Erratum: Therapeutic landscape of metastatic non-small-cell lung cancer in Canada in 2020.

[This corrects the article DOI: 10.3747/co.27.5953.].

Prognosis in young women less than 40 years of age with brain metastasis from breast cancer.

Background: Brain metastasis from breast cancer (bca) in young women is doubly devastating because both quality of life and life expectancy are significantly reduced. With new radiation technology and drugs that have emerged, survival is expected to increase for these young women. Methods: Using the oacis and sardo patient databases, we identified 121 patients diagnosed with bca and brain metastasis between 2006 and 2016 at the University of Montreal Hospital Centre. Those patients were divided into Group A, patients who developed brain metastasis during the evolution of metastatic bca, and Group B, patients whose first metastasis was to the brain. For each group, we compared young patients (<40 years of age) with older patients (≥40 years of age). Results: Among the 121 patients with brain metastasis, median overall survival (mos) was significantly longer for those less than 40 years of age than for those 40 or more years of age (18 months vs. 4 months, p < 0.001). With respect to the timing of brain metastasis, survival was significantly longer in Group B than in Group A (7 months vs. 4 months, p = 0.032). In Group A, mos was significantly longer for patients less than 40 years of age than for patients 40 or more years of age (18 months vs. 3 months, p = 0.0089). In Group B, the 2-year overall survival rate was 57% for patients less than 40 years of age and 12% for those 40 or more years of age (mos: not reached vs. 7 months; p = 0.259). Conclusions: In our single-centre retrospective cohort of women with brain metastasis from bca, prognosis was better for young women (<40 years) than for older women (≥40 years). Survival was also longer for patients whose initial metastasis was to the brain than for patients whose brain metastasis developed later in the disease course. In patients who received systemic treatment, median survival remained significantly higher in women less than 40 years of age. Further studies are needed to validate those results.

Therapeutic landscape of metastatic non-small-cell lung cancer in Canada in 2020.

Lung cancer is the most commonly diagnosed cancer in Canada and remains associated with high mortality. Nevertheless, recent advances in the fields of immuno-oncology and precision medicine have led to significant improvements in clinical outcome in metastatic non-small-cell lung cancer (nsclc). Those improvements were facilitated by a greater understanding of the biologic classification of nsclc, which catalyzed discoveries of novel therapies. Here, we present a comprehensive review of the recent avalanche of practice-changing trials in metastatic nsclc, and we offer an approach to the management of this disease from a Canadian perspective. We begin with an overview of the pathologic and molecular characterization of metastatic nsclc. Next, we review the indications for currently approved immune checkpoint inhibitors, and we provide an approach to the management of disease with a driver mutation. Finally, we address future avenues in both diagnostics and therapeutics for patients with advanced and metastatic nsclc.

Procarbazine, lomustine and vincristine toxicity in low-grade gliomas.

BACKGROUND: Procarbazine, lomustine, and vincristine (pcv) significantly improve survival outcomes in lgg (low-grade gliomas). Administration of pcv to lgg patients increased tremendously over the past years as it went from 2 patients per year between 2005 and 2012 to 23 patients in 2015 only in our centre. However, serious hematological and non-hematological adverse events may occur. The purpose of this study was to evaluate the toxicity of pcv and its clinical relevance in our practice. METHODS: We retrospectively reviewed the charts of 57 patients with lgg who received pcv at the Centre hospitalier de l'Université de Montréal between 1 January 2005 and 27 July 2016. RESULTS: Procarbazine, lomustine, and vincristine were associated with severe hematological toxicity as clinically significant grade 3 anemia, neutropenia, and thrombocytopenia occurred in 7%, 10%, and 28% of patients, respectively. Other frequent adverse events such as the increase of liver enzymes, cutaneous rash, neurotoxicity, and vomiting occurred in 65%, 26%, 60%, and 40% of patients, respectively. Patients with prophylactic trimethoprim/sulfamethoxazole had more grade 3 hematological toxicity with pcv, especially anemia (p = 0.040) and thrombocytopenia (p = 0.003) but we found no increase in pcv toxicity in patients on concurrent anticonvulsants. Patients with grade 3 neutropenia had a significantly lower survival (median survival 44.0 months vs. 114.0 months, p = 0.001). Patients who were given pcv at diagnosis had more grade 3 anemia than those who received it at subsequent lines of treatment (p = 0.042). CONCLUSION: Procarbazine, lomustine, and vincristine increase survival in lgg but were also associated with major hematologic, hepatic, neurologic, and cutaneous toxicity. Anti-Pneumocystis jiroveci pneumonia (pjp) prophylaxis, but not anticonvulsants, enhances hematologic toxicity.

Histopathological Prognostic Factors for Colic Adenocarcinoma.

The majority of colorectal carcinomas are adenocarcinomas derived from the colic mucosae cell, more frequently moderately differentiated. The purpose of this study was to determine de incidence of CRC and the relationship between histopathological risk factors in patients with colic adenocarcinomas. The study included 144 cases of CRC diagnosed within the Pathology Laboratory of the Clinical County Hospital of Craiova in the year 2017.The biological material consisted in samples from colectomies and hemicolectomies provided from patients admitted within the surgical clinics of the same hospital, then fixed with 10% buffered formalin and afterwards processed using the classic histopathological technique of paraffin inclusion and staining with hematoxylin and eosin. We observed certain histopathological parameters such as: pattern, grading, stage, vascular invasion and neural invasion. The mean age of diagnostic was 68.6 ± 11.2, and it was predominantly male patients (64.6%). Most cases presented with mucinous pattern (31.9%) and cribriform comedocarcinoma type (29.9%). The majority were classified as stage III B (34%), being moderately differentiated (64.6%) and associated with vascular invasion (47.2%) and perineural invasion (25.7%). Statistical analysis indicated significant relationships between tumor stage and differentiation grade (p<0.01, χ²test), as well as between tumor stage and vascular invasion (p<0.05, χ²test), without including perineural invasion (p<0.05, χ²test).

Histopathological Prognostic Factors in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (CCRCC) are the most frequent type of renal cell carcinoma. Fuhrman grade and tumor stage are prognostic factors with great importance in survival rate. This study was performed on 75 cases of CCRCC diagnosed by the Anatomical Pathology Laboratory of the County Clinical Emergency Hospital of Craiova between 2014 and 2017. The biological material was represented by pieces of nephrectomy. The cases were analyzed on two criteria: epidemiology (age, sex) and histopathology (Fuhrman grade, tumor stage, architectural pattern, sarcomatoid transformation, and necrosis). Statistical analysis was done using Chi Square tests in IBM SPSS software. Average diagnosis age of CCRCC was 58.8±10.2 years, predominantly in male patients (66.7%). Tumor sizes were between 2 and 14cm, with an average of 6.7±2.9cm. Most cases were determined to be tumor stage III (60%) and Fuhrman grade 2 (56%), followed, in order of frequency, by tumor stages I and II (28% and 10.7%) and Fuhrman grades 3 and 1 (21.3% and 20%). High Fuhrman grade CCRCC were significantly associated with advanced tumor stage (p<0.05, χ2 test). Most cases presented a mixed pattern, significantly associated with advanced tumor stages (p<0.05, χ2 test). Even though the presence of sarcomatoid transformation was more frequent in advanced tumor stages, it wasn't significantly linked to them (p<0.05, χ2 test). Conclusions: Analyzed histopathological parameters are useful for determining CCRCC aggressiveness. CCRCC in advanced tumor stages is associated with high Fuhrman grade and mixed architectural pattern.

Pancreatic Head Carcinoma-Implications and Correlations in a Romanian Population.

INTRODUCTION: Pancreatic cancers are often an aggressive type of malignancy, with a 5-year survival rate estimated at around 5%. The main purpose of our study was to determine whether or not tumor dimensions influence the presence of jaundice and the diameters of the CBD and Wirsung duct. MATERIAL AND METHODS: The study group included 32 patients (19 males, 13 females) diagnosed with various histological types of pancreatic head cancers who were hospitalized in the Surgery Department of the County Clinical Emergency Hospital of Craiova during 2016-2018. All 32 patients underwent an initial abdominal ultrasonography (US), followed by an abdominal computed tomography (CT) scan and an abdominal magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) sequences. RESULTS: Based on tumor dimensions, 19 (59.38%) were equal to or larger than 30mm, while 13 (40.62%) were smaller than 30mm. The average age of male patients was 65.15 years, while the average age of female patients was 60.07 years. Tumor dimensions ranged between 22mm and 52mm (33.53mm on average). Furthermore, the diameter of the CBD ranged from 5mm to 20mm (13.40mm on average), while the diameter of the Wirsung duct ranged from 3mm to 12mm (5.75 mm on average). CONCLUSION: In conclusion, our study reached its' initial purpose and revealed a significant association between the tumor dimensions and the diameter of the Wirsung duct and also between the diameter of the CBD and the presence of jaundice.

Factors influencing treatment selection and survival in advanced lung cancer.

PURPOSE: Despite numerous breakthrough therapies, inoperable lung cancer still places a heavy burden on patients who might not be candidates for chemotherapy. To identify potential candidates for the newly emerging immunotherapy-based treatment paradigms, we explored the clinical and biologic factors affecting treatment decisions. METHODS: We retrospectively reviewed the records of patients diagnosed at our university-affiliated cancer centre between 1 January 2011 and 31 December 2013. Patient demographics, systemic treatment, and survival were examined. RESULTS: During the 3-year study period, 683 patients fitting the inclusion criteria were identified. First-line therapy was administered in 49.5% of patients; only 22.4% received further lines of therapy. The main reasons for withholding therapy were poor performance status [ps (43.2%)], rapidly deteriorating ps (31.9%), patient refusal of therapy (20.9%), and associated comorbidities (4%). Older age, the presence of brain metastasis at diagnosis, and non-small-cell histology were also associated with therapeutic restraint. Oncology referrals were infrequent in patients who did not receive therapy (32.2%). Older patients and those with a poor ps experienced superior survival when treatment was administered (hazard ratio: 0.25; 95% confidence interval: 0.16 to 0.38; and hazard ratio: 0.44; 95% confidence interval: 0.23 to 0.87 respectively; p < 0.001). CONCLUSIONS: Advanced lung cancer still poses a therapeutic challenge, with a high proportion of patients being deemed unfit for therapy. This issue cannot be resolved until appropriate measures are taken to ensure the inclusion of older patients and those with a relatively poor ps in large clinical trials. Immunotherapy might be interesting in this setting, given that it appears to be more tolerable. Another consequential undertaking would be the deployment of strategies to reduce wait times during the diagnostic process for patients with a high index of suspicion for lung cancer.

RADIOLOGICAL SAFETY ASSESSMENT FOR THE EXPERIMENTAL AREA OF A HYPER-INTENSE LASER WITH PEAK-POWER OF 1PW-CETAL.

Ultra-high intensity lasers in use are connected with ionizing radiation sources that raise a real concern in relation to installations, personnel, population and environment protection. The shielding of target areas in these facilities has to be evaluated from the conceptual stage of the building design. The sizing of the protective concrete walls was determined using computer codes such as Fluka. For the experiments to be carried out in the facility of the Center for Advanced Laser Technologies (CETAL), both proton beams with the energy of 100 MeV and electron beams with 300 MeV energy were considered to calculate the dimensions of structural shielding and to establish technical solutions fulfilling the radiation protection constraints imposed by the National Commission for Nuclear Activities Control.

Histopathological Prognostic Factors for Endometrial Carcinoma.

The purpose of our study was to determine the incidence and the relationship between prognostic factors (age at diagnosis, pTNM stage, histological grade, lymph vascular and myometrium invasion) in patients with endometrial carcinoma. We evaluated in terms of diagnosis 50 cases of endometrial carcinomas that were hospitalized during 2011-2014 in the Obstetrics, Gynecology and Surgery clinics of the Emergency County Hospital Craiova. The procedure consisted in fixation in 10% buffered formalin, followed by processing with usual technique of paraffin embedding and finally staining in hematoxylin and eosin. The histological analysis of the 50 endometrial carcinomas revealed well-differentiated carcinomas (G1) in 24 cases (48%), moderately differentiated carcinomas (G2) in 17 cases (34%) and poorly differentiated carcinomas (G3) in further 9 cases (18%).The myometrium invasion was present in the internal half of the myometrium in 12 internal cases (24%) and in the external half of myometrium in further 36 cases (72%). In 2 cases (4%) the myometrium invasion was absent. We achieved significant association between histological grade and invasion of myometrium, also between histological grade and lymphovascular invasion, as well as tumor stage and myometrium invasion. We are also able to report significant association between lymphovascular invasion and tumor stage or tumor stage and presence of lymph nodes. The results of this study emphasize the importance of pathological parameters as prognostic factors in endometrial carcinoma.

Breast-conserving surgery in breast cancer.

The breast cancer treatment is based nowadays on new surgical options: breast-conserving surgery, which applies at least for the first and second stage cancer, with radical intention. We have been practicing breast-conserving surgery for the last 16 years and we have performed 303 breast conserving operations from a total of 673. We recorded 12 local recurrences (3,96%) and 2 deaths due to cancer progression. Our protocol includes removal of the primary tumor with enough surrounding tissue to ensure negative margins of the resectable specimen, associated with axillary lymph-node dissection and postoperative breast irradiation. Our oncologist indicated chemotherapy on different postoperative conditions: tumor size, axillary lymph node involvement, patient's age, etc. The purpose of this paper is to emphasize our modest experience, nevertheless to draw the attention on important results, obtained by long-term monitoring of the patients who underwent breast-conserving surgery, in a two prospective protocols, and demonstrate the importance and applicability of breast conserving therapy. The conclusion of this study is that breast-conserving surgery followed by breast irradiation is reliable, as the results are similar with radical mastectomies; the main objective is to obtain a good cosmetic result, which depends on tumor size / breast size.

[Diseases mimicking advanced-stage epithelial ovarian cancer]. / Afectiuni mimând cancerul ovarian epitelial în stadiu avansat.

This paper draws attention towards 3 cases with different pathologies all of which suggesting however both clinically and by imaging means as the most likely diagnosis advanced-stage epithelial ovarian cancer since all these three postmenopausal women had been admitted to the hospital with ascites, pelvic masses and deterioration of the physical wellbeing (fatigue, decreased appetite, weight loss, pallor). Findings during exploratory laparotomy on all these three pacients included ascites (hemorragic in one case) diffuse tumorous implants throughout the abdominal and pelvic peritoneal surfaces (in two cases) and the ovarian tumour. Postoperatively, the final histopathologic diagnoses consisted of primary peritoneal carcinoma (one pacient), peritoneal tuberculosis (TB, one pacient) and hepatic cirrosis with an incidental benign adnexial mass (one pacient). Moreover, nonmalignant ovarian tumours were certified in all three cases under current presentation. The differential diagnosis of the ovarian cancer and a tailored approach to treatment for each of these three pathologic entities will also be described in detail.

[Stress urinary incontinence. Diagnostic and therapeutic aspects]. / Incontinenta urinara de efort. Aspecte diagnostice si terapeutice.

OBJECTIVE: The paper analyses the incidence, diagnosis and treatment options available for stress urinary incontinence (SUI) in women with pelvic floor dysfunction admitted to Craiova's Surgery Clinic IV. METHODS: This is a retrospective 10-year study comprising a surgical cohort of 420 patients with significant enough to alter quality of life SUI associated to ureterocele and cystocele and in 353 cases with rectocele too. The highest incidence of SUI was encountered between 50 and 59 years of age (range 39 - 81 years). In 21 of this case series the diagnosis of SUI was established soon after the surgical repair of the urethro-cystocele. The diagnosis of SUI was based on careful history and physical examination with emphasis on the gynecologic survey of the abdomen and pelvis but in the absence (for objective reasons) of urodynamic testing which is especially useful for SUI pathophysiological evaluation and thus surgery success rate prediction. All our 420 severe SUI associated with vaginal wall hernias underwent surgical treatment by either open Burch retropubic urethropexy or anterior colporraphy. RESULTS: Among anterior colporraphy treated patients SUI persisted in 19.3% of the cases (33 patients). Complications of Burch urethropexy procedure (despite its high ability for cure) in our case series include: urinary retention, hemorrhage into the space of Retzius, intraoperative injury to the bladder and long-term postoperative incisional hernia. Moreover, 5 patients (2%) of the group who underwent Burch operation were readmitted with recurrent urinary incontinence between 2 and 6 months after the aforementioned surgical intervention despite its good anatomical results in all of these cases. CONCLUSIONS: SUI is a prevalent disorder of women that can be diagnosed easily with history and physical exam. If symptoms persist and severely affect quality of life, despite modern noninvasive treatments, several surgical procedures are now available.

[The mirage of the first lesion (gallstones) and laparoscopic cholecystectomy are able to defer the diagnosis of colon cancer]. / Mirajul primei leziuni (litiaza veziculara) si colecistectomia laparoscopica pot întârzia diagnosticul de cancer colic.

The study's aim was to analyze a series of colon cancer cases in which the mirage of the first (clinically most obvious) lesion (gallstones) along with its minimally invasive approach - that explored only the biliary disease - had contributed to the delay of large bowel malignancy' diagnosis and treatment. 1327 patients aged between 17 and 83 years and diagnosed with cholecystolithiasis were operated upon laparoscopically in the Department of General Surgery of Craiova CFR University Hospital from 2000 through 2004. Four out of these 1327 patients (0,3%) were readmitted with the diagnosis of colon carcinoma between 1 and 16 months after the laparoscopic cholecystectomy. Our retrospective study gives a full report on these 4 cases insisting upon the links between their clinical - laboratory evaluations and final diagnosis. Despite the low laparoscopic cholecystectomy overlooked colon cancer' incidence it seems reasonable to both improve the technique of peritoneal cavity exploration during this type of surgery and extend the preoperative evaluation whenever the slightest suspicion of associated pathology is raised especially in patients over 50 years of age.

Carbon film electrodes for oxidase-based enzyme sensors in food analysis.

Carbon film resistor electrodes have been evaluated as transducers for the development of multiple oxidase-based enzyme electrode biosensors. The resistor electrodes were first modified with Prussian Blue (PB) and then covered by a layer of covalently immobilized enzyme. Electrochemical impedance spectroscopy was used to characterize the interfacial behaviour of the Prussian Blue modified and enzyme electrodes; the spectra demonstrated that the access of the substrates is essentially unaltered by application of the enzyme layer. These enzyme electrodes were used to detect the substrate of the oxidase (glucose, ethanol, lactate, glutamate) via reduction of hydrogen peroxide at +50mV versus Ag/AgCl in the low micromolar range. Response times were 1-2min. Finally, the glucose, ethanol and lactate electrochemical biosensors were used to analyse complex food matrices-must, wine and yoghurt. Data obtained by the single standard addition method were compared with a spectrophotometric reference method and showed good correlation, indicating that the electrodes are suitable for food analysis.

[The experience at the 4th Surgery Department of the University Hospital C.F. Craiova in the surgical treatment of inguinal hernia]. / Experienta Clinicii Chirurgicale IV a Spitalului Universitar C. F. Craiova în folosirea plaselor sintetice în tratamentul chirurgical al herniilor inghinale.

This paper aim is to present the experience of Surgery Department IV of University Hospital C. R. Craiova in groin hernias treatment using prosthetic meshes, also describing an original technical procedure of mesh-plasty that we have been practicing successfully in our clinic. The study is based on a number of 1757 groin hernias operated in Surgery Department IV of University Hospital C. F. Craiova during a period of 11 years (1993-2003). There have been used prosthetic meshes in a number of 230 hernias operated for the most part in the last years since mesh repair has become habitually. We have been using so far only prosthetic mesh made in Romania (polyester mesh). We had a single recurrent hernia and the immediate complications were minimal. The study refers us to practice prosthetic mesh repair in an extensive way and offers a technical alternative in using of prosthetic meshes by a simple and efficient procedure with good postoperative results.

[Ovarian cancer--diagnostic dilemmas and unusual therapeutic response]. / Cancerul de ovar între dileme de diagnostic si "capriciile" raspunsului terapeutic.

The aims of this paper are both to highlight some dilemmas concerning the diagnosis of primary epithelial ovarian carcinoma mainly in its early stages and to underline the capricious responses of this type of malignancy to an otherwise well coded modern management. This study is based on the analysis of the records of 78 patients with ovarian carcinoma admitted for diagnosis and surgical treatment to the Department of General Surgery of Craiova C.F.R. Clinic from 1993 through 2003. The results of this analysis are difficult to interpret due to loss to follow up (in terms of response rates) of some of our 78 operated on ovarian carcinoma patients who went on with their platinum-based chemotherapy (following surgical cytoreduction) under the supervision of different Oncology Departments nationwide. Nevertheless, it is worth mentioning that most of this study patients (71.9%) presented with advanced-stage (III and IV) ovarian carcinoma which sometimes seemed quite confusing by its clinical polymorphism but its prognosis was very much related to both the degree of surgical cytoreduction accomplished and tumor sensitivity to chemotherapy. Finally, although this study does not allow us to draw firm conclusions it is an attempt to share out our current perception on the primary epithelial ovarian cancer management.

[Locoregionally advanced rectosigmoid cancer: diagnosis, surgical approach, late results]. / Neoplasmul rectosigmoidian avansat locoregional. Probleme de diagnostic, rezultate la distanta, atitudine terapeutica chirurgicala.

The colorectal cancer continues to be diagnosed in advanced stages in our country, mainly due to unapplying of a programmer of active diagnosis through screening on the population with risk for colorectal cancer, and inefficiency of primary care system. In the department of General Surgery CFR Craiova Hospital between 1991-2001 were operated a number of 231 patients with colon cancer and 104 patients with rectal cancer. The results, showing an increased number of recurrences in cases of resection performed for advanced loco-regional tumors of rectosigmoid, made us to reconsider the attitude of avoiding the abdominoperineal resection even when the distance between the inferior limits of the tumors and the anal edge exceeded the distance considered being standard for a low anastomosis performing. The follow-up of the patients with paraclinic technique that didn't prove efficient led in the most cases to a delaying in diagnosis of local recurrences until the moment of resectability was exceeded. The applying of efficient methods in early diagnosis of colorectal cancer and follow-up could provide in the future better results for anterior resections with low anastomosis.

[Clinical course of an ileal carcinoid with mesenteric metastasis]. / Evolutie particulara a unui carcinoid ileal cu metastaza ganglionara în baza mezenterului.

This paper aim is to present the case of a male patient, age 63 admitted in hospital for non-specific gastroenterologic symptoms easily attributed to colecyst calculosis; the anamnesis and careful clinical examination have avoided a useless cholecystectomy and permitted to establish indication for laparotomy; during that was found an ileal tumor with massive metastasis in the base of mesentery. The surgical attitude was dictated by histological diagnostic difficulties (prostate adenocarcinoma metastasis), so it has given up the idea of tumor excision (unjustified intraoperative risk for a metastasis), performing a bypass of the ileal tumor by an enteroenterostomy, then the patient was sent to the Oncological Department. Postoperative evaluation of the patient finally permitted to establish the neuroendocrine origin of the tumor; after oncological treatment (chemotherapy), about 10 months after operation the patient didn't present any sign of tumor (tumor markers and CT scan within normal). The paper emphasizes the problem of practicing an aggressive surgical treatment for carcinoid intestinal tumors with mesenteric metastasis but also brings attention to nonsymptomatic forms of cholecyst calculosis that may hide associated malignant tumors undetected by laparoscopic cholecystectomy.

[Breast conserving surgery --7 years of experience]. / Chirurgia conservatoare a sânului--7 ani de experienta.

The breast cancer treatment is based nowadays on a new surgical option: breast-conserving surgery, which is reliable at least for the first and second stage of cancer, with radical intention, obviously. We have started to practice the breast-conserving surgery in our surgical clinic (at CFR Hospital, from Craiova) for 7 years; until now we have performed 159 breast-conserving operation and, as results, we have recorded 3 local recurrences (2.12%) and 1 death due to cancer evolution. Our protocol includes removal of the primary tumor with enough surrounding tissue to ensure negative margins of resectable specimen, associated with total axillary lymph-node dissection and postoperative breast irradiation. Our oncologist on different postoperative conditions indicated the chemotherapy: tumor size, axillary lymph node involvement, patient age, etc. The purpose of this paper is to emphasize our unassuming experience but especially to draw attention on important results, obtained by long-term monitoring the patient who underwent breast-conserving surgery, in a two prospective protocols, which demonstrate the importance and applicability of breast-conserving therapy. The conclusion of this study is that breast-conserving surgery followed by breast irradiation is reliable, as the results are similar with the radical mastectomies; the main objective is to obtain a good cosmetic result, which depends on tumor size/size of the breast ratio.