• Graft-versus-host disease (GvHD)

      Murray, John; Stringer, Jacqui; Hutt, D; Department of Haematological Medicine, King’s College Hospital NHS Foundation Trust, London, United Kingdom (2018)
    • Granular cell angiosarcoma of the skin: histology, electron microscopy and immunohistochemistry of a newly recognized tumor.

      McWilliam, L; Harris, Martin; Departments of Pathology, Withington and Christie Hospitals, Manchester (1985-11)
      We report a unique angiosarcoma of the skin of the face in which a large part of the tumour was of granular cell appearance. Histologically the granular cells resembled those of conventional granular cell tumours. By electron microscopy the granules were identical to those of granular cell tumours but other features were lacking. Stains for vimentin and factor VIII related antigen were positive, but for S-100 protein and CEA were negative. The occurrence of granular cell change in an angiosarcoma supports the view that granular cell tumours are histogenetically diverse.
    • Granular cell variant of dermatofibrosarcoma protuberans.

      Banerjee, Saumitra S; Harris, Martin; Eyden, Brian P; Hamid, B N A; Department of Histopathology, Christie Hospital and Holt Radium Institute, Manchester, UK. (1990-10)
    • Granulocyte colony-stimulating factor to prevent dose-limiting neutropenia in non-Hodgkin's lymphoma: a randomized controlled trial.

      Pettengell, Ruth; Gurney, Howard; Radford, John A; Deakin, David P; James, Roger D; Wilkinson, Peter M; Kane, Kevin; Bentley, Jane; Crowther, Derek; Cancer Research Campaign Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, UK. (1992-09-15)
      The effect of granulocyte colony-stimulating factor (G-CSF) on neutropenia, infection, and cytotoxic chemotherapy administration was studied in a randomized trial in patients receiving intensive weekly chemotherapy for non-Hodgkin's lymphoma (NHL). Eighty patients (aged 16 to 71 years) with high-grade NHL (Kiel) of any stage were randomized to receive VAPEC-B chemotherapy alone (39 patients) or with G-CSF administered as a daily subcutaneous dose of 230 micrograms/m2 (41 patients). Prophylactic ketoconazole and cotrimoxazole were administered to all patients throughout treatment. The protocol specified identical dose modification and antibiotic treatment criteria bor both groups. Neutropenia (absolute neutrophil count [ANC] less than 1.0 x 10(9)/L) occurred in 15 of 41 (37%) of the G-CSF-treated patients and in 33 of 39 (85%) of the controls, giving a relative risk for control patients of 2.31 (95% confidence interval [CI], [1.51, 3.54]; P = .00001). Fever (greater than or equal to 37.5 degrees C) with neutropenia (ANC less than 1.0 x 10(9)/L) occurred in 9 of 41 (22%) of the G-CSF group and in 17 of 39 (44%) of the controls (relative risk for control, 2.26; 95% CI [1.01, 5.06]; P = .04). There were fewer treatment delays, with shorter duration (P = .01) in patients receiving G-CSF. Chemotherapy doses were reduced in 4 of 41 (10%) of the G-CSF patients and 13 of 39 (33%) of the controls (P = .01). The dose intensity of cytotoxic chemotherapy was significantly increased in patients receiving G-CSF (median of 95% in G-CSF group compared with 83% in control patients). Three vascular deaths occurred in the G-CSF group. Delays in the control group most commonly resulted from neutropenia (19 patients, compared with 2 patients in the G-CSF-treated group, P = .000007). Severe mucositis was the major dose-limiting toxicity in G-CSF-treated patients, but did not occur more frequently than in controls (15 patients in each group). Overall, patients randomized to receive G-CSF achieved a greater dose intensity than control patients, but this did not result in significant differences in drug toxicity (other than neutropenia), intravenous antibiotic usage, or hospitalization between the two groups.
    • Granulocyte-macrophage colony-stimulating factor allows safe escalation of dose-intensity of chemotherapy in metastatic adult soft tissue sarcomas: a study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.

      Steward, William P; Verweij, J; Somers, R; Spooner, D; Kerbrat, P; Clavel, M; Crowther, Derek; Rouesse, J; Tursz, T; Tueni, E; et al. (1993-01)
      PURPOSE: This study was designed to test the feasibility of administering doxorubicin at an optimal dose-intensity (> 70 mg/m2 per 21 days) in combination with ifosfamide under recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) cover in patients with metastatic soft tissue sarcomas. PATIENTS AND METHODS: One hundred four eligible patients (of 111 entered) in 16 centers received doxorubicin 75 mg/m2 plus ifosfamide 5 g/m2 every 3 weeks for up to seven cycles. rhGM-CSF (250 micrograms/m2) was administered once or twice daily by subcutaneous injections for up to 14 days between cycles of chemotherapy. RESULTS: Full protocol dose-intensity of chemotherapy was administered to the majority of patients with only 15 of 293 cycles being complicated by febrile episodes that required hospitalization. There were two treatment-related deaths: one from septicemia and one from cardiac failure. The main toxicities attributed to rhGM-CSF were pruritus and rash. A 45% response rate (10% complete remission [CR]) was seen, with a median response duration of 9 months and median survival of 15 months. CONCLUSION: This high-dose regimen of chemotherapy was feasible under rhGM-CSF cover and produced a higher response rate and median survival than previously seen by the European Organization for Research and Treatment of Cancer (EORTC) Soft Tissue Sarcoma Group. A randomized phase III study is now underway comparing this regimen with conventional-dose doxorubicin/ifosfamide to test the dose-response relationship.
    • The granulocytes in neutropenia 1 (GIN 1) study: a safety study of granulocytes collected from whole blood and stored in additive solution and plasma.

      Massey, E; Harding, K; Kahan, B C; Llewelyn, C; Wynn, R; Moppett, J; Robinson, S P; Green, A; Lucas, G; Sadani, D; et al. (2012-08)
      To evaluate the safety of transfusing pooled, whole blood-derived granulocytes in additive solution and plasma (GASP) in 30 recipients.
    • Granulocytic sarcoma of the cervix: an immunohistochemical, histochemical, and ultrastructural study.

      Banik, S; Grech, A B; Eyden, Brian P; Department of Histopathology, Royal Infirmary, Blackburn. (1989-05)
      Light microscopical and routine immunohistochemical studies of a cervical neoplasm in a 32 year old woman initially suggested a histiocytic lymphoma, but histochemical staining for chloroacetate esterase established the correct diagnosis. This was supported by electron microscopic findings. Eight months later the patient developed a granulocytic sarcoma in her left breast and haemotological features of acute myeloid leukaemia. Accurate initial diagnosis of granulocytic sarcoma in a non-leukaemic patient may reduce the risk of subsequent acute myeloid leukaemia if appropriate chemotherapy is begun in time.
    • Granulomatous lymphadenitis associated with metastatic malignant melanoma.

      Coyne, J D; Banerjee, Saumitra S; Menasce, Lia P; Mene, A R; Department of Histopathology, University Hospital of South Manchester, UK. (1996-05)
    • Great debate: surgery versus stereotactic radiotherapy for early-stage non-small cell lung cancer

      Hiley, Crispin T; Salem, Ahmed; Batchelor, T; McDonald, F; Evison, M; CRUK Lung Cancer Centre of Excellence, University College London & The University of Manchester, London & Manchester, UK (2020)
    • Grigoris Lambrakis (1912-1963) - a Greek obstetrician and world renowned activist.

      Gkegkes, I; Karamanou, M; Iavazzo, P; Gkegke, X; Androutsos, G; Iavazzo, Christos; Gynaecological Oncology Department, Christie Hospital, Manchester (2016-08)
      Grigoris Lambrakis was a Greek politician, doctor, athlete, and faculty member of the Medical School of Athens University. As an athlete, Lambrakis held the Greek record for long jump for twenty-three years and he also won several gold medals in the Balkan Athletic Games. Lambrakis received an excellent medical education. As lecturer at the University of Athens, Lambrakis became a pioneer of Gynecological Endocrinology. His philanthropy was always evident during his medical career, but he also consistently attended international pacifist meetings and demonstrations. His medical work, and his performance as lecturer of Obstetrics and Gynaecology, have been neglected, if not overshadowed, by his political career. Lambrakis is recognized worldwide as a martyr for peace. The aim in this essay is to present his life, and especially to elucidate his medical achievements.
    • Grist for the MLL: how do MLL oncogenic fusion proteins generate leukemia stem cells?

      Somervaille, Tim C P; Cleary, Michael L; Cancer Research UK Leukaemia Biology Group, Paterson Institute for Cancer Research, Manchester, M20 4BX, UK. (2010-06)
      MLL fusion oncogenes are pathogenically associated with 5-10% of human acute leukemias. Through multiple interactions with chromatin regulatory factors, they convert a normal hematopoietic hierarchy into a leukemia cell hierarchy sustained at its apex by a population of inappropriately self-renewing myeloid cells termed leukemia stem cells (LSCs). Initiation of the aberrant leukemia cell hierarchy is associated with an abnormal epigenetic state at Hoxa and Meis1 loci, with concomitant high level Hoxa and Meis1 expression. This introduces at the level of the myeloblast, or thereabouts, a finite probability of self-renewal division where none previously existed. In contrast, differentiation-mediated exit of LSCs from the self-renewing compartment of the leukemia clone depends on the prevailing levels of the transcription factor Myb, which functions as part of an LSC maintenance program influenced, but not directly controlled, by Hoxa and Meis1. Critical biologic and molecular differences between self-renewing progenitor-like LSCs and hematopoietic stem cells could potentially be targeted by novel therapeutic strategies.
    • Gross and cellular response of intestinal crypts to single and fractionated doses of vincristine plus radiation: the influence of time between modalities.

      Moore, James V; Pearson, D; Deakin, David P; Paterson Laboratories and Department of Radiotherapy, Christie Hospital and Holt Radium Institute, Manchester M20 9BX, England (1982-09)
      The response of intestinal crypts to single doses and four equal, daily fractions of vincristine (VCR) plus gamma-rays, has been measured by the crypt microcolony assay. Measurements were made for VCR given either 7 hours or 1 min before radiation. For the 7-hour interval, fractionating the VCR dose markedly increased the efficacy of the combination treatment. However at 1-min interval, no injury additional to that for gamma-rays alone could be demonstrated, with either one or four fractions. Histopathological studies showed that both VCR and gamma-rays alone caused cell death, but with different distributions in the crypt. For combined treatments, both VCR-and gamma-type damage could be recognized with the 7-hour interval, but at 1 min only gamma damage. It is suggested that mitotic delay induced by radiation may permit the repair of injury caused by simultaneously-delivered VCR.
    • Gross tumour volume (GTV) delineation on magnetic resonance imaging (MRI), for stage III lung cancer: consensus recommendations needed to ensure contouring consistency

      Shiarli, A.; Brown, S.; Dubec, Michael; Bainbridge, H.; Koh, D.; Lalezari, F.; van Herk, Marcel; Wetscherek, A.; Knowles, E.; Faivre-Finn, Corinne; et al. (2019)
      Introduction: MRI in the context of the radiotherapy (RT) planning workflow for locally advanced lung cancer (LALC) presents a number of advantages. MRI provides better soft tissue definition potentially reducing inter-observer contouring variability of GTV, allowing tighter margins. This could facilitate the development of intensified adaptive strategies. Defining the GTV on MRI in lung cancer is novel. Prior to inter-observer variability assessment, training of clinicians is paramount. Methods: Two training workshops were organised. The first workshop was web-based, led by an MRI radiologist. Fifteen radiation oncologists participated, from 9 centres internationally. Eight LALC cases were chosen to cover various anatomical scenarios including chest wall and mediastinal invasion, and superior sulcus tumours. The second workshop was face-to-face. The most challenging cases from the web-based workshop were reviewed, this time with applied contours checked by the same MRI radiologist. Subsequently, 10 radiation oncologists delineated the GTV on 3 separate cases. Delineation was performed on T1-weighted mid-position 4D radial VIBE MRI, registered with the mid-position 4DCT, PET CT and MRI sequences, including T2 TSE and TSE DIXON. These contours were compared with those produced by an MRI radiologist. Results: There are discrepancies in GTV delineation between MRI radiologists and radiation oncologists, particularly at sites of tumour invasion causing pleural reaction or bone oedema (Fig. 1). This demonstrates that recommendations for MRI GTV delineation must be developed collaboratively between both disciplines. Further work will involve contouring of 9 LALC cases on MRI, by a 'pair' of an MRI radiologist and a radiation oncologist from at least 8 international centres. These will be compared against blinded CT/ PET-CT contouring, and discussed, to produce recommendations for GTV delineation on MRI. Conclusion: Although GTV contouring on MRI is challenging it may provide better contrast information compared to CT. Novel MRI-guided adaptive strategies must be optimised collaboratively between MRI radiologists and radiation oncologists.
    • Growth and endocrine function after bone marrow transplantation.

      Shalet, Stephen M; Didi, Mohammed; Ogilvy-Stuart, Amanda L; Schulga, J; Donaldson, M D; Department of Endocrinology, Christie Hospital, Manchester, UK. (1995-04)
    • Growth and endocrine sequelae following the treatment of childhood-cancer.

      Shalet, Stephen M; O'Halloran, D J; Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK. (1994)
    • Growth and growth hormone status after a bone marrow transplant.

      Shalet, Stephen M; Brennan, Bernadette M; Department of Endocrinology, Christie Hospital, Manchester, UK. stephen.m.shalet@man.ac.uk (2002)
      The three most common clinical situations which have given rise to diagnostic and therapeutic issues involve the child treated for: (1) a brain tumour or extracranial tumour with radiotherapy (XRT) which includes an XRT dose of > or =30 Gy to the hypothalamic-pituitary axis; (2) acute lymphoblastic leukaemia with a cranial XRT dose of 18-24 Gy, and (3) haematological malignancy or solid tumour requiring total body irradiation (dose 10-14 Gy) and BMT. The decision about the intent to treat and the timing of GH replacement needs to be taken in collaboration with the paediatric oncologist who will provide guidance about overall prognosis and the risk of relapse. After a dose of > or =30 Gy to the hypothalamic pituitary axis the risk of GH deficiency (GHD) 2 years later is very high (>50%) and therefore there is 'solid' epidemiological evidence, which predicts outcome. Therapeutically the choice is whether or not to offer GH replacement at 2 years in the presence of biochemical evidence of GHD but independent of auxology, or wait until the growth rate declines. Diagnostically the IGF-1 SDS is more useful than previously thought, particularly if XRT-induced GHD is severe; there may, however, be systematic discordancy between the GH responses to different pharmacological stimuli (ITT vs. arginine). For irradiated children in categories 2 and 3, greater emphasis is placed on auxology in determining the need for assessment of GH status. Early rather than very precocious puberty is a real issue and needs to be actively treated with a GnRH analogue if final height appears to be significantly compromised.
    • Growth and growth hormone status following treatment for childhood leukaemia.

      Shalet, Stephen M; Brennan, Bernadette M; Christie Hospital NHS Trust, Manchester, UK. (1998)
      The exact contribution of growth hormone (GH) deficiency to the adverse growth outcome, in those receiving cranial irradiation (18-24 Gy) or total-body irradiation for haematological malignancies in childhood, remains difficult to disentangle as nearly always the cause of the growth disturbance is multifactorial: chemotherapy, graft-versus-host disease, hypothyroidism, and skeletal dysplasia may all impact on growth. There are few published data from which one can assess the efficacy of GH replacement on final height in those children who received cranial irradiation (18-24 Gy) and/or total-body irradiation; there is no evidence, however, of an increased risk of leukaemic relapse. Endocrine reassessment in the teenagers, who received cranial irradiation (18-24 Gy) for acute lymphoblastic leukaemia many years earlier, revealed a significant incidence of GH deficiency with the additional suggestion that many had been GH deficient for several years. This raises a number of important questions: What is the best way to organize long-term endocrine follow-up? How often should GH status be reassessed? What are the specific benefits of GH replacement in adult life for such individuals? These and other questions require further study.
    • Growth and hormonal status of children treated for brain tumours.

      Shalet, Stephen M; Department of Endocrinology.CHristie Hospital, Manchester, England (1982)
      The adult survivors of the treatment of brain tumours in childhood are often short. Several adverse factors contribute to the impaired growth of these children including growth hormone (GH) deficiency, impaired spinal growth following spinal irradiation, chemotherapy, poor nutritional intake and recurrent tumour. The GH deficiency is due to radiation-induced damage to the hypothalamic-pituitary axis. GH is always the first pituitary hormone to be affected by such radiation damage but panhypopituitarism may occur if the radiation dose is sufficiently great. Preliminary results suggest that GH therapy will improve the growth rate of children with radiation-induced GH deficiency. Additional endocrine complications, which may occur following spinal irradiation, include thyroid dysfunction and ovarian failure due to direct radiation damage to the thyroid and the ovary.
    • Growth and pituitary function in children treated for brain tumours or acute lymphoblastic leukaemia.

      Shalet, Stephen M; Clayton, Peter E; Price, David A; Department of Endocrinology, Christie Hospital, Manchester, UK. (1988)
    • Growth and puberty after growth hormone treatment after irradiation for brain tumours.

      Ogilvy-Stuart, Amanda L; Shalet, Stephen M; Department of Endocrinology, Christie Hospital, Withington, Manchester. (1995-08)
      The impact of treatment with either cranial or craniospinal irradiation with or without cytotoxic chemotherapy for a brain tumour distant from the hypothalamic-pituitary axis was assessed in 29 children who had reached final height. All had received growth hormone treatment for radiation induced growth hormone deficiency. Final height, segmental growth during puberty, and duration of puberty were studied. Both craniospinal irradiation and the use of chemotherapy resulted in a significant and equal reduction in final height; this effect in those children who received both craniospinal irradiation and chemotherapy was additive. The degree of height loss was related to the age at irradiation, the most profound effect on final height occurring in the youngest at irradiation. The mean duration of puberty from G2-G4/B2-B4 (1.97 years) was not significantly different from the duration of puberty in normal children. Growth hormone increases growth velocity in children with radiation induced growth hormone deficiency but their final height is significantly less than their mid-parental height. The use of spinal irradiation and chemotherapy in the original treatment of brain tumours has a marked effect on growth which is not overcome with the use of growth hormone treatment in current doses. Early puberty of normal duration contributes to poor growth.