Serum and salivary sialic acid as a biomarker in oral potentially malignant disorders and oral cancer.

Background: Aberrant glycosylation is the universal feature of cancer and components of various glycoconjugates, such as sialic acid is found to rise in various malignancies. The objective of this study was to evaluate the serum and salivary sialic acid in oral potentially malignant disorders (OPMD) and oral cancer (OC) to investigate the possibility of using this as a diagnostic marker. Materials and Methods: The study included 85 subjects, who were grouped as control (30), OPMD patients (25), and oral cancer patients (30). Serum and unstimulated whole saliva was collected from subjects of all groups and sialic acid estimation was done using spectrophotometry. The results were tabulated and analyzed statistically. Results: The mean serum sialic acid levels in normal, OPMD, and oral cancer group were 7.515, 19.620, and 55.235 mg/dL, respectively, whereas the levels of salivary sialic acid were 1.5113, 2.3302, and 9.0304 mg/dL, respectively. A very highly significant rise (P < 0.005) in serum and salivary sialic acid was observed in the study subjects compared with that of the control. Conclusions: The present study showed a significant and gradual increase in serum and salivary sialic acid from control to oral potentially malignant disorders to oral cancer. From this study we can suggest that sialic acid can be used as a reliable biomarker. As this monosaccharide is observed in saliva in detectable quantity, saliva can be used as a diagnostic medium for screening and early detection of oral cancer.

In vitro chemosensitivity profile of oral squamous cell cancer and its correlation with clinical response to chemotherapy.

CONTEXT: Oral cancers represent a disparate group of tumors with diverse clinical behavior and chemosensitivity profile. Currently, it is difficult to predict whether a tumor will respond to chemotherapy and which drug(s) will achieve the maximum clinical response. AIMS: To study in vitro chemosensitivity profile of oral cancers and to correlate the in vitro chemosensitivity of oral cancer to clinical response to chemotherapy. SETTINGS AND DESIGN: Prospective study in a tertiary cancer care center. METHODS AND MATERIAL: We prospectively studied the chemosensitivity profile of 57 untreated, advanced, unresectable oral cancers to cisplatin, methotrexate, 5-fluorouracil and their combinations by using histoculture drug response assay (HDRA) and correlated them to the clinical response to chemotherapy. STATISTICAL ANALYSIS USED: Chi Square test. RESULTS: Biopsy samples were successfully histocultured in 52/57 (91%) cases. Of these 52 evaluable patients, 47 had primary gingivo-buccal cancers and five had tongue / floor of mouth cancers. Based on the assay, 27 (52%) tumors were sensitive to cisplatin, 27 (52%) to methotrexate, 24 (46%) to 5-fluorouracil, 38 (73%) to combination of cisplatin and methotrexate and 36 (69%) to combination of cisplatin and 5-fluorouracil. Of these, 31 patients with good performance status received two cycles of chemotherapy using one or more of these test drugs. There was a significant correlation (p=0.03) between the in vitro chemosensitivity and the clinical response. Negative predictive value of the test was 80%, positive predictive value-69%, sensitivity-79% and specificity -71%. The overall accuracy of the assay was 74%. CONCLUSIONS: We found HDRA to be a fairly good predictor of chemo-response of oral cancer.

Rituximab (anti-CD20 monoclonal antibody) in lymphoproliferative malignancies: Tata Memorial experience.

Rituximab has been used extensively in lymphoproliferative disorders. We evaluated the results of 64 consecutive patients treated between 2001 and 2004 at our institution. This included 54 males and 10 females. The median age was 54 years (range 17 to 85 years). One-fourth of patients were above 60 years. The histology was aggressive NHL in 35, indolent NHL in 22 and 7 cases were diagnosed as CLL. Among NHL, sixteen were in early stage (I/II) and the remaining forty-one were in advanced stage (III/IV) of disease. B symptoms were present in 47% of cases. A total of 33 were de novo cases and 31 were previously treated. Rituximab monotherapy was used in 17 cases. Rituximab was used in combination with chemotherapy in the other 47 cases. Infusional toxicity included anaphylaxis in one, hypotension in one and minor infusional reactions in four others. The patient who developed anaphylaxis required discontinuation of further Rituximab. Growth factors were used in 25 patients. Febrile neutropenia occurred in 19 patients. The overall RR (CR + PR) was 72%. One patient had stable disease and progressive disease was documented in 17 patients. A total of seven patients died, three due to progressive disease, three due to chemotherapy related toxicity and one due to an unrelated cause. We conclude that Rituximab is a valuable addition to the treatment armamentarium of lymphoproliferative disorders.

A phase II study of gemcitabine and cisplatin in patients with advanced hepatocellular carcinoma.

The primary objective of this study was to determine the response rates of a combination of gemcitabine and cisplatin in unresectable hepatocellular carcinoma (HCC) in Indian patients. The secondary objectives were to evaluate the toxicity, time to progressive disease and overall survival for this combination. Chemonaive patients with histopathologically proven, bidimensionally measurable, stage Ill or IV unresectable HCC were enrolled into this study. All the patients were required to have a Zubrod's performance status not greater than 2, should not have undergone prior radiotherapy and were required to have adequate major organ function. Patients received gemcitabine (1250 mg/m2 intravenously over 30 to 60 min) on days 1 and 8, and cisplatin (70 mg/m2 intravenously over 2 hours) on day land every 21 days. Response assessment was done by a Computed Tomography scan after every two cycles of chemotherapy. From May to December 1999, 30 patients were enrolled in the study; they were all eligible for efficacy and toxicity analysis. Six (20%) patients achieved a partial response and 13 (43%) patients demonstrated stable disease with 11 (37%) patients showing disease progression. The median time to progression was 18 weeks (range 1 to 74 weeks) and the median duration of response was 13 weeks (range 4 to 68 weeks). The 1-year survival rate was 27% and the median overall survival was 21 weeks (95% CI: 17 to 43 weeks). WHO grade 3 and 4 anemia was seen in 11 (37%) and 2 (7%) patients, respectively. Four (13%) patients each experienced grade 3 and 4 neutropenia and grade 3 and 4 thrombocytopenia was seen in 2 (7%) patients each. Major, non-hematologic toxicities were grade 4 elevated bilirubin levels and grade 3 oral toxicity, in 1 patient (3%) each. This regimen was well tolerated and did show activity in Indian patients with advanced unresectable HCC. There is a need to further evaluate this combination in order to define its role in the treatment of HCC.

Myelodysplastic syndrome. A clinical and pathological analysis of 88 patients.

Eighty eight patients with myelodysplastic syndromes were studied to determine the clinical and pathological features and the prognosis. All the patients had anemia. Neutropenia was seen in 44% and thrombocytopenia in 78% patients. The subtypes included refractory anemia in six, refractory anemia with ringed sideroblasts in three, refractory anemia with excess blasts in 30, refractory anemia with excess blasts in transformation in 32 and chronic myelomonocytic anemia in 17 patients. Forty four patients who received chemotherapy were evaluable for response. Three of the 15 patients treated with hydroxyurea achieved partial remission. Eighteen patients were treated with low dose cytosine arabinoside and complete remission was achieved in five and partial response in six patients. Aggressive chemotherapy was given to 11 patients at the onset of the illness resulting in complete remission in six and partial response in two patients. Nineteen of the 88 patients transformed to acute myeloid leukemia. The crude survival of all the patients ranged from 15 days to 22.5 months. The mortality was due to hemorrhage in 15% and septicemia in 85%. Our data reveals ineffectiveness of the current therapy and emphasizes on the need to develop newer therapeutic approaches.

Primary lymphoreticular tumors of the orbit.

Primary orbital lymphomas are rare. We report nine such cases (4 with DWDL, 3 with DPDL, 1 with DHL and 1 unclassifiable lymphoma). All patients achieved clinical complete remission (CR). Of those who completed treatment more than a year ago, three continue to be in CR at 17, 24 & 25 months and two are lost to follow up.

Prognostic significance of myeloperoxidase containing blast cells in acute myelogenous leukaemia.

Fifty three newly diagnosed patients of de novo acute myelogenous leukaemia (AML) received treatment consisting of remission induction with daunorubicin 60 mg/m2 on day one and continuous infusion of cytosine arabinoside 200 mg/m2/day over 24 h from day one to 7. Thereafter patients in complete remission received consolidation chemotherapy with two identical courses. Complete remission (CR) could be achieved in 40 patients (75.5%). Seven patients (13.2%) died with complications during aplasia phase following remission induction therapy while six patients (11.3%) had resistant disease. Twenty seven patients (67.5%) developed relapse while eight patients (15.1%) continue to remain in complete remission ranging from 51 to 68 months (median 62.5). The projected event free survival and disease free survival at 60 months is 15 per cent (SE + 11.9%) and 21 per cent (+6%) respectively. Evaluation of the prognostic significance of pretherapy characteristics showed that infection at presentation and low number of myeloperoxidase (MPO) containing blasts affected the achievement of complete remission adversely on univariate analysis. Similarly age at diagnosis, of more than 45 yr, total leucocyte count of 50,000/cumm or more and low number of MPO containing blasts affected the remission duration (disease free survival) adversely on univariate analysis. On multivariate analysis, MPO positivity of blast cells, remained the only significant independent characteristic. High MPO positivity affected the remission duration favourably (P < 0.01). Patients with high MPO positivity also achieved CR with one induction cycle in 32 out of 40 instances while only 2 out of 5 patients with low MPO positivity, achieved CR with one chemotherapy cycle (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Alpha-interferon in hairy cell leukemia: an initial Indian experience.

In the last decade, 14 patients were diagnosed as having hairy cell leukemia (HCL) at our hospital; five of these were treated with the biological response modifier, recombinant alpha-interferon (IFN), as their initial treatment. Four of these cases showed a complete remission of the disease while one had a good partial response after a few months of therapy. One case is in unmaintained remission while one has relapsed with a just palpable spleen on stopping the drug; two are still on intermittent IFN therapy while one has been lost to follow up. Fever and skin rash were the most common side effects observed but did not warrant reduction of dose or stoppage of treatment. We conclude that IFN is highly effective and well tolerated as initial treatment of HCL in a country like India. Splenectomy will continue to be the first line therapy in the majority of cases but, in certain selected situations, IFN can be an extremely useful alternative.

Cytotoxic therapy. Role of durable venous access.

Aggressive chemotherapy regimens and supportive measures in haemato-oncology patients demand reliable venous access. Experience with this method in India has been limited. During a period of six months, we have used 42 subclavian indwelling catheters and 31 cubital Cavafix long lines. The mean age of patients in the two groups was 32 years and 7 years respectively. Subclavian catheters had a median duration of catheter placement of 46 days (range 4-145) and total 1494 catheter days, while cubital longlines yielded a median duration of insertion of 14 days (range 4-27) and total 508 catheter days. Catheter related complications were infection in 25% of patients, thrombophlebitis in 22%, blockade in 12% and misplacement in 17% in both groups taken together. The patients and families were extremely satisfied with the devices. Our experience supports further use of durable venous access in cancer patients. Implanted central venous catheters should be preferred whenever feasible.

Autologous bone marrow transplantation (ABMT) in acute myelogenous leukaemia--Heidelberg experience.

Thirty-seven patients with acute myelogenous leukaemia, 17 in the first clinical remission (CR; low risk) and 20 in the second or subsequent CR (high risk), underwent total body irradiation (12.1-16.7 GY) and cyclophosphamide treatment (200 mg/kg), followed by autologous bone marrow transplantation. The autograft was incubated with the active cyclophosphamide derivative mafosfamide to reduce the number of possible contaminating clonogenic tumour cells. The transplant related death rate was low (8.1%). The probability of disease free survival after marrow transplantation in the first CR was 62% compared to 28% in the second or subsequent CR at a median follow up to 22 months. The survival plateau of low risk patients after transplantation seems to be stable with no relapses occurring more than one year later, whereas three late relapses were seen in high risk patients.

Acute non-lymphoblastic leukemia in children: prognostic factors and results of chemotherapy.

Twenty-nine children (age range 1-14, median 8 years) with acute non-lymphoblastic leukemia (ANLL) were induced in remission with daunorubicin and cytosine arabinoside. Twenty-three (79.3%) patients achieved complete remission (CR) and were administered two cycles of the same drugs as consolidation therapy; no maintenance treatment was given. Three (10.3%) patients died during induction; 3 (10.3%) patients were resistant to therapy. Multivariate analysis showed that female sex, TLC less than 50 X 10(9)/L, absence of in ection, albumin greater than 3.5 g/dl and high myeloperoxidase activity had a favourable influence on achievement of CR. TLC less than 50 X 10(9)/L and albumin greater than 3.5 g/dl also had a favourable prognostic value. Eight patients are alive between 13 and 32 months with overall survival at 2 years being 27.5%; four patients are free of disease with projected DFS at 2 years being 13.7%. The present data indicates the need for newer approaches to improve the long term survival in childhood ANLL.

Acute lymphoblastic leukemia in childhood: treatment, results and prognostic factors.

Two hundred and nine children (20 years and below) diagnosed as acute lymphoblastic leukemia between January 1980 and December 1983 were retrospectively analysed to evaluate the clinical features, prognostic factors and the results of therapy. One hundred and eighty one evaluable patients were treated with three different chemotherapy regimens consisting of vincristine and prednisolone (Group-A), vincristine, prednisolone and L-asparaginase (Group B-60 patients), and vincristine, prednisolone and adriamycin (Group C-81 patients). Complete remission was achieved in 152 (84%) patients, remission induction being 75 percent, 85 percent and 88 percent in Group A, B and C respectively. At a median follow-up of 36 months the disease free survival for complete responders was 35.5 patient. The disease-free survival for Group A, B and C was 20 percent, 47 percent 34 percent respectively indicating the superiority of a three drug regimen over the conventional two drug regimen. Patients at standard risk in each group had significantly better survival when compared to those at high risk. A 3-drug treatment regimen was superior to the 2-drug regimen and a low initial leucocyte count was an important favourable prognostic factor.

Limitations of the therapeutic regimens for myelodysplastic syndrome.

Thirty patients of myelodysplastic syndrome (MDS) were treated over a period of 2 yr using 3 different treatment regimens. Twelve patients received hydroxyurea, 4 were given low dose cytosine arabinoside and 14 others were treated with an aggressive acute myeloid leukaemia (AML) induction regimen. A low complete remission was obtained in the first 2 groups (17 and 25% respectively), whereas 9 (64%) patients attained complete remission with the AML induction regimen. Remission in the latter group was associated with prolonged and severe pancytopenia requiring intensive support. Patients in all the 3 groups had a short duration of remission culminating in death with progressive marrow failure or evolution to AML, indicating the limitations of the current treatment strategies for MDS and highlighting the need for exploring newer therapeutic approaches.

Cisplatin-based chemotherapy in advanced ovarian cancer: initial experience in an Indian set-up.

Forty patients of advanced ovarian carcinoma were treated with monthly cycles of cyclophosphamide, adriamycin and cisplatin. Debulking surgery was done in 29 cases. Clinical complete response was seen in 70 percent and an overall response in 85 percent of cases. The median follow-up was 30 months. The actuarial overall survival was 45 percent and the disease free survival was 35 percent at 3 years. The present protocol appears to have an important influence on initial control of disease but relapses continue to occur following the treatment. Cytoreductive surgery before or after three cycles of chemotherapy has a favourable influence on disease free survival (DFS). Prolonged follow up will be necessary to determine the overall influence on long term survival.

Multiple myeloma. Analysis of fifty cases.

Fifty patients of multiple myeloma have been studied. Seventy eight per cent of the patients were in the 5th, 6th and 7th decades of life. Commonest presenting feature was bone pains (76%). 8%, 20% belonged to stage I, II and III respectively. Skull (58%), ribs (52%) and pelvis (24%) were most commonly involved. Immunoelectrophoresis revealed IgG type of myeloma in 76% and IgA type in 10% cases. Bence-Jones proteinuria was seen in 60% of patients; Kappa specificity was commoner than lambda. Overall survival at 30 months was 50%. The survival was adversely influenced by advanced stage, higher plasma cell count in the bone marrow, low haemoglobin and high serum creatinine values.