Isolated bladder metastasis causing large bowel obstruction: a case report of an atypical presentation of intussusception

Intussusception of the large bowel is a rare clinical entity. In adults, this pathology is usually associated with a malignant lead point and often requires operative management. Reported is the case of an 83-year-old female who was recently diagnosed with superficial bladder cancer (T1) treated by partial cystectomy. She presented 3 months post-operatively with an isolated mucosal metastasis of the transverse colon causing intussusception and large bowel obstruction. The patient was successfully treated by colonic resection with primary anastomosis. Histology was significant for a pedunculated sarcomatoid bladder carcinoma originating from the colonic mucosa with incomplete invasion of the bowel wall. An isolated mucosal metastasis of this variety has not been reported in the literature to date

Robotic Surgery for Non-Small Cell Lung Cancer

Pulmonary resection has been a cornerstone in the management of patients with non-small cell lung cancer (NSCLC) for decades. In recent years, the popularity of minimally-invasive techniques as the primary method to manage NSCLC has grown significantly. With smaller incisions and a lower incidence of peri-operative complications, minimally-invasive lung resection, accomplished through keyhole incisions with miniaturized cameras and similarly small instruments that work through surgical ports, has been shown to retain equivalent oncologic outcomes to the traditional gold standard open thoracotomy. This technique allows for the safe performance of anatomic lung resection with complete lymphadenectomy and has been a part of thoracic surgery practice for three decades. Robotic-assisted thoracoscopic surgery (RATS) represents another major advancement for lung resection, broadening the opportunity for patients to undergo minimally invasive surgery for NSCLC, and therefore allowing a greater percentage of the lung cancer population to benefit from many of the advantages previously demonstrated from video assisted thoracoscopic surgery (VATS) techniques. RATS surgery is also associated with several technical advantages to the surgeon. For a surgeon who performs open procedures and is looking to adopt a minimally invasive approach, RATS ergonomics are a natural transition compared to VATS, particularly given the multiple degrees of freedom associated with robotic articulating instruments. As a result, this platform has been adopted as a primary approach in numerous institutions across the United States. In this chapter, we will explore the advantages and disadvantages of robotic-assisted surgery for NSCLC and discuss the implications for increased adoption of minimally invasive surgery in the future of lung cancer treatment

A guide for managing patients with stage I NSCLC: Deciding between lobectomy, segmentectomy, wedge, SBRT and ablation-part 2: Systematic review of evidence regarding resection extent in generally healthy patients

Background: Clinical decision-making for patients with stage I lung cancer is complex. It involves multiple options (lobectomy, segmentectomy, wedge, stereotactic body radiotherapy, thermal ablation), weighing multiple outcomes (e.g., short-, intermediate-, long-term) and multiple aspects of each (e.g., magnitude of a difference, the degree of confidence in the evidence, and the applicability to the patient and setting at hand). A structure is needed to summarize the relevant evidence for an individual patient and to identify which outcomes have the greatest impact on the decision-making. Methods: A PubMed systematic review from 2000-2021 of outcomes after lobectomy, segmentectomy and wedge resection in generally healthy patients is the focus of this paper. Evidence was abstracted from randomized trials and non-randomized comparisons with at least some adjustment for confounders. The analysis involved careful assessment, including characteristics of patients, settings, residual confounding etc. to expose degrees of uncertainty and applicability to individual patients. Evidence is summarized that provides an at-a-glance overall impression as well as the ability to delve into layers of details of the patients, settings and treatments involved. Results: In healthy patients there is no short-term benefit to sublobar resection Conclusions: A systematic, comprehensive summary of evidence regarding resection extent in healthy patients with attention to aspects of applicability, uncertainty and effect modifiers provides a foundation on which to build a framework for individualized clinical decision-making

A guide for managing patients with stage I NSCLC: Deciding between lobectomy, segmentectomy, wedge, SBRT and ablation-part 3: Systematic review of evidence regarding surgery in compromised patients or specific tumors

Background: Clinical decision-making for patients with stage I lung cancer is complex. It involves multiple options [lobectomy, segmentectomy, wedge, stereotactic body radiotherapy (SBRT), thermal ablation], weighing multiple outcomes (e.g., short-, intermediate-, long-term) and multiple aspects of each (e.g., magnitude of a difference, the degree of confidence in the evidence, and the applicability to the patient and setting at hand). A structure is needed to summarize the relevant evidence for an individual patient and to identify which outcomes have the greatest impact on the decision-making. Methods: A PubMed systematic review from 2000-2021 of outcomes after lobectomy, segmentectomy and wedge resection in older patients, patients with limited pulmonary reserve and favorable tumors is the focus of this paper. Evidence was abstracted from randomized trials and non-randomized comparisons (NRCs) with adjustment for confounders. The analysis involved careful assessment, including characteristics of patients, settings, residual confounding etc. to expose degrees of uncertainty and applicability to individual patients. Evidence is summarized that provides an at-a-glance overall impression as well as the ability to delve into layers of details of the patients, settings and treatments involved. Results: In older patients, perioperative mortality is minimally altered by resection extent and only slightly affected by increasing age; sublobar resection may slightly decrease morbidity. Long-term outcomes are worse after lesser resection; the difference is slightly attenuated with increasing age. Reported short-term outcomes are quite acceptable in (selected) patients with severely limited pulmonary reserve, not clearly altered by resection extent but substantially improved by a minimally invasive approach. Quality-of-life (QOL) and impact on pulmonary function hasn\u27t been well studied, but there appears to be little difference by resection extent in older or compromised patients. Patient selection is paramount but not well defined. Ground-glass and screen-detected tumors exhibit favorable long-term outcomes regardless of resection extent; however solid tumors \u3c1 cm are not a reliably favorable group. Conclusions: A systematic, comprehensive summary of evidence regarding resection extent in compromised patients and favorable tumors with attention to aspects of applicability, uncertainty and effect modifiers provides a foundation for a framework for individualized decision-making

A guide for managing patients with stage I NSCLC: Deciding between lobectomy, segmentectomy, wedge, SBRT and ablation-part 4: Systematic review of evidence involving SBRT and ablation

Background: Clinical decision-making for patients with stage I lung cancer is complex. It involves multiple options [lobectomy, segmentectomy, wedge, stereotactic body radiotherapy (SBRT), thermal ablation], weighing multiple outcomes (e.g., short-, intermediate-, long-term) and multiple aspects of each (e.g., magnitude of a difference, the degree of confidence in the evidence, and the applicability to the patient and setting at hand). A structure is needed to summarize the relevant evidence for an individual patient and to identify which outcomes have the greatest impact on the decision-making. Methods: A PubMed systematic review from 2000-2021 of outcomes after SBRT or thermal ablation Results: Short-term outcomes are meaningfully better after SBRT than resection. SBRT doesn\u27t affect quality-of-life (QOL), on average pulmonary function is not altered, but a minority of patients may experience gradual late toxicity. Adjusted non-randomized comparisons demonstrate a clinically relevant detriment in long-term outcomes after SBRT Conclusions: A systematic, comprehensive summary of evidence regarding Stereotactic Body Radiotherapy or thermal ablatio

Autologous humanized PDX modeling for immuno-oncology recapitulates features of the human tumor microenvironment.

BACKGROUND: Interactions between immune and tumor cells are critical to determining cancer progression and response. In addition, preclinical prediction of immune-related drug efficacy is limited by interspecies differences between human and mouse, as well as inter-person germline and somatic variation. To address these gaps, we developed an autologous system that models the tumor microenvironment (TME) from individual patients with solid tumors. METHOD: With patient-derived bone marrow hematopoietic stem and progenitor cells (HSPCs), we engrafted a patient\u27s hematopoietic system in MISTRG6 mice, followed by transfer of patient-derived xenograft (PDX) tissue, providing a fully genetically matched model to recapitulate the individual\u27s TME. We used this system to prospectively study tumor-immune interactions in patients with solid tumor. RESULTS: Autologous PDX mice generated innate and adaptive immune populations; these cells populated the TME; and tumors from autologously engrafted mice grew larger than tumors from non-engrafted littermate controls. Single-cell transcriptomics revealed a prominent vascular endothelial growth factor A (VEGFA) signature in TME myeloid cells, and inhibition of human VEGF-A abrogated enhanced growth. CONCLUSIONS: Humanization of the interleukin 6 locus in MISTRG6 mice enhances HSPC engraftment, making it feasible to model tumor-immune interactions in an autologous manner from a bedside bone marrow aspirate. The TME from these autologous tumors display hallmarks of the human TME including innate and adaptive immune activation and provide a platform for preclinical drug testing

Lung cancer osteopontin isoforms exhibit angiogenic functional heterogeneity

ObjectiveOsteopontin is a multifunctional phosphoprotein with an important but poorly understood role in non–small cell lung cancer pathogenesis. We hypothesize that osteopontin isoforms (OPNa, OPNb, and OPNc) have divergent roles in non–small-cell lung cancer angiogenesis and divergent impact on vascular endothelial growth factor secretion.MethodsWe examined mRNA expression using reverse transcriptase-polymerase chain reaction primers for 3 osteopontin isoforms in non–small-cell lung cancer and immortalized bronchial epithelial cell lines, and correlated expression with osteopontin secretion into media detected by enzyme-linked immunosorbent assay. Angiogenic properties conferred by osteopontin isoforms were evaluated by transfecting cDNA plasmids specific to each isoform and controls into non–small-cell lung cancer cell lines, H153 and H358 (low endogenous osteopontin) and A549 and H460 (high endogenous osteopontin), analyzing conditioned media on a bovine capillary endothelial platform, and measuring vascular endothelial growth factor levels by enzyme-linked immunosorbent assay.ResultsOPNa mRNA expression correlated with osteopontin secretion in cell lines (r = 0.912, P = .0006). OPNa overexpression significantly increased tubule length compared with controls, OPNb had a similar, but less pronounced effect, and OPNc significantly decreased tubule length compared with controls in each cell line. OPNa overexpression was associated with significant increases in vascular endothelial growth factor secretion, whereas OPNb had no effect and OPNc overexpression was associated with significant decreases in vascular endothelial growth factor compared with controls in each cell line.ConclusionWe demonstrated divergent effects of osteopontin isoforms on non–small-cell lung cancer angiogenesis and vascular endothelial growth factor secretion. OPNa overexpression was associated with increased bovine capillary endothelial tubule length and vascular endothelial growth factor secretion, whereas OPNc was associated with decreases in both. These findings may lead to therapeutic strategies for selective isoform inhibition in non–small cell lung cancer