Follow-up Of Large Series Research Articles

Early Experience With the Bentley BeGraft Aortic Stent for the Management of Aortic Arch Pathology in the Paediatric Population.

Aortic arch pathology in older children is often treated preferentially with stenting. Both bare metal and covered stents have been utilised, with potential advantages of covered stents. The search for the ideal covered stent continues. Retrospective review of all paediatric patients undergoing treatment of aortic arch pathology utilising the Bentley BeGraft Aortic stent (BeGraft Aortic, Bentley InnoMed, Hechingen, Germany) from June 2017 to May 2021. Outcome measures were procedural success, complications, medium-term patency and need for re-intervention. Fourteen (14) stents were placed in 12 children (seven males). Indications were coarctation of the aorta in 10 and aneurysm in two. Median age was 11.8 years (8.7-16.6 years) and median weight 42.5 kg (24.8-84 kg). Median coarctation narrowing of 4 mm (range 1-9 mm), improved to 11 mm (range 9-15 mm). The median coarctation gradient improved from 32 mmHg (range 11-42 mmHg) to 7 mmHg (range 0-14 mmHg). Both aneurysms were successfully occluded. There was no mortality or major morbidity. In one patient balloon rupture occurred requiring a second balloon for full inflation and one patient had a minor access site bleed. Follow-up median was 28 months (range 13-65 months). One patient underwent repeat balloon dilation for increased blood pressure gradient at 47 months post implant and a second patient additional stent insertion for a mid-stent aneurysm at 65 months. The Bentley BeGraft Aortic stent can be safely deployed in children for the treatment of aortic arch pathology. Medium-term patency is acceptable. Longer term follow-up in larger series will be required to assess stent performance.

The use of the cyberknife stereotactic radiosurgery system for the treatment of intracranial and extracranial residual or recurrent chordoma

Objectives: Chordomas are relatively rare primary malignant bone tumors that arise from remnants of the notochord along the craniospinal axis. They tend to be locally invasive around the clival or sacro-coccygeal regions and critical neurological structures are often involved. Complete surgical excision is rarely possible and post-resection radiation enhances local control of the disease. The CyberKnife is a frameless imageguided LINAC radiosurgical system that allows treatment of both intracranial and extracranial lesion. We review here the methodology of the system and present our experience of treating skull base and spinal chordomas. Methods: Between 1994 and 2008, 22 patients with a histological diagnosis of a chordoma underwent stereotactic radiosurgery (SRS) at Stanford University Hospitals. 17 patients underwent frameless SRS at the Stanford CyberKnife Center. A retrospective and prospective review of these patients was undertaken by obtaining clinical and radiological information from an institutional review board-approved prospective database. Results: There were 11 males and 6 females with an average age of 42 years (range 10-73). 12 lesions were in the clivus, 3 in the cervical spine below C2, 1 lumbar and 1 sacral region. All but one patient had prior surgery. 9 had undergone one resection, 5 had two and 2 had three resections. Three patients had prior radiation or proton beam therapy. The average tumor volume treated was 10.9 cm3 (range 1.9-31.6 cm3), with a mean radiation dose of 29.3 Gy (range 18-50 Gy), and a mean maximum intratumoral dose of 41.0 Gy (range 24.1-67.6 Gy). Patients were followed up for an average of 4 years. Tumor control was achieved in 12 out of the 17 cases (70.6%). 5 of the 12 patients showed tumor size reduction. However, 5 out of the 17 cases showed progression with one developing a new lesion at a lower cervical vertebra despite good local control. None of the patients with tumor control developed new neurological deficits, but 4 of the 5 cases with tumor progression showed worsening neurological deficits. There was no radiation associated complications. Conclusions: Good tumor control rates can be achieved with no significant morbidity with CyberKnife based stereotactic radiosurgery. Cases with poor control tended to have complexmultiple surgical resections. Longer follow-up in larger series is required to adequately compare this technique with other forms of radiation therapy.

Surgical Management of Adult Acquired Buried Penis: Escutcheonectomy, Scrotectomy, and Penile Split-thickness Skin Graft

To demonstrate the surgical management of adult acquired buried penis (AABP). Affected patients have poor sexual function, urinary dribbling with subsequent skin breakdown, mood disturbance, lichen sclerosus with subsequent urethral stricture, and poor quality of life. Previous efforts have described limited repairs including an isolated resection of the escutcheon, which unfortunately often leads to reburying. We present a more extensive surgical repair including escutcheonectomy, scrotoplasty, and penile split-thickness skin graft (STSG) to provide a durable definitive repair. A retrospective review was conducted of patients managed in 2015-2016. Twelve patients who underwent escutcheonectomy, scrotoplasty, and penile STSG were identified. All patients had morbid obesity as a sole etiology or a significant contributing factor. Outcomes evaluated were surgical complications, reburying of the penis, and graft take rates. Twelve patients underwent repair of AABP. All patients had durable unburying at the intermediate-term follow-up (mean of 8 months). The mean patient body mass index was 45.4 ± 13.8. The operative times, the length of stay, and the estimated blood loss were 312 ± 59 minutes, 5.3 ± 1.1 days, and 304 ± 133 cc, respectively. The STSG take rate was 80%-100% (mean of 91.7%). AABP is a challenging condition to treat. Limited surgical repairs can lead to a reburying of the penis and a progression of urethral disease. Escutcheonectomy, scrotoplasty, and STSG have encouraging intermediate-term outcomes with durable unburying of the penis and good STSG take rates. Further follow-up in larger series is needed, but results are thus far encouraging.

V1-12 SURGICAL MANAGEMENT OF ADULT ACQUIRED BURIED PENIS (AABP)

You have accessJournal of UrologyReconstruction Lower Tract (I)1 Apr 2017V1-12 SURGICAL MANAGEMENT OF ADULT ACQUIRED BURIED PENIS (AABP) Thomas Fuller, Katherine Theisen, and Paul Rusilko Thomas FullerThomas Fuller More articles by this author , Katherine TheisenKatherine Theisen More articles by this author , and Paul RusilkoPaul Rusilko More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.244AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Adult acquired buried penis as a result of obesity is a morbid condition. Affected patients have poor sexual function, urinary dribbling, mood disturbance, and poor quality of life (QoL). Weight loss is ineffective due to chronic skin changes and suprapubic fat pad (termed the escutcheon) lymphedema. Previous efforts have described limited repairs including isolated resection of the escutcheon which unfortunately often leads to reburying. We present a surgical repair including escutcheonectomy, scrotoplasty, and penile degloving with split-thickness skin graft (STSG) to provide definitive repair and halt the progression of the disease process. METHODS A retrospective chart review was conducted of patients managed surgically for adult acquired buried penis in 2015-2016. Twelve patients were identified that underwent escutcheonectomy, scrotoplasty, penile degloving and STSG repair. All patients had morbid obesity as a sole etiology or significant contributing factor. Outcomes evaluated were surgical complications, reburying of the penis, graft take rate, and urinary symptoms. RESULTS Twelve patients underwent repair of adult acquired buried penis. All patients had good cosmetic results and durable unburying at intermediate term follow-up. Mean patient body mass index (BMI) was 45.4 ± 3.7. Fifty percent of the patients in the series were diabetics and 50% had hypertension and hyperlipidemia (Table 1). Mean operative time, length of stay (LOS), and estimated blood loss (EBL) were 312 ± 59 min, 5.3 ± 1.1 days, and 304 ± 133 cc respectively. STSG take rate was 80-100% (mean 92%) (Table 2). CONCLUSIONS Adult acquired buried penis is a challenging condition to treat. Limited surgical repairs can lead to reburying of the penis, need for further procedures, and the progression of urethral disease with voiding dysfunction. Escutcheonectomy, scrotoplasty, and STSG has encouraging intermediate term outcomes with durable unburying of the penis and good STSG take rates. Further follow-up in larger series is needed but results are thus far encouraging. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e71 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Thomas Fuller More articles by this author Katherine Theisen More articles by this author Paul Rusilko More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Use of balloon expandable transcatheter valves for valve-in-valve implantation in patients with degenerative stentless aortic bioprostheses: Technical considerations and results

Transcatheter valve-in-valve is an accepted treatment in high-risk patients with degenerative stented bioprostheses in the aortic position. Experience in treating stentless valves is, however, limited. Our aim was to determine the feasibility and single-center outcome of balloon expandable SAPIEN valve placement in degenerated stentless aortic valve bioprostheses. From February 2010 to January 2014, 10 patients with failing stentless bioprostheses underwent transcatheter aortic valve implantation using the Edwards SAPIEN transcatheter heart valve (SAPIEN, SAPIEN XT, and SAPIEN 3) at our institution. Seven patients had valve failure due to regurgitation and three to stenosis. The mean age was 73.3 ± 15.0 years. The mean logistic EuroSCORE was 31.8 ± 20.3, and the Society of Thoracic Surgeons score was 7.6 ± 5.4. Technical success was achieved in 9 of 10 patients. One patient required immediate placement of a second valve owing to low placement of the first. Two intraoperative complications developed that needed additional procedures. One patient underwent immediate repair of a right ventricular perforation from a pacing lead, the other, reexploration for epicardial bleeding. No deaths occurred. The median length of stay was 8.5 days (range, 3-44). The mean follow-up was 8.1 months (range, 1-21). No late reoperations or reinterventions were required. Transcatheter aortic valve implantation after previous stentless aortic valve replacement is technically demanding but a safe and feasible approach. The early results were excellent, with consistent improvement in hemodynamics. Prospective long-term follow-up in larger series is needed to evaluate this technique further.

Endoscopic Endonasal Approaches for Malignant Tumours Involving the Skull Base

The treatment of skull base malignancies has evolved significantly during recent decades, requiring the contribution of multidisciplinary teams. Surgery, which plays a pivotal role, ranges from traditional external pro- cedures to endoscopic endonasal approaches (EEA). Recent reports have demonstrated that EEA is feasible, safe, and able to achieve the radical resection of selected lesions, while minimising the morbidity in patients. At the present time, the major criticisms that are made focus on oncologic outcomes, in view of the limited number of patients studied and the short/intermediate follow-up of larger series, which have grouped together different his- tologies associated with different prognoses. An extensive review of the pertinent literature is addressed here in order to analyse the endoscopic surgical techniques employed, the evolution of indications and the oncologic outcomes. The promising results that have emerged seem to indicate that EEA, when properly planned and performed by experienced surgeons, has nowadays acquired an accepted role with precise indications in the whole armamentarium available for the treatment of skull base malignancies.

Italian patent foramen ovale survey (I.P.O.S.): Early results

Summary Background Percutaneous patent foramen ovale (PFO) closure is gaining wide acceptance. Aims of the study were to analyse clinical practice regarding PFO closure in Italy, to study indications, devices, results, and the follow-up of large series of patients treated by percutaneous PFO closure. Methods and patients Italian patent foramen ovale survey (IPOS) is a prospective, observational, multi-centric survey that uses a web-based database. The survey lasted 12 months, (November 2007–October 2008). 50 centres participated. Ongoing follow-up will continue up to 36 months. 1035 patients (m.a. 46 years, 60% females) were included in the registry. Most subjects were treated due to a previous history of TIA/ischemic stroke (∼80% of patients). PFO diagnosis and right-to-left shunt (RLS) were assessed by contrast-enhanced transesophageal (cTEE) and/or transthoracic echocardiography and/or transcranial doppler. An aneurysm of the interatrial septum was associated in 41% of patients. Intraprocedural monitoring was assessed by using cTEE and fluoroscopy in 70% and intracardiac echocardiography in 30% of subjects. Procedures were performed under general anesthesia and local anesthesia/conscious sedation in 54% and 46% of patients respectively. The most used device for PFO closure was Amplatzer (∼70% of cases). Results The procedure was successful in all patients. Early complications occurred in 24/1035 patients (2.3%): 12/24 (50%) of them had cardiac arrhythmias, 1 subject had a TIA. Data regarding both clinical and cardio-neurosonological follow-up were assessed in 444/1035 (43%) subjects. The rate of neurological events and cardiac and extra-cardiac complications were around 3% and 9% up to the 24-month follow-up respectively. A large permanent residual RLS and no RLS were observed in less than 1% and in ∼82% of patients at the 1-year follow-up, respectively. Conclusions Our data confirm that percutaneous PFO closure is a safe procedure. Early complications and those during follow-up are mostly related to arrhythmias. Longer follow-up is under way.

Endoscopic Resection of Sinonasal Malignancies

Malignant tumors of the sinonasal tract are rare, accounting for only 1% of all malignancies. Although they are associated with substantial histological heterogeneity, surgery plays a key role in their management. This review addresses the evolution of current treatments in view of the introduction of endoscopic resection techniques. The absence of facial incisions and osteotomies, decreased hospitalization time, better control of bleeding, improved visualization of tumor borders, and reduced morbidity and mortality rate are the major advantages of endoscopic techniques in comparison to traditional external approaches. The major criticisms focus on oncologic results in view of the short/intermediate follow-up of large series, which have commonly grouped together several histologies that may be associated with different prognoses. Since prospective studies contrasting the results of endoscopic and craniofacial resections are difficult to carry out given the rarity of the disease together with ethical issues, the creation of a large database would favor the analysis of several variables related to the patient, tumor, and treatment on survival performed on a large number of patients.

Keratocystic odontogenic tumour: systematic review

The aim of this review is to evaluate the principal clinical and conventional radiographic features of non-syndromic keratocystic odontogenic tumour (KCOT) by systematic review (SR), and to compare the frequencies between four global groups. The databases searched were the PubMed interface of Medline and LILACS. Only those reports of KCOTs that occurred in a series of consecutive cases, in the reporting authors' caseload, were considered. 51 reports, of 49 series of cases, were included in the SR. 11 SR-included series were in languages other than English. KCOTs affected males more frequently and were three times more prevalent in the mandible. Although the mean age at first presentation was 37 years, the largest proportion of cases first presented in the third decade. The main symptom was swelling. Over a third were found incidentally. Nearly two-thirds displayed buccolingual expansion. Over a quarter of cases recurred. Only a quarter of all SR-included reported series of cases included details of at least one radiological feature. The East Asian global group presented significantly as well-defined, even corticated, multilocular radiolucencies with buccolingual expansion. The KCOTs affecting the Western global group significantly displayed an association with unerupted teeth. Long-term follow-up of large series that would have revealed detailed radiographic description and long-term outcomes of non-syndromic KCOT was lacking.

Fibrous dysplasia: a systematic review

To evaluate the principal features of fibrous dysplasia (FD) by systematic review (SR) and to compare their frequencies between four global groups. The databases searched were the PubMed interface of Medline and LILACS. Only those reports of FD which occurred in a series in the reporting authors' caseload were considered. All cases were confirmed fibro-osseous lesions histopathologically. The SR-included series must also have included radiographs. Of the 106 reports considered (including the Hong Kong report), 31 reports and a total of 788 cases were included in the SR. 11 SR-included series were in languages other than English. FD affected both genders equally, but was 50% more prevalent in the maxilla. The mean age at first presentation was 24 years. The decade with the greatest frequency was the second, in which males accounted for 63%. The main symptom in 90% of all SR-included cases was swelling (including deformation of the jaws). Not one SR-included case directly involved the ocular apparatus. All cases displayed buccolingual expansion; all mandibular cases exhibited downward displacement of the lower border of the mandible and almost all maxillary cases involved the maxillary antrum. Only 35% of reports included follow-up; 18% of cases recurred or were reactivated. Not one case displayed sarcomatous change. Long-term follow-up of large series that would have revealed the long-term outcomes of FD was lacking. This is necessary because many cases do not burn out at the end of adolescence, as expected of a hamartoma, but are reactivated.

Laparoscopic Radical Nephrectomy for Patients with Pathologic T3b Renal-Cell Carcinoma: The Johns Hopkins Experience

Surgical therapy for renal-cell carcinoma (RCC) with vascular involvement has traditionally been performed via an open approach. As laparoscopic techniques have improved, more surgeons are attempting laparoscopic nephrectomy for higher stage RCC. The goal of our study was to evaluate the safety and short-tem oncologic efficacy of laparoscopic radical nephrectomy in patients with renal vein involvement. We reviewed the clinical and pathologic data for 37 patients who underwent a pure laparoscopic radical nephrectomy for RCC with renal vein thrombus from 2005 to 2008 by dedicated laparoscopic surgeons. Perioperative and oncologic outcomes were assessed. Median age of our study population was 65 years, and mean follow-up was 14 months. Median pathologic tumor size was 7.5 cm. One (2.7%) patient needed conversion to an open procedure. Median estimated blood loss (EBL) was 200 mL (interquartile range [IQR]) 100-850), and median length of stay (LOS) was 3 days (range 3-5 d). The overall perioperative complication rate was 14%, and there were no perioperative mortalities. Of the 32 patients without metastatic disease at the time of surgery, 29 (91%) are alive without evidence of disease. Laparoscopic radical nephrectomy in the setting of renal vein thrombus is a complex surgical procedure that necessitates significant laparoscopic skills. Our data demonstrate that laparoscopic radical nephrectomy is safe and effective in patients with RCC who have renal vein involvement, albeit with short-term oncologic follow-up. Long-term follow-up in larger series of patients is necessary to further define the role of laparoscopic nephrectomy in this subset of patients.

Efficacy of elastic compression stockings used early or after resolution of the edema on recanalization after deep venous thrombosis: the COM.PRE Trial

Elastic compression stockings are useful for preventing post-thrombotic syndrome after deep venous thrombosis (DVT). Less is known about their effects on thrombus recanalization and the optimal timing for starting compression. This study investigated whether compression applied early was more effective than when started 2 weeks after DVT. Seventy-three patients with DVT were randomly assigned to elastic compression hosiery starting either immediately after diagnosis or 2 weeks later. After 14 and 90 days the residual thrombus was measured by compression ultrasonography, and venous patency and any pathological reflux were recorded. There were significantly more recanalized venous segments in the group treated with early compression. Recanalization of popliteal DVT veins, expressed as the reduction of vein diameter, was also better in the early compression group than controls (day 14, 6.5 +/- 3 versus 5 +/- 2 mm, P = 0.035; day 90, 3.7 +/- 3 versus 2.1 +/- 1.7 mm; P = 0.014). On day 14 the mean score for popliteal patency was significantly better for the early compression patients (1.0 +/- 0.6 versus 1.5 +/- 0.5, P = 0.0015). In conclusion, elastic compression applied immediately at diagnosis of DVT was safe and effective on the surrogate end-points investigated in this study. Longer follow-up in larger series is needed to verify the patterns of recurrence of DVT and post-thrombotic syndrome.

Clinical characteristics and outcome of pregnancy in women with gestational hyperglycaemia with and without antibodies to beta-cell antigens.

To evaluate the prevalence of beta-cell autoantibodies in women with gestational diabetes and impaired glucose tolerance, and identify clinical characteristics differentiating hyperglycaemic patients with and without autoantibodies. One hundred and twenty-three pregnant patients with gestational diabetes, 84 with impaired glucose tolerance and 290 with normoglycaemia were evaluated for anti-islet cell antibodies, glutamic acid decarboxylase (GAD) autoantibodies, and the components of the metabolic syndrome. Autoantibody positivity was 8.9%, 17.9% and 0.3% in patients with diabetes, impaired tolerance and normoglycaemia, respectively. Hyperglycaemic patients with autoantibodies had lower body mass index, waist, weight gain at the time of the screening test and a lower percentage of previous pregnancies than those without autoantibodies. In addition, their fasting insulin values were significantly lower and inversely related to the presence of autoantibodies (odds ratio (OR) = 0.64; 95% confidence interval (CI) 0.42-0.96), the lowest values being found in anti-GAD+ patients. Autoantibody-positive women with diabetes were more frequently treated with insulin than negative patients (OR = 7.21; 95% CI 1.85-28.08). Autoantibody-positive women with gestational hyperglycaemia displayed fewer features of insulin resistance and required more frequent insulin therapy than negative women and presumably had presymptomatic Type 1 diabetes. If this conclusion is corroborated by the follow-up of larger series, clinical and immunological distinction of types of gestational hyperglycaemia would be useful.

Color duplex ultrasonography of the superior mesenteric artery after placement of endografts with suprarenal stents.

After endovascular repair of abdominal aortic aneurysm with endografts with suprarenal stents, the proximal uncovered stent may cross the origin of the superior mesenteric artery. Effects on splanchnic circulation are unknown and may include development of stenosis at the vicinity of the stent. The criteria of high-grade superior mesenteric artery stenosis using color duplex ultrasonography have been previously reported. The purpose of this study is to examine the incidence of high-grade superior mesenteric artery stenosis in patients with endografts with suprarenal stents using color duplex ultrasonography. Candidates for the study were patients who had placement of an aortic endograft with a suprarenal stent and were able to undergo ultrasonography of the superior mesenteric artery. After reviewing computed tomography scans, patients who had the origin of the superior mesenteric artery crossed by the suprarenal stent underwent color duplex ultrasonography of this vessel. Presence of turbulence or narrowing of the superior mesenteric artery, or a peak systolic velocity greater than 2.75 m/sec, or an end-diastolic velocity greater than 0.45 m/sec were considered significant for the presence of high-grade superior mesenteric artery stenosis. There were 24 patients (21 males, three females), median age 71 years (range, 59-83). The suprarenal stent was crossing the superior mesenteric artery in 17 of 24 patients (71%). Color duplex ultrasound was technically successful in 13 of 17 (76%). The test was performed after a median follow-up of 9 months (range, 3 days to 34 months). No patient had evidence of turbulence or narrowing of the superior mesenteric artery during ultrasonography. The median peak systolic velocity was 0.92 m/sec (range, 0.53-1.21 m/sec). No patient had peak systolic velocity greater than 2.75 m/sec. The median end-diastolic velocity was 0.10 m/sec (range, 0.09-0.14 m/sec). No patient had end-diastolic velocity greater than 0.45 m/sec. Color duplex ultrasonography did not demonstrate the presence of high-grade superior mesenteric artery stenosis during early follow-up of patients with endografts with suprarenal stents. Longer follow-up of larger series of patients is needed to determine the long-term effects of suprarenal stents on splanchnic circulation.

The follicular non-Hodgkin's Lymphomas—I. The possibility of cure

The follicular lymphomas pursue an indolent course in many patients. Long-term follow-up in large series is therefore necessary to establish whether cure is taking place, and if so, at what stage in the dissemination of the disease process it becomes unlikely. The time to, and site of relapse, together with its impact on survival has been studied in 398 patients entered into the British National Lymphoma Investigation limited and disseminated disease trials between 1974 and 1980. Relapse data were compared with various models to obtain maximum likelihood estimates of the proportions permanently remaining relapse-free following treatment. Long-term relapse-free survival was observed in 54.8 ± 14.9% (95% CI) of patients at 15 years with Ann Arbor stage I disease, 29.2 ± 13.6% in patients with stage II disease, 18.1 ± 6.6% with stage III and 13.0 ± 5.9% with IV disease. Relapse time-course data for all trial arms conform closely to lognormal distributions allowing maximum likelihood estimates of proportions remaining permanently relapse-free to be derived. Using this methodology, over a quarter of patients treated with involved radiotherapy alone or radiotherapy plus 6 months of chlorambucil in the limited disease (Ann Arbor stage I and II) trial are unlikely to relapse at any time in the future. Over 10% of patients treated in the disseminated disease trials with disease classified as Ann Arbor stage III are also statistically unlikely to relapse. The finding that a proportion of patients is statistically unlikely to experience a clinically obvious relapse is consistent with clinical cure. It is especially interesting that a small proportion of patients with disseminated disease and treated by chemotherapy have fallen into this category, but additional data are required to know at what point statistical cure becomes unlikely. Whether “clinical cure” is the same as “pathological cure” in this disease remains uncertain.

Blood and spinal fluid tests for regain after treatment of neurosyphilis.

It has long been known that in patients treated for late neurosyphilis blood serum and spinal fluid tests for syphilis continue to give positive results for varying periods after treatment. Yet, many patients are still treated unnecessarily in the hope of reversing such positive reactions. This practice continues because few reports on the long-term follow-up of large series of patients have been published. Physicians are disturbed by the great variety of serologic responses that may be encountered in treated patients, some of whom become seronegative relatively soon while others remain seropositive for years. Even more disconcerting are the great fluctuations in titers obtained in quantitative tests and the great discrepancies in titers obtained by different kinds of tests that occur in some patients and not in others. Such serologic phenomena are not easily interpreted, but, as this report attempts to show, the persistence of reagin in varying amounts following treatment