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Background: High-volume pancreatic surgery centers require a significant investment in expertise, time, and resources to achieve optimal patient outcomes. A detailed understanding of the economics of major pancreatic surgery is limited among many clinicians and hospital administrators. A greater consideration of these financial aspects may in fact have implications for enhancing clinical care and for a broader sustainability of high-volume pancreatic surgery programs. Methods: In this retrospective observational study, patients who underwent pancreaticoduodenectomy (PD), total pancreatectomy, or distal pancreatectomy at one academic medical center during the fiscal year 2021 were evaluated. Detailed hospital charges and professional fees were obtained for patients using the Qlik perioperative database. Clinical data for the study cohort were gathered from a prospectively maintained, IRB-approved pancreatic surgery database. Charges for the 91-day perioperative period were included. A P < 0.05 was considered significant. Results: During the study period, 159 evaluable patients underwent 1 of 3 designated pancreatic resections included in the analysis. Ninety-seven patients (61%) were diagnosed with adenocarcinoma and 70% (n = 110) underwent PD. The total charges (combined professional and hospital charges) for the cohort encompassing the entire perioperative period were $20,661,759. The median charge per patient was $130,306 (interquartile range [IQR], $34,534). The median direct cost of care was $23,219 (IQR, $6321) and the median contribution margin per case was $10,092 (IQR, $22,949). The median surgeon professional fee charges were $7700 per patient (IQR, $1296) as compared to $3453 (IQR, $1,144) for professional fee receipts (45% of the surgeon charge). The differences between the professional fee charges and receipts per patient were also considerable for other health care professionals such as anesthesiologists ($4945 charges vs $1406 receipts [28%]) and pathologists ($3035 charges vs $680 receipts [22%]). The surgeon professional fees were only 6% of the total charges, while the professional fees for anesthesiology and pathology were 4% and 2% of the total charges, respectively. Supply charges were 3% of the total charges. Longer operative time was correlated with increased hospital and anesthesia charges, without a significant increase in surgeon charges (P < 0.001, P < 0.001, and P = 0.2, respectively). Male sex, diabetes, and low serum albumin correlated with greater total hospital charges (P = 0.01, P = 0.01, and P = 0.03, respectively). Conclusions: The role of the surgeon in the perioperative clinical care of major pancreatic resection patients is crucial and important and is by no means limited to the operative day. Nevertheless, in the context of the current US health care system, the reimbursement to the surgeon in the form of professional fees is a relatively small fraction of the total health care receipts for these patients. This imbalance necessitates a substantial financial partnership between hospitals and their pancreatic surgery units to ensure the long-term viability of these programs.

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BACKGROUND: Euglycemic diabetic ketoacidosis is a metabolic condition characterized by relative euglycemia, ketonemia, and metabolic acidosis that occurs through mechanisms resembling starvation. Pancreaticoduodenectomy is a complex abdominal operation that subjects patients to a prolonged fasting and an inflammatory state. This study examined the incidence of euglycemic diabetic ketoacidosis and potential opportunities for early diagnosis and management in patients undergoing pancreaticoduodenectomy. METHODS: A single-institution retrospective review of 350 patients who underwent pancreaticoduodenectomy between 2017 and 2020 was performed. Primary endpoints were peak beta-hydroxybutyrate levels, peak lactate levels, lowest pH, peak base deficits, and urinary output within the first 24 hours, postoperatively. Additional endpoints included incidence of postoperative pancreatic fistula, delayed gastric emptying, total complications, postoperative hospital length of stay, readmission rates, and changes in insulin regimen at discharge. RESULTS: Of the 350 cases reviewed, 39 (11.1%) patients developed euglycemic diabetic ketoacidosis. Male sex and pancreatic cancer were associated with a risk for euglycemic diabetic ketoacidosis (P < .05). Patients with euglycemic diabetic ketoacidosis had significantly higher peak beta-hydroxybutyrate levels than patients without euglycemic diabetic ketoacidosis (mean difference = 19.8 mg/dL, 95% confidence interval = 14.7-24.9, P < .001), and were nearly four times more likely to require insulin at discharge (odds ratio 3.8, 95% confidence interval = 1.1-13.0, P < .05). CONCLUSION: This is the first large descriptive study that investigates euglycemic diabetic ketoacidosis after pancreaticoduodenectomy. Euglycemic diabetic ketoacidosis after pancreaticoduodenectomy is associated with significantly higher beta-hydroxybutyrate levels and new or increased insulin requirement at discharge. Our study demonstrates potential markers for euglycemic diabetic ketoacidosis after pancreaticoduodenectomy, offering an opportunity to identify and successfully treat this disease in a timely manner.

Assuntos

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OBJECTIVE: Patients with epithelial ovarian cancers experience the highest fatality rates among all gynecological malignancies which require development of novel treatment strategies. Tumor cell necrosis was previously reported in a number of cancer cell lines following treatment with a p53-derived anti-cancer peptide called PNC-27. This peptide induces necrosis by transmembrane pore formation with HDM-2 protein that is expressed in the cancer cell membrane. We aimed to extend these studies further by investigating expression of membrane HDM-2 protein in ovarian cancer as it relates to susceptibility to PNC-27. PROCEDURES: Herein, we measured HDM-2 membrane expression in two ovarian cancer cell lines (SKOV-3 and OVCAR-3) and a non-transformed control cell line (HUVEC) by flow cytometric and western blot analysis. Immunofluorescence was used to visualize colocalization of PNC-27 with membrane HDM-2. Treatment effects with PNC-27 and control peptide were assessed using a MTT cell proliferation assay while direct cytotoxicity was measured by lactate dehydrogenase (LDH) release and induction of apoptotic markers; annexin V and caspase-3. RESULTS: HDM-2 protein was highly expressed and frequently detected in the membranes of SKOV-3 and OVCAR-3 cells; a prominent 47.6 kDa HDM-2 plasma membrane isoform was present in both cell lines whereas 25, 29, and 30 kDa isoforms were preferentially expressed in OVCAR-3. Notably, PNC-27 colocalized with HDM-2 in the membranes of both cancer cell lines that resulted in rapid cellular necrosis. In contrast, no PNC-27 colocalization and cytotoxicity was observed with non-transformed HUVEC demonstrating minimal expression of membrane HDM-2. CONCLUSIONS: Our results suggest that HDM-2 is highly expressed in the membranes of these ovarian cancer cell lines and colocalizes with PNC-27. We therefore conclude that the association of PNC-27 with preferentially expressed membrane HDM-2 isoforms results in the proposed model for the formation of transmembrane pores and epithelial ovarian cancer tumor cell necrosis, as previously described in a number of solid tissue and hematologic malignancies.

Assuntos

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Recent advances in biomedical research in cancer immunotherapy have identified the use of an oxidative stress-based approach to treat cancers, which works by inducing immunogenic cell death (ICD) in cancer cells. Since the anti-cancer effects of non-thermal plasma (NTP) are largely attributed to the reactive oxygen and nitrogen species that are delivered to and generated inside the target cancer cells, it is reasonable to postulate that NTP would be an effective modality for ICD induction. NTP treatment of tumors has been shown to destroy cancer cells rapidly and, under specific treatment regimens, this leads to systemic tumor-specific immunity. The translational benefit of NTP for treatment of cancer relies on its ability to enhance the interactions between NTP-exposed tumor cells and local immune cells which initiates subsequent protective immune responses. This review discusses results from recent investigations of NTP application to induce immunogenic cell death in cancer cells. With further optimization of clinical devices and treatment protocols, NTP can become an essential part of the therapeutic armament against cancer.

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BACKGROUND: Pancreaticoduodenectomy (PD) with right hemicolectomy (RH) to treat locally advanced right colon cancer (LARCC) has been rarely reported in the literature. Herein, we characterize clinicopathologic factors and evaluate outcomes of en bloc PD and RH for LARCC. METHODS: A systematic review of the literature was conducted on PubMed using MeSH terms ("pancreaticoduodenectomy" or "pancreas/surgery" or "duodenum/surgery" or "colectomy") and ("colonic neoplasms"). Data was extracted from patients who underwent en bloc PD and RH for LARCC. Factors investigated included patient demographics, surgical and pathologic parameters, postoperative complications, disease recurrence, and survival. RESULTS: Our search yielded 27 articles (106 patients), including 1 case from our institution. Most patients were male (62.1%), median age 58 years (range 34-83). Surgical procedures performed included en bloc RH with PD (n = 91, 85.8%) and en bloc RH with pylorus-preserving PD (n = 15, 14.2%). Among reported, 95.5% of patients (n = 63), underwent R0 resection. One or more complications were reported in 33 patients (52.4%). Median survival was 168 months. Survival after resection was 75.9% at 2 years and 66.3% at 5 years. Overall survival was greater in patients with no lymph node involvement (IIC versus IIIC, hazard ratio 8.4, P = .003). Five-year survival for patients was 84.9% in patients with stage IIC versus 46.4% in patients with stage IIIC. There were 3 postoperative mortalities. CONCLUSION: This data demonstrates that en bloc PD and RH is rarely performed yet can be a potentially safe treatment option in patients with LARCC. Lymph node involvement was the only independent prognostic factor.

Assuntos

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OBJECTIVES: Pseudomyxoma peritonei (PMP) is a rare malignancy originating from the appendix, characterized by disseminated mucinous tumor implants on peritoneal surfaces. We examined the role of multiplatform molecular profiling to study biomarker-guided treatment strategies for this rare malignancy. METHODS: A total of 54 patients with appendix-derived PMP were included in the study. Tests included one or more of the following: gene sequencing (Sanger or next generation sequencing), protein expression (immunohistochemistry), and gene amplification (C/fluorescent in situ hybridization). RESULTS: Targeted sequencing of 47 genes detected variants in KRAS (81%), GNAS (74%), SMAD4 (16%), and ATM (16%). Mutations were found at low frequencies (n=1 to 2) in APC, BRAF, PIK3CA, MLH1, and TP53. GNAS and KRAS co-occurrence was found in 87%. Protein overexpression was found in epidermal growth factor receptor (83%), cyclooxygenase-2 (73%), cMET (63%), cKIT (58%), and platelet-derived growth factor receptor alpha (58%). Immune checkpoint expression was found in 36% (programmed cell death protein 1) and 18% (programmed death-ligand 1). Surrogate markers of cell proliferation were found at low rates (TLE3 23%, TOP2A 22%), consistent with the slow-growing biology of PMP. Phosophatase and tensin homolog was intact (wild type [100%]) and positive (immunohistochemistry [80%]). Patients exhibited stable microsatellite status and mismatch repair proficiency (93%). Importantly, multidrug resistance protein expression was elevated (100% BCRP, 94% MRP1, 88% PGP). Markers for gemcitabine (RRM1), fluorouracil (TS), oxaliplatin (ERCC1), and irinotecan (TOPO1) chemosensitivities were detected at favorable rates: 93%, 87%, 77% and 65%, respectively. CONCLUSIONS: Molecular profiling by multiple platforms identified potential therapies for the nontargetable KRAS-mutated population. The role of cMET-targeted therapeutics and immune checkpoint inhibitors merits further investigation. Biomarker-guided selection of cytotoxic chemotherapies may facilitate efficacy to systemic treatment.

Assuntos

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GOALS: We have developed the anti-cancer peptide, PNC-27, which is a membrane-active peptide that binds to the HDM-2 protein expressed in the cancer cell membranes of solid tissue tumor cells and induces transmembrane pore formation in cancer, but not in normal cells, resulting in tumor cell necrosis that is independent of p53 activity in these cells. We now extend our study to non-solid tissue tumor cells, in this case, a primitive, possible stem cell human leukemia cell line (K562) that is also p53-homozygously deleted. Our purpose was twofold: to investigate if these cells likewise express HDM-2 in their plasma membranes and to determine if our anti-cancer peptide induces tumor cell necrosis in these non-solid tissue tumor cells in a manner that depends on the interaction between the peptide and membrane-bound HDM-2. PROCEDURES: The anti-cancer activity and mechanism of PNC-27, which carries a p53 aa12-26-leader sequence connected on its carboxyl terminal end to a trans-membrane-penetrating sequence or membrane residency peptide (MRP), was studied against p53-null K562 leukemia cells. Murine leukocytes were used as a non-cancer cell control. Necrosis was determined by measuring the lactate dehydrogenase (LDH) release and apoptosis was determined by the detection of Caspases 3 and 7. Membrane colocalization of PNC-27 with HDM-2 was analyzed microscopically using fluorescently labeled antibodies against HDM-2 and PNC-27 peptides. RESULTS: We found that K562 cells strongly express HDM-2 protein in their membranes and that PNC-27 co-localizes with this protein in the membranes of these cells. PNC-27, but not the negative control peptide PNC-29, is selectively cytotoxic to K562 cells, inducing nearly 100 percent cell killing with LDH release. In contrast, this peptide had no effect on the lymphocyte control cells. CONCLUSIONS: The results suggest that HDM-2 is expressed in the membranes of non-solid tissue tumor cells in addition to the membranes of solid tissue tumor cells. Since K-562 cells appear to be in the stem cell family, the results suggest that early developing tumor cells also express HDM-2 protein in their membranes. Since PNC-27 induces necrosis of K-562 leukemia cells and co-localizes with HDM-2 in the tumor cell membrane as an early event, we conclude that the association of PNC-27 with HDM-2 in the cancer cell membrane results in trans-membrane pore formation which results in cancer cell death, as previously discovered in a number of different solid tissue tumor cells. Since K562 cells lack p53 expression, these effects of PNC-27 on this leukemia cell line occur by a p53-independent pathway.

Assuntos