Novel Application of Hydrodissection in Laparoscopic Cholecystectomy for Gangrenous Gallbladders.

INTRODUCTION: Laparoscopic cholecystectomy (LC) for gangrenous gallbladders (GGBs) can be challenging and represent a significant number of LC cases, necessitating more efficacious surgical techniques. Currently, the standard treatment for GGBs is blunt dissection which can have high iatrogenic complication rates. To our knowledge, this is the first large retrospective study conducted on the novel application of hydrodissection (HD) in LCs for GGBs. METHODS: In this retrospective study of 386 LCs, data were collected for patient demographics, medical comorbidities, operating time (OT), anesthesia time (AT), length of stay (LOS), estimated blood loss, conversion to open procedures, 30-day readmissions, and mortality. Patients were categorized into four groups: (1) Vyas employing HD for GGBs (VHG), (2) non-Vyas group of five surgeons not employing HD for GGBs (NVG), (3) Vyas treating non-GGBs, and (4) non-Vyas group of five surgeons treating non-GGBs. Control groups were age-matched and sex-matched. Statistical analysis used descriptive statistics, Mann-Whitney U testing, and chi-squared testing (α = 0.05). RESULTS: This study demonstrated significantly decreased (P < 0.05) OT (P = 0.001), AT (P < 0.001), LOS (P = 0.015), and conversion to open procedures (P = 0.047) between the VHG and NVG groups, with HD reducing OT by 35.5% compared to blunt dissection. This study did not demonstrate significantly decreased (P > 0.05) estimated blood loss (P = 0.185) and 30-day readmissions (P = 0.531) between the VHG and NVG groups, but they were trending toward significant. There were no mortalities in this study. CONCLUSIONS: HD is associated with improved surgical outcomes of LCs for GGBs demonstrated by reduced OT, AT, LOS, and conversion to open procedures. Further multi-institutional studies are needed to validate HD implementation and further dissemination.

Delay of treatment change after objective progression on first-line erlotinib in epidermal growth factor receptor-mutant lung cancer.

BACKGROUND: Erlotinib is a highly active epidermal growth factor receptor (EGFR) kinase inhibitor that is approved for first-line use in lung cancers harboring EGFR mutations. Anecdotal experience suggests that this drug may provide continued disease control after patients develop objective progression of disease (PD), although this has not been systematically studied to date. METHODS: Patients who had Response Evaluation Criteria In Solid Tumors-defined PD who were participating in 3 prospective trials of first-line erlotinib in advanced lung cancer were studied retrospectively, and the progression characteristics were compared between patients with and without EGFR-sensitizing mutations. Factors were studied that influenced the time until treatment change (TTC), defined as the time from PD to the start of a new systemic therapy or death. The rate of tumor progression was assessed by comparing tumor measurements between the computed tomography scan obtained at the time of PD and the preceding scan. RESULTS: In total, 92 eligible patients were studied, including 42 with and 50 without an EGFR-sensitizing mutation. The EGFR-mutant cohort had a slower rate of progression (P = .003) and a longer TTC (P < .001). Among the patients with EGFR-mutant cancers, 28 (66%) continued single-agent erlotinib after PD, and 21 (50%) were able to delay a change in systemic therapy for >3 months; only 2 patients received local debulking therapy during that period. Multivariate analysis of the patients with EGFR-mutant tumors demonstrated that a longer time to progression, a slower rate of progression, and a lack of new extrathoracic metastases were associated with a longer TTC. CONCLUSIONS: A change in systemic therapy commonly can be delayed in patients with EGFR-mutant lung cancer who objectively progress on first-line erlotinib, particularly in those with a longer time to progression, a slow rate of progression, and a lack of new extrathoracic metastases.

Definitive primary therapy in patients presenting with oligometastatic non-small cell lung cancer.

PURPOSE: Although palliative chemotherapy is the standard of care for patients with diagnoses of stage IV non-small cell lung cancer (NSCLC), patients with a small metastatic burden, "oligometastatic" disease, may benefit from more aggressive local therapy. METHODS AND MATERIALS: We identified 186 patients (26% of stage IV patients) prospectively enrolled in our institutional database from 2002 to 2012 with oligometastatic disease, which we defined as 5 or fewer distant metastatic lesions at diagnosis. Univariate and multivariable Cox proportional hazards models were used to identify patient and disease factors associated with improved survival. Using propensity score methods, we investigated the effect of definitive local therapy to the primary tumor on overall survival. RESULTS: Median age at diagnosis was 61 years of age; 51% of patients were female; 12% had squamous histology; and 33% had N0-1 disease. On multivariable analysis, Eastern Cooperate Oncology Group performance status ≥ 2 (hazard ratio [HR], 2.43), nodal status, N2-3 (HR, 2.16), squamous pathology, and metastases to multiple organs (HR, 2.11) were associated with a greater hazard of death (all P<.01). The number of metastatic lesions and radiologic size of the primary tumor were not significantly associated with overall survival. Definitive local therapy to the primary tumor was associated with prolonged survival (HR, 0.65, P=.043). CONCLUSIONS: Definitive local therapy to the primary tumor appears to be associated with improved survival in patients with oligometastatic NSCLC. Select patient and tumor characteristics, including good performance status, nonsquamous histology, and limited nodal disease, may predict for improved survival in these patients.

Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions.

INTRODUCTION: Exon 20 insertions are the third most common family of epidermal growth factor receptor (EGFR) mutations found in non-small-cell lung cancer (NSCLC). Little is known about cancers harboring these mutations aside from their lack of response to EGFR tyrosine kinase inhibitors, impairing the development of effective targeted therapies. METHODS: NSCLC patients with EGFR genotyping were studied using a mechanism approved by the Institutional Review Board. Cancers with exon 20 insertions were indentified, sequences were characterized, and effectiveness of different treatment regimens was reviewed retrospectively. Clinical characteristics and survival were compared with cancers harboring common EGFR mutations and cancers with wild-type EGFR. RESULTS: One thousand eighty-six patients underwent EGFR genotyping from 2004 to 2012. Twenty seven (2.5%) harbored exon 20 insertions, making up 9.2% of all cancers with documented EGFR mutations. Compared with wild-type cancers, those with exon 20 insertions were more commonly found in never-smokers and Asian patients. Insertion sequences were highly variable, with the most common variant (V769_D770insASV) making up only 22% of cases. Median survival of patients with exon 20 insertions was 16 months, similar to the survival of wild-type cancers and shorter than the survival of cancers with common EGFR mutations. CONCLUSIONS: Patients with EGFR exon 20 insertions have similar clinical characteristics to those with common EGFR mutations but a poorer prognosis. The prevalence of this subset of NSCLC is similar to that of other genotype-defined subsets of lung adenocarcinoma (e.g. those with BRAF mutations, HER2 insertions, ROS1 rearrangements) and is a population of interest for trials of new targeted therapies.