Laparoscopic Deployment of Biliary Self-Expandable Metal Stent (SEMS) for One-Step Palliation in 23 Patients with Advanced Pancreatico-Biliary Tumors—a Pilot Trial

Background Exploratory laparoscopy is commonly undertaken in patients with highly suspicious biliary and pancreatic lesions to facilitate diagnosis and staging cancer is present. If an unresectable tumor is identified, a second endoscopic procedure may be required do deploy a self-expandable metal stent (SEMS) for palliation. As endoscopic retrograde cholangio pancreatography (ERCP) may be unsuccessful in up to 20% of patients, we evaluated the feasibility and safety of deployment of self-expandable metal stents at the same time as the initial laparoscopy. Patients and Methods A total of 23 eligible patients (8 male and 15 female) with malignant obstruction of the common bile duct underwent deployment of SEMS at laparoscopy. Primary outcome measure was the successful laparoscopic deployment of stent and secondary outcome measure was complications rates. Results Indications for stent deployment were unresectable pancreatic cancer in 18, cholangiocarcinoma in two, neuroendocrine tumor in one and ampullary adenocarcinoma in two patients. The median age was 73 years (range 49–93). Twenty-two of 23 stents were deployed successfully: 17 stents were deployed transcystically and five via a choledochotomy. Median times for laparoscopic exploration and SEMS deployment were 165 min (range 105–230) and 20 min (range 10–50), respectively. Pre- and post-procedures median total bilirubin were 9.4 mg/dl (range 5.4–17.5) and 4.0 (range 2.6–7.1). The median size of the pancreatic mass was 3 cm (range 2–5 cm) and that of the common bile duct (CBD) from 9.2 mm (range 7.2–17.4). The mean duration of laparoscopy was 170 min (range 120–230 min) and that for stent deployment 23 min (range 10–50 min). Complications included bleeding, obstruction, and wound infection. Bleeding occurred on day 7 in two patients and on day 30 in one patient; bleeding occurred at the gastrojejunal anastomosis site and was successfully treated with endoscopic hemostasis. A total of three stent obstructions were identified: one each at 60, 90, and 120 days follow-up. All complications were successfully managed endoscopically. There were a total of seven deaths, six as a result of progressive cancer and one of surgical wound infection and ensuing complications. Conclusion This study demonstrates that laparoscopic deployment of self-expandable metal bile duct stents is feasible and safe. This option appears to be a reasonable option in patients with inoperable malignant obstruction of the distal common bile duct.     

Needle necropsy in AIDS

The value of autopsy in understanding the natural course of any disease is beyond any argument. The reluctance of pathologists to perform autopsy in HIV infected cadavers is justified due to the risks involved to the prosector and the morgue attendants. A relative low risk needle necropsy protocol is proposed using fine needle aspiration cytology, tru-cut biopsies and microbiological examination. Diagnosis could be offered in all the forty-four needle necropsies performed. Disseminated tuberculosis in 18/44 (40.9%) cases, disseminated cryptococcosis in 12/44 (27.2%) cases, poly-microbial infections in 27.2% cases and non-Hodgkin's lymphoma in 9% cases were detected in the study. Infectious agents like Histoplasma capsulatum, Isospora belli, tachyzoites of Toxoplasma gondii, Candida sp and Cryptococcus sp could be demonstrated in the samples obtained in the study. Lack of material for study of gross pathology, inaccessibility of deep-seated lesions and risk of needle stick injury to the prosector though low are the limitations of this procedure.     

Haploidentical vs autologous hematopoietic stem cell transplantation in patients with acute leukemia beyond first remission

This is a retrospective comparison of partially mismatched related donor transplantation (PMRDT) and autotransplantation (ABMT) in advanced acute leukemia. Patients underwent T-cell-depleted PMRDT (n=164) or ABMT (n=131) for acute myeloid leukemia (n=130) or acute lymphoblastic leukemia (n=165). Fewer PMRDT patients were in remission (29 vs 85%; P<0.0001). The 5-year cumulative incidence of transplant-related mortality (TRM) was 52% after PMRDT and 16% after ABMT (P<0.0001). The 5-year cumulative incidence of relapse was 32% after PMRDT and 54% after ABMT (P=0.006). The actuarial unadjusted 5-year disease-free survival (DFS) was 16% after PMRDT and 30% after ABMT. In Cox's regression analysis, PMRDT (P<0.0001) and age >15 years (P=0.002) were associated with higher TRM, active disease (P=0.0021), ABMT (P=0.0074) and male sex (P=0.011) with higher relapse, and age >15 years (P=0.0007) and PMRDT (P=0.047) with lower DFS. Amongst second remission patients, TRM was higher after PMRDT (P=0.0003), relapse was higher after ABMT (P=0.034), and 5-year DFS was comparable (32% ABMT and 25% PMRDT). ABMT, if feasible, may be preferable to PMRDT in advanced acute leukemia patients since lower relapse after PMRDT is offset by higher TRM. If an autograft is not feasible because of nonavailability of autologous cells or very advanced disease, PMRDT is a potential alternative.     

Impact of cytogenetics on the outcome of autotransplantation for acute myeloid leukemia in first remission: is the benefit of intensive pretransplant therapy limited to patients with good karyotypes?

A total of 81 adults with acute myeloid leukemia (AML) (47% favorable karyotypes) were autografted in first remission after melphalan-total body irradiation, having received 0 (n=7), 1 (n=19), 2 (n=51), or 3 (n=4) consolidation chemotherapy cycles before harvest. The cumulative 5-year incidences of relapse and transplant-related mortality were 37 and 17%, respectively. The actuarial 5-year probability of disease-free survival (DFS) was 46%. In Cox analysis, favorable karyotypes, increasing numbers of consolidation cycles (0 vs > or =1 or 1 vs >1), and higher nucleated cell doses were associated with lower relapse rates and higher DFS. Patients with favorable karyotypes benefited from every additional cycle of consolidation therapy (0 vs > or =1 as well as 1 vs >1). Among patients with other karyotypes, while the benefit of one cycle of consolidation was clear (0 vs > or =1), there was no obvious beneficial impact of further consolidation therapy (1 vs >1). Administration of consolidation chemotherapy prior to harvest is essential in AML. While it is possible to enhance the benefit of consolidation with favorable karyotypes by delivering two cycles, its usefulness is limited in others. In them, it may be worthwhile exploring alternatives not normally used in AML (eg high-dose cyclophosphamide) that could have antileukemic effects while permitting mobilization of stem cells.     

Collection of peripheral blood stem cells in newly diagnosed myeloma patients without any prior cytoreductive therapy: the first step towards an 'operational cure'?

We have shown that primary therapy with non-myeloablative (140 mg/m(2)) high-dose melphalan (HDM) without hematopoietic support results in high response rates in untreated myeloma and very long-term survival of some patients. This study was designed to see if sufficient CD34 (+) cells can be harvested at presentation in newly diagnosed patients to administer myeloablative HDM (200 mg/m(2); HDM200) with autograft as primary therapy. This may improve outcome by rapid achievement of complete remission (CR) and possible avoidance of late myelodysplasia as a consequence of non-transplant induction chemotherapy. Thirty untreated patients received 1 g/m(2) methylprednisolone daily (days 1-6) and 12-16 micro g/kg G-CSF daily (days 3-6), and underwent leukapheresis on days 6 and 7. The median CD34(+) cell yield was 1.31 x10(6)/kg (range, 0.23-5.63), and was > or =1 x10(6)/kg in 73%. Cell yields were significantly lower than in 82 historical controls apheresed after completion of induction chemotherapy (median 2.16 x 10(6)/kg), and improved in patients who were apheresed again after induction chemotherapy. Three patients received primary therapy with HDM200 and autograft using these cells and attained CR. We conclude that it is possible to harvest stem cells in three-quarters of untreated myeloma patients. Increasing the number of apheresis procedures is needed to improve the number of CD34(+) cells collected.     

Performance of Crossbred Heifers Supplemented with Linseed Oil,Either Alone or in Combination with Myristic Acid

In order to assess the impact of supplementing linseed oil (LO) and myristic acid (MA) on intake, digestibility and growth, fifteen Karan-Fries heifers (6–12 months of age and 120.15 ± 17.5 kg average body weight) were assigned randomly into three groups of five animals each. Group T1 served as control, fed with hand-mixed basal total mixed ration (TMR) containing concentrate mixture, wheat straw and green berseem (Trifolium alexandrinum) in proportion of 40, 40 and 20 %, respectively. In addition to basal TMR, animals in group T2 were supplemented with 2 % LO and group T3 with 1 % LO + 1 % MA for 120 days. Results revealed that, supplementation of fat sources in both the treatment groups (T2 and T3) did not exhibit any effect on intake of dry matter and crude protein in comparison with group T1. Digestibility coefficients of nutrients did not differ due to treatments, except that of EE, which was greater (P < 0.05) in groups T2 and T3 as compared with control. Furthermore, average daily gain and feed conversion ratio were not influenced by dietary treatments. Additionally, predicted methane emission was decreased up to 20.3 and 18.3 % in groups T2 and T3, respectively than that of group T1. Based on these findings, it was concluded that supplementing either 2 % LO or 1 % LO + 1 % MA may not be a viable nutritional strategy for achieving faster growth response in tropical crossbred dairy heifers at field level.     

Thalidomide after allogeneic haematopoietic stem cell transplantation: activity in chronic but not in acute graft-versus-host disease

Thalidomide was used to treat acute (n=21) or chronic (n=59) graft-vs-host disease (GVHD) in 80 haematopoietic stem cell allograft recipients after failure to respond to the combination of cyclosporine and corticosteroids with or without other agents. The median time to onset of acute GVHD was 11 days, and thalidomide was started at a median of 48 days post transplant. In addition to corticosteroids and cyclosporine, 13 patients had also received other agents before thalidomide. None of the patients responded and all died of acute GVHD. For chronic GVHD (limited in 13, extensive in 46), thalidomide was started at a median of 385 days post transplant. In addition to corticosteroids and cyclosporine, 34 patients received azathioprine concomitantly. In all patients, thalidomide was added to the ongoing immunosuppressive regimen. The median duration of therapy with thalidomide was 60 days (range, 11-1210; <2 weeks in 11). In total, 13 patients (22%) had complete response, eight (14%) partial response and 38 (64%) no response. Response rates were comparable for limited (39%) and extensive (33%) chronic GVHD. At a median of 53 months, 19 patients are alive, 13 without evidence of chronic GVHD. Survival was significantly better in patients who responded to thalidomide. The principal causes of death were progressive chronic GVHD (n=29) and relapsed leukaemia (n=7). In conclusion, thalidomide has no activity in acute GVHD, but has some activity in chronic GVHD in combination with other agents.