Lip symmetry following rotation advancement cleft lip repair in 5-year-old children treated by Ralph Millard and Ron Pigott.

Objective: To compare the symmetry of the lip following Rotation-Advancement cleft lip repair by Millard and Pigott and to investigate the effect on the symmetry of cleft side and gender by using different surgical protocols. Symmetry following cleft surgery was compared to that of non-cleft children. Design: Retrospective study of photographs of children aged 5 years. Setting: Three decades of post-operative photographs of children treated by Millard and Pigott. Patients: Eighty-nine children treated by Millard, 87 by Pigott and 91 non-cleft children. Interventions: Photographs were assessed using the Symnose Computer program, a rapid semi-objective quantitative assessment of lip symmetry. Main Outcome Measures: Asymmetry score for each surgeon, and non-cleft children. Results: There was no significant difference in the median lip % mismatch score of Millard, 36.65% and Pigott, 38.52%. Right-sided clefts showed better symmetry than left-sided clefts for Millard (p<.001). This was reversed for Pigott (P=.0121). There was a difference (P<.001) between the symmetry of the two cleft cohorts and the non-cleft children (asymmetry 19.9%), and between Millard's outcomes following different lip surgical protocols (P < .0001), but no difference between Pigott's outcomes using different palate surgical protocols (P = 0.59). Conclusions: Cleft lip repair by Millard and Pigott resulted in similar lip asymmetry (37% and 39% symmetry mismatch, respectively). Lip surgical protocol and cleft side may affect lip asymmetry. Palate surgery did not affect lip asymmetry. Following cleft surgery, children were more asymmetric than non-cleft children.

Unicortical fixation of metacarpal fractures: is it strong enough?

Unicortical fixation has some practical and theoretical advantages over bicortical fixation. Questions have been raised to its adequacy for post-operative mobilization. We hypothesized that fixation using a plate and eight unicortical screws would be as strong as using a plate and four bicortical screws. A total of 40 unicortical and 40 bicortical fixations were compared using a cadaveric metacarpal model. Unicortical fixation was performed using an eight-hole parallel plate and bicortical fixation with a four-hole straight plate. Fixations were tested to failure using four-point bending load. The mean load to failure was 414 N SD 38(SE) for the unicortical group and 296 N SD 29(SE) for the bicortical group. Significant differences between these two constructs were observed. The mean stiffness of the fixation was higher for the bicortical group than the unicortical, although this difference did not reach significance. Unicortical fixation alone is sufficient to enable early post-operative mobilization in a live model.

Treatment results in advanced stage Hodgkin's lymphoma: a retrospective study.

BACKGROUND: Hodgkin's lymphoma displays distinct epidemiological attributes in Asian population thus making it relevant to study whether there are any differences in treatment outcomes too when treated with current standard of care. AIM: To evaluate the treatment outcomes of de-novo advanced stage HL in adults. MATERIALS AND METHODS: This retrospective study included de-novo advanced stage HL patients (≥15 years) registered at our center from January 2004 to December 2007. Treatment outcomes were measured in terms of response rates, overall survival (OS) and progression-free survival (PFS). Overall and PFS were calculated with Kaplan-Meier methodology and Cox-proportional hazards model was used for multivariate analysis to identify prognostic factors. RESULTS: There were 125 patients (males 77%) who received minimum one cycle of chemotherapy with median age of 32 years (Range 15-65 years). Stage IV disease was seen in (46 patients) 37%; 75% (94 patients) patients had B symptoms. International prognostic score (IPS) ≤4 was seen in 95/112 (85%) patients. ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy was given to 94%. Radiation to residual/bulky sites was given to 36% (45 patients). Response data was available for 112 patients; complete response in 76%; partial response in 10 % and progressive disease in 3 patients. Nineteen deaths (progressive disease-7, toxicity-8, unrelated cause-4) were observed. At median follow-up of 28 months, estimated 5-year OS and PFS were 60% and 58%, respectively. On multivariate analysis, IPS and response to treatment were significant factors for both OS and PFS. CONCLUSIONS: The treatment outcomes in this study are comparable with the published literature with limited follow-up data.

Clinico-pathological impact of cytogenetic subgroups in B-cell chronic lymphocytic leukemia: experience from India.

BACKGROUND: The present study of 238 B-cell Chronic Lymphocytic Leukemia (B-CLL) patients were undertaken to seek the prevalence and to evaluate clinico-pathological significance of recurrent genetic abnormalities such as del(13q14.3), trisomy 12, del(11q22.3) (ATM), TP53 deletion, del(6q21) and IgH translocation/deletion. MATERIALS AND METHODS: We applied interphase - fluorescence in situ hybridization (FISH) on total 238 cases of B-CLL. RESULTS: Our study disclosed 69% of patients with genetic aberrations such as 13q deletion (63%), trisomy 12 (28%), 11q deletion (18%), 6q21 deletion (11%) with comparatively higher frequency of TP53 deletion (22%). Deletion 13q displayed as a most frequent sole abnormality. In group with coexistence of ≥2 aberrations, 13q deletion was a major clone indicating del(13q) as a primary event followed by 11q deletion, TP53 deletion, trisomy 12, 6q deletion as secondary progressive events. In comparison with del(13q), trisomy 12, group with coexistence of ≥2 aberrations associated with poor risk factors such as hyperleukocytosis, advanced stage, and multiple nodes involvement. In a separate study of 116 patients, analysis of IgH abnormalities revealed either partial deletion (24%) or translocation (5%) and were associated with del(13q), trisomy 12, TP53 and ATM deletion. Two of 7 cases had t(14;18), one case had t(8;14), and four cases had other variant IgH translocation t(?;14). CONCLUSION: Detail characterization and clinical impact are necessary to ensure that IgH translocation positive CLL is a distinct pathological entity. Our data suggests that CLL with various cytogenetic subsets, group with coexistence of ≥2 aberrations seems to be a complex cytogenetic subset, needs more attention to understand biological significance and to seek clinical impact for better management of disease.

Is there a role for metronomic induction (and maintenance) therapy in elderly patients with acute myeloid leukemia? A literature review.

Acute myeloid leukemia (AML) in older adults differs biologically and clinically from that in younger patients and is characterized by adverse chromosomal abnormalities, stronger intrinsic resistance, and lower tolerance to chemotherapy. In patients over age 60 with AML, cure rates are under 10% despite intensive chemotherapy, and most of them die within a year of diagnosis. Over the last decade, metronomic chemotherapy has emerged as a potential strategy to control advanced/refractory cancer. Here, we report a case of a 68-year-old gentleman having AML with high-risk cytogenetic features, who achieved complete remission on our oral metronomic PrET (PrET: Prednisolone, etoposide, thioguanine) protocol on an outpatient basis. He was later treated with standard high-dose (HD) cytosine arabinoside (Ara-C) consolidation followed by maintenance with etoposide, thioguanine, and sodium valproate. Presently, the patient is nearly 35 months since diagnosis and 21 months off treatment. This case report and review highlights that the combination of oral low-intensity metronomic therapy, followed by standard HD consolidation therapy and metronomic maintenance therapy may be well tolerated by elderly patients especially with less proliferative, high (cytogenetic)-risk AML who are otherwise deemed to be unfit for intensive intravenous induction chemotherapy regimens. References for this review were identified through searches of Pubmed for recent publications on the subject as well as searches of the files of the authors themselves. The final list was generated on the basis of originality and relevance to this review.

The current practice of the management of little finger metacarpal fractures--a review of the literature and results of a survey conducted among upper limb surgeons in the United Kingdom.

Little finger metacarpal fractures are the most common type of metacarpal fractures and the treatment is quite variable as it is a multifactorial entity comprised of subcapital, metacarpal shaft and base fractures. These fractures are common presentations in the fracture clinics and the general orthopaedic surgeons treat them until a complex case warrants specific decision making by a hand surgeon. The management of many of these fractures is still a matter of debate and differ widely in the various parts of the United Kingdom. The aim of this study was to investigate the current practice of little finger metacarpal fractures among upper limb surgeons in the UK. We conducted an online survey among 278 upper limb orthopaedic specialist surgeons throughout the UK. Our response rate was 58%. There are various factors which dictate the treatment as suggested by these respondent upper limb consultants. For example, for fifth metacarpal neck fractures, it was generally recognised that 43% of upper limb surgeons prefer neighbour strapping alone for non-operative management of little finger metacarpal fractures. For little finger metacarpal shaft fractures, 39.3% of surgeons suggested that they would contemplate intervention, i.e. manipulation under anaesthesia/surgery if beyond 30° of volar angulation is present. For little finger metacarpal neck fractures, 33.7% would only consider surgical intervention beyond 60° of volar angulation. 91.6% of upper limb specialists agreed that they would operate on little finger metacarpal base fractures only if it was a fracture dislocation, while 71.8% suggested that they would proceed to operate on even a pure dislocation. We have illustrated the various permutations and combinations of these fractures with the results of our survey in this article in detail. The vast majority of metacarpal bone fractures are stable and treated conservatively. The different types of injury patterns must be recognised by the orthopaedic surgeons and appropriate treatment then should be executed to serve the patient optimally in due course.

A retrospective audit of clinicopathological attributes and treatment outcomes of adolescent and young adult non-Hodgkin lymphomas from a tertiary care center.

BACKGROUND: The uniqueness of adolescent and young adult (AYA) non-Hodgkin lymphomas (NHL) with respect to biology and treatment have largely remained unanswered due to marked heterogeneity in treatment, paucity of prospective, or retrospective studies and poor representation of AYA in clinical trials. This audit attempts to put forward the clinicopathological attributes and treatment outcomes of AYA NHL treated with both pediatric and adult protocols from a single centre in a developing country. PATIENTS AND METHODS: Hospital records of all consecutive NHL patients registered in lymphoma clinic from January 2007 to May 2010 were reviewed for information on demography, clinical features, histology subtype, staging, treatment regimen, response rates, toxicities, and follow up. Two-year progression-free (PFS) and overall survival (OS) were calculated with Kaplan-Meier method. RESULTS: AYA NHL constituted 4% of all lymphomas. Diffuse large B-cell (DLBL) was the most frequent subtype. Following were the 2-year PFS and OS - DLBL 64%, 76.9%, Burkitt's lymphoma: 56%, 56%, lymphoblastic lymphoma: 33.2%, 44%. Our results did not show any improvement in outcome of DLBL with the use of Burkitt's lymphoma like regimen. CONCLUSIONS: This study highlights some of the key features of AYA NHL occurring in developing world.

Study of the morphological patterns and association of Epstein-Barr virus and human herpes virus 8 in acquired immunodeficiency deficiency syndrome-related reactive lymphadenopathy.

AIMS: Study of the morphological patterns of acquired immunodeficiency syndrome (AIDS)-related lymphadenopathy. SETTINGS AND DESIGN: We retrospectively selected cases of AIDS-related benign lymphadenopathy. Cases with lymphomas, frank granulomas and necrosis were excluded. We analyzed different morphological patterns and correlated these with immunophenotypic markers along with viral markers human herpesvirus 8-latency-associated nuclear antigen (HHV8-LANA), and Epstein-Barr virus-encoded ribonucleic acid (EBER) studies via in situ hybridization (EBER-ISH). MATERIALS AND METHODS: We present the morphological patterns of 13 cases of human immunodeficiency virus (HIV)-reactive lymph nodes and their clinical, hematological, biochemical and radiological parameters with special emphasis on the presence or absence of viral markers, including HHV8 and EBV. RESULTS: Common patterns included follicular hyperplasia only (five cases), mixed pattern of follicular hyperplasia with burnt-out germinal centres (four cases), completely atretic follicle (two cases), folliculolysis (11 cases), dumbbell-shaped follicles (three each), progressive transformation of germinal centers (four cases), T-zone expansion (two cases), Reed Sternberg (RS) cells like immunoblasts (two cases), Castleman's-like features with lollipop-like follicles (three cases) and a spindle cell prominence (one case). CD8+ T-cells were predominant in 12 cases. CD8+ T-cells were prominent in germinal centers (eight cases). Plasmablasts were seen in four cases within the perigerminal center area. Immunohistochemistry for HHV8, i.e. HHV8-LANA were negative in all cases while EBER was detected in 11 cases in the centrocyte-like B cells. Two cases of multicentric Castleman's disease expressed EBER; however, they did not express HHV8. CONCLUSION: The wide spectrum of histological changes in HIV-associated lymphadenopathy requires recognition. The histological changes can mimic those of other infective lymphadenitis, follicular lymphoma, Castleman's disease, progressive transformation of germinal center, Hodgkin's disease and spindle cell neoplasms. Presence of EBV is common while HHV8 was not seen.

Immunophenotyping of mature T/NK cell neoplasm presenting as leukemia.

INTRODUCTION: Mature T/NK cell lymphomas (MTNKL) presenting as leukemia are rare and show considerable overlapping of clinical, morphological and immunophenotypic features. AIM: Critical analysis of the morphology and immunophenotypic profile of MTNKL. MATERIALS AND METHODS: We reviewed 380 consecutive cases of mature lymphoid neoplasm that presented as leukemia and were diagnosed on morphology and immunophenotyping of bone marrow and/or peripheral blood samples. RESULTS: Peripheral blood and bone marrow involvement was seen in all cases. MTNKL constituted 4% (nine cases) of all mature lymphoid neoplasms presenting as leukemia. It included four cases of T-large granular leukemia (T-LGL), two of T-cell prolymphocytic leukemia small cell variant (T-PLL), two of adult T-cell leukemia/lymphoma (ATLL) and one of primary cutaneous gamma delta T-cell lymphoma (PCGDTCL). T-LGL revealed CD4-/CD8+ phenotype in three, and CD4+/CD8+ phenotype in one case. CD56 was absent in all the cases of T-LGL. One case of T- PLL small cell variant showed CD4+/CD8- phenotype, while the other revealed CD4-/CD8+ phenotype. Both cases of ATLL showed CD4+/CD8+/CD25+ phenotype. The single case of PCGDTCL showed CD4-/CD8- phenotype pattern. CD3 and CD5 were expressed in all MTNKL. CD7 was absent in three cases of T-LGL. TCRalpha/beta was performed in three cases of T-LGL and was positive in all. TCRalpha/beta was also seen in both the cases of T-PLL small variant. However, TCRalpha/beta was seen in the single case of PCGDTCL. CONCLUSION: Mature nodal T/NK cell neoplasms are rare and MTNKL presenting as leukemia are even rarer. There is an overlap between the immunophenotypic profiles of different MTNKL subtypes and elaborate T/NK cell panels are required for their evaluation.

Positron emission tomography / computerized tomography evaluation of primary Hodgkin's disease of liver.

Occurrence of primary Hodgkin's lymphoma (PHL) of the liver is extremely rare. We report on a case of a 60-year-old male who presented with liver mass and B-symptomatology. Hepatoma or hepatic metastasis from a gastrointestinal primary was initially suspected. Tumor markers like AFP, CEA, Total PSA, and CA-19.9 were within normal limits. Positron Emission Tomography / Computerized Tomography (PET/CT) revealed a large hepatic lesion and a nodal mass in the porta hepatis. A liver biopsy was consistent with Hodgkin's lymphoma. There was complete regression of the hepatic lesion and evidence of shrinkage of the nodal mass following four cycles of chemotherapy. 18F Fluro -de-oxy Glucose (FDG) PET / CT in this case helped in establishing a primary hepatic lymphoma by demonstrating the absence of pathologically hypermetabolic foci in any other nodes or organs. PET / CT scan is a useful adjunct to conventional imaging and histopathology, not only to establish the initial diagnosis, but also to monitor treatment response in PHL.

Clinico-hematological profile in biphenotypic acute leukemia.

BACKGROUND: We present a clinico-hematological profile and treatment outcome of Biphenotypic Acute Leukemia (BAL). AIM: Study incidence and subtypes of BAL, correlate with age, morphology, and cytogenetic findings and correlate the clinico-hematological data with the treatment response. St Jude's and the EGIL's criteria have been compared for their diagnostic and clinical relevance. MATERIAL AND METHODS: Diagnosis was based on WHO classification, including clinical details, morphology, cytochemistry, immunophenotyping, and molecular genetics. We included those cases, which fulfilled the European Group for the Immunological Characterization of Acute Leukemia's (EGIL's) scoring system criteria for the diagnosis of BAL, as per recommendation of the WHO classification. RESULTS: There were 32 patients diagnosed with BAL, based on EGIL's criteria. Incidence of BAL was 1.2%. B-Myeloid (14 cases) followed by T-Myeloid BAL (13 cases) were the commonest subtypes. Polymorphous population of blasts (16 cases) was commonly associated with T-Myeloid BAL (10 cases). BCR ABL fusion positivity was a common cytogenetic abnormality (seven cases). Fifteen patients received chemotherapy; eight achieved complete remission (CR) at the end of the induction period. CONCLUSIONS: Pediatric BAL and T-B lymphoid BAL have a better prognosis. A comprehensive panel of reagents is required, including cytoplasmic markers; to diagnose BAL. St Jude's criteria is a simple, easy, and cost-effective method to diagnose BAL. The outcome-related prognostic factors include age, HLA-DR, CD34 negativity, and subtype of BAL. BCR-ABL expression is an important prognostic factor, as these cases will be labeled as Chronic myeloid leukemia (CML) in blast crisis with biphenotypic expression and treated accordingly.

Rapidly expanding thenar eminence ganglion: a case report.

INTRODUCTION: This study documents the first reported case of a rapidly growing (volar) thenar eminence ganglion arising form the first carpometacarpal joint, masquerading as a sarcoma. The discussion informs the hand surgeon on the evidence regarding the unusual presenting features. CASE PRESENTATION: An 85 year old left hand dominant female presented with a six week history of rapidly growing lump on the thenar eminence. Clinical examination revealed a non-tender large lobulated mobile swelling measuring 5 x 4 cm and involving the whole thenar eminence. CONCLUSION: Ganglia may present from the thenar eminence and are a source of diagnostic confusion.

Identification of PML/RARalpha fusion gene transcripts that showed no t(15;17) with conventional karyotyping and fluorescent in situ hybridization.

Acute promyelocytic leukemia (APL) is characterized by a reciprocal translocation, t(15;17)(q22;q11-21), resulting in the fusion of the promyelocytic leukemia (PML) and retinoic acid receptor alpha (RARalpha) genes. Using conventional cytogenetic methods, these translocations are normally detected in about 70-90% of patients; most negative results are due to technical problems or cryptic variants. These masked PML/RARalpha fusions can be identified by molecular analyses, such as reverse transcriptase-polymerase chain reaction (RT-PCR) or fluorescence in situ hybridization (FISH). Approximately 5 to 10% of all APL cases reported do not show PML/RARalpha fusion transcripts, even with dual-colored FISH. We report three of 40 diagnosed APL cases that showed morphological, cytochemical, and immunophenotypic features of hypergranular APL, but did not show a PML/RARalpha fusion signal or any of its variants, on FISH. All cases were identified by RT-PCR, which was further confirmed by cDNA sequencing. Conventional karyotyping showed other clonal aberrations in these cases, but failed to show t(15;17) or any other variants or complex translocations.

Immunophenotypic profile of acute leukemia: critical analysis and insights gained at a tertiary care center in India.

BACKGROUND: To analyze the spectrum of various types and subtypes of acute leukemia. METHODS: Two thousand five hundred and eleven consecutive new referral cases of acute leukemia (AL) were evaluated based on WHO classification. RESULTS: It included 1,471 cases (58%) of acute lymphoblastic leukemia (ALL), 964 cases (38%) of acute myeloid leukemia (AML), 45 cases (1.8%) of chronic myelogenous leukemia in blast crisis (CMLBC), 37 cases (1.5%) of biphenotypic acute leukemia (BAL), 1 case of Triphenotypic AL, and 2 cases of acute undifferentiated leukemia (AUL). Common subtypes of ALL were B-cell ALL (76%), which comprised of intermediate stage/CALLA positive (73%), early precursor/proBALL (3%). T-cell ALL constituted 24% (351 cases) of ALL. Common subtypes of AML included AMLM2 (27%), AMLM5 (15%), AMLM0 (12%), AMLM1 (12%), APML (11%), and AML t(8;21) (9%). CMLBC was commonly of myeloid blast crisis subtype (40 cases). CONCLUSION: B-cell ALL was the commonest subtype in children and AML in adults. Overall incidence of AML in adults was low (53% only). CD13 was most sensitive and CD117 most specific for determining myeloid lineage. A minimal primary panel of nine antibodies consisting of three myeloid markers (CD13, CD33, and CD117), B-cell lymphoid marker (CD19), T-cell marker (CD7), with CD45, CD10, CD34, and HLADR could assign lineage to 92% of AL. Cytogenetics findings lead to a change in the diagnostic subtype of myeloid malignancy in 38 (1.5%) cases.

Analysis and comparison of clinicohematological parameters and molecular and cytogenetic response of two Bcr/Abl fusion transcripts.

Different forms of p210 are produced by alternative splicing, namely b2a2 and b3a2. There have been many contrasting data establishing a relationship between the two Bcr/Abl transcripts and platelet counts and also response to treatment. However, the data published to date have been on a small group of patients. The aim of the present study was to determine whether there was any difference between clinical and hematological parameters at diagnosis between the two Bcr/Abl fusion transcripts in our population, and whether the two transcripts responded differently or similarly to imatinib treatment. RT-PCR was performed in 202 cases for detection of Bcr/Abl transcripts in newly diagnosed chronic myelogenous leukemia cases in one year. The two transcripts were compared and correlated with clinical, hematological and FISH data and with response to treatment. A total of 138 cases were of b3a2 and 64 were of b2a2 transcript. There was no correlation between the hematological parameters and the type of transcript. There was a significant association of blast crisis with b2a2, especially with myeloid blast crisis. When compared to FISH results, 10% of b3a2 were found to have a significant association with 5'Abl deletion as compared to 3% of b2a2. On analyzing the therapeutic response, we did not find any difference between the two transcripts. In conclusion, our findings confirm that the b3a2 type transcript is not significantly associated with thrombocytosis, that the short transcript, b2a2, occurs with acute phase, i.e., blast crisis, and that there is no difference in treatment response between the two transcripts. However, further studies are required to understand the molecular pathways involved in the Bcr/Abl mechanism.