Impact of involved free light chain (FLC) levels in patients achieving normal FLC ratio after initial therapy in light chain amyloidosis (AL)

Achievement of a normal FLC ratio (FLCr) following treatment indicates hematologic response and suggests better outcomes in light chain amyloidosis (AL). We examined if elevated involved free light chain (hiFLC) impacts outcomes in patients achieving normal FLCr. We retrospectively analyzed 345 AL patients who were diagnosed within a 10‐year period (2006‐2015) and had 2 consecutive normal FLCr values after 1st line treatment. Among these, patients with hiFLC at 1^st reading of normal FLCr (hiFLC1; n = 166; 48.1%) were compared to those who did not (n = 179; 51.9%). Patients with AL who have hiFLC1 after initial therapy had higher rates of multi‐organ involvement (63.3 vs 46.4%; P = .002) and patients in advanced Mayo stage (42.9 vs 32.2%; P = .04) at diagnosis. The median progression free survival [PFS; 38.2 (95%CI; 26.4, 55.4) vs 67.1 (95%CI; 55.8, 88) months; P = .0002] and overall survival [OS; 94.4 (95%CI; 78, 107.1) vs not reached (NR, 95%CI; 116.1, NR) months; P < .0001] were lower in those who had hiFLC1. A more stringent comparison for patients with 2 consecutive hiFLC (hIFLC2; n = 111; 32.2%) versus not (n = 2234; 67.8%) showed consistent results [PFS; 27.1 (95%CI; 23, 53.8) vs 63.3 (95%CI; 55.4, 77) months; P < .0001 and OS; 78 (95% CI; 54.6, 98.8) vs NR (95%CI; NR, NR); P < .0001]. This poor prognostic impact of hiFLC on survival was independent of serum creatinine, Mayo stage, negative immunofixation status and inclusion of transplant in initial therapy on multivariate analysis. Hence, persistent elevation of iFLC predicts poor prognosis even among patients achieving normal ratio after initial therapy in AL.     

Percutaneous Image-Guided Irreversible Electroporation for the Treatment of Unresectable,Locally Advanced Pancreatic Adenocarcinoma

Purpose

To describe safety and effectiveness of percutaneous irreversible electroporation (IRE) for treatment of unresectable, locally advanced pancreatic adenocarcinoma (LAPC).

Induction of apoptosis by [6]-gingerol associated with the modulation of p53 and involvement of mitochondrial signaling pathway in B[a]P-induced mouse skin tumorigenesis

Purpose

To unravel the molecular mechanisms underlying the chemopreventive potential of [6]-gingerol, a pungent ingredient of ginger rhizome (Zingiber officinale Roscoe, Zingiberaceae), against benzo[a]pyrene (B[a]P)-induced mouse skin tumorigenesis.

Methods

Topical treatment of [6]-gingerol (2.5 μM/animal) was given to the animals 30 min prior and post to B[a]P (5 μg/animal) for 32 weeks. At the end of the study period, the skin tumors/tissues were dissected out and examined histopathologically. Flow cytometry was employed for cell cycle analysis. Further immunohistochemical localization of p53 and regulation of related apoptogenic proteins were determined by Western blotting.

Results

Chemopreventive properties of [6]-gingerol were reflected by delay in onset of tumorigenesis, reduced cumulative number of tumors, and reduction in tumor volume. Cell cycle analysis revealed that the appearance of sub-G1 peak was significantly elevated in [6]-gingerol treated animals with post treatment showing higher efficacy in preventing tumorigenesis induced by B[a]P. Moreover, elevated apoptotic propensity was observed in tumor tissues than the corresponding non-tumor tissues. Western blot analysis also showed the same pattern of chemoprevention with [6]-gingerol treatment increasing the B[a]P suppressed p53 levels, also evident by immunohistochemistry, and Bax while decreasing the expression of Bcl-2 and Survivin. Further, [6]-gingerol treatment resulted in release of Cytochrome c, Caspases activation, increase in apoptotic protease-activating factor-1 (Apaf-1) as mechanism of apoptosis induction.

Conclusions

On the basis of the results we conclude that [6]-gingerol possesses apoptotic potential in mouse skin tumors as mechanism of chemoprevention hence deserves further investigation.     

ESCC with Metastasis in the Young Age of Caustic Ingestion of Shortest Duration

Introduction

Squamous cell carcinoma arising from caustic ingestion in the esophagus in young age of very short duration is not reported in literature.

Case report

We present the world’s first reported case from India of a 14-year-old boy with an associated 1-year history of accidental caustic ingestion who developed esophageal squamous cell carcinoma along with cervical lymph node metastasis, after a thorough review of available literature.

Discussion

Accidental caustic ingestion may have an unusual presentation and severe complications, but a favorable outcome. Guidance and education are important preventive tools, but the best approach is to restrict access to caustic agents by prohibiting their free commercialization.     

Transient myeloproliferation mimicking JMML associated with parvovirus infection of infancy

We report a 2-month-old infant with Parvovirus B19 infection presenting as transient myeloproliferation resembling juvenile myelomonocytic leukemia (JMML). Patient history, physical examination, and laboratory findings were suggestive of JMML. On viral serology, raised IgM and IgG titers for Parvovirus B19 infection were found in the absence of giant proerythroblasts and viral inclusions in the erythroid precursors. Follow-up showing a decrease in viral titers suggested parvovirus infection as an etiological factor for the development of myeloproliferative features. This case highlights the importance of viral serology in work-up myeloproliferative disorders of infancy and childhood.