The relevance of a staging laparotomy for Hodgkin's disease in India.

A retrospective analysis of 328 cases of Hodgkin's Disease (HD) subjected to a staging laparotomy at the Tata Memorial Hospital, Bombay, India, from 1974 to 1986 was undertaken to assess its relevance to our setup. Eighty percent of the patients were from clinical stages (CS) I and II, 38% with lymphocyte predominance (LP), and 41% with mixed cellularity (MC) histologies. Staging laparotomy was positive in 60% cases overall, including 50% from CS IA and IIA, 68% from CS IB and IIB, and 53% and 67%, respectively, from LP and MC histologies. Splenic involvement was seen in 54% cases. Operative complications were encountered in 2% of cases and deaths in two cases only. In view of the high propensity for abdominal spread, only selected CS IA and IIA cases would merit a staging laparotomy within which, nearly 50% cases with a negative yield could be offered radical segmental irradiation alone for cure. The majority of our patients would, however, require combination therapy.     

Intestinal neuronal disorders--a study of seven cases

Intestinal neuronal dysplasia (IND) has been reported as an innervation disorder that can present as isolated disease or may be associated with Hirschsprung's disease (HD). The interest in this disorder is growing as it mimics HD at clinical level but can be managed with a more conservative approach if an accurate diagnosis can be made. Many workers have tried to set up diagnostic criteria of this condition. But the importance of one criterion varied from one study to another. In our study we analysed seven cases of suspected innervation disorder that had undergone resection. A detailed histological study on these cases was performed and four of them were found to fulfill the diagnostic criteria of IND laid down by Kobayashi and his co-workers. These patients had hyperganglionosis, giant ganglia and ectopic ganglion cells in the lamina propria. In the other three cases some features were highly suggestive of the diagnosis of the IND and can be considered to be so if we follow other workers who have not given much importance to the simultaneous presence of all three criteria in a single case.     

Constitutional genomic instability, chromosome aberrations in tumor cells and retinoblastoma

Although retinoblastoma (Rb) is initiated as a result of biallelic inactivation of the RB1 gene, additional genetic events (M3) in tumor cells are indicative of their role in the full transformation of retinal cells. We investigated the constitutional genetic instability by fragile site (FS) expression studies and checked its relationship with loci of tumor cytogenetics in a series of 36 retinoblastoma patients (34 nonfamilial and 2 familial cases). Tumor cytogenetics revealed -13/+13, del/t(13)(q14) (50%), +1/del/t(1p/q) (65%), +6/i(6p) (60%), and del(16)(q13)/(q22 approximately q23) (60%). Conventional cytogenetics in leukocytes revealed constitutional del(13q14) in five unilateral Rb (URB) and one trilateral Rb (TRB). Constitutional del(16)(q22) and t(6;12) were also identified in two cases. Constitutional FS analysis showed a significant increase in the cellular fragility, with high prevalence at 13q14, 3p14, 6p23, 16q22 approximately q23, and 13q22 loci in retinoblastoma patients (P<0.05). Patients with constitutional del(13)(q14) demonstrated higher fragility than those with normal constitution. A strong correlation between loci of constitutional FSs and loci of recurrent chromosomal abnormalities in tumors strengthen and support the proposal that FS loci present as inherent genomic instability in retinoblastoma. The chromosomal changes and resultant genetic mutations, along with RB1 mutation events, probably contribute synergistically to the development and progression of Rb malignancy. Implementation of fluorescence in situ hybridization to nonfamilial Rb on a large scale (113 cases) could detect constitutional RB1 deletion in 12.3% of cases, with equally higher incidence in URB (14.7%) and bilateral Rb (13.6%), demonstrating that the true prevalence of patients with predisposition to RB1 mutation in sporadic URB is definitely higher in our populations. Also, higher incidence of constitutional RB1 deletion mosaicism in unilateral than in bilateral Rb indicates that the constitutional genetic mosaicism in URB should be given serious consideration during genetic counseling.     

Molecular characterization of scl rearrangements in T-cell all from India and egypt

SCL gene rearrangement is the most common molecular lesion (25%) identified so far in T-cell acute lymphoblastic leukemia (T-ALL). Since the frequency of T-ALL appears to be relatively higher in developing countries, we wished to determine as to what fraction of T-ALL from this population harbor SCL rearrangements. We show in this study that although the overall frequency of SCL/SIL rearrangements in T-ALL is similar to the Western countries this is at the expense of increased type A rearrangements. Whether the paucity of type B rearrangements reflects a difference in disease etiology in this part of the world is to be determined.     

Expression of adhesion molecules in B-cell chronic lymphocytic leukaemia: an analysis in lymphoid compartments--peripheral blood, bone marrow and lymph node

The trafficking or homing of different lymphoid subsets to particular microenvironment is mediated by specific cell adhesion molecules (CAMs) expressed on lymphocytes and endothelial cells. B-cell chronic lymphocytic leukaemia (B-CLL) or Non-Hodgkin's lymphoma of small lymphocytic, B-cell type are monoclonal expansions of mature lymphocytes. The relative distribution of the tumor lymphocytes among various lymphoid compartments vary from patient to patient. Very few studies underlying this issue are available. To this effect, we have analysed the expression of LFA-1; VLA-4, ICAM-1; CD44H and CD44v6 (haematopoietic and variant form respectively) on freshly isolated lymphocytes obtained from bone marrow (BM), peripheral blood (PB) and lymph node (LN) by flow cytometry. Overall, we find strong expression of CD44H, low to moderate expression of LFA-1, negative to low expression of VLA-4 and lack of expression of CD44v6. ICAM-1 expression was observed only in patients with prominent lymphadenopathy. Higher expression of CD44H in PB lymphoid cells relative to that of BM lymphoid cells correlated with higher PB lymphocytosis (p < 0.001). Proliferating cell nuclear antigen expression in LN sections correlated inversely with VLA-4 expression on BM and PB lymphoid cells (p < 0.05). There was no significant correlation between expression of CAMs and bcl-2 protein.     

Analysis of regulation of T-cell responses by soluble inhibitory factors from the sera of patients with Hodgkin's disease.

Soluble inhibitory factors (SIF) have been demonstrated in the sera of cancer patients, which interfere with the T-cell activation process. We have shown that the major contributory factor to the inhibitory effect of sera from patients with Hodgkin's disease (HD) could be the soluble form of Interleukin-2 receptors (sIL-2R). The parameters studied to show the presence of SIF include (i) inhibiton of mitogen-induced proliferation; (ii) status of high- and low-affinity IL-2R; and (iii) internalization of IL-2-IL-2R complex, by lymphocytes from healthy donors activated with mitogen in presence of HD sera. Parameters studied to show the inhibitory role of sIL2R include (i) quantitation of sIL-2R in HD sera; (ii) effect of high-sIL-2R-containing sera on mitogen-induced proliferation and detection of IL-2 in activated lymphocyte culture supernatants; (iii) effect of exogenous IL-2 supplementation; and (iv) abrogation of inhibitory activity of sIL-2R-containing sera after passing them through IL-2 affinity columns. Our results show that 6/23 HD sera tested had high inhibitory activity (greater than 50% inhibition of mitogen-induced proliferation). The SIF did not affect expression of high- and low-affinity IL-2 receptors, or internalization of the complex by activated lymphocytes. Ten of the 15 sera tested showed significantly high levels of sIL-2R. Pooled sera with high sIL-2R content inhibited mitogen-induced proliferation of normal lymphocytes with a concomitant reduction in IL-2 activity in the lymphocyte culture supernatants. When supplemented with exogenous IL-2, there was a partial recovery of the inhibitory effect. When sIL-2R containing serum pool was passed on IL-2 affinity columns, the inhibitory effect was reduced. The eluted "sIL-2R" adsorbed on the IL-2 column showed anti-proliferative effect.