The current application of ACOSOG Z0011 trial results: Is further implementation of sentinel lymph node intra-operative histopathological examination mandatory in breast cancer patients - a single-centre analysis.

The main objective of the ACOSOG Z0011 trial was to determine the impact of abandoning complete axillary lymph node dissection (ALND) on survival of breast cancer patients with sentinel node lymph (SLN) metastasis in whom breast conserving therapy (BCT) had been performed. The aim of our study was to assess the clinical value of intra-operative histopathological examination of SLN. Our study comprised 1284 invasive breast cancer patients in whom sentinel lymph node biopsy (SLNB) was carried out. SLN intra-operative histopathological assessment was routinely performed in patients treated within the first period (07.2013-06.2014). However, the decision regarding intra-operative assessment was made by the surgeon for the patients who underwent this evaluation in the later period 07.2014-06.2015 and were submitted for BCT. BCT was performed in 72.4% of patients. In total, 316 patients (24.6%) developed SLN-metastasis. Within the period 07.2014-06.2015, SLN intra-operative microscopic evaluation was performed in 20.8% of patients submitted for BCT. ALND was omitted in 27.5% of patients demonstrating SLN metastasis, in comparison with 15.5% of the group from the previous period (p=0.0094). The proportion of patients demonstrating macrometastasis in SLN who received conservative treatment to the axilla increased from 5.4% to 23.1% (p=0.0007). The choice of SLN final histopathological assessment may allow for deferral of decision on more extensive surgery of the axilla in patients submitted for SLNB. The omission of routinely-performed SLN intra-operative histopathological evaluation has led to a statistically significant increase in the proportion of patients in whom complete ALND was avoided.

New application of carbon nanotubes in haemostatic dressing filled with anticancer substance.

The drug-carrier system used as innovative haemostatic dressing with oncostatic action is studied. It is obtained from CDDP (cisplatin) doped SWCNT (single walled carbon nanotubes), modified and purified by H2O2 in hydrothermal treatment process. In the in vivo nephron sparing surgery (NSS) study we used 35 BALB/c nude mice with induced renal cancer using adenocarcinoma 786-o cells. Animals were divided into four groups: CDDP(M-), CDDP(M+), CONTROL(M-) and CONTROL(M+). In CDDP(M-) and CDDP(M+) groups we used, intraoperatively, carbon nanotubes filled with cisplatin (CDDP). In CONTROL(M-) and CONTROL(M+) groups carbon nanotubes were used alone. During NSS free margin (M-) or positive margin (M+) was performed. In the CDDP(M-) group, we do not observe local tumor recurrences. In Group CDDP(M+) only one animal was diagnosed with tumor recurrence. In control groups the recurrent tumor formation was observed. In our study, it is shown that CDDP filled SWCNT inhibit cancer recurrence in animal model NSS study, and can be successfully applied as haemostatic dressings for local chemoprevention.

Urine--a waste or the future of regenerative medicine?

In recent years, urine has emerged as a source of urine cells. Two different types of cells can be isolated from urine: urine derived stem cells (USCs) and renal tubular cells called urine cells (UCs). USCs have great differentiation properties and can be potentially used in genitourinary tract regeneration. Within this paper, we attempt to demonstrate that such as easily accessible source of cells, collected during completely non-invasive procedures, can be better utilized. Cells derived from urine can be isolated, stored, and used for the creation of urine stem cell banks. In the future, urine holds great potential to become a main source of cells for tissue engineering and regenerative medicine.

Morphological and urodynamic evaluation of urinary bladder wall regeneration: muscles guarantee contraction but not proper function--a rat model research study.

BACKGROUND: Numerous studies are ungoing to develop a substitute for the native urinary bladder wall. The principals of tissue engineering approaches to urinary bladder wall augmentation require a favorable environment for smooth muscle regeneration, which is crucial for bladder function. This study was performed to evaluate bone marrow mesenchymal stem cells (BMSC) seeded on to amniotic membranes fixed to Tachosil sponges as grafts for urinary bladder muscle layer augmentation in a syngenic rat model. MATERIALS AND METHODS: Amniotic membranes seeded with BMSC and covered by Tachosil sponges were implanted as multilayer grafts into nine rats to regenerate the urinary bladder wall. The control group consisted of 12 healthy rats. Urodynamic examinations included contraction, elasticity, compliance, and urinary bladder motor activity. Hematocylin and eosin and Masson's trichrome stains were used to evaluate muscle regeneration; histological data were digitally analyzed with the ImageJ tool. RESULTS: The area of muscle bundles ranged from 5% to 25% or 32% to 41% in control versus reconstructed bladders, respectively. Among nine animals with reconstructed urinary bladders, urodynamic evaluation revealed bladder motor hyperactivity with regular (n = 4) or irregular (n = 1) storage and voiding phases, as well as proper bladder motor activity with a large bladder capacity (n = 1). No bladder contractility was recorded in one case and large stones developed in two animals, which made functional studies impossible. CONCLUSIONS: Regenerated smooth muscle cells created an autonomic cell population that was poorly assimilated to the rest of the urinary bladder wall. The histological presence of a regenerated muscle layer did not guarantee proper urinary bladder function.

Acceptance of a 5-mm distal bowel resection margin for rectal cancer: is it safe?

AIM: Acceptance of a short distal bowel margin results in a higher rate of anterior resection but may compromise oncological safety. This study aimed to evaluate the safety of a 5-mm distal margin. METHOD: A retrospective analysis was carried out of 412 consecutive patients with rectal cancer treated with anterior resection with a negative circumferential resection margin. Radiotherapy was given to 63% of patients with an advanced tumour. The median follow up was 75 months. RESULTS: Fewer patients in the group with a distal margin of ≤ 5 mm had a tumour with an advanced pT stage compared to patients in the group with a distal margin of > 5 mm (P = 0.033). Two patients were converted to abdominoperineal resection because of a positive 'doughnut', leaving 410 patients, in whom 5.4% (95% CI, 0-11.3%) of the group with a distal margin of ≤ 5 mm had local recurrence at 5 years compared with 4.2% (95% CI, 2.1-6.3%) of the group with a distal margin of > 5 mm (P = 0.726). The corresponding figures for the 5-year overall survival were 82.4% (95% CI, 72.6-92.2%) vs 76.3% (95% CI, 71.8-80.8%) (P = 0.581). All four anastomotic recurrences occurred in the group with a distal margin of > 5 mm. CONCLUSION: A distal margin of ≤ 5 mm did not compromise oncological safety in patients undergoing preoperative radiation for an advanced rectal cancer.

The outcomes of treatment and the etiology of lymphoceles with a focus on hemostasis in kidney recipients: a preliminary report.

BACKGROUND: The etiopathogenesis of lymphoceles remains incompletely understood. The aim of our work was to analyze the perturbations of blood coagulation process for their possible impact on the etiology of lymphoceles. Additionally we performed an evaluation of the incidence and effectiveness of treatment methods for lymphoceles. MATERIALS AND METHODS: During 2004 to 2010, we performed 242 kidney transplantations in 92 female and 150 male patients. The hemostatic parameters included concentrations of: antithrombin, plasminogen, thrombin/antithrombin complexes (TAT), prothrombin products F1+2 (F1+2), d-dimers, and plasmin/antiplasmin complexes. RESULTS: At 7 years follow-up 27 (11%) recipients had developed symptomatic lymphoceles, namely abdominal discomfort, a palpable mess in the lower abdomen, arterial hypertension, infection of the operative site with fever, lymphorrhoea with surgical wound dehiscence, decreased diurnal urine output with an elevated plasma creatinine, voiding problems of urgency and vesical tenesmus, and/or symptoms of deep vein thrombosis. We applied the following methods of treatment aspiration alone, percutaneous drainage, laparoscopic fenestration or open surgery. In two only patients did perform open surgery. Since 2008 we have not performed an aspiration alone because of high rate of recurrence (almost 100%) and abandoned open surgery in favor of a laparoscopic approach. Our minimally invasive surgery includes percutaneous drainage guided by ultrasound and a laparoscopic procedure with 100% effectiveness. The examined hemostatic parameters revealed decreased concentrations of TAT complexes and F1+2 in subjects with lymphocele showing positive predictive values of 33% and 41% respectively. The negative predictive values for TAT complexes and F1+2 were 14% and 10%, respectively, suggesting decreased blood coagulation activity among effected recipients. Altered blood coagulation processes may explain some aspects of the disturbances of postoperative obliteration of damaged lymphatic vessels and formation of pathological lymph collection afterward. CONCLUSIONS: Perturbations of blood coagulation may be one cause for a lymphocele.

Minimally invasive methods for the treatment of lymphocele after kidney transplantation.

BACKGROUND: One common complication after kidney transplantation is a lymphocele. The aim of our work was an analysis of incidence of lymphocele and the effectiveness of minimal invasive methods in the management of this complication. MATERIALS AND METHODS: The examined group was consisted of 158 patients (68 female and 90 male) with end-stage renal disease who underwent kidney transplantation. RESULTS: Twenty-one patients (13%) developed symptoms of lymphocele after transplantation procedure within an average time of 34 weeks. The clinical symptoms included a decrease in 24-hour urine collection, an increase in plasma creatinine concentration, abdominal discomfort, lymphorrhea with a surgical wound dehiscence, voiding problems of urgency or vesical tenesmus, febrile states, or symptoms of deep vein thrombosis. The following methods were applied with variable efficacy: aspiration with recurrence 75%; percutaneous drainage with 55%, effectiveness; laparoscopic fenestration with 72% satisfactory outcomes (1 patient presented an excessive bleeding after the procedure), and classic surgery with favorable results. CONCLUSION: Percutaneous drainage guided by ultrasonic imaging should be recommended as the first attempt to cure a lymphocele. Laparoscopy is a feasible, safe technique that should be used after unsuccessful percutaneous drainage. A larger series of patients is required to confirm the superiority of minimal invasive methods to the classical approach.

Experience with autosomal dominant polycystic kidney disease in patients before and after renal transplantation: a 7-year observation.

OBJECTIVE: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the presence of multiple cysts in both kidneys. Symptoms of the disease may arise either from the presence of cysts or from increasing loss of kidney function. First symptoms usually appear in the third decade of life: lumbar pain, urinary tract infections, arterial hypertension, or renal colic due to cyst rupture or coexistent nephrolithiasis. An early diagnosis, male gender, large kidneys by sonography, arterial hypertension, hematuria, and urinary tract infections are predictive factors of a faster progression of the disease. Our aim was to establish the indications for nephrectomy among symptomatic ADPKD patients before kidney transplantation and to assess the risks of posttransplantation complications among ADPKD patients without nephrectomy. PATIENTS AND METHODS: The observed group consisted of 183 patients with ADPKD among whom 50 (27.3%) underwent kidney transplantation during a 7-year observation period (2000-2007). Among those subjects were 3 groups: (I) nephrectomy preceding transplantation; (II) nephrectomy during kidney transplantation; and (III) without nephrectomy. RESULTS: Among group I before transplantation we observed: arterial hemorrhage, wound infections, and splenectomy 4 weeks after ADPKD nephrectomy; afterward we observed: urinary tract infections and contralateral cyst infection. Among group II we only observed 1 case of wound infection. Among group III we observed: ascending urinary tract infections, cyst infections, and cyst hemorrhage. Cyst hemorrhage and cyst infections led mainly to ADPKD kidney nephrectomy. During the observation time, 80.95% of grafts were functioning. CONCLUSIONS: Unilateral nephrectomy is a well-founded preliminary surgical treatment before kidney transplantation. Bilateral nephrectomy before or during transplantation eliminates ADPKD complications and does not significantly increase general complications. The greatest numbers of complications and of graft losses were observed among the group without pretransplantation nephrectomy.

Does calcium channel blocker improvement of perfusion impact the functioning of kidney graft in early period after transplantation?

The aim of the study was to evaluate the influence of reduced vascular resistance following calcium channel blocker verapamil administration on kidney function at 3 months after transplantation. A group of 48 kidneys received 100 microg verapamil by injection directly into renal artery before starting perfusion. The control group included 48 paired kidneys without verapamil addition. Calcium channel blocker therapy with verapamil greatly decreased renal vascular resistance but it did not affect graft function. Administration of calcium channel blockers improved kidney function in the early period after transplantation. A better-functioning graft seems to be based more on metabolic than hemodynamic effects.

Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer.

BACKGROUND: Neoadjuvant chemoradiotherapy does not alter anal sphincter preservation or postoperative complications compared with short-course radiotherapy alone in patients with clinical stage T3 or T4 resectable rectal cancer. The aim of this study was to compare survival, local control and late toxicity in the two treatment groups. METHODS: The study randomized 312 patients to receive either preoperative irradiation (25 Gy in five fractions of 5 Gy) and surgery within 7 days or chemoradiation (50.4 Gy in 28 fractions of 1.8 Gy, bolus 5-fluorouracil and leucovorin) and surgery 4-6 weeks later. The median follow-up of living patients was 48 (range 31-69) months. RESULTS: Early radiation toxicity was higher in the chemoradiation group (18.2 versus 3.2 per cent; P < 0.001). The actuarial 4-year overall survival was 67.2 per cent in the short-course group and 66.2 per cent in the chemoradiation group (P = 0.960). Disease-free survival was 58.4 versus 55.6 per cent (P = 0.820), crude incidence of local recurrence was 9.0 versus 14.2 per cent (P = 0.170) and severe late toxicity was 10.1 versus 7.1 per cent (P = 0.360) respectively. CONCLUSION: Neoadjuvant chemoradiation did not increase survival, local control or late toxicity compared with short-course radiotherapy alone.

Abdominoperineal resection or anterior resection for rectal cancer: patient preferences before and after treatment.

OBJECTIVE: Literature data do not provide any evidence as to whether oncological outcome and quality of life after anterior resection (AR) are superior to those observed after abdominoperineal resection (APR) for low-lying rectal cancer. In view of this, patient preferences should play an important role in the process of decision making. The aim of this study was to investigate these preferences. PATIENTS AND METHODS: A series of consecutive patients with rectal cancer (60 prior to surgery, 65 after APR and 124 after AR) who attended our outpatient clinic were asked to express their preference as to the type of surgery. The second part of the study was performed 4 years later; 30 patients evaluated before surgery, free of disease, were again asked to express their preference as to the type of treatment. RESULTS: Patient preferences as to performing APR, AR or as to leaving the decision to the surgeon were as follows: (i) the group prior to surgery - 5%, 30% and 65%, respectively, (ii) group after APR - 46%, 22% and 32%, respectively, and (iii) group after AR - 4%, 69% and 28%, respectively. Patients after AR pointed to the type of surgery that they had undergone more frequently than patients after APR (69%vs 46%, respectively, P < 0.001). Sixty per cent of patients evaluated twice had altered their initial preferences, usually choosing the type of surgery that they had undergone. CONCLUSIONS: Our results suggest that the sequelae of AR are generally perceived as more acceptable than those of APR. Nevertheless, approximately half of the patients after APR prefer the type of surgery that they have undergone, which suggests the positive reappraisal of APR, once experienced.

Laparoscopic removal of renal cysts in patients with ADPKD as an alternative method of treatment and patient preparation for kidney transplantation: preliminary results.

BACKGROUND: The most frequent genetic disease of the kidneys occurring in 1 of 1000 inhabitants is autosomal-dominant polycystic kidney disease (ADPKD). Growing renal cysts compress the kidney resulting in damage to parenchyma and functional disorders. Around 10% of these patients are dialyzed due to terminal renal insufficiency. With the advent of laparoscopic techniques, the idea of laparoscopic excision of cysts seemed a tempting alternative to nephrectomy. We assessed the preliminary results of laparoscopic treatment of polycystic kidneys compared with open nephrectomy for patients with ADPKD. MATERIALS AND METHODS: Thirty ADPKD patients were treated between 2000 and 2004. Eleven procedures in five men and six women of mean age 51 years included laparoscopic cyst excisions. In the remaining 19 patients (six men and 13 women) of mean age 54 years, nephrectomy was done. Indications for surgery included pain due to compression by large cysts and cyst contamination. Patients after nephrectomy were prepared for renal transplantation when necessary. RESULTS: Laparoscopic polycyst removal produced better effects than nephrectomy. Mean operative time was significantly shorter (86 minutes for cyst removal vs 108 minutes for nephrectomy; P < .05). Postoperative pain measured with the VAS scale was reduced in patients after laparoscopy. Hospital stay was shorter (5 vs 9 days), as well as time to recovery. Other benefits of laparoscopic cyst removal included maintained urination in the patient and no need for erythropoietin substitution, as well as reduced risk of cyst contamination. When eligible for renal transplantation, patients after laparoscopic polycyst removal have smaller kidneys that do not interfere with the graft and the risk of infection during immunosuppression seems lower. CONCLUSION: Although larger series of patients are required in patients with ADPKD, laparoscopic polycyst removal seemed superior to early nephrectomy.

Impact of presence of HBs antigen and anti-hepatitis C virus and anti-cytomegalovirus antibodies on transplanted kidney survival.

INTRODUCTION: Infections are one of the most common complications after organ transplantation. Viral infections such as hepatitis type B (HBV) and C (HCV) or cytomegalovirus (CMV) infections are among the most serious ones. A high frequency of HBV and HCV infections has been recognized in kidney recipients. Viral infections play a special role in graft recipients because of clinical symptoms influencing graft function and recipient survival. Immunosuppressive treatment to decrease immunological reactions after organ transplantation may increase the risk of viral infections. The aim of this study was to evaluate the impact of the presence of HBs antigen and HCV and CMV antibodies on patient and graft survivals. MATERIAL AND METHODS: Two hundred one enrolled kidney transplantation patients (96 women and 105 men) were treated with the same immunosuppressive regimen. Age, sex, and viral state (HBs antigen, anti-HCV and anti-CMV antibodies) were evaluated in every patient. Statistical analysis was performed with the Gompertz model, Kaplan-Meier curves and Cox proportional hazard tests. RESULTS: The presence of HBs antigen was detected in 161 patients (20.4%), HCV antibodies in 61 recipients (30.3%); and CMV antibodies in 12 patients (5.9%). Eighty-seven recipients (43.4%) were seronegative. Average recipient age was 38.5 years. CONCLUSION: Time of graft function was independent of the presence of HBs antigen or HCV or CMV antibodies.

Clinical significance of serum cytokine measurements in untreated colorectal cancer patients: soluble tumor necrosis factor receptor type I--an independent prognostic factor.

The aim of this study was to exploit the potential clinical use of circulating cytokine measurements in colorectal cancer (CRC) patients. The levels of cytokines and cytokine receptors were assessed by ELISA in the sera of 50 healthy volunteers and 157 patients with previously untreated CRC and then related to clinicopathological features and prognosis. All tumors were verified histologically as colorectal adenocarcinomas and staged according to TNM classification. The levels of circulating interleukin (IL)-6, IL-8, macrophage colony-stimulating factor (M-CSF) and interleukin 1 receptor antagonist (IL-1ra) significantly increased with the clinical stage of CRC, and the levels of IL-6, soluble tumor necrosis factor (sTNF) receptor type I (RI), soluble interleukin 2 receptor alpha and TNFalpha with tumor grade, while IL-6, IL-8, M-CSF, IL-1ra and sTNF RI levels significantly rose with bowel wall invasion. None of the cytokine or soluble cytokine receptor levels were influenced by age, gender and colon versus rectum localization. sTNF RI, IL-8, IL-6 and vascular endothelial growth factor measurements demonstrated the highest diagnostic sensitivity. sTNF RI was found elevated in the greatest percentage of all CRC patients, in the greatest proportion of stage I patients and presented the best diagnostic sensitivity. In addition, the sTNF RI level strongly correlated with tumor grade and invasion and proved to be an independent prognostic factor.

Postoperative complications in patients irradiated pre-operatively for rectal cancer: report of a randomised trial comparing short-term radiotherapy vs chemoradiation.

OBJECTIVE: The primary outcome was sphincter preservation. No benefit was found with chemoradiation. The aim of this report is to analyse postoperative complications, which were the secondary outcome. MATERIAL AND METHODS: Patients with resectable T3-4 low rectal carcinoma were randomised to receive either pre-operative 5 x 5 Gy irradiation with subsequent total mesorectal excision (TME) performed within 7 days or chemoradiation (50.4 Gy, 1.8 Gy per fraction plus bolus 5-fluorouracil and leucovorin) followed by TME after 4-6 weeks. RESULTS: Three hundred and five patients (153 in 5 x 5 Gy group and 152 in chemoradiation group) were analysed. The rates of patients with postoperative complications for the 5 x 5 Gy group and for the chemoradiation group were 27 vs 21%, respectively (P = 0.27). If the values were expressed in terms of number of complications, the rates were 31 vs 22%, respectively (P = 0.06). The corresponding values for severe complications were 10 vs 11% (P = 0.85) of patients with complications and 12 vs 11% (P = 0.85) of events. CONCLUSION: The study did not demonstrate a statistically significant difference in the rate of postoperative complications after short-course pre-operative radiotherapy compared with full course chemoradiation.

Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomised trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy.

BACKGROUND AND PURPOSE: The aim was to verify whether preoperative conventionally fractionated chemoradiation offers an advantage in sphincter preservation in comparison with preoperative short-term irradiation. PATIENTS AND METHODS: Patients with resectable T3-4 rectal carcinoma without sphincters' infiltration and with a lesion accessible to digital rectal examination were randomised into: preoperative 5x5Gy short-term irradiation with subsequent total mesorectal excision (TME) performed within 7 days or chemoradiation to a total dose of 50.4Gy (1.8Gy per fraction) concomitantly with two courses of bolus 5-fluorouracil and leucovorin followed by TME after 4-6 weeks. Surgeons were obliged to base the type of operation on the tumour status at the time of surgery. RESULTS: Between 1999 and 2002, 316 patients from 19 institutions were enrolled. The sphincter preservation rate was 61% in the 5x5Gy arm and 58% in the radiochemotherapy arm, P = 0.57. The tumour was on average 1.9 cm smaller (P < 0.001) among patients treated with chemoradiation compared with short-term schedule. For patients who underwent sphincter-preserving procedure, the surgeons generally followed the rule of tailoring the resection according to tumour downsizing; the median distal bowel margin was identical (2 cm) for both randomised groups. However, in the chemoradiation group, five patients underwent abdominoperineal resection despite clinical complete response. CONCLUSIONS: Despite significant downsizing, chemoradiation did not result in increased sphincter preservation rate in comparison with short-term preoperative radiotherapy. The surgeons' decisions were subjective and based on pre-treatment tumour volume at least in clinical complete responders.

Emerging standards of radiotherapy combined with radical rectal cancer surgery.

For patients with resectable rectal cancer treated with total mesorectal excision, the routine use of radiotherapy should be omitted for stage I of the disease and for lesions located higher than 10 cm from the anal verge. Preoperative radiotherapy may be considered for all patients with a lesion with deep perirectal fat infiltration located in the lower two thirds of the rectum. The other option is to offer postoperative radiotherapy for patients with a positive surgical margin, N+ stage disease, mesorectal tumour implants, high tumour grade, perineural invasion, extramuscular blood and lymphatic vessel invasion and with inadvertent tumour perforation. The lower risk of small bowel damage and probable higher efficacy are arguments for the use of preoperative radiotherapy instead of postoperative radiotherapy. The impairment of anorectal function appears to be most frequent late postirradiation sequel. The analysis of acute complications (including toxic deaths) compliance, cost and convenience favours 5 x 5 Gy preoperative irradiation with immediate surgery for patients with resectable tumours in comparison to other commonly used schemes of radiotherapy. These advantages should be weighed against approximately 1.5% risk of late neurotoxicity. There is no clear answer to the question whether preoperative conventional radio(chemo)therapy offers an advantage in sphincter preservation. To answer this question, the results of two ongoing randomised trials are awaited. For patients with unresectable cancers, long-term preoperative radio(chemo)therapy with delayed surgery is a preferable scheme. The total mesorectal irradiation should be employed for mid- and low-lying lesions. Therefore, during radiotherapy planning, a contrast enema should be used to identify the anorectal ring, anatomically corresponding with the lowest edge of the mesorectum.

Contribuição ao levantamento fitossanitário do Estado do Paraná

A previous report of plants diseases, observed at the Division of Plant Biology of the Instituto de Biologia e Pesquisas Tecnológicas - Paraná - Brasil, during the years 1946-1950.