Impact of fluorescent thoracic duct lymphography via intranodal approach in minimal access esophageal cancer surgery.

PURPOSE: Chyle leak resulting from thoracic duct (TD) injury poses significant morbidity and mortality challenges. We assessed the feasibility of using near-infrared (NIR) indocyanine green (ICG) imaging for intraoperative fluorescence TD lymphography during minimal access esophagectomy (MAE) in a semiprone position with inguinal nodal injection of ICG dye. METHODS: Ninety-nine patients with esophageal or gastroesophageal junctional cancer undergoing MAE received inguinal node injections of 2.5 mg ICG dye (total 5 mg) under sonographic guidance during anesthesia induction. Stryker's 1688 AIM HD system was used in 76 cases, Karl Storz OPAL 1 S in 20, and in three cases the Karl Storz Rubina. RESULTS: In 93 patients (94%), the TD was clearly delineated along its entire length; it was not visualized in 6 patients (6%). Fluorescence guidance facilitated TD ligation in 16 cases, while 3 cases required clipping of duct tributaries for oncological considerations. Twenty-eight patients exhibited minor duct variations. Fluorescence was sustained throughout surgery (median observation time 60 min post-injection; range 30-330). No patient experienced any chyle leak within 30 days post-surgery and no adverse reactions to ICG was evident. CONCLUSIONS: Intraoperative fluorescence TD lymphography using ICG during MAE in a semiprone position with inguinal nodal injection proved safe, feasible, and effective, allowing clear visualization of the TD in almost all cases. This approach aids safe ligation and reduces chyle leak risk. It offers real-time imaging of TD anatomy and variations, providing valuable feedback to surgeons for managing TD injuries during MAE procedures and represents an excellent educational tool.

Current standards of surgical management of gastric cancer: an appraisal.

PURPOSE: Gastric cancer (GC) is the fifth most common malignancy worldwide and portends a grim prognosis due to a lack of appreciable improvement in 5-year survival. We aimed to analyze the available literature and summarize the current standards of surgical care for curative and palliative intent treatment of GC. METHODS: We conducted a systematic search on the PubMed database for studies on the management of GC. RESULTS: Endoscopic resection is an acceptable treatment option for T1a tumors. The role of optimal resection margin for GC remains unclear. D2 lymph node dissection remains the standard of care with splenectomy needed selectively for splenic hilum involvement. A distal pancreatic resection should be avoided. The advantage of bursectomy and omentectomy in GC surgery is not clear. Multi-visceral resection may be considered for locally advanced GC in carefully selected patients. Minimally invasive approaches are non-inferior to open surgery. Surgery should be abandoned prior even in metastatic GC within the frame of multimodal therapy approach. CONCLUSION: Various trials have conclusively shown improved patient outcomes when well-established surgical standards are followed.

Postpancreatectomy Acute Pancreatitis (PPAP): Definition and Grading From the International Study Group for Pancreatic Surgery (ISGPS).

OBJECTIVE: The ISGPS aimed to develop a universally accepted definition for PPAP for standardized reporting and outcome comparison. BACKGROUND: PPAP is an increasingly recognized complication after partial pancreatic resections, but its incidence and clinical impact, and even its existence are variable because an internationally accepted consensus definition and grading system are lacking. METHODS: The ISGPS developed a consensus definition and grading of PPAP with its members after an evidence review and after a series of discussions and multiple revisions from April 2020 to May 2021. RESULTS: We defined PPAP as an acute inflammatory condition of the pancreatic remnant beginning within the first 3 postoperative days after a partial pancreatic resection. The diagnosis requires (1) a sustained postoperative serum hyperamylasemia (POH) greater than the institutional upper limit of normal for at least the first 48 hours postoperatively, (2) associated with clinically relevant features, and (3) radiologic alterations consistent with PPAP. Three different PPAP grades were defined based on the clinical impact: (1) grade postoperative hyperamylasemia, biochemical changes only; (2) grade B, mild or moderate complications; and (3) grade C, severe life-threatening complications. DISCUSSIONS: The present definition and grading scale of PPAP, based on biochemical, radiologic, and clinical criteria, are instrumental for a better understanding of PPAP and the spectrum of postoperative complications related to this emerging entity. The current terminology will serve as a reference point for standard assessment and lend itself to developing specific treatments and prevention strategies.

Management and follow-up of gallbladder polyps: updated joint guidelines between the ESGAR, EAES, EFISDS and ESGE.

MAIN RECOMMENDATIONS: 1. Primary investigation of polypoid lesions of the gallbladder should be with abdominal ultrasound. Routine use of other imaging modalities is not recommended presently, but further research is needed. In centres with appropriate expertise and resources, alternative imaging modalities (such as contrast-enhanced and endoscopic ultrasound) may be useful to aid decision-making in difficult cases. Strong recommendation, low-moderate quality evidence. 2. Cholecystectomy is recommended in patients with polypoid lesions of the gallbladder measuring 10 mm or more, providing the patient is fit for, and accepts, surgery. Multidisciplinary discussion may be employed to assess perceived individual risk of malignancy. Strong recommendation, low-quality evidence. 3. Cholecystectomy is suggested for patients with a polypoid lesion and symptoms potentially attributable to the gallbladder if no alternative cause for the patient's symptoms is demonstrated and the patient is fit for, and accepts, surgery. The patient should be counselled regarding the benefit of cholecystectomy versus the risk of persistent symptoms. Strong recommendation, low-quality evidence. 4. If the patient has a 6-9 mm polypoid lesion of the gallbladder and one or more risk factors for malignancy, cholecystectomy is recommended if the patient is fit for, and accepts, surgery. These risk factors are as follows: age more than 60 years, history of primary sclerosing cholangitis (PSC), Asian ethnicity, sessile polypoid lesion (including focal gallbladder wall thickening > 4 mm). Strong recommendation, low-moderate quality evidence. 5. If the patient has either no risk factors for malignancy and a gallbladder polypoid lesion of 6-9 mm, or risk factors for malignancy and a gallbladder polypoid lesion 5 mm or less, follow-up ultrasound of the gallbladder is recommended at 6 months, 1 year and 2 years. Follow-up should be discontinued after 2 years in the absence of growth. Moderate strength recommendation, moderate-quality evidence. 6. If the patient has no risk factors for malignancy, and a gallbladder polypoid lesion of 5 mm or less, follow-up is not required. Strong recommendation, moderate-quality evidence. 7. If during follow-up the gallbladder polypoid lesion grows to 10 mm, then cholecystectomy is advised. If the polypoid lesion grows by 2 mm or more within the 2-year follow-up period, then the current size of the polypoid lesion should be considered along with patient risk factors. Multidisciplinary discussion may be employed to decide whether continuation of monitoring, or cholecystectomy, is necessary. Moderate strength recommendation, moderate-quality evidence. 8. If during follow-up the gallbladder polypoid lesion disappears, then monitoring can be discontinued. Strong recommendation, moderate-quality evidence. SOURCE AND SCOPE: These guidelines are an update of the 2017 recommendations developed between the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), European Association for Endoscopic Surgery and other Interventional Techniques (EAES), International Society of Digestive Surgery-European Federation (EFISDS) and European Society of Gastrointestinal Endoscopy (ESGE). A targeted literature search was performed to discover recent evidence concerning the management and follow-up of gallbladder polyps. The changes within these updated guidelines were formulated after consideration of the latest evidence by a group of international experts. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. KEY POINT: • These recommendations update the 2017 European guidelines regarding the management and follow-up of gallbladder polyps.

Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study.

Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score ("teloscore", which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35-1.76; p = 1.54 × 10-10 ) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73-0.88; p = 1.87 × 10-6 , ptrend = 3.27 × 10-7 ). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98 × 10-9 for highest vs. lowest quintile; p = 1.82 × 10-10 as a continuous variable). In conclusion, we present a novel genome-wide candidate SNP for PDAC risk (TERT-rs2736100), a completely new signal (NAF1-rs7675998) approaching genome-wide significance and we report a strong association between the teloscore and risk of pancreatic cancer, suggesting that telomeres are a potential risk factor for pancreatic cancer.

Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation.

Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (ORhomozygous = 1.19, 95% CI 1.02-1.38, p = 0.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1-PRSS2-rs10273639 (ORheterozygous = 0.51, 95% CI 0.39-0.67, p = 1.10 × 10-6 ) and MORC4-rs 12837024 (ORhomozygous = 2.07 (1.55-2.77, ptrend = 0.7 × 10-11 ). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639, rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants.

Hamburg-Glasgow classification: preoperative staging by combination of disseminated tumour load and systemic inflammation in oesophageal carcinoma.

BACKGROUND: The aim of this study was to establish a new preoperative staging classification and evaluate its comparability to the post-operative tumour stage, lymph node invasion and metastasis (TNM) classification. To date, adequate, preoperative staging in patients with oesophageal carcinoma (EC) is still missing but urgently needed. Systemic inflammation and disseminated tumour load have a pivotal role in recurrence and oncological outcome. To improve the clinical staging, we merged the Glasgow Prognostic Score (GPS) and disseminated tumour cells (DTC) into a new sufficient preoperative staging classification, the Hamburg-Glasgow classification (HGC). METHODS: In this prospective, single-centre study, 326 patients following curative oesophagectomy were included. From all patients preoperative bone marrow was aspirated from the iliac crest to detect DTCs by immunostaining with the pan-keratin antibody A45-B/B3. HGC was subdefined into four prognostic groups on the basis of C-reactive protein (CRP), albumin and DTC. The three prognostic groups of the GPS were supplemented by DTC detection status. Results were correlated with clinicopathological parameters and clinical outcome. RESULTS: Increasing HGC significantly correlated with lymph node invasion (P=0.022), post-operative pathohistological TNM staging (P=0.001) and tumour recurrence (P=0.001). The four HGC prognostic groups displayed a gradual decrease in overall as well as disease-free survival (P<0.001, each). Hamburg-Glasgow classification was a strong, significant independent predictor of overall survival and disease-free survival (P<0.001, both) in multivariate analysis. CONCLUSIONS: Hamburg-Glasgow classification seems to be a promising preoperative additive staging classification for accurate and simple outcome stratification.

HSP90 is a promising target in gemcitabine and 5-fluorouracil resistant pancreatic cancer.

Chemotherapy (CT) options in pancreatic cancer (PC) are limited to gemcitabine and 5-fluorouracil (5-FU). Several identified molecular targets in PC represent client proteins of HSP90. HSP90 is a promising target since it interferes with many oncogenic signaling pathways simultaneously. The aim of this study was to evaluate the efficacy of different HSP90 inhibitors in gemcitabine and 5-FU resistant PC. PC cell lines 5061, 5072 and 5156 were isolated and brought in to culture from patients being operated at our institution. L3.6pl cell line served as a control. Anti-proliferative efficacy of three different HSP90 inhibitors (17-AAG, 17-DMAG and 17-AEPGA) was evaluated by the MTT assay. Alterations in signaling pathway effectors and apoptosis upon HSP90 inhibition were determined by western blot analysis and annexin V/PI staining. The cell lines 5061, 5072 and 5156 were resistant to gemcitabine and 5-FU. In contrast 17-AAG and the water-soluble derivates 17-DMAG and 17-AEPGA displayed high anti-proliferative activity in all tested cell lines. The calculated IC50 was below 1 µM. Highly significant down regulation of epidermal-growth-factor-receptor, insulin-like-growth-factor-receptor-1, AKT and MAPK reflected the intracellular molecular signaling-network disruption. Furthermore, besides HSP70 also HSP27 was upregulated in all cell lines. Apoptosis occurred early under HSP90 inhibition and was determined by annexin V/PI staining and CASPASE-3 and PARP assay. In contrast, gemcitabine treated cells did not show any apoptosis. HSP90 inhibition disrupts multiple signaling cascades in gemcitabine and 5-FU resistant PC simultaneously and promotes cancer cell apoptosis. Watersoluble 17-DMAG is equally effective as 17-AAG. HSP27, besides HSP70, may represent an effective response marker of successful HSP90 inhibition.

Prognostic Significant or Not? The Positive Circumferential Resection Margin in Esophageal Cancer: Impact on Local Recurrence and Overall Survival in Patients Without Neoadjuvant Treatment.

OBJECTIVE: The aim of this study is to investigate the impact of the circumferential resection margin (CRM) in esophageal cancer on survival and recurrence in patients without pretreatment. BACKGROUND: Whereas the infiltration of the proximal or distal resection margin is associated with poor survival and higher recurrence, studies looking at the role of the circumferential resection margin on survival and local recurrence after esophagectomy are conflicting. METHODS: Influence of CRM infiltration according to the College of American Pathologists (CAP) and Royal College of Pathologists (RCP) on long-term survival of 180 patients with resected pT3 tumors and without neoadjuvant therapy was analyzed. RESULTS: A positive CRM was found in 76 (42.4%) patients according to RCP and 44 (24.4%) patients according to CAP. The CRM status had neither according to CAP nor according to RCP a significant impact on overall survival (P = 0.317 and 0.655, respectively), local recurrence (P = 0.716 and 0.900, respectively), or distant tumor relapse (P = 0.303 and 0.471, respectively).Lymphatic tumor spread found in 129 (71.7%) patients was an independent prognosticator (P = 0.002). In 137 (76.1%) patients who had a transthoracic esophagectomy a CRM infiltration was significantly lower according to CAP compared with 43 (23.9%) patients who had a transhiatal esophagectomy (P = 0.026). CONCLUSIONS: CRM was found to have no impact on survival and recurrence in esophageal cancer. Therefore, the possible impact of neoadjuvant pretreatment in locally advanced tumors should be considered with caution in terms of an improved resectability.

Management and follow-up of gallbladder polyps : Joint guidelines between the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), European Association for Endoscopic Surgery and other Interventional Techniques (EAES), International Society of Digestive Surgery - European Federation (EFISDS) and European Society of Gastrointestinal Endoscopy (ESGE).

OBJECTIVES: The management of incidentally detected gallbladder polyps on radiological examinations is contentious. The incidental radiological finding of a gallbladder polyp can therefore be problematic for the radiologist and the clinician who referred the patient for the radiological examination. To address this a joint guideline was created by the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), European Association for Endoscopic Surgery and other Interventional Techniques (EAES), International Society of Digestive Surgery - European Federation (EFISDS) and European Society of Gastrointestinal Endoscopy (ESGE). METHODS: A targeted literature search was performed and consensus guidelines were created using a series of Delphi questionnaires and a seven-point Likert scale. RESULTS: A total of three Delphi rounds were performed. Consensus regarding which patients should have cholecystectomy, which patients should have ultrasound follow-up and the nature and duration of that follow-up was established. The full recommendations as well as a summary algorithm are provided. CONCLUSIONS: These expert consensus recommendations can be used as guidance when a gallbladder polyp is encountered in clinical practice. KEY POINTS: • Management of gallbladder polyps is contentious • Cholecystectomy is recommended for gallbladder polyps >10 mm • Management of polyps <10 mm depends on patient and polyp characteristics • Further research is required to determine optimal management of gallbladder polyps.

Allogenic Blood Transfusion is Associated with Poor Perioperative and Long-Term Outcome in Esophageal Cancer.

BACKGROUND: Esophageal resection for cancer (EC) is still associated with considerable mortality and morbidity rates. Allogenic blood transfusion (aBT) is associated with poor short-term and long-term outcome in surgical oncology. We aimed to evaluate the effect of aBT in a homogeneous population of EC patients undergoing esophagectomy without perioperative treatment. METHODS: We analyzed 565 esophagectomies performed due to EC. Allogenic blood transfusion was correlated to clinicopathological parameters, perioperative mortality and morbidity as well as the long-term outcome. Results are presented as adjusted odds ratio (OR) or hazard ratio (HR) with 95 % confidence interval (95 % CI). RESULTS: Patients receiving aBT (aBT(+)) had no higher tumor stages or higher rates of lymph node metastasis (P = 0.65 and 0.17, respectively) compared to patients without aBT (aBT(-)). Allogenic blood transfusion was strongly associated with perioperative morbidity (OR 1.9, 95 % CI 1.1-3.5, P = 0.02) and mortality (OR 2.9, 95 % CI 1.0-8.6, P = 0.04). Tumor recurrence rate was significantly higher in aBT(+) patients (P = 0.001). The disease-free and overall survival were significantly longer in aBT(-) compared to aBT(+) patients (P = 0.016 and <0.001, respectively). Patients receiving aBT had almost doubled risk for tumor recurrence (HR 1.8, 95 % CI 1.2-2.5, P = 0.001) and death (HR 2.2, 95 % CI 1.5-3.2, P < 0.001). CONCLUSION: Allogenic blood transfusion has a significant impact on the natural course of EC after complete resection. The poor short-term and long-term outcome warrants further evaluation of the underlying molecular mechanisms induced by allogenic blood transfusion in cancer patients.

How we do it: double in situ split for staged mesohepatectomy in patients with advanced gall bladder cancer and marginal future liver remnant.

PURPOSE: Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) has increased the rate of liver resections in patients with marginal future liver remnant. We here describe a modified ALPPS procedure with splitting-off the central liver segments for staged mesohepatectomy in patients with advanced gall bladder cancer. METHODS: A double in situ split for ALPPS (DALPPS) is performed with splitting-off the central liver segments (segments 1, 4, 5, and 8). This induces a rapid hypertrophy of the left lateral (segments 2/3) and right posterior sectors (segments 6/7). An intrahepatic right posterior approach during splitting-off the right posterior sector is introduced as a part of this new procedure. This approach facilitates the dissection and ligation of the right anterior branch of the portal vein (segments 5 and 8) while the liver hilum remains untouched during the first step of surgery. RESULTS: Two patients with advanced gall bladder cancer were treated with the DALPPS procedure till date. After a short interval (7-9 days), a rapid hypertrophy of the left lateral and right posterior sector was observed (hypertrophy up to 72.6 and 54.6 %, respectively). A staged mesohepatectomy including caudate lobectomy and resection of the extrahepatic bile duct was then performed safely. There was no surgical-technical morbidity. No signs of posthepatectomy liver failure according to the 50-50 criteria were seen. However, one patient died from severe ARDS attributed to the preoperative chemotherapy. Nevertheless, this complication is deemed to be surgery related. CONCLUSIONS: The DALPPS procedure is a new surgical technique for staged mesohepatectomy for patients with small future liver remnant in size or in function. However, appropriate patient selection is mandatory to avoid morbidity and mortality.

Circulating Tumor Cells as a Biomarker for Preoperative Prognostic Staging in Patients With Esophageal Cancer.

OBJECTIVE: We evaluated the prognostic significance of circulating tumor cells (CTCs) in patients with esophageal cancer (EC). BACKGROUND: Despite the availability of several preoperative diagnostic techniques, accurate pretreatment staging of EC remains challenging. METHODS: In this single-center, prospective study, peripheral blood samples for CTC analyses were obtained preoperatively from 100 patients who were judged to have resectable EC. CTC detection was performed using the CellSearch System. Data were correlated with clinicopathological parameters and patient outcomes. RESULTS: CTCs were detected in 18% (18/100) of all eligible patients. Patients with CTCs showed significantly shorter relapse-free (P < 0.001) and overall survival (P < 0.001) than CTC-negative patients. Even in patients with lymph node invasion and without distant metastases (pN+, M0, N = 45), CTC detection indicated significantly worse relapse-free (P < 0.001) and overall survival (P = 0.007). Multivariate analyses of eligible patients identified CTCs as a strong, independent, prognostic indicator of tumor recurrence (hazard ratio, 5.063; 95% confidence interval, 2.233-11.480; P < 0.001) and overall survival (hazard ratio, 3.128; 95% confidence interval, 1.492-6.559; P = 0.003). CONCLUSIONS: This is the first study to report that CTCs detected by an automated immunomagnetic detection system are independent, prognostic indicators of patients' outcome in EC. Thus, implementation of CTCs may improve accuracy of preoperative staging in EC.

Resection margin clearance in pancreatic cancer after implementation of the Leeds Pathology Protocol (LEEPP): clinically relevant or just academic?

BACKGROUND AND OBJECTIVES: The aim of this study was to assess the overall survival (OS) after R0/R1 resections in patients with pancreatic ductal adenocarcinoma (PDAC) of the pancreatic head after implementation of a standardized histopathologic protocol (Leeds Pathology Protocol, LEEPP). METHODS: One hundred and twenty-five patients underwent surgical resection because of PDAC of the pancreatic head. Patients were histopathologically examined according to a standardized protocol. Their oncologic outcome and clinicopathologic data were compared with those of a patient group before implementation of the LEEPP (n = 116). RESULTS: The R1 rate increased significantly from 13 to 52 %. There was no significant difference in OS between R0 and R1 resections. The median OS in patients with a tumor clearance of less than 2 mm from the resection margin was 15.1 months (12.1-18.1 months) versus 22.2 months (7.8-36.7 months) (P = 0.046). Multivariate analysis revealed a margin clearance or 2 mm and more as an independent prognosticator for OS. CONCLUSIONS: With applying the LEEPP, there was still no significant correlation between the R-status and OS in patients with PDAC. However, since a margin clearance of 2 mm or more is a predictive factor for OS, the R1 definition might have to be adapted in PDAC.

Preoperative Pancreatic Resection (PREPARE) score: a prospective multicenter-based morbidity risk score.

OBJECTIVES: Development of a simple preoperative risk score to predict morbidity related to pancreatic surgery. BACKGROUND: Pancreatic surgery is standardized with little technical diversity among institutions and unchanging morbidity and mortality rates in recent years. Preoperative identification of high-risk patients is potentially one of the rare avenues for improving the clinical course of patients undergoing pancreatic surgery. METHODS: Using a prospectively collected multicenter database of patients undergoing pancreatic surgery (n=703), surgical complications were classified according to the Clavien-Dindo classification. A new scoring system for preoperative identification of high-risk patients that included only objective preoperatively assessable variables was developed using a multivariate regression model. Subsequently, this scoring system was prospectively validated from 2011 to 2013 (n=429) in a multicenter setting. RESULTS: Eight independent preoperatively assessable variables were identified and included in the scoring system: systolic blood pressure, heart rate, hemoglobin level, albumin level, ASA (American Society of Anesthesiologists) score, surgical procedure, elective surgery or not, and disease of pancreatic origin or not. On the basis of 3 subgroups (low risk, intermediate risk, high risk), the proposed scoring system reached an accuracy of 75% for correctly predicting occurrence or nonoccurrence of major surgical complications in 80% of all analyzed patients within the validation cohort (c-statistic index=0.709, P<0.001, 95% confidence interval=0.657-0.760). CONCLUSIONS: We present an easily applied scoring system with convincing accuracy for identifying low-risk and high-risk patients. In contrast to other systems, the score is exclusively based on objective preoperatively assessable characteristics and can be rapidly and easily calculated.

An A/C germline single-nucleotide polymorphism in the TNFAIP3 gene is associated with advanced disease stage and survival in only surgically treated esophageal cancer.

Prognostication of disease relapse and survival is essential for cancer patients and genetic variations in cancer patients may serve as important indicators. A single-nucleotide polymorphism (SNP) mapping to the tumor necrosis factor, alpha-induced protein 3 (TNFAIP3) gene at position 138241110 displays three genotypes (AA, AC and CC). The aim of this study was to evaluate the potential prognostic value of the TNFAIP3-SNP in esophageal cancer (EC). Genomic DNA was extracted from peripheral blood leukocytes of 173 patients who underwent complete surgical resection for EC and did not receive any neoadjuvant or adjuvant therapy. For SNP detection, a 260- bp fragment was PCR amplified, purified and sequenced with tested primers. The product was analyzed by automatic DNA sequencer.The TNFAIP3 genotypes were correlated with clinico-pathological parameters, tumor cell dissemination in bone marrow and clinical outcome. The C-allele carrier presented with higher disease stage (P<0.001). This was predominantly because of the presence of lymph node metastasis (P<0.001). The recurrence rate was higher in C-allele carriers (AC and CC genotype; P=0.004). Kaplan-Meier plots for disease-free (P=0.017) and overall survival (P<0.001) displayed a gene dosage-associated outcome with AA genotype patients presenting the longest and CC genotype patients the poorest survival. In disease stage-adjusted multivariate analysis the TNFAIP3-SNP was identified as an independent prognostic factor for survival (hazard ratio 1.9; P=0.008). The TNFAIP3-SNP allows risk stratification of EC patients and may be a useful tool to identify patients eligible for multimodal therapy concepts.

Single versus double Roux-en-Y reconstruction techniques in pancreaticoduodenectomy: a comparative single-center study.

BACKGROUND: The aim of this study was to analyze the impact of single Roux-en-Y reconstruction (RYR) and double Roux-en-Y reconstruction (dRYR) on intraoperative outcome and postoperative morbidity and mortality after pancreaticoduodenectomy (PD) or pylorus-preserving pancreaticoduodenectomy (PPPD). METHODS: All patients who underwent surgery between 2000 and 2005 for dRYR and RYR after PD or PPPD at the study hospital were evaluated for inclusion. Comparison of categorical patient characteristics was performed using the χ (2) test. Data were reported as median and range. Differences were analyzed with the Mann-Whitney U test. Postoperative complications were graded according to the Clavien-Dindo classification scheme and the recommendations of the International Study Group of Pancreatic Surgery (ISGPS). RESULTS: A total of 319 patients were included in final analysis. The median time of surgery was significantly shorter when performing a single Roux-en-Y loop reconstruction (55 min in PD and 50 min in PPPD) (p < 0.001). Saved time had a significant effect on the cost of surgery (p < 0.001). No impact on postoperative outcome according to the Clavien-Dindo classification, the ISGPS definitions of pancreatic fistulas, and delayed gastric emptying was evident. The relaparotomy rate due to severe postoperative hemorrhage was significantly higher in the dRYR PD cohort (2.2 vs. 11.9 %, p < 0.001). CONCLUSIONS: Double Roux-en-Y reconstruction of the alimentary tract is not beneficial in terms of surgical outcome and postoperative morbidity and mortality and should be avoided due to unnecessarily prolonged surgery.

Bioengineered Organoids Offer New Possibilities for Liver Cancer Studies: A Review of Key Milestones and Challenges.

Hepatic cancer is widely regarded as the leading cause of cancer-related mortality worldwide. Despite recent advances in treatment options, the prognosis of liver cancer remains poor. Therefore, there is an urgent need to develop more representative in vitro models of liver cancer for pathophysiology and drug screening studies. Fortunately, an exciting new development for generating liver models in recent years has been the advent of organoid technology. Organoid models hold huge potential as an in vitro research tool because they can recapitulate the spatial architecture of primary liver cancers and maintain the molecular and functional variations of the native tissue counterparts during long-term culture in vitro. This review provides a comprehensive overview and discussion of the establishment and application of liver organoid models in vitro. Bioengineering strategies used to construct organoid models are also discussed. In addition, the clinical potential and other relevant applications of liver organoid models in different functional states are explored. In the end, this review discusses current limitations and future prospects to encourage further development.

Heat shock protein 90 (HSP90) inhibitors in gastrointestinal cancer: where do we currently stand?-A systematic review.

PURPOSE: Dysregulated expression of heat shock proteins (HSP) plays a fundamental role in tumor development and progression. Consequently, HSP90 may be an effective tumor target in oncology, including the treatment of gastrointestinal cancers. METHODS: We carried out a systematic review of data extracted from clinicaltrials.gov and pubmed.gov, which included all studies available until January 1st, 2022. The published data was evaluated using primary and secondary endpoints, particularly with focus on overall survival, progression-free survival, and rate of stable disease. RESULTS: Twenty trials used HSP90 inhibitors in GI cancers, ranging from phase I to III clinical trials. Most studies assessed HSP90 inhibitors as a second line treatment. Seventeen of the 20 studies were performed prior to 2015 and only few studies have results pending. Several studies were terminated prematurely, due to insufficient efficacy or toxicity. Thus far, the data suggests that HSP90 inhibitor NVP-AUY922 might improve outcome for colorectal cancer and gastrointestinal stromal tumors. CONCLUSION: It currently remains unclear which subgroup of patients might benefit from HSP90 inhibitors and at what time point these inhibitors may be beneficial. There are only few new or ongoing studies initiated during the last decade.

Disseminated tumor cells in pancreatic cancer-an independent prognosticator of disease progression and survival.

Pancreatic cancer is one of the most devastating cancers with a 6-month median survival and a 5-year survival rate of 3-5%. Still important aspects of its aggressive biology remain elusive and advanced therapeutic regimens have not been substantially successful. We investigated the prognostic role of disseminated tumor cells (DTC) in bone marrow, a reservoir for early DTC potentially contributing to metastatic progression, of pancreatic cancer patients. After exclusion of patients with different postsurgery diagnosis or missing DTC status (n = 40) a total of 175 patients remained for final analyses. One-hundred and nineteen patients were male and 96 female with a median age of 67 years, 96 patients underwent complete resection. Bone marrow aspirates taken at primary surgery were analyzed for DTC by an immunocytochemical cytokeratin assay and correlated to survival data. Overall 13.7% of patient samples (24/175) harbored DTC in their bone marrow. Histopathological parameters did not correlate significantly. Univariate survival analysis revealed a borderline significant correlation between DTC and decreased progression-free survival (p = 0.069), and was significant for overall survival (p = 0.036). Regarding patients with resected tumors, the respective p-values were 0.058 for progression-free and 0.016 for overall survival. Importantly, the prognostic influence was independent from other risk factors as shown by multivariate analyses for progression-free (p = 0.030, HR: 2.057; CI (95%): 1.073-3.943) and overall survival (p = 0.006, HR: 2.283; CI (95%): 1.260-4.135). The presence of DTC in bone marrow is a strong and independent prognostic factor of survival in patients with pancreatic cancer. Thus, bone-targeting may be a new future therapeutic option for DTC-positive patients.