Haematology is one of the Pathology groups located at the Christie

Recent Submissions

  • Response of ETV6-FLT3-positive myeloid/lymphoid neoplasm with eosinophilia to inhibitors of FMS-like tyrosine kinase 3.

    Walz, C; Erben, P; Ritter, M; Bloor, Adrian; Metzgeroth, G; Telford, Nicholas; Haferlach, C; Haferlach, T; Gesk, S; Score, J; et al. (2011-08-25)
    Imatinib-resistant tyrosine kinase (TK) fusions involving FGFR1, JAK2, or FLT3 are rare but recurrent in patients with eosinophilia-associated neoplasms. We report here 2 male patients with ETV6-FLT3(+) myeloid/lymphoid neoplasms with eosinophilia who were treated with the multitargeted TK inhibitors sunitinib and sorafenib. Patient 1 achieved rapid complete hematologic response and complete cytogenetic response after 3 months of taking sunitinib. A secondary blast phase caused by clonal evolution was diagnosed after 6 months. He achieved a second complete hematologic response after taking sorafenib but relapsed 2 months later. An N841K point mutation within the TK domain of FLT3, previously reported in acute myeloid leukemia and potentially conferring resistance to sorafenib, was subsequently identified. Patient 2 was heavily pretreated according to the initial diagnosis of T-lymphoblastic lymphoma and died in sunitinib-induced pancytopenia. This report highlights the importance of a careful diagnostic workup for eosinophilia-associated neoplasms to evaluate the possibility of TK inhibitor therapy.
  • Evidence of simian virus 40 infection in multiple organ transplant recipients with renal dysfunction.

    Kiasari B A; Vallely, P J; Corless, C E; Curry, A; Cotterill, H; Murray, John; Ramjug, S; Klapper, P E; Human Viral Vaccine Department, Razi Vaccine & Serum Research Institute, Hesarak, Karaj, Iran. (2011-09)
    Electron microscopy (EM), real-time polymerase chain reaction (PCR) and conventional PCR were used to identify viruses associated with infection in 2 transplantation patients. An autologous haematopoietic stem cell, liver and renal transplant recipient was found to be positive for simian virus 40 (SV40). Dual BK virus and SV40 infection was found in a heart and renal transplantation patient. SV40 infection can occur in immunocompromised patients.
  • Understanding distress and distressing experiences in patients living with multiple myeloma: an exploratory study.

    Potrata, B; Cavet, James; Blair, Susan; Howe, Tracy; Molassiotis, A; University of Leeds, City Centre, Leeds, UK. (2011-02)
    The aim of this study was to gain greater insight into the symptoms and distressing experiences of patients living with myeloma.
  • Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study.

    Moreau, P; Pylypenko, H; Grosicki, S; Karamanesht, L; Leleu, X; Grishunina, M; Rekhtman, G; Masliak, Z; Robak, T; Shubina, A; et al. (2011-05)
    Intravenous injection is the standard administration route of bortezomib; however, subcutaneous administration is an important alternative. We compared the efficacy and safety of subcutaneous versus intravenous bortezomib at the approved 1·3 mg/m(2) dose and twice per week schedule in patients with relapsed multiple myeloma.
  • Voriconazole for secondary prophylaxis of invasive fungal infections in allogeneic stem cell transplant recipients: results of the VOSIFI study.

    Cordonnier, C; Rovira, M; Maertens, J; Olavarria, E; Faucher, C; Bilger, K; Pigneux, A; Cornely, O; Ullmann, A; Bofarull, R; et al. (2010-10)
    BACKGROUND: Recurrence of prior invasive fungal infection (relapse rate of 30-50%) limits the success of stem cell transplantation. Secondary prophylaxis could reduce disease burden and improve survival. DESIGN AND METHODS: A prospective, open-label, multicenter trial was conducted evaluating voriconazole (4 mg/kg/12 h intravenously or 200 mg/12 h orally) as secondary antifungal prophylaxis in allogeneic stem cell transplant recipients with previous proven or probable invasive fungal infection. Voriconazole was started 48 h or more after completion of conditioning chemotherapy and was planned to be continued for 100-150 days. Patients were followed for 12 months. The primary end-point of the study was the incidence of proven or probable invasive fungal infection. RESULTS: Forty-five patients were enrolled, 41 of whom had acute leukemia. Previous invasive fungal infections were proven or probable aspergillosis (n=31), proven candidiasis (n=5) and other proven or probable infections (n=6); prior infection could not be confirmed in three patients. The median duration of voriconazole prophylaxis was 94 days. Eleven patients (24%) died within 12 months of transplantation, but only one due to systemic fungal disease. Three invasive fungal infections occurred post-transplant: two relapses (one candidemia and one fatal scedosporiosis) and one new zygomycosis in a patient with previous aspergillosis. The 1-year cumulative incidence of invasive fungal disease was 6.7±3.6%. Two patients were withdrawn from the study due to treatment-related adverse events (i.e. liver toxicity). CONCLUSIONS: Voriconazole appears to be safe and effective for secondary prophylaxis of systemic fungal infection after allogeneic stem cell transplantation. The observed incidence of 6.7% (with one attributable death) is considerably lower than the relapse rate reported in historical controls, thus suggesting that voriconazole is a promising prophylactic agent in this population.
  • 'Like a sieve': an exploratory study on cognitive impairments in patients with multiple myeloma.

    Potrata, B; Cavet, James; Blair, Susan; Howe, T; Molassiotis, A; School of Nursing, Midwifery & Social Work, University of Manchester, Manchester, UK. (2010-11)
    The aim of this study was to obtain a more in-depth understanding of cognitive impairments and concerns as described by patients with multiple myeloma and the strategies used to cope with them. Semi-structured qualitative interviews were undertaken with 15 multiple myeloma patients of differing age ranges and at various stages of their disease. Various cognitive impairments, such as problems with short-term memory, poor recall and lack of concentration were observed and/or expressed in at least 10 out of 15 patients, all of them long(er)-term survivors. In some patients cognitive impairments significantly interfered with their personal and professional lives, and for some patients these were described as permanent. The patients used various coping strategies, from denial, taking notes, writing diaries, reading simpler texts, using talking books and videos, to using systems for counting medication to cope with the results of their cognitive impairment. Our findings differ from much of the contemporary literature which states that if cognitive impairments in cancer patients occur, they are mostly mild and transient. More proactive supportive care is needed to help patients with multiple myeloma to cope with poorer cognitive functioning.
  • T-cell-depleted reduced-intensity transplantation followed by donor leukocyte infusions to promote graft-versus-lymphoma activity results in excellent long-term survival in patients with multiply relapsed follicular lymphoma.

    Thomson, Kirsty J; Morris, Emma C; Milligan, Donald W; Parker, Anne; Hunter, Ann; Cook, Gordon; Bloor, Adrian; Clark, Fiona; Kazmi, Majid; Linch, David C; et al. (2010-08-10)
    PURPOSE: Follicular lymphoma (FL) is an indolent disorder that is treatable but considered incurable with chemotherapy alone. The curative potential of allogeneic transplantation using conventional myeloablative conditioning has been demonstrated, but this approach is precluded in the majority of patients with FL because of excessive toxicity. Thus, reduced-intensity conditioning regimens are being explored. PATIENTS AND METHODS: This study reports the outcome of 82 consecutive patients with FL who underwent transplantation using fludarabine, melphalan, and alemtuzumab for in vivo T-cell depletion. Patients were heavily pretreated, having received a median of four lines of prior therapy, and 26% had experienced treatment failure with previous autologous transplantation. Median patient age was 45 years, and 52% of patients received stem cells from unrelated donors. RESULTS: With a median follow-up time of 43 months, the nonrelapse mortality was 15% at 4 years (8% for sibling and 22% for unrelated donor transplantations), acute grade 2 or 3 graft-versus-host disease (GVHD) occurred in 13%, and the incidence of extensive chronic GVHD was only 18%. Although relapse risk was 26%, this was significantly reduced where mixed chimerism had been converted to full donor chimerism by the use of donor lymphocyte infusion (DLI; P = .03). In addition, 10 (77%) of 13 patients given DLI for relapse after transplantation experienced remission, with nine of these responses being sustained. Current progression-free survival at 4 years was 76% for the whole cohort (90% for those with sibling donors and 64% for those with unrelated donors). CONCLUSION: The excellent long-term survival with associated low rates of GVHD and the frequency and durability of DLI responses make this an extremely encouraging strategy for the treatment and potential cure of FL.
  • European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy.

    Burnett, Alan K; Russell, Nigel; Kell, W Jonathan; Dennis, Michael; Milligan, Donald W; Paolini, Stefania; Yin, John A; Culligan, Dominic; Johnston, Peter; Murphy, John; et al. (2010-05-10)
    PURPOSE: Treatment options for older patients with acute myeloid leukemia (AML) who are not considered suitable for intensive chemotherapy are limited. We assessed the second-generation purine nucleoside analog, clofarabine, in two similar phase II studies in this group of patients. PATIENTS AND METHODS: Two consecutive studies, UWCM-001 and BIOV-121, recruited untreated older patients with AML to receive up to four or six 5-day courses of clofarabine. Patients in UWCM-001 were either older than 70 years or 60 to 69 years of age with poor performance status (WHO > 2) or with cardiac comorbidity. Patients in BIOV-121 were >or= 65 years of age and deemed unsuitable for intensive chemotherapy. RESULTS: A total of 106 patients were treated in the two monotherapy studies. Median age was 71 years (range, 60 to 84 years), 30% had adverse-risk cytogenetics, and 36% had a WHO performance score >or= 2. Forty-eight percent had a complete response (32% complete remission, 16% complete remission with incomplete peripheral blood count recovery), and 18% died within 30 days. Interestingly, response and overall survival were not inferior in the adverse cytogenetic risk group. The safety profile of clofarabine in these elderly patients with AML who were unsuitable for intensive chemotherapy was manageable and typical of a cytotoxic agent in patients with acute leukemia. Patients had similar prognostic characteristics to matched patients treated with low-dose cytarabine in the United Kingdom AML14 trial, but had significantly superior response and overall survival. CONCLUSION: Clofarabine is active and generally well tolerated in this patient group. It is worthy of further evaluation in comparative trials and might be of particular use in patients with adverse cytogenetics.
  • Favorable outcomes with alemtuzumab-conditioned unrelated donor stem cell transplantation in adults with high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in first complete remission.

    Patel, Bella; Kirkland, Keiren E; Szydlo, Richard; Pearce, Rachel M; Clark, Richard E; Craddock, Charles; Liakopoulou, Effie F; Fielding, Adele K; Mackinnon, Stephen; Olavarria, Eduardo; et al. (2009-10)
    BACKGROUND: Approximately 40% of adults with Philadelphia chromosome-negative acute lymphoblastic leukemia achieve long-term survival following unrelated donor hematopoietic stem cell transplantation in first complete remission but severe graft-versus-host disease remains a problem affecting survival. Although T-cell depletion abrogates graft-versus-host disease, the impact on disease-free survival in acute lymphoblastic leukemia is not known. DESIGN AND METHODS: We analyzed the outcome of 48 adults (median age 26 years) with high-risk, Philadelphia-chromosome-negative acute lymphoblastic leukemia undergoing T-cell depleted unrelated donor-hematopoietic stem cell transplantation (67% 10 of 10 loci matched) in first complete remission reported to the British Society of Blood and Marrow Transplantation Registry from 1993 to 2005. RESULTS: T-cell depletion was carried out by in vivo alemtuzumab administration. Additional, ex vivo T-cell depletion was performed in 21% of patients. Overall survival, disease-free survival and non-relapse mortality rates at 5 years were 61% (95% CI 46-75), 59% (95% CI 45-74) and 13% (95% CI 3-25), respectively. The incidences of grades II-IV and III-IV acute graft-versus-host disease were 27% (95% CI 16-44) and 10% (95% CI 4-25), respectively. The actuarial estimate of extensive chronic graft-versus-host disease at 5 years was 22% (95%CI 13-38). High-risk cytogenetics at diagnosis was associated with a lower 5-year overall survival (47% (95% CI 27-71) vs. 68% (95% CI 44-84), p=0.045). CONCLUSIONS: T-cell depleted hematopoietic stem cell transplantation from unrelated donors can result in good overall survival and low non-relapse mortality for adults with high-risk acute lymphoblastic leukemia in first complete remission and merits prospective evaluation.
  • Learning through experience.

    Mitton, Simeon; The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK. (2009)
  • Complementary therapists' motivation to work in cancer/supportive and palliative care: a multi-centre case study.

    Mackereth, Peter A; Carter, Ann; Parkin, Sam; Stringer, Jacqui; Roberts, Dai; Long, Andrew; Todd, Chris; Caress, Ann-Louise; The Christie Foundation NHS Trust, Manchester, University of Derby, UK. peter.mackereth@christie.nhs.uk (2009-08)
    PURPOSE: To uncover complementary therapists' motivation to work in cancer/supportive and palliative care. METHOD: The study employed a multiple case-study design, involving three cancer/supportive and palliative care settings in the North West of England. A questionnaire survey (n=51) was undertaken, followed by semi-structured interviews with a subgroup of the sample (n=28). RESULTS: Participants had a mean age of 50 years, were predominantly female and had varied career backgrounds, including prior professional experience in healthcare, teaching and private complementary therapy practice. Motivation for working in cancer/supportive and palliative care included vocational drive with a desire to provide individualised treatment and adopt a person centred, empowering and caring approach; disillusionment with conventional care; career development and personal experience of cancer or other serious illness. CONCLUSION: Findings indicated that motivational factors for therapists working in cancer care/supportive and palliative care were varied and highlighted a combination of 'push and pull' factors, particularly for therapists who are also health care practitioners. Further research related to volunteering, sustainable services and support and training for therapists is required.
  • The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial.

    Burnett, Alan K; Milligan, Donald W; Goldstone, Anthony H; Prentice, Archibald G; McMullin, Mary-Frances; Dennis, Michael; Sellwood, Elizabeth; Pallis, Monica; Russell, Nigel; Hills, Robert K; et al. (2009-05)
    The acute myeloid leukaemia (AML)14 trial addressed four therapeutic questions in patients predominantly aged over 60 years with AML and High Risk Myelodysplastic Syndrome: (i) Daunorubicin 50 mg/m(2) vs. 35 mg/m(2); (ii) Cytarabine 200 mg/m(2) vs. 400 mg/m(2) in two courses of DA induction; (iii) for part of the trial, patients allocated Daunorubicin 35 mg/m(2) were also randomized to receive, or not, the multidrug resistance modulator PSC-833 in a 1:1:1 randomization; and (iv) a total of three versus four courses of treatment. A total of 1273 patients were recruited. The response rate was 62% (complete remission 54%, complete remission without platelet/neutrophil recovery 8%); 5-year survival was 12%. No benefits were observed in either dose escalation randomization, or from a fourth course of treatment. There was a trend for inferior response in the PSC-833 arm due to deaths in induction. Multivariable analysis identified cytogenetics, presenting white blood count, age and secondary disease as the main predictors of outcome. Although patients with high Pgp expression and function had worse response and survival, this was not an independent prognostic factor, and was not modified by PSC-833. In conclusion, these four interventions have not improved outcomes in older patients. New agents need to be explored and novel trial designs are required to maximise prospects of achieving timely progress.
  • Reduced intensity conditioning allogeneic stem cell transplantation for Hodgkin's lymphoma: identification of prognostic factors predicting outcome.

    Robinson, Stephen P; Sureda, Anna; Canals, Carmen; Russell, Nigel; Caballero, Dolores; Bacigalupo, Andrea; Iriondo, Arturo; Cook, Gordon; Pettitt, Andrew; Socie, Gerard; et al. (2009-02)
    BACKGROUND: The role of reduced intensity conditioning allogeneic stem transplantation (RICalloSCT) in the management of patients with Hodgkin's lymphoma remains controversial. DESIGN AND METHODS: To further define its role we have conducted a retrospective analysis of 285 patients with HL who underwent a RICalloSCT in order to identify prognostic factors that predict outcome. Eighty percent of patients had undergone a prior autologous stem cell transplantation and 25% had refractory disease at transplant. RESULTS: Non-relapse mortality was associated with chemorefractory disease, poor performance status, age >45 and transplantation before 2002. For patients with no risk factors the 3-year non-relapse mortality rate was 12.5% compared to 46.2% for patients with 2 or more risk factors. The use of an unrelated donor had no adverse effect on the non-relapse mortality. Acute graft versus host disease (aGVHD) grades II-IV developed in 30% and chronic GVHD in 42%. The development of cGVHD was associated with a lower relapse rate. The disease progression rate at one and five years was 41% and 58.7% respectively and was associated with chemorefractory disease and extent of prior therapy. Donor lymphocyte infusions were administered to 64 patients for active disease of whom 32% showed a clinical response. Eight out of 18 patients receiving donor lymphocyte infusions alone had clinical responses. Progression-free and overall survival were both associated with performance status and disease status at transplant. Patients with neither risk factor had a 3-year PFS and overall survival of 42% and 56% respectively compared to 8% and 25% for patients with one or more risk factors. Relapse within six months of a prior autologous transplant was associated with a higher relapse rate and a lower progression-free. CONCLUSIONS: This analysis identifies important clinical parameters that may be useful in predicting the outcome of RICaIICalloSCT in Hodgkin's lymphoma.
  • Favorable long-term survival after reduced-intensity allogeneic transplantation for multiple-relapse aggressive non-Hodgkin's lymphoma.

    Thomson, Kirsty J; Morris, Emma C; Bloor, Adrian; Cook, Gordon; Milligan, Donald W; Parker, Anne; Clark, Fiona; Yung, Lynny; Linch, David C; Chakraverty, Ronjon; et al. (2009-01-20)
    PURPOSE: The role of allogeneic transplantation with reduced-intensity conditioning in diffuse large B-cell lymphoma (DLBCL) is currently unclear, with relatively little published data. We report the outcome of reduced-intensity transplantation (RIT) in a cohort of 48 consecutive patients with relapsed/refractory DLBCL (30 patients with de novo disease and 18 patients with transformed follicular lymphoma) who underwent transplantation with an alemtuzumab-containing regimen, with a median follow-up of 52 months. PATIENTS AND METHODS: Patients had experienced treatment failure with a median of five lines of prior therapy, including autologous transplantation in 69%, and 17% of patients were chemotherapy refractory at transplantation. Median age was 46 years, and 38% of patients had matched/mismatched unrelated donors. Conditioning was with alemtuzumab, fludarabine, and melphalan, and additional graft-versus-host disease (GVHD) prophylaxis was with cyclosporine. RESULTS: All patients were successfully engrafted. Only 17% of patients developed grade 2 to 4 acute GVHD, with 13% experiencing extensive chronic GVHD. Four-year estimated nonrelapse mortality was 32%, and relapse risk was 33%. Twelve patients received donor lymphocyte infusions +/- chemoimmunotherapy for relapse, and five patients obtained durable remissions, giving current progression-free survival (PFS) and overall survival (OS) rates at 4 years of 48% and 47%, respectively. Patients who had chemotherapy-sensitive disease before RIT had current PFS and OS rates at 4 years of 55% and 54%, respectively. Chemotherapy-refractory patients had a poor outcome. CONCLUSION: The encouraging survival rates with extended follow-up suggest a role for RIT in chemotherapy-sensitive relapsed DLBCL, even in patients who have previously experienced treatment failure with autologous transplantation. Future studies will be required to determine whether any subset of patients with relapsed DLBCL should be considered for RIT versus autologous transplantation.
  • Superiority of reduced-intensity allogeneic transplantation over conventional treatment for relapse of Hodgkin's lymphoma following autologous stem cell transplantation.

    Thomson, Kirsty J; Peggs, Karl S; Smith, P; Cavet, James; Hunter, Ann; Parker, Anne; Pettengell, Ruth; Milligan, Donald W; Morris, Emma C; Goldstone, Anthony H; et al. (2008-05)
    This study compares outcome of reduced-intensity conditioned transplant (RIT) with outcome of conventional non-transplant therapy in patients with Hodgkin's lymphoma relapsing following autograft. There were 72 patients in two groups who had relapsed, and received salvage therapy with chemotherapy+/-radiotherapy. One group (n=38) then underwent alemtuzumab-containing RIT. The second group-historical controls (n=34), relapsing before the advent of RIT-had no further high-dose therapy. This group was required to respond to salvage therapy and live for over 12 months post-relapse, demonstrating potential eligibility for RIT, had this been available. Overall survival (OS) from diagnosis was superior following RIT (48% at 10 years versus 15%; P=0.0014), as was survival from autograft (65% at 5 years versus 15%; P< or =0.0001). For the RIT group, OS at 5 years from allograft was 51%, and in chemoresponsive patients was 58%, with current progression-free survival of 42%. Responses were seen in 8 of 15 patients receiving donor lymphocyte infusions (DLI) for relapse/progression, with durable remission in five patients at median follow-up from DLI of 45 months (28-55). These data demonstrate the potential efficacy of RIT in heavily pre-treated patients whose outlook with conventional therapy is dismal, and provide evidence of a clinically relevant graft-versus-lymphoma effect.
  • Massage in patients undergoing intensive chemotherapy reduces serum cortisol and prolactin.

    Stringer, Jacqui; Swindell, Ric; Dennis, Michael; Haematology and Transplant Unit, Christie Hospital NHS Foundation Trust, Manchester, UK. jacqui.stringer@christie.nhs.uk (2008-10)
    OBJECTIVE: The objective is to identify whether single 20 min massage sessions were safe and effective in reducing stress levels of isolated haematological oncology patients. DESIGN: Based on a randomised controlled trial, 39 patients were randomised to aromatherapy, massage or rest (control) arm. MEASURES: The measures were serum cortisol and prolactin levels, quality of life (EORTC QLQ-C30) and semi-structured interviews. Primary outcome measure was the fall in serum cortisol levels. RESULTS: A significant difference was seen between arms in cortisol (P=0.002) and prolactin (p=0.031) levels from baseline to 30 min post-session. Aromatherapy and massage arms showed a significantly greater drop in cortisol than the rest arm. Only the massage arm had a significantly greater reduction in prolactin then the rest arm. The EORTC QLQ-C30 showed a significant reduction in 'need for rest' for patients in both experimental arms compared with the control arm, whereas the semi-structured interviews identified a universal feeling of relaxation in patients in the experimental arms. CONCLUSION: This pilot study demonstrated that in isolated haematological oncology patients, a significant reduction in cortisol could be safely achieved through massage, with associated improvement in psychological well-being. The implications are discussed.
  • Examining low bacterial dietary practice: a survey on low bacterial food.

    Mank, Arno P; Davies, Michelle; Department of Oncology/Hematology, Academic Medical Centre, Meibergreef 9, NL-1105 AZ Amsterdam, The Netherlands. a.p.mank@amc.uva.nl (2008-09)
    Patients with haematological malignancies have periods of neutropenia caused by the disease process and subsequent treatments, during which time they are at an increased risk of developing life threatening infections. Historically, many measures have been initiated to protect patients during this time. One such measure has been to provide a low bacterial diet to minimise the number of pathogens ingested from food. However, scientific literature lacks any substantial evidence confirming whether this is beneficial in the management of these patients while guidelines are often unclear and give conflicting advice. A detailed survey was carried out to examine the use of low bacterial diets considering criteria, conditions and specific dietary products. One hundred and eight questionnaires were completed, mainly European. Ninety-five (88%) centres used guidelines to advise practice for inpatients. Although 88% of the hospitals have guidelines, when these were examined there were enormous differences in both the guidelines themselves and the way in which they are implemented. The restrictions seen are varied and sometimes even contradict each other. Forty-eight (44%) of the respondents imposed restrictions on all products mentioned. Conditions for starting or stopping dietary restrictions were also diverse. This survey highlights the need to attempt to standardise dietary restrictions in a patient group for whom good nutrition is paramount.
  • Successful treatment of refractory joint contractures caused by sclerodermatous graft versus host disease.

    Kim, J B; Liakopoulou, Effie F; Watson, J S; Department of Plastic Surgery, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester M23 9LT, UK. jongbkim2001@yahoo.co.uk (2008-10)
    Sclerodermatous or cutaneous chronic graft versus host disease is characterised by deposition of collagen in the skin and possibly other soft tissues, resulting in loss of range of motion and functional capabilities. A patient with refractory joint contractures caused by sclerodermatous graft versus host disease is presented, and the successful surgical management of the case described.