Evolving multidisciplinary treatment of squamous cell carcinoma of the head and neck in India✰.

In this article, we highlight the evolution of a multimodal approach in the overall management of squamous cell carcinoma of the head and neck (SCCHN) in India; present advances in technology (newer surgical techniques), novel medical and radiotherapy (RT) approaches; review their roles for an integrated approach for treating SCCHN and discuss the current role of immunotherapy in SCCHN. For locally advanced (LA) SCCHN, the multidisciplinary approach includes surgery followed by RT, with or without chemotherapy (CT) or concurrent chemoradiotherapy. Improved surgical techniques of reconstruction and voice-preservation are being implemented. Advanced forms of high-precision conformal techniques like intensity-modulated radiotherapy are used to deliver highly conformal doses to tumors, sparing the surrounding normal tissue. Compared with RT alone, novel CT regimens and targeted therapeutic agents have the potential to improve locoregional control and survival and reduce treatment-induced toxicities. Several clinical trials have demonstrated efficacy, safety, and quality of life benefits of adding cetuximab to RT regimens in LASCCHN. Studies have also suggested a cetuximab-related laryngeal preservation benefit. At progression, platinum-based CT combined with cetuximab (a monoclonal anti-epidermal growth factor receptor antibody) is the only validated option available as the first-line therapy. Thus, an integrated multidisciplinary approach plays a key role in maximizing patient outcomes, reduction in treatment related morbidities that consequently impact quality of life of survivors.

Two new sesquiterpenoids from the rhizomes of Nardostachys jatamansi.

Phytochemical investigation of CHCl(3):MeOH (1:1) extract from the rhizomes of Nardostachys jatamansi led to the isolation of two new sesquiterpenoids (5 and 6), along with six known compounds (1-4, 7, and 8). The structures of two new compounds were established using IR, MS, 1D, and 2D NMR techniques. In addition, all the isolates were tested for their cytotoxicities against the A549 (lung cancer), DU-145 (prostate cancer), MCF-7 (breast cancer), and SK-N-SH (neuroblastoma).

Antifungal cyclic peptides from the marine sponge Microscleroderma herdmani.

Screening natural product extracts from the National Cancer Institute Open Repository for antifungal discovery afforded hits for bioassay-guided fractionation. Using LC-MS analysis to generate chemical structure information on potentially active compounds, two new cyclic hexapeptides, microsclerodermins J (1) and K (2), were isolated from the deep-water sponge Microscleroderma herdmani, along with microsclerodermins A (3) and B (4), previously isolated from an unidentified Microscleroderma species. The structures of the new compounds were elucidated by spectroscopic analysis and chemical methods. In vitro antifungal testing showed that the four compounds possessed strong activities against the opportunistic fungal pathogens Candida albicans, Candida glabrata, Candida krusei, Cryptococcus neoformans, and Aspergillus fumigatus.

Phytochemical investigation of labdane diterpenes from the rhizomes of Hedychium spicatum and their cytotoxic activity.

A comprehensive reinvestigation of chemical constituents from the rhizomes of Hedychium spicatum led to the isolation of two new labdane-type diterpene (1, 2), together with six known compounds (3-8). Their structures were established on the basis of extensive spectroscopic (IR, MS, 2D NMR) data analysis and by comparison with the spectroscopic data reported in the literature. In addition, all the isolates were tested for their cytotoxicity against the THP-1 (human acute monocytic leukemia), HL-60 (human promyelocytic leukemia), A-375 (human malignant melanoma) and A-549 (human lung carcinoma) cancerous cell lines.

Two new cytotoxic diterpenes from the rhizomes of Hedychium spicatum.

Phytochemical investigation of CHCl(3) extract of the rhizomes of Hedychium spicatum led to the isolation of two new labdane-type diterpenes, compounds 1 and 2 along with five known compounds (3-7). Their structures were established on the basis of NMR (1D and 2D) and mass spectroscopic analysis. In addition, all the isolates were tested for their cytotoxicity against the Colo-205 (Colo-cancer), A-431 (skin cancer), MCF-7 (breast cancer), A-549 (lung cancer) and Chinese hamster ovary cells (CHO). Two new compounds 1 and 2 were shown good cytotoxic activity.

Two new tetracyclic triterpenes from the heartwood of Ailanthus excelsa Roxb.

Two new dammarane-type triterpenes, ailexcelone and ailexcelol, together with ocotillone, malabaricol, epoxymalabaricol, lupeol, and sitosterol-3-O-beta-D-glucoside were isolated from the heartwood of Ailanthus excelsa. The structures of the new compounds were established on the basis of 1D- and 2D-NMR data. Ocotillone, malabaricol and epoxymalabaricol were isolated for the first time from A. excelsa. All of the isolates were tested for their antifungal activity.

Isolation and synthesis of analgesic and anti-inflammatory compounds from Ochna squarrosa L.

Two new furanoflavonoids (1, 2), one new chalcone dimer (3) along with six known compounds, chrysophanol, 5-O-methyl squarrosin, 5-methoxy furano[4'',5'',6,7]flavone, calodenone, lophirone A and lophirone H were isolated from the ethyl acetate-soluble fraction of methanol extract of root bark of Ochna squarrosa. Chrysophanol, calodenone, lophirone A and lophirone H were isolated from this plant for the first time. The structures of all the isolated compounds were confirmed by 1D and 2D spectroscopic data. These compounds were tested for analgesic and anti-inflammatory activity. All the new compounds showed good analgesic and anti-inflammatory activity. A simple and facile method for the cleavage of benzyl ethers using I(2) in trigol is also reported.

THE CD 10 MARKER IN THE INVESTIGATION OF ACUTE LYMPHOBLASTIC LEUKAEMIA.

Immunophenotyping of leukaemias is presently well established. It is invaluable for proper case management [1]. The most useful information on the management of cases of Acute Lymphocytic Leukaemia (ALL) is provided by the detection of the CD 10 marker on the leukaemic cell. The CD 10 positive ALL has since long been associated with a favourable prognosis as compared to the CD 10 negative ALL [1, 2]. As immunophenotyping is resource intensive, the monoclonal antibodies (MO ABS), are not in widespread use in our country. The expenses involved make this procedure prohibitive in most institutions. For this reason, a limited panel of MO ABS has been used in this study, with a special emphasis on the CD 10 marker. A total of 25 cases of ALL were studied. 17 cases were found to be positive for the CD 10 marker (68%). These cases were associated with a favourable prognosis as compared to the CD 10 negative group. Although, the diagnosis of ALL and leukaemias in general, is essentially based on the study of Romanowsky stained smears [3, 4], the additional information provided by the cell surface marker study results in better case management [1].

IMPACT OF PROPHYLACTIC USE OF COLONY STIMULATING FACTORS ON THE PATTERN OF NEUTROPENIA AND INFECTIONS IN MODERATELY INTENSIVE CHEMOTHERAPY.

In this study, colony stimulating factors (CSF) were used to prevent neutropenia during moderately intensive chemotherapy in 26 episodes of chemotherapy (12 of acute lymphoblastic leukaemia (ALL) and 14 patients with other malignancies). CSF was administered in doses of 5 µg/kg of body weight within 24 hours of completion of chemotherapy for 7 days in 6 patients and for 10 days in others. Twenty six age and sex matched patients of ALL were included as controls. In the CSF group, incidence of severe neutropenia (grades 3 and 4) reduced significantly by 42.3 per cent though overall incidence of neutropenia did not differ much. Mean duration of neutropenia reduced by 4 days. Nadir total leucocyte count and absolute neutrophil count were significantly higher. There was no difference in the incidence of anaemia, thrombocytopenia and requirement of blood transfusions. Overall infections were less and incidence of severe infections reduced by 42.3 per cent. The duration of infection and of fever was shortened. Requirement of antibiotics was also reduced. All patients in CSF group recovered from infection, while 1 patient died in the control group. Mean duration of delay in chemotherapy was reduced from 10 days in control group to 3 days in CSF group. CSF administration resulted in an escalation of the cost by 112.24 per cent. However shortened duration of antibiotics, hospitalisation, reduced laboratory expenses compensated it by 66.94 per cent Our study indicates that the prophylactic use of CSF is beneficial and cost effective in moderately intensive chemotherapy with a high incidence of febrile neutropenia. Administration for 10 days appears to be more beneficial than 7 days.

IMMUNOPHENOTYPING OF ACUTE LEUKAEMIAS : A CRITICAL ANALYSIS OF 35 CASES.

Accurate classification of acute leukaemias is essential for proper case management. The utility of monoclonal antibodies in the diagnosis and classification of acute leukaemias is well established. This diagnostic utility relates primarily to two points : firstly the distinction between acute myeloid leukaemia and acute lymphoblastic leukaemia and secondly to subtypes of acute lymphoblastic leukaemia. Leukaemic cells were immunophenotyped using the alkaline phosphatase antialkaline phosphatase techniques. The monoclonal antibodies were very useful in distinguishing cases of acute myeloid leukaemia from acute lymphoblastic leukaemia. Cases of acute lymphoblastic leukaemia with CD10 positivity showed a better prognosis. T-cell acute lymphoblastic leukaemia was uncommon and was associated with unfavourable prognosis. The alkaline phosphatase antialkaline phosphatase technique served as a reliable and convenient method for immunophenotyping of leukaemias.

LONG TERM VENOUS ACCESS IN PATIENTS WITH ACUTE LEUKEMIA AND HIGH GRADE LYMPHOMAS (Based on AFMRC Project 1868/91).

Twenty Hickman catheters were passed in 19 patients undergoing chemotherapy for acute leukemia (15 patients) and high grade lymphoma (4 patients). The catheters were inserted into the superior vena cava through the cephalic or external jugular vein with subcutaneous tunneling and exit through the anterior chest wall, and were functionally effective in 19 cases. The catheters remained in situ for a mean period of 50.5 days (range 1-266 days). The catheters were well tolerated eliminating the need for repeated venepuncture. The complications encountered were: hemorrhage - 1 case, thrombosis - 1 case, catheter related bacteremia - 2 cases, tunnel infection - 1 case, and exit site infection - 5 cases. Most of the complications were managed conservatively. These catheters ensured safe and reliable venous access in these high risk patients during episodes of severe neutropenia, sepsis and thrombocytopenia.