Chemoradiation-Related Lymphopenia and Its Association with Survival in Patients with Squamous Cell Carcinoma of the Anal Canal

BackgroundAlthough treatment‐related lymphopenia (TRL) is common and associated with poorer survival in multiple solid malignancies, few data exist for anal cancer. We evaluated TRL and its association with survival in patients with anal cancer treated with chemoradiation (CRT).Materials and MethodsA retrospective analysis of 140 patients with nonmetastatic anal squamous cell carcinoma (SCC) treated with definitive CRT was performed. Total lymphocyte counts (TLC) at baseline and monthly intervals up to 12 months after initiating CRT were analyzed. Multivariable Cox regression analysis was performed to evaluate the association between overall survival (OS) and TRL, dichotomized by grade (G)4 TRL (<0.2k/μL) 2 months after initiating CRT. Kaplan‐Meier and log‐rank tests were used to compare OS between patients with versus without G4 TRL.ResultsMedian time of follow‐up was 55 months. Prior to CRT, 95% of patients had a normal TLC (>1k/μL). Two months after initiating CRT, there was a median of 71% reduction in TLC from baseline and 84% of patients had TRL: 11% G1, 31% G2, 34% G3, and 8% G4. On multivariable Cox model, G4 TRL at two months was associated with a 3.7‐fold increased risk of death. On log‐rank test, the 5‐year OS rate was 32% in the cohort with G4 TRL versus 86% in the cohort without G4 TRL.ConclusionTRL is common and may be another prognostic marker of OS in anal cancer patients treated with CRT. The association between TRL and OS suggests an important role of the host immunity in anal cancer outcomes.Implications for PracticeThis is the first detailed report demonstrating that standard chemoradiation (CRT) commonly results in treatment‐related lymphopenia (TRL), which may be associated with a poorer overall survival (OS) in patients with anal squamous cell carcinoma. The association between TRL and worse OS observed in this study supports the importance of host immunity in survival among patients with anal cancer. These findings encourage larger, prospective studies to further investigate TRL, its predictors, and its relationship with survival outcomes. Furthermore, the results of this study support ongoing efforts of clinical trials to investigate the potential role of immunotherapy in anal cancer.     

Bone marrow manifestations in multicentric Castleman disease

This study aimed to document the morphological and immunophenotypic features, and describe the diagnostic features of bone marrow (BM) involvement in human herpes virus 8 Multicentric Castleman disease (HHV8‐MCD). BM trephine biopsy (BMTB) specimens from 28 patients were revisited. Samples were evaluated for expression of CD3, CD20, CD138, CD68R, glycophorin C, CD42b, HHV8‐latency‐associated nuclear antigen (LANA1), Epstein–Barr virus‐encoded small RNA and light chains. Presence of significant numbers of HHV8‐LANA1⁺ lymphoid/plasmacytic cells, noted in 10/28 cases, was indicative of BM involvement and was associated with low CD4 and CD8 counts in peripheral blood. The characteristic morphological appearance of MCD seen in lymph nodes is a rare finding in BMTB. 4/5 cases with lymphoid aggregates were involved by MCD, whereas 6/23 cases without lymphoid aggregates were involved by MCD (P = 0·023). 9/18 cases with hypercellular marrow were involved by MCD, whilst only 1/8 cases with normo/hypocellular marrow showed involvement by MCD (P = 0·070). While 9/21 cases with increased marrow reticulin were involved by MCD, none of the cases with no increase in reticulin were involved by MCD (P = 0·080). Reactive plasmacytosis is a frequent finding. We conclude that bone marrow is involved in a significant proportion of patients with MCD (36%), and involvement can be identified by HHV8‐LANA1 immunohistochemistry.     

Dolichandroside A,a new α‐glucosidase inhibitor and DPPH free‐radical Scavenger from Dolichandrone falcata seem

A new phenylpropanoid glycoside, dolichandroside‐A, together with seven known compounds α‐lapachone, lapachol, aloesaponarin II, 8‐hydroxydehydroiso‐α‐lapachone, β‐sitosterol, 3,8‐dihydroxydehydroiso‐α‐lapachone and verbascoside were isolated from the active ethyl acetate soluble extract of heartwood of Dolichandrone falcata. All except for dolichandroside‐A are known compounds, but have been isolated for the first time from this plant. The structure of all these compounds was determined on the basis of 1D‐ and 2D‐NMR spectral data. All the isolates were tested for α‐glucosidase inhibitory and DPPH radical scavenging activity. This is the first report identifying DPPH scavenging activity and α‐glucosidase inhibitory activity in D. falcata. Furthermore, along with a new compound, dolichandroside‐A, this study also assigns for the first time α‐glucosidase inhibitory activity to verbascoside and aloe saponarin‐II. Copyright © 2008 John Wiley & Sons, Ltd.     

Antimitotic actions of a novel analog of the fungal metabolite palmarumycin CP1

The pentacyclic palmarumycins are structurally unique natural products with both antifungal and antibacterial activities but their antineoplastic effects are not well established. We have examined their antiproliferative actions against tumor cells using a temperature-sensitive tsFT210 mouse mammary carcinoma cell line and found that a novel palmarumycin analog, [8-(furan-3-ylmethoxy)-1-oxo-1,4-dihydronaphthalene-4-spiro-2'-naphtho[1",8"-de][1',3'][dioxin] or SR-7, prominently blocked mammalian cell cycle transition in G2/M but not in G1 phase. We found no evidence for inhibition of the critical mitosis-controlling cyclin-dependent kinase Cdk1, or its regulator, the dual specificity phosphatase Cdc25. Moreover, Cdk1 was hypophosphorylated and not directly inhibited by SR-7. SR-7 also failed in vitro to hypernucleate bovine tubulin, did not compete with colchicine for tubulin binding, and only modestly blocked GTP-induced assembly. In addition, SR-7 caused almost equal inhibition of paclitaxel-sensitive and -resistant cell growth. Moreover, unlike benchmark tubulin-disrupting agents, SR-7 did not cause hyperphosphorylation of the antiapoptotic protein Bcl-2. Thus, SR-7 represents a novel chemical structure that can inhibit G2/M transition by a mechanism that appears to be independent of marked tubulin disruption.     

Laparoscopic management of a large recurrent benign mucinous cystadenoma of the ovary

Introduction Benign mucinous cystadenomas account for 15% of all ovarian neoplasms and up to 80% of all mucinous tumors. Laparoscopy has become an accepted method of management for ovarian cysts and its role is expanding as large benign adnexal masses more than 10 cm can be managed safely and effectively. Case report We report a 25-year-old nulliparous lady with a huge benign mucinous cystadenoma managed by laparoscopic cystectomy, followed by an early recurrence within 2 months. Left salpingo-oophorectomy was performed on a repeat laparoscopy due to suspicion of malignancy on ultrasound. Pathology revealed a benign cyst. Conclusion Since mucinous tumors are usually benign and multilocular, management of young patients is challenging, especially in the case of recurrence which is very rare.     

Haemorrhagic complications of pancreaticoduodenectomy

BACKGROUND: Haemorrhagic complication occurs in 5-16% of patients following pancreaticoduodenectomy (PD). We report an analysis of patients with post-PD bleed, to identify predictors of bleed, predictors of survival following bleed and the management of post-PD bleed. METHODS: Two hundred and eighteen patients with periampullary cancers underwent PD from 1989 to 2002. Forty-four (20.2%) patients had a bleeding complication. Of these, 25 patients had an intra-abdominal (IA) bleed and 21 had gastrointestinal (GI) bleed (two had both IA and GI bleed). Clinical, biochemical and tumour characteristics were analysed to identify factors influencing bleeding complications. RESULTS: The median time to presentation was 4.5 days (0-21 days). Serum bilirubin (P = 0.000, OR: 1.090) and pancreaticojejunostomy (PJ) leak (P = 0.009, OR: 3.174) were significant independent factors predicting bleeding complications. Forty-three per cent of patients each had early bleed (<48 h after PD) or delayed bleed (7 days after PD). Comparison of early and late bleeds showed that IA bleed (P = 0.02) presented as early bleeds. Male sex (P = 0.00) longer duration of jaundice (P = 0.02), PJ leak (P = 0.001), HJ leak (P = 0.001), duct to mucosa type of PJ anastomosis (P = 0.03) and IA abscess (P = 0.00) were associated with a significantly higher incidence of late bleeds. Overall mortality after PD was 9.6% with 34% and 3% in bleeders and non-bleeders, respectively. Septicaemia (P = 0.01, OR: 5.49), and acute renal failure (P = 0.01) were associated with increased mortality. CONCLUSIONS: Bleeding complications following PD were seen in one-fifth of patients and were associated with high mortality. Serum bilirubin levels and PJ leak were significant factors associated with bleeding complications. Septicaemia and acute renal failure were significant factors associated with mortality in the bleeders.     

Report: Asian Consensus Meeting on Metabolic Surgery. Recommendations for the use of Bariatric and Gastrointestinal Metabolic Surgery for Treatment of Obesity and Type II Diabetes Mellitus in the Asian Population

Background  

The report submitted is a detailed analysis of the happenings and outcomes of a two day deliberation that was organized in Trivandrum, India on the 9th and 10th August 2009.