Linking factors to incisional hernia following pancreatic surgery: a 14-year retrospective analysis.

BACKGROUND: Incisional hernias (IH) are a significant postoperative complication with profound implications for patient morbidity and healthcare costs. The relationship between IH and perioperative factors in pancreatic surgery, with particular attention to preoperative biliary stents and pancreatic fistulas requires further exploration. METHODS: This retrospective observational study examined adult patients who underwent open pancreatic surgeries via midline incision at a high-volume tertiary hepatopancreatobiliary center from January 2008 to December 2021. The study focused on IH incidence and associated risk factors, with particular attention to preoperative biliary stents and pancreatic fistulas. RESULTS: In a cohort of 620 individuals undergoing pancreatic surgery, 351 had open surgery with at least one-year follow-up. Within a median follow-up of 794 days (IQR 1694-537), the overall incidence of IH was 17.38%. The highest frequency of IH was observed among patients who had a Pancreaticoduodenectomy (PD). Significant predictors for the development of IH within the entire study population in a multivariable analysis included perioperative biliary stenting (OR 2.05; 95% CI 1.06-3.96; p = 0.03), increased age at diagnosis (OR 2.05; 95% CI 1.06-3.96; p = 0.01), and BMI (OR 1.08; 95% CI 1.01-1.15; p = 0.01). In the subset of patients who underwent Pancreaticoduodenectomy (PD), although the presence of biliary stents was associated with a heightened occurrence of SSIs, it did not demonstrate a direct correlation with an increased incidence of incisional hernias (IH). The development of pancreatic fistulas did not show a significant correlation with IH in either the Distal Pancreatectomy with Splenectomy (DPS) or the PD patient groups. CONCLUSIONS: The study underscores a notable association between biliary stent placement and increased IH risk after PD, mediated by elevated SSI incidence. Pancreatic fistulas were not directly correlated with IH in the studied cohorts. Further research is necessary to validate these findings and guide clinical practice.

Perioperative Platelet Count Ratio Predicts Long-Term Survival after Left Pancreatectomy and Splenectomy for Pancreatic Adenocarcinoma.

BACKGROUND: The value of platelet characteristics as a prognostic factor in patients with pancreatic adenocarcinoma (PDAC) remains unclear. METHODS: We assessed the prognostic ability of post-splenectomy thrombocytosis in patients who underwent left pancreatectomy for PDAC. Perioperative platelet count ratio (PPR), defined as the ratio between the maximum platelet count during the first five days following surgery and the preoperative level, was assessed in relation to long-term outcomes in patients who underwent left pancreatectomy for PDAC between November 2008 and October 2022. RESULTS: A comparative cohort of 245 patients who underwent pancreaticoduodenectomy for PDAC was also evaluated. The median PPR among 106 patients who underwent left pancreatectomy was 1.4 (IQR1.1, 1.8). Forty-six had a PPR ≥ 1.5 (median 1.9, IQR1.7, 2.4) and 60 had a PPR < 1.5 (median 1.2, IQR1.0, 1.3). Patients with a PPR ≥ 1.5 had increased median overall survival (OS) compared to patients with a PPR < 1.5 (40 months vs. 20 months, p < 0.001). In multivariate analysis, PPR < 1.5 remained a strong predictor of worse OS (HR 2.24, p = 0.008). Among patients who underwent pancreaticoduodenectomy, the median PPR was 1.1 (IQR1.0, 1.3), which was significantly lower compared to patients who underwent left pancreatectomy (p > 0.001) and did not predict OS. CONCLUSION: PPR is a biomarker for OS after left pancreatectomy for PDAC. Further studies are warranted to consolidate these findings.

Highly complex liver resections: Exploring the boundaries of feasibility and safety.

INTRODUCTION: In select clinical scenarios, advanced techniques for volume manipulation and vascular reconstruction are needed for complete hepatic tumor removal. These highly complex liver resections (HCLRs) entail a heightened risk of severe complications. Here, we describe the results of HCLR performed in a 3-year time period. MATERIALS AND METHODS: We conducted a retrospective analysis encompassing patients who underwent hepatic resections between June 15, 2020, and June 15, 2023. HCLR was defined according to previously established criteria, and included associating liver partition and portal vein ligation for staged hepatectomy. The outcomes of HCLR were compared to all non-HCLR performed within the same time frame. RESULTS: Among 167 hepatic resections, 26 were considered HCLR, and all were major resections. Five utilized total vascular exclusion, with venovenous bypass in three, and hypothermic liver perfusion in three. Five resections included vascular reconstructions, and one included hypothermic circulatory arrest for extraction of a tumor extending to the right atrium. Of the non-HCLR, 38 (26.9%) were major, and 49 (34.7%) were performed laparoscopically. The rates of overall major postoperative complications were comparable between those who underwent HCLR versus non-HCLR. HCLR was associated with increased rates of biliary complications, readmissions, and reoperation. However, no postoperative 90-day mortality was documented within patients that underwent HCLR compared to two in the non-HCLR group. CONCLUSIONS: In expert hands, HCLR can be performed with acceptable complication profile, akin to that of major non-HCLR. Those with questionable resectability should be referred to tertiary hepato-pancreato-biliary centers.

Outcomes of Kidney Transplantation in Patients That Underwent Bariatric Surgery: A Systematic Review and Meta-analysis.

The impact of bariatric surgery (BS) on kidney transplantation (KT) outcomes in patients with obesity remains controversial. We systematically searched MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials for studies reporting outcomes of KT recipients that underwent prior BS. Common/random effects meta-analyses were performed to obtain summary ratios of the postoperative outcomes. Eighteen eligible studies involving 315 patients were identified. Sleeve gastrectomy was the most common BS type (65.7%) followed by Roux-en-Y gastric bypass (27.6%) and gastric banding (4.4%). Across studies that provided the data, the %excess weight loss from BS to KT was 62.79% (95% confidence interval [CI], 52.01-73.56; range, 46.2%-80.3%). The rates of delayed graft function and acute rejection were 16% (95% CI, 7%-28%) and 16% (95% CI, 11%-23%) in 14 and 11 studies that provided this data, respectively. The rates of wound, urinary, and vascular complications following KT were 5% (95% CI, 0%-13%),19% (95% CI, 2%-42%), and 2% (95% CI, 0%-5%), in 12, 9, and 11 studies that provided this data, respectively. Follow-up time after KT was reported in 11 studies (61.1%) and ranged from 16 mo to >5 y. Graft loss was reported in 14 studies with an average of 3% (95% CI, 1%-6%). Four studies that included a comparator group of patients with obesity who did not undergo BS before KT showed comparable outcomes between the groups. We conclude that currently there is a paucity of robust evidence to suggest that pretransplant BS has a major effect on post-KT outcomes. High-quality studies are needed to fully evaluate the impact of BS on KT outcomes.

Severe Ketoacidosis After One Anastomosis Gastric Bypass Surgery.

BACKGROUND Bariatric surgeries, such as one anastomosis gastric bypass (OAGB), has become a popular treatment option for managing obesity and associated comorbidities, including type-2 diabetes mellitus (T2DM). However, severe starvation ketoacidosis is a rare but potentially life-threatening complication that can occur postoperatively in patients with T2DM. Despite the increasing prevalence of these surgeries, the existing literature has limited information on severe starvation ketoacidosis as a postoperative complication. It is essential for healthcare professionals to be aware of this complication, its manifestations, and risk factors to ensure patient safety and improve outcomes. Therefore, this article aims to address the current gap in the literature and provide a comprehensive review of severe starvation ketoacidosis as a postoperative complication of bariatric surgeries, specifically OAGB, and its associated risk factors and manifestations. CASE REPORT A 38-year-old man with severe obesity and inadequately managed T2DM underwent OAGB surgery. On the second postoperative day, the patient experienced severe starvation ketoacidosis, exhibiting symptoms such as drowsiness, fatigue, weakness, and Kussmaul breathing. Blood gas analysis indicated significant metabolic acidosis. He was quickly transferred to the Intensive Care Unit (ICU) and given intravenous glucose and insulin therapy. Following this intervention, he showed rapid recovery and normalization of blood gases. He was discharged 6 days after surgery with normal clinical examination results and laboratory indices. CONCLUSIONS This case study emphasizes the significance of thorough preoperative glycemic control, comprehensive perioperative multidisciplinary management, and close postoperative monitoring for diabetic patients undergoing metabolic and bariatric surgeries. By implementing these strategies, healthcare professionals can reduce the risk of complications such as hypoglycemia or hyperglycemia/diabetic ketoacidosis (DKA) and enhance patient outcomes. The case also highlights the need for continuous education and training for healthcare providers to identify and manage such rare complications effectively.

Readmission with acute kidney injury following ileostomy: patterns and predictors of a common phenomenon.

PURPOSE: Ileostomy is associated with various complications, often necessitating rehospitalization. High-output ileostomy is common and may lead to acute kidney injury (AKI). Here we describe the temporal pattern of readmission with AKI following ileostomy formation and identify risk factors. METHODS: Patients that underwent formation of ileostomy between 2008 and 2021 were included in this study. Readmission with AKI with high output ileostomy was defined as readmission with serum creatinine > 1.5-fold compared to the level at discharge or latest baseline (at least stage-1 AKI according to Kidney Disease: Improving Global Outcome (KDIGO) criteria), accompanied by ileostomy output > 1000 ml in 24 h. Patient characteristics and perioperative course were assessed to identify predictors for readmission with AKI. RESULTS: Of 1191 patients who underwent ileostomy, 198 (16.6%) were readmitted with a high output stoma and AKI. The mean time to readmission with AKI was 98.97 ± 156.36 days. Eighty-six patients (43.4%) had early readmission (within 30 days), and 66 (33%) were readmitted after more than 90 days. Over 90% of patients had more than one readmission, and 110 patients (55%) had 5 or more. Patient-related predictors for readmission with AKI were age > 65, body mass index > 30 kg/m2, and hypertension. Factors related to the postoperative course were AKI with creatinine > 2 mg/dl, postoperative hemoglobin < 8 g/dl or blood transfusion, albumin < 20 g/dl, high output stoma and need for loperamide, and length of hospital stay > 20 days. Factors related to early versus late readmissions and multiple readmissions were also analyzed. CONCLUSIONS: Readmission with AKI following ileostomy formation is a consequential event with distinct risk factors. Acknowledging these risk factors is the foundation for designing interventions aiming to reduce frequency of AKI readmissions in predisposed patient populations.

Laparoscopic versus open liver resections for intrahepatic cholangiocarcinoma and gallbladder cancer: the Mayo clinic experience.

BACKGROUND: Data regarding laparoscopic liver resections(LLRs) for Gallbladder cancer(GBC) and Intrahepatic Cholangiocarcinoma(iCCA) are sparse. This study compared LLRs with open liver resections(OLRs) in a high-volume center. METHODS: Data of patients who underwent LLR or OLR for GBC or iCCA at Mayo-Clinic between 01/2016 and 04/2021 were retrospectively compared. Proportional hazards models were used to compare the approach on survival. RESULTS: 32 and 52 patients underwent LLR and OLR during the study period, respectively. 64 and 20 patients had iCCA and GBC, respectively. LLR had lower median blood loss (250 mL vs. 475 mL, p = 0.001) and shorter median length of stay compared to OLR (3.0 days vs. 6.0 days, p = 0.001). LLR and OLR did not differ in post-operative major complication (25% vs. 32.7%, p = 0.62), negative margin (100% vs. 90.4%, p = 0.15) and completeness of lymphadenectomy rates (36.8% vs. 45.5%, p = 0.59). The median number of harvested lymph node was 4.0 and 5.0 for LLR and OLR, respectively (p = 0.347). There were no associations between approach and 3-year overall and disease-free survival between LLR and OLR (49.8% vs. 63.2% and 39.6% vs. 21.5%, p = 0.66 and p = 0.69). DISCUSSION: With appropriate patient selection and when compared to OLRs, LLRs for GBC and iCCA are feasible, safe and offer potential short-term benefits without compromising on oncological resection principals and long-term outcomes.

Artificial intelligence for identification of focal lesions in intraoperative liver ultrasonography.

PURPOSE: Intraoperative ultrasonography (IOUS) of the liver is a crucial adjunct in every liver resection and may significantly impact intraoperative surgical decisions. However, IOUS is highly operator dependent and has a steep learning curve. We describe the design and assessment of an artificial intelligence (AI) system to identify focal liver lesions in IOUS. METHODS: IOUS images were collected during liver resections performed between November 2020 and November 2021. The images were labeled by radiologists and surgeons as normal liver tissue versus images that contain liver lesions. A convolutional neural network (CNN) was trained and tested to classify images based on the labeling. Algorithm performance was tested in terms of area under the curves (AUCs), accuracy, sensitivity, specificity, F1 score, positive predictive value, and negative predictive value. RESULTS: Overall, the dataset included 5043 IOUS images from 16 patients. Of these, 2576 were labeled as normal liver tissue and 2467 as containing focal liver lesions. Training and testing image sets were taken from different patients. Network performance area under the curve (AUC) was 80.2 ± 2.9%, and the overall classification accuracy was 74.6% ± 3.1%. For maximal sensitivity of 99%, the classification specificity is 36.4 ± 9.4%. CONCLUSIONS: This study provides for the first time a proof of concept for the use of AI in IOUS and show that high accuracy can be achieved. Further studies using high volume data are warranted to increase accuracy and differentiate between lesion types.

Surgical Treatment for Choledocholithiasis Following Repeated Failed Endoscopic Retrograde Cholangiopancreatography.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is the first line treatment for choledocholithiasis. In many occasions, several attempts of ERCP are performed until failure is declared and surgical treatment is applied, in many times following procedure-related complications. We present the results of surgical management of patients with choledocholithiasis following repeated failures of ERCP due to impaction of multiple large stones. METHODS: Patients that underwent surgical treatment for choledocholithiasis following repeated ERCP attempts between January 2006 and December 2018 were retrospectively assessed. Post-ERCP complications were evaluated and the surgical approach, technique, and outcomes were assessed. RESULTS: One hundred and two patients were operated on for choledocholithiasis following repeated failed ERCP. All the patients had at least 2 failed attempts (mean = 3.2 ± 1.7), and 25 (23.5%) suffered major ERCP-related complications. Following choledochotomy and stone extraction, bilioenteric anastomosis was done in the vast majority of patients (90.2%), most commonly choledochoduodenostomy (62%). Thirty-eight (37%) patients had minimally invasive procedure (laparoscopic n = 26, robotic assisted n = 12). Major post-operative complications (Clavien-Dindo ≥ 3) occurred in 24 patients (23.5%). Nine patients (8.8%) were re-operated and 10 (9.8%) were readmitted within 30 days from surgery. Three patients died within 30 days from surgery. Older patients had significantly more ERCP attempts and suffered higher post-operative mortality. During a median follow-up of 70 months, the only biliary complication was an anastomotic stricture in one patient. CONCLUSION: Surgery for CBDS after failure of ERCP is safe and provides a highly effective long-term solution.

Preoperative biopsy for suspected adenocarcinoma of the pancreatic head: yield and complications.

BACKGROUND: Histologic confirmation before pancreaticoduodenectomy (PD) for suspected pancreatic cancer is often performed. We assessed the yield of preoperative biopsy in these patients considering the associated complications. METHODS: We retrospectively evaluated 216 patients that underwent PD for suspected carcinoma (CA) between 2012 and 2018. Post procedure complications and delay in surgery were assessed, as well as the postoperative diagnosis in relation to preoperative parameters. RESULTS: Preoperative biopsy was performed in 142 patients (65.7%). Pathologic findings suggestive of CA were found in 106 (74.6%), while benign histology was found in 23 (16.1%), and non-diagnostic findings in 12 (8.4%). Seventy-four patients (34.3%) were operated without a preoperative biopsy. The time from diagnosis to surgery was significantly prolonged in those that underwent biopsy compared to patients that were taken straight to surgery (40±14 versus 18±15 days, P<0.001), and 18 patients (12.6%) suffered from clinically significant post procedure complications. Patients with a preoperative biopsy suggestive of CA, and those that were operated without a preoperative histologic confirmation had comparable rates of CA as a final pathological diagnosis (95.2% and 94.5%, respectively). Nevertheless, in patients with a benign or a non-diagnostic biopsy, the rates of pathologic diagnosis of CA were 69.6% and 73.6% respectively. Elevated levels of CA19-9 and a positive preoperative biopsy were associated with a final pathology of CA. CONCLUSIONS: Preoperative histology is not uniformly required in patients with suspected pancreatic cancer. If preoperative biopsy is performed, benign histology does not rule out cancer but warrants additional evaluation prior to surgery.

T Cells Retain Pivotal Antitumoral Functions under Tumor-Treating Electric Fields.

Tumor-treating fields (TTFields) are a localized, antitumoral therapy using alternating electric fields, which impair cell proliferation. Combining TTFields with tumor immunotherapy constitutes a rational approach; however, it is currently unknown whether TTFields' locoregional effects are compatible with T cell functionality. Healthy donor PBMCs and viably dissociated human glioblastoma samples were cultured under either standard or TTFields conditions. Select pivotal T cell functions were measured by multiparametric flow cytometry. Cytotoxicity was evaluated using a chimeric Ag receptor (CAR)-T-based assay. Glioblastoma patient samples were acquired before and after standard chemoradiation or standard chemoradiation + TTFields treatment and examined by immunohistochemistry and by RNA sequencing. TTFields reduced the viability of proliferating T cells, but had little or no effect on the viability of nonproliferating T cells. The functionality of T cells cultured under TTFields was retained: they exhibited similar IFN-γ secretion, cytotoxic degranulation, and PD1 upregulation as controls with similar polyfunctional patterns. Glioblastoma Ag-specific T cells exhibited unaltered viability and functionality under TTFields. CAR-T cells cultured under TTFields exhibited similar cytotoxicity as controls toward their CAR target. Transcriptomic analysis of patients' glioblastoma samples revealed a significant shift in the TTFields-treated versus the standard-treated samples, from a protumoral to an antitumoral immune signature. Immunohistochemistry of samples before and after TTFields treatment showed no reduction in T cell infiltration. T cells were found to retain key antitumoral functions under TTFields settings. Our data provide a mechanistic insight and a rationale for ongoing and future clinical trials that combine TTFields with immunotherapy.

Giant leiomyosarcoma of the inferior vena cava necessitating extended liver resection: A case report and review of the literature.

Leiomyosarcoma of the inferior vena cava (IVC) is a rare malignant tumour of smooth muscle origin. It commonly presents with non-specific symptoms including abdominal pain, distention, and lower extremity edema. Surgical resection with macroscopically clear margins is the only potential curative treatment for the disease. Here we present the case of a previously healthy 38-year-old woman with a subacute one-month increase of a four-year slowly progressive right sided abdominal pain and back pain. Imaging revealed a 14.5x12x15cm mass in the right hepatic lobe causing mass effect on adjacent abdominal and retroperitoneal organs, and involving the retrohepatic IVC. En-bloc resection of the right hemi-liver, most of segment four, the caudate lobe, and approximately a 10 cm section of the retrohepatic IVC, along with IVC reconstruction, was performed. Histologic examination revealed the diagnosis of a high grade leiomyosarcoma.

Postoperative Rise of Circulating Mitochondrial DNA Is Associated with Inflammatory Response in Patients following Pancreaticoduodenectomy.

INTRODUCTION: Accumulation of plasma mitochondrial DNA (mtDNA) following severe trauma has been shown to correlate with the development of systemic inflammatory response syndrome (SIRS) and may predict mortality. Our objective was to investigate the relationship between levels of circulatory mtDNA following pancreaticoduodenectomy (PD) and the postoperative course. METHODS: Levels of plasma mtDNA were assessed by real-time PCR of the mitochondrial genes ND1 and COX3 in 23 consecutive patients who underwent PD 1 day prior to surgery, within 8 h after surgery, and on postoperative day (POD)1 and POD5. The abundance of mtDNA was assessed relative to preoperative levels and in relation to parameters reflecting the postoperative clinical course. RESULTS: When pooled for all patients, the circulating mtDNA levels were significantly increased after surgery. However, while a significant (at least >2-fold and up to >20-fold) rise was noted in 11 patients, no change in mtDNA levels was noted in the other 12 following surgery. Postoperative rise in circulating mtDNA was associated with an increased rate of postoperative fever until day 5, decreased hemoglobin and albumin levels, and increased white blood cell counts. These patients also suffered from increased rates of delayed gastric emptying. No significant differences were demonstrated in other postoperative parameters. CONCLUSION: Circulating mtDNA surge is associated with an inflammatory response following PD and may potentially be used as an early marker for postoperative course. Studies of larger patient cohorts are warranted.

One Anastomosis Gastric Bypass as a Revisional Procedure After Failed Laparoscopic Adjustable Gastric Banding.

BACKGROUND: Recent data demonstrates that laparoscopic adjustable gastric banding (LAGB) is found to be associated with high rates of weight loss failure and long-term complications. Therefore, the search for the optimal revisional bariatric procedure is ongoing. OBJECTIVE: We aim to assess the safety and efficacy of converting a failed LAGB to laparoscopic one anastomosis gastric bypass (OAGB) as a revisional procedure. SETTING: Large, metropolitan, tertiary, university hospital. METHODS: Retrospective review of patients who underwent OAGB after LAGB.Demographics, comorbidities, BMI before and after the procedure, complications, and length of stay were documented. RESULTS: Fifty-seven patients underwent OAGB after LAGB. For 41 patients, the band was removed, and an OAGB was performed in a single procedure (71.9%), and 96.5% of the cases were completed laparoscopically. Postoperative complications occurred in 9 patients (15.7%), including one mortality. Average BMI decreased from 42.8 ± 7.0 to 31.3 ± 5.2 kg/m2 at least 1 year after surgery, representing a mean %EWL of 64.5%. There was no statistical difference in complication rates between the 1-stage and 2-stage approach. CONCLUSIONS: Conversion of a failed LAGB to OAGB is effective but carries higher complication rates. Randomized controlled studies comparing different procedures are necessary to further clarify the optimal revisional bariatric operation.

Palliative bypass surgery for patients with advanced pancreatic adenocarcinoma: experience from a tertiary center.

BACKGROUND: As advances in oncological treatment continue to prolong the survival of patients with non-resectable pancreatic ductal adenocarcinoma (PDAC), decision-making regarding palliative surgical bypass in patients with a heavy disease burden turns challenging. Here we present the results of a pancreatic surgery referral center. METHODS: Patients that underwent palliative gastrojejunostomy and/or hepaticojejunostomy for advanced, non-resectable PDAC between January 2010 and November 2018 were retrospectively assessed. All patients were taken to a purely palliative surgery with no curative intent. The postoperative course as well as short and long-term outcomes was evaluated in relation to preoperative parameters. RESULTS: Forty-two patients (19 females) underwent palliative bypass. Thirty-one underwent only gastrojejunostomy (22 laparoscopic) and 11 underwent both gastrojejunostomy and hepaticojejunostomy (all by an open approach). Although 34 patients (80.9%) were able to return temporarily to oral intake during the index admission, 15 (35.7%) suffered from a major postoperative complication. Seven patients (16.6%) died from surgery and another seven within the following month. Nine patients (21.4%) never left the hospital following the surgery. Mean length of hospital stay was 18 ± 17 days (range 3-88 days). Mean overall survival was 172.8 ± 179.2 and median survival was 94.5 days. Age, preoperative hypoalbuminemia, sarcopenia, and disseminated disease were associated with palliation failure, defined as inability to regain oral intake, leave the hospital, or early mortality. CONCLUSIONS: Although palliative gastrojejunostomy and hepaticojejunostomy may be beneficial for specific patients, severe postoperative morbidity and high mortality rates are still common. Patient selection remains crucial for achieving acceptable outcomes.

The transcriptional profile of circulating myeloid derived suppressor cells correlates with tumor development and progression in mouse.

Myeloid derived suppressor cells (MDSCs) play key roles in cancer development. Accumulation of peripheral-blood MDSCs (PB-MDSCs) corresponds to the progression of various cancers, but provides only a crude indicator. We aimed toward identifying changes in the transcriptional profile of PB-MDSCs in response to tumor growth. CT26 colon cancer cells and B16 melanoma cells (106) were inoculated into peritoneal cavities of BALB/c mice and subcutaneously to C57-black mice, respectively. The circulating levels and global transcriptional patterns of PB CD11b+Ly6g+ MDSCs were assessed in control mice, and 4, 8, and 11 days following tumor cell inoculation. Although a significant accumulation of PB-MDSCs was demonstrated only 11 days following tumor induction, a pronounced transcriptional response was identified already on day 4 while the tumor was ~1 mm in size. Further transcriptional changes correlated with different stages of tumor growth. Key MDSC genes and canonical signaling pathways were activated along tumor progression. This phenomenon was demonstrated in both cancer models, and a consensus set of 817 genes, involved in myeloid cell recruitment and angiogenesis, was identified. The data suggest that the transcriptional signatures of PB-MDSC may serve as markers for tumor progression, as well as providing potential targets for future therapies.

CD11b+Ly6G+ myeloid-derived suppressor cells promote liver regeneration in a murine model of major hepatectomy.

Liver regeneration depends on sequential activation of pathways and cells involving the remaining organ in recovery of mass. Proliferation of parenchyma is dependent on angiogenesis. Understanding liver regeneration-associated neovascularization may be useful for development of clinical interventions. Myeloid-derived suppressor cells (MDSCs) promote tumor angiogenesis and play a role in developmental processes that necessitate rapid vascularization. We therefore hypothesized that the MDSCs could play a role in liver regeneration. Following partial hepatectomy, MDSCs were enriched within regenerating livers, and their depletion led to increased liver injury and postoperative mortality, reduced liver weights, decreased hepatic vascularization, reduced hepatocyte hypertrophy and proliferation, and aberrant liver function. Gene expression profiling of regenerating liver-derived MDSCs demonstrated a large-scale transcriptional response involving key pathways related to angiogenesis. Functionally, enhanced reactive oxygen species production and angiogenic capacities of regenerating liver-derived MDSCs were confirmed. A comparative analysis revealed that the transcriptional response of MDSCs during liver regeneration resembled that of peripheral blood MDSCs during progression of abdominal tumors, suggesting a common MDSC gene expression profile promoting angiogenesis. In summary, our study shows that MDSCs contribute to early stages of liver regeneration possibly by exerting proangiogenic functions using a unique transcriptional program.-Nachmany, I., Bogoch, Y., Sivan, A., Amar, O., Bondar, E., Zohar, N., Yakubovsky, O., Fainaru, O., Klausner, J. M., Pencovich, N. CD11b+Ly6G+ myeloid-derived suppressor cells promote liver regeneration in a murine model of major hepatectomy.

Early reoperation following pancreaticoduodenectomy: impact on morbidity, mortality, and long-term survival.

BACKGROUND: Reoperation following PD is a surrogate marker for a complex post-operative course and may lead to devastating consequences. We evaluate the indications for early reoperation following PD and analyze its effect on short- and long-term outcome. METHODS: Four hundred and thirty-three patients that underwent PD between August 2006 and June 2016 were retrospectively analyzed. RESULTS: Forty-eight patients (11%; ROp group) underwent 60 reoperations within 60 days from PD. Forty-two patients underwent 1 reoperation, and 6 had up to 6 reoperations. The average time to first reoperation was 10.1 ± 13.4 days. The most common indications were anastomotic leaks (22 operations in 18 patients; 37.5% of ROp), followed by post-pancreatectomy hemorrhage (PPH) (14 reoperations in 12 patients; 25%), and wound complications in 10 (20.8%). Patients with cholangiocarcinoma had the highest reoperation rate (25%) followed by ductal adenocarcinoma (12.3%). Reoperation was associated with increased length of hospital stay and a high post-operative mortality of 18.7%, compared to 2.6% for the non-reoperated group. For those who survived the post-operative period, the overall and disease-free survival were not affected by reoperation. CONCLUSIONS: Early reoperations following PD carries a dramatically increased mortality rate, but has no impact on long-term survival.

Major liver resection in pregnancy: three cases with different etiologies and review of the literature.

BACKGROUND: Major liver resection during pregnancy is extremely rare. When required, the associated physiologic and anatomic changes pose specific challenges and greater risk for both mother and fetus Materials and methods: Three cases of major liver resection during pregnancy due to different etiologies are presented. The relevant literature is reviewed and discussed. RESULTS: We present three cases of major liver resection due to giant liver hemangioma with Kasabach-Merrit syndrome, giant hydatid cyst, and intrahepatic cholangiocarcinoma, at gestational week (GW) 17, 19, and 30, respectively. All patients had an uneventful postoperative course, continued the pregnancy and gave birth at GW 38. CONCLUSION: Major liver resection can be performed safely during pregnancy. A multidisciplinary team of surgeons, anesthesiologists and gynecologists, in a highly experienced tertiary hepatobiliary center, should be involved.

Progesterone treatment enhances the expansion of placental immature myeloid cells in a mouse model of premature labor.

INTRODUCTION: immature-myeloid cells (IMCs) are proangiogenic bone marrow (BM)-derived cells that normally differentiate into inflammatory cells such as neutrophils, monocytes and dendritic cells (DCs). We characterized placental IMCs comparing their gene expression and subpopulations to tumor IMCs, and tested our hypothesis that progesterone that inhibits preterm labor, may affect their abundance and differentiation. METHODS: differences between IMC-subpopulations in subcutaneous tumors versus placentas in C57BL/6 or ICR (CD-1) mice were analyzed by flow cytometry and gene expression was detected by microarrays. BM- and placental cells were incubated with or without progesterone and IMC subpopulations were analyzed. For preterm labor induction pregnant mice pretreated or not with progesterone were or were not treated with Lipopolysaccharide (LPS). RESULTS: we detected enrichment of granulocytic-IMCs in placentas compared to tumors, paralleled by a decrease in monocytic-IMCs. mRNA expression of placenta- versus tumor IMCs revealed profound transcriptional alterations. Progesterone treated BM-CD11b+ cells ex-vivo induced enrichment of granulocytic-IMCs and a decrease in monocytic-IMCs and DCs. LPS treatment in-vivo led to an increase in BM-IMCs in both progesterone pretreated or non-pretreated mice. In the placenta LPS decreased the IMC population while progesterone led to complete abrogation of this effect. DISCUSSION: placental IMCs differ from tumor-IMCs in both subpopulations and gene expression. Progesterone enhances the proliferation of placenta-specific granulocytic IMCs ex-vivo and LPS induced labor is accompanied by a decrease in placental IMCs only in progesterone non-pretreated mice. We thus speculate that the protective effect of progesterone in preventing preterm labor may be explained at least in part by this specific anti-inflammatory effect.