing. Multiplex ligation-dependent probe amplification confirmed the deletion of three exons. PCR and sequencing were used to characterize the breakpoint. Despite the high density of Alu elements in MLH1, there is no homology at the deletion breakpoints or insertion junctions in this case to suggest that homologous recombination has occurred. We propose a mechanism involving non-homologous end joining to explain the occurrence of this complex deletion.