Optimal Future Liver Remnant in Patients Treated with Extensive Preoperative Chemotherapy for Colorectal Liver Metastases

Background

Patients with colorectal liver metastases (CLM) are increasingly treated with preoperative chemotherapy. Chemotherapy associated liver injury is associated with postoperative hepatic insufficiency (PHI) and mortality. The adequate minimum future liver remnant (FLR) volume in patients treated with extensive chemotherapy remains unknown.

Methods

All patients with standardized FLR > 20 %, who underwent extended right hepatectomy for CLM from 1993-2011, were divided into three cohorts by chemotherapy duration: no chemotherapy (NC, n = 30), short duration (SD, ≤12 weeks, n = 78), long duration (LD, >12 weeks, n = 86). PHI and mortality were compared by using uni-/multivariate analyses. Optimal FLR for LD chemotherapy was determined using a minimum p-value approach.

Results

A total of 194 patients met inclusion criteria. LD chemotherapy was significantly associated with PHI (NC + SD 3.7 vs. LD 16.3%, p = 0.006). Ninety-day mortality rates were 0 % in NC, 1.3 % in SD, and 2.3% in LD patients, respectively (p = 0.95). In patients with FLR > 30 %, PHI occurred in only two patients (both LD, 2/20, 10 %), but all patients with FLR > 30 % survived. The best cutoff of FLR for preventing PHI after chemotherapy >12 weeks was estimated as >30 %. Both LD chemotherapy (odds ratio [OR] 5.4, p = 0.004) and FLR ≤ 30 % (OR 6.3, p = 0.019) were independent predictors of PHI.

Conclusions

Preoperative chemotherapy >12 weeks increases the risk of PHI after extended right hepatectomy. In patients treated with long-duration chemotherapy, FLR > 30 % reduces the rate of PHI and may provide enough functional reserve for clinical rescue if PHI develops.     

Frequency and Intensity of Postoperative Surveillance After Curative Treatment of Pancreatic Cancer: A Cost-Effectiveness Analysis

Background

Few data exist to guide oncologic surveillance following curative treatment of pancreatic cancer. We sought to identify a rational, cost-effective postoperative surveillance strategy.

Methods

We constructed a Markov model to compare the cost-effectiveness of 5 postoperative surveillance strategies. No scheduled surveillance served as the baseline strategy. Clinical evaluation and carbohydrate antigen (CA) 19-9 testing without/with routine computed tomography and chest X-ray at either 6- or 3-month intervals served as the 4 comparison strategies of increasing intensity. We populated the model with symptom, recurrence, treatment, and survival data from patients who had received intensive surveillance after multimodality treatment at our institution between 1998 and 2008. Costs were based on Medicare payments (2011 US dollars).

Results

The baseline strategy of no scheduled surveillance was associated with a postoperative overall survival (OS) of 24.6 months and a cost of $3837/patient. Clinical evaluation and CA 19-9 assay every 6 months until recurrence was associated with a 32.8-month OS and a cost of $7496/patient, with an incremental cost-effectiveness ratio (ICER) of $5364/life-year (LY). Additional routine imaging every 6 months incrementally increased total cost by $3465 without increasing OS. ICERs associated with clinic visits every 3 months without/with routine imaging were $127,680 and $294,696/LY, respectively. Sensitivity analyses changed the strategies’ absolute costs but not the relative ranks of their ICERs.

Conclusions

Increasing the frequency and intensity of postoperative surveillance of patients after curative therapy for pancreatic cancer beyond clinical evaluation and CA 19-9 testing every 6 months increases cost but confers no clinically significant survival benefit.     

Judgements of grammaticality in aphasia: The special case of Chinese

Theories of agrammatism have been challenged by the discovery that agrammatic patients can make above - chance judgements of grammaticality. Chinese poses an interesting test of this phenomenon, because its grammar is so austere, with few obligatory features. An on - line grammaticality judgement task was conducted with normal and aphasic speakers of Chinese, using the small set of constructions that do permit judgements of grammaticality in this language. Broca's and Wernicke's aphasics showed similar patterns, with above - chance discrimination between grammatical and ungrammatical forms, suggesting once again that Broca's aphasics are not unique in the degree of sparing or impairment that they show in receptive grammar. However, even for young normals, false - negative rates were high. We conclude that there is some sensitivity to grammatical well - formedness in Chinese aphasics, but the effect is fragile for aphasics and probabilistic for normals, reflecting the peculiar status of grammaticality in this language.     

Differential response to H. pylori eradication therapy of co-existing diffuse large B-cell lymphoma and MALT lymphoma of stomach-significance of tumour cell clonality and BCL10 expression

We recently reported that low-grade mucosa-associated lymphoid tissue lymphoma (MALToma) and diffuse large B-cell lymphoma (DLBCL) with MALToma (DLBCL[MALT]) of stomach are equally responsive to H. pylori eradication therapy (HPET) and that H. pylori-independent status is closely associated with nuclear translocation of BCL10. However, co-existing MALToma and DLBCL components of gastric DLBCL(MALT) may respond differentially to HPET and the underlying mechanism remains unclear. Tumour tissue samples from 18 patients with microdissectable co-existing MALToma and DLBCL cells were studied. The clonality of lymphoma cells was examined by polymerase chain reaction-based amplification of the CDR3 region of the IgH gene and confirmed by DNA sequence analysis. BCL10 expression was determined by immunohistochemistry. Differential response of co-existing MALToma and DLBCL to HPET was defined as complete eradication of one component while the other component remained. Five (27.8%) of the 18 patients showed different IgH gene rearrangements in the two components and three (60%) of these five patients had differential response of MALToma and DLBCL to HPET. By contrast, 13 patients showed identical IgH gene rearrangements and only one (8%) of them had differential response of the two components to HPET (p = 0.044). Further, all four patients with differential response of MALToma and DLBCL to HPET showed nuclear expression of BCL10 in the H. pylori-independent component and cytoplasmic expression of BCL10 in the H. pylori-dependent component while the expression patterns of BCL10 were identical in both of these components in the 14 patients who had similar tumour response to HPET. We conclude that different clonality is a common reason for the differential response of co-existing MALToma and DLBCL of gastric DLBCL(MALT) to HPET and that immunohistochemical examination of BCL10 expression may help to identify the co-existence of these components.     

Morbidity and Mortality after Pancreaticoduodenectomy in Patients with Borderline Resectable Type C Clinical Classification

Background

We previously described the clinical classification of patients with resectable pancreatic tumor anatomy but marginal performance status (PS) or reversible comorbidities as “borderline resectable type C” (BR-C). This study was designed to analyze the incidence and risk factors for post-pancreaticoduodenectomy (PD) morbidity/mortality in a multi-institutional cohort of BR-C patients.

Methods

Elective PDs were evaluated from the 2005-10 ACS-NSQIP database. BR-C was defined as age?≥?80, poor PS, weight loss?>?10 %, pulmonary disease, recent myocardial infarction/angina, stroke history, and/or preoperative sepsis. Variables associated with 30-day postoperative major complications (PMC) and mortality were analyzed.

Results

A total of 3,033/8,266 (36.7 %) patients were BR-C. BR-C patients were more likely to suffer PMC (31.3 vs. 26.2 %) and mortality (4.1 vs. 2.3 %). BR-C patients with PMC suffered 50 % higher mortality versus non-BR-C patients with PMC (11.5 vs. 7.7 %) (all p?<?0.001). For BR-C patients, multivariate analysis identified the following risk factors for PMC or mortality: albumin?<?3.5 g/dL, dyspnea, preoperative sepsis, age?≥?80, poor PS, anesthesia score?≥?4, and intraoperative transfusion?≥?4 units.

Conclusions

Nationwide, one third of patients undergoing PD are medically borderline. These BR-C patients are at higher risk for and less able to be rescued from PMC. Surgeons should identify and optimize comorbidities and utilize prehabilitation to address functional deficits before elective PD.     

Development and characterization of nine polymorphic microsatellite markers from the sword prawn Parapenaeopsis hardwickii using PCR-based isolation of microsatellite arrays (PIMA)

Nine polymorphic microsatellite makers were isolated and characterized in 20 individuals of Parapenaeopsis hardwickii collected from the fishing ground near Ilan, Taiwan. Number of alleles per locus ranged from 3 to 8, observed and expected heterozygosities ranged from 0.5263 to 0.7632, and from 0.4225 to 0.8044, respectively. Only one locus showed a Hardy–Weinberg equilibrium deviation. No linkage disequilibrium was found among these studied loci. This set of microsatellites provides a suitable tool for population genetic structure and fishery management of this species in Asian coastal waters.