FOLFIRI chemotherapy in patients with advanced non resectable esophageal or junctional adenocarcinoma: a pilot study

In this prospective pilot study, we assessed the efficacy and safety of the FOLFIRI regimen (irinotecan 180 mg/m2, leucovorin 200 mg/m2 d1 followed by bolus 400 mg/m2 5-fluorouracil (5-FU) and by a 46-h 2400 mg/m2 5-FU infusion, every 2 weeks) in patients with advanced esophageal or junctional adenocarcinoma. Twenty-nine patients were included. A complete response was obtained in 2 patients, a partial response in 7 patients (objective response rate 31.0%). Stable disease was obtained in 13 patients (disease control rate 75.9%). The median progression-free and overall survivals were 5.9 and 8.6 months, respectively. One patient died from chemotherapy-related diarrhea after one cycle but this patient presented concomitant disease progression with cerebral metastases. We observed one additional grade 4 diarrhea, one grade 3 vomiting, and two grade 3 neutropenias. To conclude, FOLFIRI regimen appears quite active, with an acceptable safety profile in patients with advanced esophageal or junctional adenocarcinoma.     

Use of vascularised cartilage as an additional interposition in temporomandibular ankylosis surgery: Rationale, advantages and potential benefits

Context:

Surgery for the release of temporomandibular joint (TMJ) ankylosis is a commonly performed procedure. Various interposition materials have been tried with varying success rates. However, none of these procedures attempt to recreate the architecture of the joint as the glenoid surface is usually left raw.

Aims:

We aimed to use a vascularised cartilage flap and to line the raw surface of the bone to recreate the articular surface of the joint.

Settings and Design:

There is a rich blood supply in the region of the helical root, based on branches from the Superficial Temporal Artery (STA), which enables the harvest of vascularised cartilage from the helical root for use in the temporomandibular joint.

Materials and Methods:

Two cases, one adult and the other a child, of unilateral ankylosis were operated upon using this additional technique. The adult patient had a bony segment excised along with a vascularised cartilage flap for lining the glenoid. The child was managed with an interposition graft of costochondral cartilage following the release of the ankylosis, in addition to the vascularised cartilage flap for lining the glenoid.

Results:

The postoperative mouth opening was good in both the cases with significant reduction in pain. However, the long-term results of this procedure are yet to be ascertained.

Conclusions:

The vascularised cartilage flap as an additional interposition material in temporomandibular joint surgery enables early and painless mouth-opening with good short-term results. The potential applicability of this flap in various pathologies of the temporomandibular joint is enormous.     

Tumor-associated leukemia inhibitory factor and IL-6 skew monocyte differentiation into tumor-associated macrophage-like cells

Tumor-associated macrophages (TAMs), the most abundant immunosuppressive cells in the tumor microenvironment, originate from blood monocytes and exhibit an IL-10(high)IL-12(low) M2 profile. The factors involved in TAM generation remain unidentified. We identify here leukemia inhibitory factor (LIF) and IL-6 as tumor microenvironmental factors that can promote TAM generation. Ovarian cancer ascites switched monocyte differentiation into TAM-like cells that exhibit most ovarian TAM functional and phenotypic characteristics. Ovarian cancer ascites contained high concentrations of LIF and IL-6. Recombinant LIF and IL-6 skew monocyte differentiation into TAM-like cells by enabling monocytes to consume monocyte-colony-stimulating factor (M-CSF). Depletion of LIF, IL-6, and M-CSF in ovarian cancer ascites suppressed TAM-like cell induction. We extended these observations to different tumor-cell line supernatants. In addition to revealing a new tumor-escape mechanism associated with TAM generation via LIF and IL-6, these findings offer novel therapeutic perspectives to subvert TAM-induced immunosuppression and hence improve T-cell-based antitumor immunotherapy efficacy.     

The Role of Intensive Chemotherapy in Myelodysplastic Syndromes

We review results of intensive chemotherapy (IC) obtained in myelodysplastic syndromes (MDS). Overall, the complete remission (CR) rates and median CR duration obtained with IC are low in MDS, especially when compared to results obtained in de novo AML treated with the same chemotherapy regimens; very few MDS patients achieve prolonged remissions. Failure to achieve CR, in MDS, results both from a high incidence of resistant disease and toxic deaths, the latter being due to longer periods of aplasia than in de novo AML. However some subgroups of MDS seem to obtain higher CR rates and more prolonged remissions. These include patients younger than 45 to 50 years, those with a large excess of marrow blasts or Auer rods at diagnosis, and patients with a normal karyotype or at least without involvement of chromosomes 5 and/or 7.

Results of IC clearly have to be improved in MDS. Higher CR rates may possibly be obtained by intensifying induction regimens, but this will probably require the addition of growth factors, in order to reduce the already very long periods of aplasia seen with IC in MDS. For consolidation therapy, new approaches, and especially autologous bone marrow transplantation, will have to be investigated.     

Antiphospholipid antibodies in primary Sjögren's syndrome: prevalence and clinical significance in a series of 74 patients

The aim of this study is to determine prevalence, clinical significance of antiphospholipid antibodies (aPL) including anticardiolipin antibodies (aCL), anti-beta2GP1 and lupus anticoagulant (LA) in a cohort of 74 patients with primary Sj?gren's syndrome (pSS) according to revised European criteria. aPL were found in 25 (34%) patients; IgG in 23 (12 had low titres, six moderate titres and five high titres) and IgM in five (three and two had respectively moderate and high titres). Eight (11%) patients were found to have LA; anti-beta2GP1 antibodies were detected only in three (4%) patients. Only two patients with LA, aPL and beta2GP1 had recurrent venous thrombosis. One patient with moderate titres of aPL exhibited recurrent spontaneous foetal losses. Peripheral neuropathies without cryoglobulinemia were more frequent in the aPL group. Other systemic involvements of pSS were the same in both groups with or without aPL. Patients with aPL have more concurrent immunological diseases such as thyroiditis and primary biliary cirrhosis and a higher prevalence of hypergammaglobulinemia (P < 0.05). Even if aPL prevalence reached 30% in pSS, titres were usually low, with a close correlation with hypergammaglobulinemia but not with antiphospholipid syndrome, which is related to positivity of both LA and aPL.     

Increased concentrations of the circulating angiogenesis inhibitor endostatin in patients with systemic sclerosis

OBJECTIVE: Endostatin is an angiogenesis inhibitor derived from type XVIII collagen. The aim of this study was to determine the concentrations of circulating endostatin in patients with systemic sclerosis (SSc), and to assess the relationship between these concentrations, extension of tissular sclerosis, and presence of cutaneous scars or ulcers. METHODS: The study involved 50 patients with SSc and 30 healthy subjects. Cutaneous extension of sclerosis was graded according to Barnett's classification system: 33 patients had grade I SSc and 17 patients had grades II or III SSc. The results of pulmonary function tests were abnormal in 31 of 50 patients, 8 of whom also had abnormalities on chest radiograms. Cutaneous scars or ulcers were found in 22 of 50 patients. Endostatin concentrations were determined using a competitive enzyme immunoassay method. RESULTS: The mean circulating endostatin concentration was significantly higher in the SSc group than in the healthy subjects group (mean +/- SD 53.2 +/- 22.4 ng/ml versus 9.9 +/- 9.7 ng/ml; P < 10(-4)), in patients with grade II or grade III SSc than in patients with grade I SSc (63.2 +/- 20.2 ng/ml versus 45.1 +/- 15.6 ng/ml; P < 10(-2)), in patients with abnormal findings on chest radiograms than in patients with normal findings on chest radiograms (67.6 +/- 22.4 ng/ml versus 50.4 +/- 21.6 ng/ml; P < 0.05), and in patients with cutaneous scars or ulcers than in patients without these manifestations (60.9 +/- 25.9 ng/ml versus 47.2 +/- 13.3 ng/ml; P < 10(-2)). CONCLUSION: Circulating endostatin concentrations are significantly increased in patients with SSc. Production of endostatin may result from tissular sclerosis and could contribute to the development of ischemic manifestations.     

Virgin Coconut Oil (VCO) Ameliorates High Fat Diet (HFD)-Induced Obesity,Dyslipidemia and Bestows Cardiovascular Protection in Rats

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Effects of hot process-derived virgin coconut oil (VCO) on antiobesity, lipid-lowering and cardio-protection...     

The value of computed tomography in the diagnostics of recurrent rectal tumors

Computed tomography as a noninvasive X-ray method offers new facilities for detecting and diagnosing recurrences after surgical treatment of rectal carcinomas. In a comparative study the CT findings of 14 patients with recurrent rectal tumors of the Kuwait Cancer Control Center and of 77 patients of the Central Institute for Cancer Research in Berlin-Buch/GDR were reviewed. CT is of high sensitivity and specificity for the detection and the extent diagnosis of recurrent rectal tumors and is helpful in taking the appropriate therapeutic decision (surgery, radiotherapy). CT examination becomes mandatory for the postoperative follow-up and further assessment.