Treatment of Locally Advanced Rectal Cancer in the Era of Total Neoadjuvant Therapy: A Systematic Review and Network Meta-Analysis.

Importance: Treatment of locally advanced rectal cancer (LARC) involves neoadjuvant chemoradiotherapy plus total mesorectal excision and adjuvant chemotherapy. However, total neoadjuvant therapy (TNT) protocols (ie, preoperative chemotherapy in addition to radiotherapy) may allow better adherence and early treatment of distant micrometastases and may increase pathological complete response (pCR) rates. Objective: To assess the efficacy and tolerability of TNT protocols for LARC. Data Sources: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science Core Collection electronic databases and ClinicalTrials.gov for unpublished studies were searched from inception to March 2, 2024. Study Selection: Randomized clinical trials including adults with LARC who underwent rectal resection as a final treatment were included. Studies including nonoperative treatment (watch-and-wait strategy), treatments other than rectal resection, immunotherapy, or antiangiogenic agents were excluded. Among the initially identified studies, 2.9% met the selection criteria. Data Extraction and Synthesis: Two authors independently screened the records and extracted data. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-compliant pairwise and network meta-analyses with a random-effects model were performed in a frequentist framework, and the certainty of evidence was assessed according to the confidence in network meta-analysis approach. Main Outcomes and Measures: The primary outcome was pCR, defined as the absence of residual tumor at pathological assessment after surgery. Secondary outcomes included tolerability, toxic effects, perioperative outcomes, and long-term survival. Results: Of 925 records identified, 27 randomized clinical trials, including 13 413 adults aged 18 years or older (median age, 60.0 years [range, 42.0-63.5 years]; 67.2% male) contributed to the primary network meta-analysis. With regard to pCR, long-course chemoradiotherapy (L-CRT) plus consolidation chemotherapy (relative risk [RR], 1.96; 95% CI, 1.25-3.06), short-course radiotherapy (S-RT) plus consolidation chemotherapy (RR, 1.76; 95% CI, 1.34-2.30), and induction chemotherapy plus L-CRT (RR, 1.57; 95% CI, 1.09-2.25) outperformed standard L-CRT with single-agent fluoropyrimidine-based chemotherapy. Considering 3-year disease-free survival, S-RT plus consolidation chemotherapy (RR, 1.08; 95% CI, 1.01-1.14) and induction chemotherapy plus L-CRT (RR, 1.12; 95% CI, 1.01-1.24) outperformed L-CRT, in spite of an increased 5-year locoregional recurrence rate of S-RT plus consolidation chemotherapy (RR, 1.65; 95% CI, 1.03-2.63). Conclusions and Relevance: In this systematic review and network meta-analysis, 3 TNT protocols were identified to outperform the current standard of care in terms of pCR rates, with good tolerability and optimal postoperative outcomes, suggesting they should be recognized as first-line treatments.

The pan - COVID - AGICT study. The impact of COVID-19 pandemic on surgically treated pancreatic cancer patients. A multicentric Italian study.

BACKGROUND: In this article we aimed to perform a subgroup analysis using data from the COVID-AGICT study, to investigate the perioperative outcomes of patients undergoing surgery for pancreatic cancers (PC) during the COVID-19 pandemic. METHODS: The primary endpoint of the study was to find out any difference in the tumoral stage of surgically treated PC patients between 2019 and 2020. Surgical and oncological outcomes of the entire cohort of patients were also appraised dividing the entire peri-pandemic period into six three-month timeframes to balance out the comparison between 2019 and 2020. RESULTS: Overall, a total of 1815 patients were surgically treated during 2019 and 2020 in 14 Italian surgical Units. In 2020, the rate of patients treated with an advanced pathological stage was not different compared to 2019 (p = 0.846). During the pandemic, neoadjuvant chemotherapy (NCT) has dropped significantly (6.2% vs 21.4%, p < 0.001) and, for patients who didn't undergo NCT, the latency between diagnosis and surgery was shortened (49.58 ± 37 days vs 77.40 ± 83 days, p < 0.001). During 2020 there was a significant increase in minimally invasive procedures (p < 0.001). The rate of postoperative complication was the same in the two years but during 2020 there was an increase of the medical ones (19% vs 16.1%, p = 0.001). CONCLUSIONS: The post-pandemic dramatic modifications in healthcare provision, in Italy, did not significantly impair the clinical history of PC patients receiving surgical resection. The present study is one of the largest reports available on the argument and may provide the basis for long-term analyses.

Laparoscopic double mesh repair of a large Morgagni hernia: a video vignette.

Morgagni hernia (MH) is a rare congenital diaphragmatic hernia (CDH) that accounts for less than 2% of surgically repaired CDH in adulthood. Even if this condition is often asymptomatic, surgery is advised due to the risk of life-threatening complications such as volvulus or bowel strangulation. Surgery for MH repair can be performed by transthoracic, transabdominal, laparoscopic, or thoracoscopic approaches. Though laparoscopy has recently improved surgical outcomes, the use of prosthetic meshes and the need for reduction of the hernia sac are still the most debated issues. We present the video of a laparoscopic repair of a large MH with the use of a double mesh technique and no resection of the hernia sac.

Pre-diagnostic prognostic value of leukocytes count and neutrophil-to-lymphocyte ratio in patients who develop colorectal cancer.

Introduction: Emerging evidence is pointing towards a relevant role of immunity in cancer development. Alterations in leukocytes count and neutrophil-to-lymphocyte ratio (NLR) at diagnosis of colorectal cancer (CRC) seems to predict poor prognosis, but no data is available for the pre-diagnostic values. Methods: Retrospective analysis of patients who underwent surgery for CRC at our center (2005 - 2020). 334 patients with a complete blood count dating at least 24 months prior to diagnosis were included. Changes in pre-diagnosis values of leukocytes (Pre-Leu), lymphocytes (Pre-Lymph), neutrophils (Pre-Neut), and NLR (Pre-NLR) and their correlation with overall- (OS) and cancer-related survival (CRS) were analyzed. Results: Pre-Leu, Pre-Neut and Pre-NLR showed an increasing trend approaching the date of diagnosis, while Pre-Lymph tended to decrease. The parameters were tested for associations with survival after surgery through multivariable analysis. After adjusting for potential confounding factors, Pre-Leu, Pre-Neut, Pre-Lymph and Pre-NLR resulted independent prognostic factors for OS and CRS. On sub-group analysis considering the interval between blood sampling and surgery, higher Pre-Leu, Pre-Neut, and Pre-NLR and lower Pre-Lymph were associated with worse CRS, and the effect was more evident when blood samples were closer to surgery. Conclusion: To our knowledge, this is the first study showing a significant correlation between pre-diagnosis immune profile and prognosis in CRC.

The MIS-COVID-AGICT Study: Trend of Minimally Invasive Surgery for Gastrointestinal Cancer Treatment During the First Waves of the COVID-19 Pandemic in Italy. Subgroup Analysis from the COVID-AGICT Study: COVID-19 and Advanced Gastrointestinal Cancer Surgical Treatment.

Background: A preliminary analysis from the COVID-Advanced Gastrointestinal Cancer Surgical Treatment (AGICT) study showed that the rate of minimally invasive surgery (MIS) for elective and urgent procedures did not decrease during the pandemic year. In this article, we aimed to perform a subgroup analysis using data from the COVID-AGICT study to evaluate the trend of MIS during the COVID-19 pandemic period in Italy. Methods: This study was conducted collecting data of MIS patients from the COVID-AGICT database. The primary endpoint was to demonstrate whether the SARS-CoV-2 pandemic scenario reduced MIS for elective treatment of gastrointestinal cancer (GIC) in Italy in 2020. The secondary endpoint was to evaluate the impact of the pandemic period on perioperative outcomes in the MIS group. Results: In the pandemic year, 62% of patients underwent surgery with a minimally invasive approach, compared to 63% in 2019 (P = .23). In 2020, the proportion of patients undergoing elective MIS decreased compared to the previous year (80% versus 82%, P = .04), and the rate of urgent MIS did not differ between the 2 years (31% and 33% in 2019 and 2020 - P = .66). Colorectal cancer was less likely to be treated with MIS approach during 2020 (78% versus 75%, P < .001). Conversely, the rate of MIS pancreatic resection was higher in 2020 (28% versus 22%, P < .002). Conversion to an open approach was lower in 2020 (7.2% versus 9.2% - P = .01). Major postoperative complications were similar in both years (11% versus 11%, P = .9). Conclusion: In conclusion, although MIS for elective treatment of GIC in Italy was reduced during the COVID-19 pandemic period, our study revealed that the overall proportion of MIS (elective and urgent) and postoperative outcomes were comparable to the prepandemic period. ClinicalTrial.gov (NCT04686747).

The COVID - AGICT study: COVID-19 and advanced gastro-intestinal cancer surgical treatment. A multicentric Italian study on the SARS-CoV-2 pandemic impact on gastro-intestinal cancers surgical treatment during the 2020. Analysis of perioperative and short-term oncological outcomes.

BACKGROUND: This Italian multicentric retrospective study aimed to investigate the possible changes in outcomes of patients undergoing surgery for gastrointestinal cancers during the COVID-19 pandemic. METHOD: Our primary endpoint was to determine whether the pandemic scenario increased the rate of patients with colorectal, gastroesophageal, and pancreatic cancers resected at an advanced stage in 2020 compared to 2019. Considering different cancer staging systems, we divided tumors into early stages and advanced stages, using pathological outcomes. Furthermore, to assess the impact of the COVID-19 pandemic on surgical outcomes, perioperative data of both 2020 and 2019 were also examined. RESULTS: Overall, a total of 8250 patients, 4370 (53%) and 3880 (47%) were surgically treated during 2019 and 2020 respectively, in 62 Italian surgical Units. In 2020, the rate of patients treated with an advanced pathological stage was not different compared to 2019 (P = 0.25). Nevertheless, the analysis of quarters revealed that in the second half of 2020 the rate of advanced cancer resected, tented to be higher compared with the same months of 2019 (P = 0.05). During the pandemic year 'Charlson Comorbidity Index score of cancer patients (5.38 ± 2.08 vs 5.28 ± 2.22, P = 0.036), neoadjuvant treatments (23.9% vs. 19.5%, P < 0.001), rate of urgent diagnosis (24.2% vs 20.3%, P < 0.001), colorectal cancer urgent resection (9.4% vs. 7.37, P < 0.001), and the rate of positive nodes on the total nodes resected per surgery increased significantly (7 vs 9% - 2.02 ± 4.21 vs 2.39 ± 5.23, P < 0.001). CONCLUSIONS: Although the SARS-CoV-2 pandemic did not influence the pathological stage of colorectal, gastroesophageal, and pancreatic cancers at the time of surgery, our study revealed that the pandemic scenario negatively impacted on several perioperative and post-operative outcomes.

Atypical myelin oligodendrocyte glycoprotein antibody-associated optic neuritis and acute demyelinating polyneuropathy after SARS-CoV-2 infection: Case report and literature review.

Post-infectious immune-mediated neurological complications of Sars-Cov-2 have been increasingly recognized since the novel pandemic emerged. We describe the case of a 74 years-old patient who developed a Myelin Oligodendrocyte Glycoprotein (MOG) antibody-associated unilateral retrobulbar optic neuritis a few weeks after paucisymptomatic COVID-19 disease and, subsequently, after the resolution of the optic neuritis, an acute inflammatory demyelinating polyneuropathy. So far, no cases of these two neurological manifestations have been reported in the same patient. We herein report a case characterized by both manifestations and review the accumulating literature regarding MOG antibody-associated disease following SarsCov-2 infection.

Tumor-Educated Platelet Extracellular Vesicles: Proteomic Profiling and Crosstalk with Colorectal Cancer Cells.

BACKGROUND: Platelet-cancer cell interactions modulate tumor metastasis and thrombosis in cancer. Platelet-derived extracellular vesicles (EVs) can contribute to these outcomes. METHODS: We characterized the medium-sized EVs (mEVs) released by thrombin-stimulated platelets of colorectal cancer (CRC) patients and healthy subjects (HS) on the capacity to induce epithelial-mesenchymal transition (EMT)-related genes and cyclooxygenase (COX)-2(PTGS2), and thromboxane (TX)B2 production in cocultures with four colorectal cancer cell lines. Platelet-derived mEVs were assessed for their size distribution and proteomics signature. RESULTS: The mEV population released from thrombin-activated platelets of CRC patients had a different size distribution vs. HS. Platelet-derived mEVs from CRC patients, but not from HS, upregulated EMT marker genes, such as TWIST1 and VIM, and downregulated CDH1. PTGS2 was also upregulated. In cocultures of platelet-derived mEVs with cancer cells, TXB2 generation was enhanced. The proteomics profile of mEVs released from activated platelets of CRC patients revealed that 119 proteins were downregulated and 89 upregulated vs. HS. CONCLUSIONS: We show that mEVs released from thrombin-activated platelets of CRC patients have distinct features (size distribution and proteomics cargo) vs. HS and promote prometastatic and prothrombotic phenotypes in cancer cells. The analysis of platelet-derived mEVs from CRC patients could provide valuable information for developing an appropriate treatment plan.

Impact of age and comorbidities on short- and long-term outcomes of patients undergoing surgery for colorectal cancer.

Background: As the world population is progressively ageing, more and more elderly patients will require cancer surgery. Although curative surgery is the treatment of choice for resectable colorectal cancer (CRC), it is still debated whether elderly frail patients should undergo major cancer surgery due to the increased risk of postoperative and long-term mortality. The aim of this retrospective study was to evaluate the impact of age and comorbidities on postoperative mortality/morbidity and long-term outcomes, looking for potential age-related survival differences. Methods: A total of 1,482 patients operated for CRC at our institution between January 2005 and October 2020 were analysed. The independent effect of age and comorbidities on postoperative complications was assessed by a logistic model, while the effect on overall survival (OS) and cancer-related survival (CRS) was estimated by a Cox regression model. Results: The median age in the cohort was 67.8 years. Postoperative mortality was very low in the whole cohort (0.8%) and contained even in older age groups (3.2% in patients aged 80-84 years, 4% in the 85-90-year age group). The cumulative incidence of postoperative complications was doubled in patients with comorbidities (32.8% vs. 15.1%, p = 0.002). With regard to OS, as expected, it exponentially decreased with advancing age. Conversely, differences in CRS were less pronounced between age groups and absent in patients with stage 0-I CRC. Analysis of all causes and cancer-related mortality revealed a peak within 2 years from surgery, suggesting a prolonged impact of surgery. In patients aged 75 years and above, all-cause mortality showed a steep increase 1 year after surgery, while cancer-related mortality plateaued at about 4 years after surgery. On multivariable analysis, OS, but not CRS, was significantly influenced by age. Conclusions: Although acceptable results of surgery in elderly patients, OS is strongly dependent on age: older people die more from competing causes than cancer-related treatments compared to younger age classes. The preoperative identification of risk factors for low OS may help the selection of those elderly patients who would benefit from curative CRC surgery.

Immediate versus early (24-hours) urinary catheter removal after elective minimally invasive colonic resection: study protocol for a randomized, multicenter, non-inferiority trial.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) represents the standard of care in colorectal surgery. Among ERAS items, early removal of urinary catheter (UC) is considered a key issue, though adherence to this specific item still varies among centers. UC placement allows for monitoring of post-operative urinary output but relates to an increased risk of urinary tract infection (UTI), reduced mobility, and patient's discomfort. Several studies investigated the role of early UC removal specifically looking at the rate of acute urinary retention (AUR) but most of them were retrospective, single-center, underpowered, cohort studies. The main purpose of this study is to compare the rate of AUR after immediate (at the end of the surgery) versus early (within 24 h from the completion of surgery) removal of UC in patients undergoing minimally invasive colonic resection (MICR). The secondary outcomes focus on goals that could be positively impacted by the immediate removal of the UC at the end of the surgery. In particular, the rate of UTIs, perception of pain, time-to-return of bowel and physical functions, postoperative complications, and length of hospital stay will be measured. METHODS: This is a prospective, randomized, controlled, two-arm, multi-center, study comparing the rate of AUR after immediate versus early removal of UC in patients undergoing MICR. The investigators hypothesize that immediate UC removal is non-inferior to 24-h UC removal in terms of AUR rate. Randomization is at the patient level and participants are randomized 1:1 to remove their UC either immediately or within 24 h from the completion of surgery. Those eligible for inclusion were patients undergoing any MICR with an anastomosis above the peritoneal reflection. Those patients who need to continue urinary output monitoring after the surgery will be excluded. The number of patients calculated to be enrolled in each group is 108 based on an expected AUR rate of 3% for the 24-h UC removal group and considering acceptable an AUR of 9% for the immediate UC removal group. DISCUSSION: The demonstration of a non-inferiority of immediate versus 24-h removal of UC would call into question the usefulness of urinary drainage in the setting of MICR. TRIAL REGISTRATION: ClinicalTrials.gov NCT05249192. Prospectively registered on February 21, 2022.

Intriguing Role of the Mesentery in Ileocolic Crohn's Disease.

Crohn's disease (CD) is a chronic relapsing inflammatory bowel disease with unknown etiology. Up to 80% of patients will eventually require surgery throughout their lifetime, and often repeated resections are required for disease recurrence. Observations of "creeping fat" surrounding the diseased intestine renewed interest in the mesentery, recently defined as an organ with endocrine and immune functions. According to the inside-out model, the mesentery may be primarily affected in CD and subsequent cause alterations in the mucosa. Recently, lower surgical recurrence rates have been reported with en-bloc excision of the mesentery adjoining the diseased intestine. Results of ongoing randomized controlled trials may clarify the role of the mesentery in CD and possibly lead to its adoption as standard during surgery for Crohn's disease.

H3K27me3 Immunohistochemical Loss Predicts Lower Response to Neo-Adjuvant Chemo-Radiotherapy in Rectal Carcinoma.

A watch-and-wait approach was suggested to avoid the possible complications related to surgery in patients with rectal carcinoma showing clinical complete response after neoadjuvant chemo-radiotherapy (CRT). Since clinical response may not correlate with pathological response, markers with higher accuracy are needed to identify patients who are likely responders and could be spared surgery. This study aims to assess whether H3K27me3 immunohistochemical expression in pre-treatment rectal carcinoma predicts response to neoadjuvant CRT or shows prognostic relevance. We assessed H3K27me3 immunostaining in 46 endoscopic biopsies of rectal carcinomas treated with neoadjuvant CRT and surgery. H3K27me3 immunostaining was lost in 20, retained in 19, and inconclusive (absent in neoplastic and non-neoplastic cells) in 7 cases. Retained H3K27me3 immuno-expression was significantly associated with ypTNM stage 0 (p = 0.0111) and high tumor regression, measured using either five-tiered (p = 0.0042) or two-tiered Dworak tumor regression grade (p = 0.0009). Poor differentiation, determined counting the number of poorly differentiated clusters (PDC grade) or tumor budding (TB) foci (TB grade), in the pre-treatment biopsy, was significantly associated with a shorter time to progression after surgery (p = 0.008; p = 0.0093). However, only PDC grade (p = 0.0023), together with radial margin involvement (p = 0.0001), retained prognostic significance in the multivariate analysis. The assessment of H3K27me3 immunostaining in pre-treatment endoscopic biopsy of rectal carcinoma could be useful to predict response to neo-adjuvant CRT and to identify patients who could safely undergo watch-and-wait approach. PDC and TB grade in the pre-treatment biopsy could provide additional prognostic information in patients with rectal carcinoma treated with neoadjuvant CRT and surgery.

Prediction of Metachronous Peritoneal Metastases After Radical Surgery for Colon Cancer: A Scoring System Obtained from an International Multicenter Cohort.

BACKGROUND: Since novel strategies for prevention and treatment of metachronous peritoneal metastases (mPM) are under study, it appears crucial to identify their risk factors. Our aim is to establish the incidence of mPM after surgery for colon cancer (CC) and to build a statistical model to predict the risk of recurrence. PATIENTS AND METHODS: Retrospective analysis of consecutive pT3-4 CC operated at five referral centers (2014-2018). Patients who developed mPM were compared with patients who were PM-free at follow-up. A scoring system was built on the basis of a logistic regression model. RESULTS: Of the 1423 included patients, 74 (5.2%) developed mPM. Patients in the PM group presented higher preoperative carcinoembryonic antigen (CEA) [median (IQR): 4.5 (2.5-13.0) vs. 2.7 (1.5-5.9), P = 0.001] and CA 19-9 [median (IQR): 17.7 (12.0-37.0) vs. 10.8 (5.0-21.0), P = 0.001], advanced disease (pT4a 42.6% vs. 13.5%; pT4b 16.2% vs. 3.2%; P < 0.001), and negative pathological characteristics. Multivariate logistic regression identified CA 19-9, pT stage, pN stage, extent of lymphadenectomy, and lymphovascular invasion as significant predictors, and individual risk scores were calculated for each patient. The risk of recurrence increased remarkably with score values, and the model demonstrated a high negative predictive value (98.8%) and accuracy (83.9%) for scores below five. CONCLUSIONS: Besides confirming incidence and risk factors for mPM, our study developed a useful clinical tool for prediction of mPM risk. After external validation, this scoring system may guide personalized decision-making for patients with locally advanced CC.

Sarcobesity Index Predicts Poor Disease-Specific Survival After Resection for Colorectal Cancer.

INTRODUCTION: Sarcobesity (SO) is traditionally defined as the association between low muscle mass and obesity and has been reported to worsen prognosis after curative resection for colorectal cancer (CRC). This study aimed to propose a new definition of SO based on computed tomography measurements of the skeletal muscle area (SMA) and visceral adipose tissue (VAT) and to assess its implications on long-term survival after curative resection for stage I-III CRC. METHODS: We retrospectively analyzed 506 patients with stage I-III CRC who underwent surgery between January 2010 and December 2019. Preoperative computed tomography images were analyzed and the sarcobesity index (SI) was calculated for each patient as the VAT/SMA ratio. The optimal cutoff value for predicting survival was determined using time-dependent receiver operating characteristic analysis. Overall survival and disease-specific survival (DSS) were compared between SO (SI > 1.25) and non-SO (SI ≤ 1.25) patients. The rates and modes of recurrence were also compared between the two groups. RESULTS: Three hundred (59.3%) patients were identified to be sarcobese. No differences in short-term outcomes and administration of adjuvant chemotherapy were found, except for a longer length of stay in patients with SO. In a univariable analysis, SO was associated with a worse 5-y overall survival and DSS, considering the whole population and stages II and III separately. A multivariable analysis confirmed SO to be an independent risk factor for DSS (hazard ratio 2.29; 95% confidence interval 1.13-4.62, P = 0.02). Although the overall recurrence rate did not differ between the groups, a significantly higher rate of recurrence at multiple sites was observed in patients with SO (P = 0.01). CONCLUSIONS: The SI, defined as per the VAT/SMA ratio, seems to be a reliable tool for identifying patients with worse DSS after potentially curative surgery for stage I-III CRC.

Does laparoscopy increase the risk of peritoneal recurrence after resection for pT4 colon cancer? Results of a propensity score-matched analysis from an international cohort.

BACKGROUND: Peritoneal metastases (PM) occur in 15-20% of surgically resected pT4 colon cancer (CC) and strongly affect prognosis. Since no standard treatment has been established, efforts should be addressed toward its prevention. Some literature suggests a detrimental effect of laparoscopy in pT4 CC, hence we aimed to determine its impact on the development of PM after potentially curative resection. METHODS: International multicenter retrospective cohort study including consecutive patients undergoing surgery for pT4a and pT4b CC (2014-2018) at 5 referral centers. The inclusion criteria were absence of distant metastasis, elective surgery, curative-intent resection (R0-1), and a minimum follow-up of 24 months (median, IQR: 35, 25.8-50.5 months). RESULTS: 276 patients fulfilled the inclusion criteria and were selected for analysis. After 1:1 propensity score matching (PSM), 63 patients in the laparoscopic group (LapGroup) were compared with 63 patients in the open surgery group (OpenGroup). The two groups were comparable in terms of demographic and clinical parameters, operative data, and specimen characteristics. The OpenGroup presented a higher estimated intraoperative blood loss (P < .001) and postoperative length of stay (P < .001). Overall survival, cancer-specific survival, and disease-free survival resulted comparable. The 5-year probability of developing PM was 16.2% after laparoscopy and 19.5% after open surgery (P = .686). Multivariate analysis confirmed laparoscopy not to be an independent risk factor for PM. CONCLUSIONS: Elective laparoscopic surgery for pT4 CC does not seem to increase the risk of metachronous PM after potentially curative surgery. Long-term outcomes after laparoscopy are not inferior to conventional open resections.

High Values of Drain Fluid Epidermal Growth Factor and Transforming Growth Factor-Beta Are Associated with the Development of Pancreatic Fistula after Pancreatoduodenectomy.

INTRODUCTION: Postoperative inflammatory response may act as a major determinant of anastomotic failure after pancreaticoduodenectomy. In this pilot study, we investigated the potential role of drain fluid cytokines in predicting postoperative pancreatic fistula (POPF). METHODS: Drain fluid TGF-ß, IGF-1, EGF, and IL-6, together with serum amylase and drain fluid amylase, were measured on POD1 and correlated with the development of POPF. RESULTS: The study population consisted of 66 patients. POPF and Clavien-Dindo ≥3 morbidity rates were 12.1% and 9.1%, respectively. Patients developing POPF presented significantly higher values of POD1 serum amylase level (477 vs. 54 UI/L, p < 0.001), drain fluid amylase (7,500 vs. 127 UI/L, p < 0.001), TGFß (94 vs. 40 pg/g, p = 0.045), and EGF (17 vs. 13, p = 0.015). There were no differences in terms of IGF-1 and IL-6 values. CONCLUSION: Assessing the local inflammatory response after pancreatoduodenectomy could represent a promising field of research since both TGFß and EGF seem to be associated with the occurrence of POPF.