Extensive Cytoreductive Surgery for Appendiceal Carcinomatosis: Morbidity, Mortality, and Survival

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) are frequently used to treat appendiceal carcinomatosis. Some patients require multivisceral resection because of the volume of disease. It is unclear whether extent of CRS impacts survival in appendiceal carcinomatosis.

Methods

We analyzed 282 patients undergoing attempted CRS/HIPEC for appendiceal carcinomatosis. Patients were defined as having undergone Extensive CRS (n = 60) if they had >3 organ resections or >2 anastomoses; a subgroup of Extreme CRS patients (n = 10) had ≥5 organ resections and ≥3 anastomoses. Kaplan–Meier survival curves and multivariate Cox-regression models were used to identify prognostic factors affecting outcomes.

Results

Relative to the comparison group, patients undergoing Extensive CRS had a higher median peritoneal carcinomatosis index, operative duration, blood loss, and length of stay. No difference in completeness of cytoreduction, severe morbidity, or 60-day mortality was evident. Subgroup analysis of 10 patients undergoing extreme CRS likewise revealed no increase in severe morbidity or mortality. Median progression-free (PFS) and overall survival (OS) were 23.5 and 74 months in the comparison group; 18.5 (p = 0.086) and 51 (p = 0.85) months in the Extensive CRS group; and 40 months and not reached in the Extreme CRS subgroup. In a multivariable analysis, extent of CRS was not independently associated with PFS or OS.

Conclusions

Extensive CRS is associated with greater OR time, blood loss, and length of stay, but is not associated with higher morbidity, mortality, or inferior oncologic outcomes in patients with appendiceal carcinomatosis.     

Locking Compression Plate in Musculoskeletal Oncology 'a Friend in Need'

Background

We are presenting our experience in the use of locking compression plate (LCP) after juxta-articular oncological resections in addition to its use in pathologic fracture.

Methods

A retrospective audit of skeletal reconstruction using LCP in 25 cases of long bone tumors was performed from 2008 to 2010. Reconstruction following limb salvage surgery was done in 17 patients and internal fixation of pathological fracture was done in 8 patients. All patients were available for > 12 months of follow-up, and thus assessed for union at the resected ends.

Results

There were 8 males and 17 females in the study. The average age at the time of surgery was 30 years (range, 9 to 66 years). The minimum follow-up was 12 months (range, 12 to 32 months). All patients except three went on to heal successfully. Complications occurred in those three patients: wound infection in one, nonunion in another, and periprosthetic fracture in the other patient. In the remaining patients, union was achieved at an average of 6.5 months after reconstruction in curative resection and 4.75 months after fixation of pathological fractures.

Conclusions

Joint sparing limb salvage surgery was made successfully possible after sekeletal reconstruction with LCP. Its use was also quite effective in pathological fractures with poor bone quality. Use of locking plates for musculoskeletal oncological reconstruction resulted in a good and predictable rate of union.     

Repurposing niclosamide for intestinal decolonization of vancomycin-resistant enterococci

Enterococci are commensal micro-organisms present in the gastrointestinal tract of humans. Although normally innocuous to the host, strains of enterococcus exhibiting resistance to vancomycin (VRE) have been associated with high rates of infection and mortality in immunocompromised patients. Decolonization of VRE represents a key strategy to curb infection in highly-susceptible patients. However, there is a dearth of decolonizing agents available clinically that are effective against VRE. The present study found that niclosamide, an anthelmintic drug, has potent antibacterial activity against clinical isolates of vancomycin-resistant Enterococcus faecium (minimum inhibitory concentration 1–8?µg/mL). E. faecium mutants exhibiting resistance to niclosamide could not be isolated even after multiple (10) serial passages. Based upon these promising in-vitro results and the limited permeability of niclosamide across the gastrointestinal tract (when administered orally), niclosamide was evaluated in a VRE colonization-reduction murine model. Remarkably, niclosamide outperformed linezolid, an antibiotic used clinically to treat VRE infections. Niclosamide was as effective as ramoplanin in reducing the burden of vancomycin-resistant E. faecium in the faeces, caecal content and ileal content of infected mice after only 8 days of treatment. Linezolid, in contrast, was unable to decrease the burden of VRE in the gastrointestinal tract of mice. The results obtained indicate that niclosamide warrants further evaluation as a novel decolonizing agent to suppress VRE infections.     

Withanolides isolated from Withania somnifera with α-glucosidase inhibition

Phytochemical investigations on the chloroform soluble fraction of the whole plant of Withania somnifera led to the isolation of 20β hydroxy-1-oxo(22R)-witha-2,5,24 trienolide 1, (20R, 22R-14α, 20α)-dihydroxy-1-oxowitha-2,5,16,24 tetraenolide 2, and (20R, 22R)-1-oxo-5α, 8β-dihydroxywitha-6α, 7β-epoxide-2,24-dienolide (withasomilide) 3. The structures of these compounds were confirmed through spectral studies in comparison with data in the literature. These isolated compounds (1–3) exhibited potent inhibition against α-glucosidase with IC₅₀ values of 98.60, 38.20, and 40.65 μg/ml respectively.     

Impact of Aggressive Histology and Location of Primary Tumor on the Efficacy of Surgical Therapy for Peritoneal Carcinomatosis of Colorectal Origin

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) for peritoneal carcinomatosis (PC) of colorectal origin increases survival (OS) compared to systemic chemotherapy alone. Signet ring histology demonstrates aggressive behavior with poor survival. We sought to determine whether CRS/HIPEC increases survival in this subset of patients.

Methods

We reviewed 67 patients with PC of appendiceal (AP, n = 37) or colorectal origin (CRC, n = 30) with signet cell histology from a prospective database between May 2001 and August 2011. Survival analysis and multivariate Cox regression were used to determine prognostic factors for survival.

Results

Complete CRS (CC-0/1) was achieved in 77 % (CRC) and 73 % (AP) of patients. Progression-free survival (PFS) and OS were 9 and 12 months in CRC and 12 and 21 months in AP patients. In the CRC group, univariate predictors of poor survival included female gender, age, American Society of Anesthesiologists score, preoperative albumin, completeness of cytoreduction, and morbidity. In a multivariate Cox regression model, incomplete cytoreduction (CC-2/3) and female gender were joint significant predictors of poor survival. In the AP group, significant univariate predictors of poor survival included higher EBL and PCI score. In a multivariate Cox regression model, blood loss of >500 ml and a body mass index of <25 kg/m² were joint significant predictors of poor survival.

Conclusions

AP signet cell tumors demonstrate a more favorable outcome than CRC signet cell tumors after CRC/HIPEC for carcinomatosis, suggesting an underlying difference in biology. CRS/HIPEC does not confer survival benefit in colorectal signet ring carcinomatosis unless complete cytoreduction can be achieved, whereas appendiceal signet ring carcinomatosis may benefit, regardless of resectability.