Time Of Histological Diagnosis Research Articles

Papillary Thyroid Microcarcinoma: Differences between Lesions in Incidental and Nonincidental Settings-Considerations on These Clinical Entities and Personal Experience.

Papillary thyroid microcarcinoma (PTMC) represents 35-40% of all papillary cancers; it is defined as a nodule ≤ 10 mm at the time of histological diagnosis. The clinical significance of PTMC is still controversial, and it may be discovered in two settings: incidental PTMC (iPTMC), in which it is identified postoperatively upon histological examination of thyroid specimens following thyroid surgery for benign disease, and nonincidental PTMC (niPTMC), in which it is diagnosed before surgery. While iPTMC appears to be related to mild behavior and favorable clinical outcomes, niPTMC may exhibit markers of aggressiveness. We retrospectively review our experience, selecting 54 PTMCs: 28 classified as niPTMC (52%) and 26 classified as iPTMC (48%). Patients with niPTMC showed significant differences, such as younger age at diagnosis (p < 0.001); a lower male/female ratio (p < 0.01); a larger mean nodule diameter (p < 0.001); and a higher rate of aggressive pathological findings, such as multifocality, capsular invasion and/or lymphovascular invasion (p = 0.035). Other differences found in the niPTMC subgroup included a higher preoperative serum TSH level, higher hospital morbidity and a greater need for postoperative iodine ablation therapy (p < 0.05), while disease-free long-term survival did not differ between subgroups (p = 0.331) after a mean follow-up (FU) of 87 months, with one nodal recurrence among niPTMCs. The differences between iPTMC and niPTMC were consistent: patients operated on for total thyroidectomy and showing iPTMC can be considered healed after surgery, and follow-up should be designed to properly calibrate hormonal supplementation; conversely, niPTMC may sometimes exhibit aggressive behavior, and so the FU regimen should be closer and aimed at early detection of cancer recurrence.

Clinical characteristics and radiological features of glioblastoma, IDH-wildtype, grade 4 with histologically lower-grade gliomas.

The 2021 World Health Organization (WHO) classification of central nervous system tumors applied molecular criteria and further integrated histological and molecular diagnosis of gliomas. This classification allows for the diagnosis of isocitrate dehydrogenase wild-type (IDHwt) glioblastoma (GBM), and WHO grade 4 with histologically lower-grade gliomas (LrGGs), even in the absence of high-grade histopathologic features, such as necrosis and/or microvascular proliferation. They contain at least one of the following molecular features: epidermal growth factor receptor amplification, chromosome 7 gain/10 loss, or telomerase reverse transcriptase promoter mutation. In the imaging features at the time of histological diagnosis, a gliomatosis cerebri growth pattern was frequently observed in these tumors. Furthermore, this growth pattern was significantly higher in IDHwt GBM, WHO grade 4, with histological grade II gliomas. Although the exact prognosis of IDHwt GBM, WHO grade 4, with histologically LGGs remains unknown, its OS was approximately 1-2years similar to that of histologically IDHwt GBM, WHO grade 4, despite histopathological features similar to IDHmut LrGGs. These findings reinforce the need for the analysis of molecular features, regardless of presenting similar clinical characteristics and imaging features to IDHmut LrGGs.

Airway interventions for tracheobronchial involvement in esophageal carcinoma: a retrospective cohort outcome study and algorithmic approach.

BackgroundIn advanced esophageal carcinoma (EC), there is limited data on risk factors predicting tracheobronchoesophageal fistula (TEF) formation and survival among patients who required airway interventions.MethodsA retrospective analysis of consecutive patients with EC, who had airway involvement requiring intervention, was conducted from 1998 to 2018. Demographics, clinical progress, disease stage, treatment and survival outcomes were recorded. Patients were followed up till death or until completion of the study. Survival was estimated with the Kaplan-Meier method and curves compared by log-rank test. Multivariate analyses of risk factors were performed using Cox proportional hazard regression.ResultsA total of 122 patients were included. The median (IQR) survival from time of airway intervention was 3.30 (1.57–6.88) months, while the median (IQR) survival from time of histological diagnosis was 8.90 (4.91–14.45) months. Tumour location within 20 mm of the carina, prior radiotherapy and/or esophageal stenting were significantly associated with formation of TEF. Mid EC [adjusted hazard ratio (HR) 1.9; 95% confidence interval (CI): 1.1–3.2] or presence of TEF (adjusted HR 1.8; 95% CI: 1.0–3.2) were associated with lower survival. Patients receiving chemotherapy (adjusted HR 0.46; 95% CI: 0.25–0.84), or esophageal stenting whether before or after airway intervention (adjusted HR 0.32; 95% CI: 0.15–0.68 and adjusted HR 0.51; 95% CI: 0.29–0.90) were associated with increased survival.ConclusionsFactors associated with TEF formation include airway location, radiotherapy and prior esophageal stenting, and the development of TEF was associated with poorer survival. An algorithmic approach towards tracheobronchial involvement in EC is proposed based on these findings and a review of the literature.

Sinusoidal obstruction syndrome after liver transplantation: A multicenter observational study.

Sinusoidal obstruction syndrome after liver transplantation: A multicenter observational study.

INNV-04. A MULTI-INSTITUTIONAL CLINICAL AND MRI REPOSITORY OF NEUROFIBROMATOSIS TYPE 1-ASSOCIATED PERIPHERAL NERVE SHEATH TUMORS

Abstract BACKGROUND Individuals with neurofibromatosis type 1 (NF1) frequently have peripheral nerve sheath tumors (PNST), including plexiform neurofibromas (PNF), atypical neurofibromas (ANF), and malignant peripheral nerve sheath tumors (MPNST). These tumors reflect a histologic spectrum from benign to malignant. Various clinical and MRI-based features are proposed as risk factors for MPNST development based on small single-institution studies. A major barrier to study these risk factors is collation and annotation of multi-center serial MRIs. To address this, we created a standardized database of clinical data and longitudinal MRIs from NF1-associated PNST from nine international NF1 referral centers. METHODS Clinical data from NF1 patients are collected in Research Electronic Data Capture databases housed at Massachusetts General Hospital and Washington University, including demographic information, genotype, disease course, treatment history, and survival. ANF and MPNST require histologic confirmation whereas a diagnosis of PNF can also be made based on clinical/radiographic stability. Longitudinal MRIs predating the histologic diagnosis are uploaded to a HIPAA-compliant cloud-based system. RESULTS Data from 200 patients (87 females, 113 males) with 217 tumors (75 PNF, 40 ANF, 102 MPNST) have been collected. 280 regional and 108 whole-body MRIs have been identified. Median age at the time of histologic diagnosis is 30 years (range 5-64). All tumors are histologically confirmed except for 6 PNF which remained stable over time. Median follow-up time is 32 months. Of 147 patients with available survival data, 32 (21.7%) have died from MPNST progression; estimated median overall survival is 20 months. CONCLUSIONS In this ongoing work, we have assembled one of the largest systematically annotated clinical and MRI repositories of NF1-associated PNST from pediatric and adult NF1 patients. The data will be accessible to outside researchers which will promote interdisciplinary and multi-center collaborations. Active efforts include the identification of radiomic MRI features to differentiate between PNF and MPNST.

Pediatric Mycosis Fungoides: Retrospective Analysis of a Series With CD8 + Profile and Female Predominance.

Mycosis fungoides (MF) in children is a rare disease and there are limited data regarding the behavior of the disease in this age group. We aimed to collect additional data to better understand the clinicopathologic features of MF in children. This study was a retrospective analysis of pediatric MF patients (diagnosed at age 0 to 18 y). Thirteen pediatric patients with MF were identified. Female predominance was observed with a ratio of 1.6:1. Median values for age of onset of skin lesions and age at the time of histologic diagnosis were 5 and 12 years, respectively. All patients had early stage (stage IA to IIA) of MF at the time of diagnosis. Hypopigmented MF comprised 77% of all study patients, followed by classic MF (15%) and pagetoid reticulosis (8%). The lower extremity (especially proximal leg) followed by trunk and upper extremity were most commonly affected sites. Seven of 9 patients who had available immunohistochemistry data showed CD8 + predominance. Five of 8 patients whose follow-up data was available, achieved complete response with narrowband ultraviolet B treatment, while 2 and 1 had near complete response and partial response, respectively. Our study demonstrated female sex and CD8 + profile predominance. Hypopigmented MF constituted the majority of cases. We observed good responses with narrowband ultraviolet B treatment.

P1701ANTIBODY MEDIATED REJECTION: CLINICAL PHENOTYPE MATTERS

Abstract Background and Aims Protocol biopsies following kidney transplantation (KT) allow the histological diagnosis of antibody-mediated rejection (ABMR) with stable renal function (RF). Controversy arises when considering isolated proteinuria as a clinical biomarker. Currently, there is no effective treatment for ABMR and transplant units may decide on treatment independently of the clinical expression. Method KT recipients (1987-2017) with post-KT biopsies (2008-2018) showing ABMR graft lesions (category 2-Banff’2015) &amp;gt;1year post-KT were included. Cases were grouped into phenotypes of ABMR according to the clinical picture at biopsy : 1) acute RF impairment (↑creatinine &amp;gt;15% three weeks before biopsy) with/without proteinuria and with/without DSA detection. 2) sub-acute RF impairment (↑creatinine &amp;gt;15% six months before biopsy) with/without proteinuria and with/without DSA detection, 3) performed for DSA detection with stable RF and no proteinuria or 4) protocol biopsy, with stable RF, no proteinuria or DSA detection. We considered an additional category: 5) isolated proteinuria (↑&amp;gt;500 mg or x2 six months before biopsy). Categories 1), 2) and 5) were considered clinical ABMR. Categories 3) and 4) were considered subclinical ABMR. We aimed to evaluate graft outcomes in the different ABMR phenotypes. Results In a cohort of 105 KT recipients with histologic lesions of ABMR, biopsies corresponded to phenotypes 1) in 35 (33%), 2) 10 (9,5%), 3) 21 (20,3%), 4) 14 (13,4%) and y 5) in 25 23,8%). No differences between clinical and subclinical ABMR were found in baseline characteristics except for donors ‘age, who were older within the clinical group (51.8±18.8 vs. 43.88 ±16.1; p=0.04). At time of biopsy, subclinical had better RF than clinical ABMR (creatinine 1.3±0.4 mg/dl vs. 2.2±1.1 mg/dl; p=0.02) and less proteinuria (161 mg/g [IQR 93-269] vs 939 mg/g [IQR 412-2000]; p=0.001) Graft survival was worse in those patients with acute and sub-acute RF impairment, followed by those with isolated proteinuria (Figure 1). In comparison to subclinical ABMR, those with RF impairment and isolated proteinuria had an increased risk of graft lost; HR 9.4 (95% IC 2.2-40.7, p=0.002) and 4.8 (95% IC 1.01-23.2, P=0.05) respectively. DSA detection in these groups did not impact graft survival. Specific treatment was not different among groups, except for steroid pulses, which were more frequently applied in cases of ABMR with clinical manifestation. Conclusion The clinical phenotypes of ABMR influence long-term graft survival independently from treatment. Understanding graft evolution according to clinical phenotype at the time of histologic diagnosis should guide the therapeutic strategy, to balance risk-benefit ratio.

OS10.1 Survival analysis of IDH wildtype astrocytomas with molecular features of glioblastoma, WHO grade IV

Abstract BACKGROUND Recently, isocitrate dehydrogenase wildtype (IDHwt) lower grade gliomas (LGGs) that have a telomerase reverse transcriptase (TERT) promoter mutation and/or gain of chromosome 7 combined with loss of chromosome 10 and/or epidermal growth factor receptor amplification have been reclassified as IDHwt astrocytomas with molecular features of glioblastoma, WHO grade IV (‘astrocytomas IDHwt, WHO IV’). Survival of these tumors meeting the criteria of these tumors is less well studied. The objective of this study is to compare the overall survival (OS) between the IDHwt astrocytomas, WHO IV and histological glioblastomas (GBMs). MATERIAL AND METHODS In this retrospective multicenter cohort study, all adult patients with a newly diagnosed IDHwt LGG (histologically WHO grade II or III) and with molecular data available were selected from the Erasmus MC and the LUMC from October 2002 to April 2019. LGG patients showing contrast enhancement with necrosis on the MRI at the time of histological diagnosis were excluded. Molecular data were determined using a diagnostic NGS panel. A historical cohort of 195 patients with IDHwt GBMs with molecular data available was used to compare OS. OS was measured from the date of the first diagnostic MR scan. RESULTS 79 IDHwt LGG patients were identified of which 62 patients had molecular features of glioblastoma (‘astrocytomas IDHwt, WHO IV’), 11 patients did not have these molecular features (‘astrocytomas IDHwt, WHO II &amp; III’). In the remaining 6 patients the molecular data were not conclusive (astrocytomas IDHwt, WHO NOS). Patients with astrocytomas IDHwt, WHO IV were slightly older at diagnosis (median age = 57 years) than patients with GBMs IDHwt in the reference cohort or astrocytomas IDHwt, WHO II &amp; III (respectively: median age 55 years, p=0.032 and 47 years, p=0.035). The relatively young age of our GBM IDHwt cohort reflects more extensive molecular testing in younger patients and histologically lower grade tumors. The median OS of astrocytomas IDHwt, WHO IV (23.8 months) was similar to the median OS of GBMs (19.2 months, log-rank test p=0.37). The median OS in 19 patients with only TERT promoter mutations was 16.8 months, similar to GBMs (p=0.94). CONCLUSION There is no statistically significant difference between the OS of IDHwt astrocytomas with molecular features of glioblastoma and the OS of true glioblastomas. Grade II and III IDHwt astrocytoma with molecular features of glioblastoma should be designated WHO grade IV. The presence of TERT promoter mutations alone in this histological context also qualifies for this designation.

Whole-Blood Taurine Concentrations in Cats With Intestinal Disease.

BackgroundIncreased delivery of taurine‐conjugated bile acids to the distal bowel can lead to dysbiosis resulting in colitis in mouse models of inflammatory bowel disease. A similar situation also could occur in cats with intestinal disease and might therefore result in decreased whole‐body taurine concentration.Hypothesis/ObjectivesTo determine whether whole‐blood taurine concentrations are decreased at the time of diagnosis in cats with intestinal disease and to correlate concentrations with clinical and laboratory variables.AnimalsTwenty‐one cats with chronic inflammatory enteropathy and 7 cats with intestinal neoplasia from the University of Bristol.MethodsCats that had undergone a thorough investigation consisting of a CBC, serum biochemistry, serum cobalamin and folate concentrations, transabdominal ultrasound examination and histopathology of intestinal biopsy specimens, as well as additional testing if indicated, were included. Whole‐blood from these cats collected at the time of histologic diagnosis and stored in ethylenediaminetetraacetic acid was retrospectively analyzed for taurine with an automated high‐performance liquid chromatography amino acid analyzer.ResultsAlthough whole‐blood taurine concentrations remained within the reference range, those cats with predominantly large intestinal clinical signs had significantly lower concentrations than did cats with small intestinal and mixed bowel clinical signs (P = 0.033) and this difference also was significant when assessed only in cats with chronic inflammatory enteropathy (P = 0.019).Conclusions and Clinical ImportanceAdditional studies are needed to determine whether large intestinal signs in cats with chronic inflammatory enteropathy are caused by alterations in the microbiota arising as a consequence of increased delivery of taurine‐conjugated bile acids.

Impact of Cytological Sampling on EGFR Mutation Testing in Stage III-IV Lung Adenocarcinoma.

Objectives. There have been advances in the identification and understanding of molecular subsets of lung cancer, defined by specific oncogenic aberrations. A number of actionable genetic alterations have been identified, such as the epidermal growth factor receptor (EGFR) mutation. We aimed to establish the reasons why patients were not undergoing EGFR mutation testing at the time of histological diagnosis. Methods. The records of 70 patients with advanced adenocarcinoma of the lung managed through a single multidisciplinary team at a single institution were reviewed. Data were collected on method of tumour sample collection, whether this was sent for EGFR testing, and the result. Results. Seventy patients were identified. In 21/25 (84%) cases, cytological sampling was sufficient for EGFR mutation analysis, compared with 40/45 (89%) cases with histological sampling. EGFR mutation testing was not carried out in 22/70 (31.4%) patients. There was insufficient tumour sample for EGFR testing in 9/22 (40.9%) patients. Other reasons for not testing included poor patient fitness and problems in the diagnostic pathway. Conclusions. In this series, cytological tumour sampling was not the predominant reason why cancers failed to have EGFR mutation status established.

Does the addition of adjuvant intraoperative postdissection tumor bed chemotherapy during GI neuroendocrine tumor debulking benefit patients?

442 Background: Midgut neuroendocrine tumor (NET) patients are often diagnosed at an advanced stage with extensive mesenteric lymph node and liver metastasis. The only treatment for potential cure and durable results is resection with extensive debulking. However, even with the most elegant surgical dissection/resection, macro and microscopic residual disease at the tumor resection bed remains a distinctive possibility. We hypothesize that local application of 5-florouracil (5-FU) within tumor bed would eliminate the microscopic residual disease post operatively. Methods: Surgical records of 188 consecutive patients who underwent extensive cytoreductive surgeries for stage IV, small bowel NETs with boggy mesenteric lymphadenopathy between 2003-2012 were reviewed. 85 Patients who had 5-Florouracil saturated gelfoam strips secured into their mesenteric resection defects served as the study group (n=85) with one hundred three patients who did not receive such intra-operative chemotherapy as the control (n=103). Survival from the time of diagnosis, postoperative morbidity and mortality between the two groups were collected and compared. Results: Mortality rates at immediate, 30, 60 and 90 days post operative period were 3; 0; 1; 0; and 0; 2; 0; 4 respectively for study and control group. Minor complications (Clavien-Dindo Grade I and II) at 30, 60 and 90 day postoperative period were 12; 0; 1 and 12; 5; 5 respectively. Major complications (Grade III and IV) at the same time intervals were 2; 0; 2 and 2; 3; 2 for study and control groups. Most of all, the mean survival from time of histological diagnosis for the study patients was 210 months (17.5 years) as compared to 177 months (14.7 years) for the control group with a difference of 33 months (2.75 years). Conclusions: Intra-operative tumor resection bed chemotherapy is a safe adjuvant without any discernible toxicity. Furthermore, it might provide survival benefit to midgut NET patients with extensive mesenteric lymphadenopathy undergoing extensive cytoreductive surgery without additional procedure related complications.

Chemoradiotherapy for locally advanced head and neck cancers: Two-year survival and toxicity outcomes from a regional cancer centre in UK.

e16020 Background: To evaluate the 2-year overall survival (OS), cause-specific survival and toxicities of locally advanced head and neck cancer patients treated with primary chemo-radiotherapy (CRT) over a two year period. Methods: Between June 2006 and May 2008, sixty patients with locally advanced head and neck cancers were treated (excluding skin and thyroid). Of these, seventeen (28.33%) were stage III, thirty nine (65%) were stage IVA and four (6.66%) were stage IVB. All received concurrent 3 weekly cisplatin (75-80 mg/m2) and radiotherapy dose of 66-70 Gy in 33-35 fractions, treated daily in three phases by conformal 3-dimensional CT-planning. Treatment response was assessed radiologically 3 months post primary CRT. Survival was calculated from the time of histological diagnosis and time to treatment tailure (TTF) from the completion of treatment. Results: The median age was 57 years (range 18-79) and M:F ratio was 3:1.The 2-year OS was 73.3 % and loco-regional control rate was 83.3 %. The treatment failure rate was 16.6 % (10/60 patients) with a median TTF of 5 months (range= 1 to 24 months). Sixteen patients (26.6%) died with in 2 years of treatment of which five (4%) died of progression from residual disease, six (4.8%) died of loco-regional recurrence and three (5%) died of distant recurrence. Rest of the three died of other causes and includes two (3.33%) from second primary (lung and oesophageal) cancers. The incidence of acute severe or persistent oral mucositis was 4% (RTOG grade 3) and none had grade 3/4 skin toxicity. The incidence of late toxicities was 4% for osteoradionecrosis (ORN) of the mandible, 3.2% for severe trismus and 2.4% had sinus/fistula formation. The incidence of severe oropharyngeal stenosis/total dysphagia was 3.2% and 3 patients (2.4%) were on long term (15-32 months) gastrostomy feeding tube for nutrition. One patient (0.8%) developed severe carotid artery disease in the RT field. None of the patients had treatment related death. Conclusions: Our results are on par with international standards published in the literature. This data will be followed up for long-term outcomes and can be used as a bench mark for comparison with current modern planning techniques like intensity modulated radiotherapy (IMRT).

An epidermal growth factor receptor variant III–targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme

Conventional therapies for glioblastoma multiforme (GBM) fail to target tumor cells exclusively, such that their efficacy is ultimately limited by nonspecific toxicity. Immunologic targeting of tumor-specific gene mutations, however, may allow more precise eradication of neoplastic cells. The epidermal growth factor receptor variant III (EGFRvIII) is a consistent and tumor-specific mutation widely expressed in GBMs and other neoplasms. The safety and immunogenicity of a dendritic cell (DC)-based vaccine targeting the EGFRvIII antigen was evaluated in this study. Adults with newly diagnosed GBM, who had undergone gross-total resection and standard conformal external beam radiotherapy, received three consecutive intradermal vaccinations with autologous mature DCs pulsed with an EGFRvIII-specific peptide conjugated to keyhole limpet hemocyanin. The dose of DCs was escalated in cohorts of three patients. Patients were monitored for toxicity, immune response, radiographic and clinical progression, and death. No allergic reactions or serious adverse events were seen. Adverse events were limited to grade 2 toxicities. The maximum feasible dose of antigen-pulsed mature DCs was reached at 5.7 x 10(7) +/- 2.9 x 10(7) SD without dose-limiting toxicity. EGFRvIII-specific immune responses were evident in most patients. The mean time from histologic diagnosis to vaccination was 3.6 +/- 0.6 SD months. Median time to progression from vaccination was 6.8 months [95% confidence interval (C.I.(95)), 2.5-8.8], and median survival time from vaccination was 18.7 months (C.I.(95), 14.5-25.6). Overall median survival from time of histologic diagnosis was 22.8 months (C.I.(95), 17.5-29). This study establishes the EGFRvIII mutation as a safe and immunogenic tumor-specific target for immunotherapy.

Prognostic significance of imaging contrast enhancement for WHO grade II gliomas

In this study, we investigated the prognostic value of MRI contrast enhancement (CE) at the time of histological diagnosis specifically in a selected population of WHO grade II gliomas. We reviewed 927 histologically proven WHO grade II gliomas for which contrast-enhanced MR images were available at the time of histological diagnosis. CE patterns were classified into three categories: "patchy and faint," "nodular-like," and "ring-like." CE progression over time was recorded before oncological treatment on successive MR images, when available. CE was present in 143 cases (15.9%), with 93 patchy and faint, 50 nodular-like, and no ring-like patterns. CE areas were time progressive before oncological treatment in 35 of the 56 available cases (62.5%). Regardless of its pattern, the presence of CE was not significantly associated with a worsened prognosis (p = 0.415) by univariate analysis. Only the nodular-like pattern of CE (p < 0.01) and the time-progressive CE (p < 0.001) in the available subgroup proved to be statistically associated with survival since first oncological treatment. The present results show the necessity, in cases of WHO grade II gliomas, to study CE at the time of histological diagnosis and, whenever possible, to follow its progression over time before oncological treatment. Nodular-like CE and time-progressive CE are associated with a worsened prognosis, both suggesting malignant transformation, even though histopathological examination cannot initially disclose signs of malignancy in those areas.

Autologous (Auto) and Allogeneic (Allo) Stem Cell Transplantation (SCT) for Pateints (pts) with Advanced Chronic Lymphoctic Leukemia (CLL): A Comparative Study.

Background: AlloSCT is a potential curative treatment for pts with advanced CLL but alloSCT is limited by significant acute and chronic treatment related toxicities and the availability of HLA matched donors. AutoSCT is widely used for treatment of acute leukemia and aggressive lymphoma but rarely used for pts with CLL. This retrospective analysis describes the outcomes of 27 patients from our institution who have undergone either autologous or allogenic SCT for treatment of their advanced CLL. We also compare their transplant outcomes.Patients and methods: Between 08/98 and 07/07, 27 pts (M;22; median age 54.1, range 37–61) with variable RAI-Sawistsky stage CLL at the time of histological diagnosis (RAI I for 14 patients) underwent SCT (10 autoSCT, 17 matched related donors, 3 matched unrelated donors) Fourteen patients (52%) had a normal karyotype, 13q deletion and trisomy 12 occurring in six and four patients respectively. Median disease duration prior to transplant was 41.7 months (range 5–121). The indication for transplant was refractory disease for most patients. Preparative regimens consisted of Cyclophosphamide (Cy) + TBI (6), Fludarabine (Flu)+Cy (6), Rituximab (R) +Cy+TBI (4) R +melphalan + flu (4) and others (7). NCI complete remission (CR) criteria, flow cytometry, cytogenetics and chimerism data, as available, were used to assess response to therapy.Results: All 27 patients engrafted, with a mean neutrophil engraftment time of 13.5 days (range 9–24). From the group of patients that received allogeneic transplant, eight (47%) developed acute GVHD, with a median time of 18 days after transplant. Seventeen patients (62%) achieved CR on day +100 by marrow morphology, 15 out of 19 by flow cytometry and 13 out of 15 patients had normal chimerism studies. Non relapse mortality (NRM) on day +100 was 14.8% (17.6% for allo, 0% for auto). Estimated actuarial survival at 3 years for all patients was 68% (65% for alloSCT and 72% for the autoSCT group).Disease free survival at 3 years was defined as the percentage of patients who remained in CR 3 years following transplant. DFS was 62% for the whole group (77% for autoSCT and 51% for the patients who received an alloSCT).Conclusion: In this study, we have demonstrated high remission rate after both autologous and allogeneic SCT, however, the transplant outcomes (day 100 NRM, DFS and OS) favors autologous over allogeneic with toxicity related death accounted for most of the treatment failures after an alloSCT. Our results suggested that AutoSCT warranted further studies, in particular for older patients and those without a suitable donor.

Malignant Carcinoid Tumors An Analysis of 103 Patients with Regard to Tumor Localization, Hormone Production, and Survival

In a prospective study of 103 patients with carcinoid tumors consecutively referred for medical treatment, the most common sites of the primary tumors were the ileum (73%), bronchi (7%), and jejunum (4%). All patients had local metastases, and 96 (93%) also had liver metastases. The most common initial symptoms were diarrhea (32%), ileus (25%), and flush (23%). The overall frequency of diarrhea was 84% and of flush was 75%. Heart insufficiency caused by cardiac valve disease was seen in 33% of the patients. The carcinoid syndrome, including flush, diarrhea, and elevated urinary 5-hydroxyindole acetic acid (5-HIAA) concentrations, was manifested by 69 patients (67%), 64 of whom (93%) had carcinoid tumors of mid-gut origin. Elevated urinary 5-HIAA was found in 91 patients (88%), of which 89 displayed liver metastases. The plasma concentration of the tachykinin neuropeptide K (NPK) was elevated in 67 patients (66%), 63 of whom had tumors of the mid-gut region. Serum pancreatic polypeptide (PP) and human chorionic gonadotrophin alpha levels were elevated in 43% and 28% of the patients, respectively, and the highest levels were found in patients with metastatic bronchial carcinoid tumors. Thirty-nine of the 103 patients are now dead; 18 died of tumor progression, whereas 14 patients died of heart failure secondary to a carcinoid tricuspidal valve insufficiency. The estimated median survival from the time of histologic diagnosis was 14 years, and from the time of carcinoid syndrome was 8 years.

Adjuvant immunotherapy with bacillus Calmette-Guérin in prostatic cancer

Ninety-two patients with histologically proved prostatic cancer were studied. Forty-six patients were treated with bacillus Calmette-Guerin (BCG) adjuvant immunotherapy, and 46 other patients, matched for stage and hormone therapy, served as controls. Survival from the time of histologic diagnosis was sixteen and one-half months longer (thirty-seven and one-half versus twenty-one months) in the BCG-treated patients. There was no mortality and only minimal morbidity. Changes in some immunologic parameters (white blood cell count, skin tests) suggest an immune response.

Carcinoma of the thyroid gland in children and adolescents.

Thirty-six children and adolescents were treated for carcinoma of the thyroid gland over a 30-year period. The average age at the time of histological diagnosis was 11.8 years. Seventeen patients (47%) gave a history of previous exposure to ionizing radiation for benign disorders in the head and neck area. Two patients died from neoplasm. The longest period of survival has been 26 years after diagnosis. Twenty-six carcinomas were a mixed papillary and follicular type, 5 were pure papillary, and 5 were wholly follicular. Thirty-two patients had regional lymph node metastases. Nine patients had roentgenographic evidence of pulmonary metastases. Two of this group died; of the remaining 7 patients, all but 1 have had complete resolution after administration of radioactive iodine. This study supports the impression of an increasing incidence of thyroid carcinoma, which may be related to exposure to previous irradiation.