Outcomes Following Surgery for Locally Advanced Pancreatic Cancer - Single Center Experience. A Retrospective Study.

Background: Pancreatic cancer represents one of the most frequent cancers with an increased incidence. Most cases on initial diagnosis are considered to be locally advanced and surgery remains the most important therapeutic option. The aim of this study was to evaluate postoperative morbidity that can impair the association of adjuvant therapy. Methods: We performed a retrospective study on a prospective database that includes all the patients diagnosed with pancreatic cancer in which surgery was performed between 2012 and 2021. We divided the patients in advanced tumours and localized tumours and we compared the outcomes after surgery. Results: On 58 patients with pancreatic tumours surgery was performed: 28(48.3%) pancreaticoduodenectomies and 30 (51.7%) distal pancreatectomies. Localized tumours (T1 and T2) were encountered in 32 patients (55.2%) and more advanced tumours (T3 and T4) were present in 26 cases (44.8%). Although there was no significant difference either for major complications, we observed a tendency for patients with advanced tumours to develop a major complication (15.6% vs 34.6%, p=0.09). The occurrence of major complication, such as pancreatic fistula and postoperative hemorrhage, there was no significant difference (6.25% vs 7.69% and 6.25% vs. 23.1%). On multivariate analysis of preoperative factors associated with the occurrence of a severe complication only the CA19-9 levels were associated with an increased risk (odds ratio 0.666, 95% CI 0.5-1.01; p= 0.04) Conclusions: This study showed no significant differences in terms of postoperative complications between the two subgroups. CA 19-9 is an accurate biomarker for the prediction of postoperative complications.

The Influence of Neoadjuvant Treatment on the Number of Lymph Nodes on the Surgical Specimen in Mid and Low Rectal Cancer - A Retrospective Single-Centre Study.

Introduction: In this study, we aim to identify the impact of neoadjuvant radiation treatment upon the number of harvested and positive lymph nodes in the surgical specimen; in addition, we tried to identify the impact of chemotherapy in association with radiotherapy on said structures. Patients and methods: In the study we included patients treated for rectal cancer within a single oncologic surgical Unit serving the north-eastern part of Romania, over a period of 5 and a half years, between May 2013 and April 2018. Firstly, we compared pathologic lymph node status to pretherapeutic staging. Secondly, we compared lymph node values in relation to the treatment scheme. Results: There was a total of 498 patients treated radically through open surgery for low and mid rectal cancer. We saw a decrease in N staging in 218 cases, 65 remaining stationary and 10 increasing their lymph node staging on the surgical specimen. We identified significant differences between the total number of lymph nodes (17.4 vs 24.2, p 0.001), the number of positive lymph nodes (1.4 vs 3.4, p 0.001) and the ratio between positive and total lymph nodes (0.08 vs 0.14, p 0.001) in patients with and without neoadjuvant treatment respectively. However, there was no statistical difference between patients with and without chemotherapy associated to radiotherapy in the neoadjuvant treatment plan (p=0.539, p=0.58, p=0.575). Conclusion: This study shows there are significant variations according to the application of neoadjuvant treatment, between the numbers of positive and total lymph nodes, as well as the positive/total lymph node ratio.

Hindgut and Midgut Neuroendocrine Tumors - Therapeutic Approach.

Introduction: Neuroendocrine tumors of the gastro-entero-pancreatic system have a variety of components, clinical manifestations and prognostic indices according to their anatomical site. Therefore, their diagnostic and management strategies differ a great deal. Prognosis concerning NETs can be poor due to the degree of differentiation, early metastasizing and the high degree of invasiveness. Material and Methods: For the present study, the patient files were evaluated and the parameters of interest were followed. Results: Over the course of 6 years there were 37 patients diagnosed with and treated for NETs, regardless of primary tumor site. There were 9 patients with NETs of the primite mid- and hindgut thusly: 5 cases with colorectal NETs and 4 cases of small bowel NETs. 6 patients benefited from radical surgical treatment, 2 cases with palliative procedures and only one patient with tumor biopsy. The tumors were evaluated according to the 2010 WHO classification based on the number of mitoses and the Ki67 proliferation index. Adjuvant treatment was adapted according to staging and histopathological parameters. Conclusions: Despite recent progress in managing NETs, there are still many controversial aspects regarding the management of these cases, mainly about timing the right sequence of therapy.

Functional Results Following Pylorus-Preserving Pancreatoduodenectomy with Pancreaticogastrostomy.

Background: Pylorus preserving (PP) pancreaticoduodenectomy (PD) has several advantages in terms of shorter operation time and improved nutritional status but with an increased risk for delayed gastric emptying. Methods: We performed a retrospective study on all patients in which PD was performed from May 2012 to May 2018. It was analyzed early postoperative outcomes and the incidence of delayed gastric emptying (DGE) syndrome for patients with pylorus PP PD technique and pancreaticogastrostomy (PG). Results: There were 47 PD, in which PP technique was performed in 42 cases. The tumour location was in the pancreatic head (n=21, 44.68%), periampullary (ampulla of Vater) (n=14,29.78%), distal bile duct (n=7,14.89%), duodenum (n=2, 4.25%) and advanced right colon cancer (n=3, 6.38%). There were 10 cases (21.2%) of grade III-V complications, grade A pancreatic fistula (PF)8 cases (17%), grade B in 3 cases (6.4%) and grade C in 1 case (2.12%). DGE was encountered in 17 cases (36.17%), grade A 2 cases (4.25%), grade B in 4 cases (8.5%) and grade C in 2 cases (4.25%). Biliary fistula occurred in 3 cases (6.4%) and in 4 cases relaparotomy was needed. Conclusions: The results of our study are concluding with the previous studies, the addition of PG to PP PD does not increase the risk of DGE.

An Attempt to Build a National Prospective Electronic Database for Pancreaticoduodenectomies in Romania - Preliminary Results of the First Year Enrollment.

Introduction: National databases for pancreaticoduodenectomies (PD) have contributed to better postoperative outcomes after such complex surgical procedure because the multicentre collection of data allowed more reliable analyses with quality assessment and further improvement of technical issues and perioperative management. The current practice and outcomes after PD are poorly known in Romania because there was no national database for these patients. Thus, in 2016 a national-intent electronic registry for PD was proposed for all Romanian surgical centers. The study aims to present the preliminary results of this national-intent registry for PD after one-year enrollment. Patients Methods: The database was started on October 1st, 2016. Data were prospectively collected with an electronic online form including 102 items for each patient. The registry was opened to all the Departments of Surgery from Romania performing PD, with no restriction. Results: During the first year of enrollment were collected the data of 181 patients with PD performed by 24 surgeons from four surgical centers. The age of patients was 64 years (28 - 81 years), with slightly male predominance (61.3%). Computed tomography was the main preoperative imaging investigation (84.5%). All the PDs were performed by an open approach. The Whipple technique was used in 53% of patients, and a venous resection was required in 14.3% of cases. A posterior approach PD was considered in 16.6% of patients. The stomach was used to treat the distal remnant pancreas in 50.1% of patients. The operative time was 285 min (110 - 615 min), and the estimated blood loss was 400 ml (80 - 3000 ml). The overall morbidity rate was 55.8%, with severe (i.e., grade III-IV Dindo-Clavien) morbidity rate of 10%, and 3.9% in-hospital mortality rate. The overall pancreatic fistula, delayed gastric emptying and hemorrhage rates were 19.9%, 39.8% and 15.5%. Periampullary malignancies were the main indications for PD (78.9%), with pancreatic cancer on the top (48%). Conclusions: To build a prospective electronic online database for PD in Romania appears to be a feasible project and a useful tool to know the current practice and outcomes after PD in our country. However, improvements are still required to encourage a larger number of surgical centers to introduce the data of patients with PD.

Clinical Value of Hematological Biomarkers in Uterine Cervical Cancer.

Certain combinations of the hematological components, specifically, neutrophils and lymphocytes, named neutrophil to lymphocyte ratio (NLR) or multiplication of neutrophil and monocyte (MNM) have been shown to have prognostic value in a variety of cancers. MATERIAL AND METHODS: Retrospective study which included 133 patients with uterine cervical cancer with or without neoadjuvant therapy based on prognostic factors and correlations between NLR and MNM values, markers that were analyzed as continuous variables. This study aimed to establish the critical value of hematological markers. Results: NLR is significantly lower for preoperative stages I and II (p = 0.0004). There is a significant association between NLR and lymph node metastasis (p = 0.016), parametrial invasion (p = 0.035), lymphovascular space invasion (p = 0.0151) and tumor size (p = 0.0017). Correlational analysis showed that there is a significant association between MNM and lymph node metastasis (p = 0.020), parametrial invasion (p = 0.00010), lymphovascular space invasion materially affecting the value MNM (p = 0.0018), tumor size more than 4 cm (p = 0.0314). NLR and MNM were significantly lower in patients with complete response to neoadjuvant treatment. Discussion: The results of this study outlines the importance of hematological panel and parameters that can be easily used at no extra cost to establish further evolution of patients to treatment.

The role of perioperative systemic chemotherapy in diffuse malignant peritoneal mesothelioma patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: The aim of this study was to evaluate the effects of perioperative systemic chemotherapy (CT) on short-term surgical and long-term oncologic results in diffuse malignant peritoneal mesothelioma (DMPM) patients treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). PATIENTS AND METHODS: We retrospectively analyzed data obtained from an institutional prospective database at NCI of Milan. The study group comprised 116 DMPM patients treated with CRS + HIPEC from August 1995 to October 2011. A total of 60 cases underwent preoperative CT (PRECT), 30 underwent postoperative CT (POSTCT), and 26 did not undergo any CT (NOCT). Also, 55 cases used the perioperative combination of platinum and pemetrexed. We tested whether covariates related to clinical, histologic, PRECT, and surgical treatment were correlated with completeness of cytoreduction (CC), postoperative G3-5 morbidity, and progression-free survival and overall survival (OS). Univariate and multivariate analyses were performed. RESULTS: Factors independently associated with CC were ECOG performance status (PF) of 0, and PCI <20. Factors independently associated with postoperative G3-5 morbidity were ECOG >1, bowel anastomosis, and number of peritonectomy procedures. Preoperative platelet count >400 × 103/mm(3), histological subtype (biphasic and sarcomatoid vs epithelial), CC, and G3-5 morbidity were independent prognostic factors. PRECT was not associated with CC or G3-5 morbidity. There was no significant difference in terms of survival between the PRECT, POSTCT, and NOCT groups. CONCLUSIONS: The CC, G3-5, and OS were not influenced by aspects related to perioperative CT. The present data warrants confirmation reconducting the comparative analysis in a larger multi-institutional series preferably using matching control techniques.

Circulating tumor markers: predictors of incomplete cytoreduction and powerful determinants of outcome in pseudomyxoma peritonei.

BACKGROUND: Incomplete cytoreduction (IC) is one of the main prognostic factor in pseudomyxoma peritonei (PMP). We evaluated the ability of preoperative Ca125, CEA, and Ca19-9 to predict IC and prognosis in PMP. METHODS: One hundred fifty-six cases elected candidate to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy from 1996 to 2011 were included in the study. We assessed the: (1) optimal cut-off values for circulating Tumor markers (CTM) in predicting IC (residual disease >2.5 mm) using receiver-operating characteristics (ROC); (2) discriminant power of CTM and risk prediction models for IC by calculating the area under ROC curve (AUC-ROC); (3) prognostic factors using Cox proportional-hazard model. RESULTS: Optimal cut-offs were 125 U/ml for Ca125, 18 ng/ml for CEA, and 89 U/ml for Ca19-9. The AUCs-ROC were 0.76, 0.68, and 0.69 for Ca125, CEA, and Ca19-9, respectively. The addition of CTM to risk prediction model that considered preoperative clinicopathological factors increased marginally the AUC-ROC (0.80-0.84). Ca125 > 125 U/ml, Ca19-9 > 89 U/ml independently affected overall survival. CONCLUSIONS: Preoperative CTMs were reasonable but not perfect discriminators of IC. Moreover, Ca125 and Ca19-9, using new cut-off values, were proven to be new strong prognostic factors that overcome the value of disease extension and histological subtype.

Learning curve for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal surface malignancies: analysis of two centres.

BACKGROUND: We assessed the learning curve (LC) of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in treating peritoneal surface malignancies (PSM) in two centers and evaluated in which extent surgical tutoring could abbreviate the learning process. METHODS: Six hundred and forty-one cases submitted to CRS using peritonectomy procedures and HIPEC were considered. After having overcome its own LC, the NCI of Milan has provided technical assistance to Bentivoglio's centre for the development of a new PSM program since 2003. The risk-adjusted sequential probability ratio test (RA-SPRT) was employed to assess the LC of the two centers. Outcomes were incomplete cytoreduction, G3-5 morbidity (NCI-CTCAE.v3) and procedure-related mortality (PRM). RESULTS: Rates of incomplete cytoreduction, G3-5 morbidity, and PRM were 8.4%, 30.1%, and 3.9%, respectively, in the entire series. The breaking points of the LC concerning incomplete cytoreduction, G3-5 morbidity, and PRM were achieved at 141, 158, and 144 cases, in the Milan's experience, and at 126, 134, and 60 cases in the Bentivoglio's experience. CONCLUSIONS: Surgical tutoring could substantially shorten the steep LC associated with CRS and HIPEC. Our data should be confirmed by further studies on LC focusing oncological outcomes. Other factors that could influence the length of learning process should be identified.

Evaluation of circulating tumor cells in colorectal cancer using flow cytometry.

OBJECTIVE: We aimed to evaluate the prognostic value of circulating tumor cells (CTCs) and the impact of intraoperative tumor manipulation on CTCs in colorectal cancer (CRC) patients. METHODS: We performed a prospective study on 40 patients with CRC stages I to IV who received curative surgery using the no-touch technique. Flow cytometry was used to identify CTCs in peripheral blood samples (4 mL/sample) collected at two surgical moments: skin incision (T1) and after surgical resection (T2). A threshold of ≥4 CTCs/4 mL blood was established for considering patients CTC positive. RESULTS: In the univariate analysis, CTC evaluation at T2 was correlated with female sex, vascular invasion, tumor localization in the colon and metastatic lymph nodes. In the multivariate analysis, only female sex and colon cancer maintained statistical significance. At a medium follow-up of 15 months (1-25 months), the mortality rate was 10% (n = 4), with no significant differences between the overall survival of T1 or T2 CTC-positive and CTC-negative patients. CONCLUSIONS: Flow cytometry is a feasible CTC identification technique in CRC, and although surgical manipulation has no influence on CTC numbers, CTCs may serve as a prognostic and predictive factor.

Pelvic exenteration, a surgical treatment option for locally advanced, primary and recurrent neoplasia.

Pelvic exenteration (PE) is an extensive surgical procedure for locally advanced primary neoplasia (LAPN) or recurrent neoplasia (RN) that consists in the en bloc removal of the pelvic organs (rectum, internal genital organs and bladder) associated with pelvic lymph nodes. PE is classified into anterior, posterior and total, supra or infralevatorian approaches. Our aim was to evaluate the surgical procedure and the resection margins in correlation with postoperative complications and morbidity rates after PE in patients treated in a single surgical unit. The study group comprised patients diagnosed with different malignancies, surgically treated by using PE procedure, during 2012-2018. The cohort included 121 cases with LAPN (n=98, 80.99%) and RN (n=23, 19%), mostly female (n=114, 94.21%), with a mean age of 61.16 (33-85) years. LAPN had predominantly digestive (n=48, 49.98%) and gynecological (n=28, 28.57%) origins, while the majority of RN cases were cervical cancers (n=9, 39.13%). The univariate analysis showed that the gynecological origin of the tumor (p=0.02), urinary stoma (p=0.02) and posterior PE (PPE) (p=0.004) were significant prognostic factors for postoperative complications. After performing the multivariate analysis, only the gynecological origin (p=0.02) of the tumor and PPE (p=0.03) remained determining factors for postoperative complications. PE is a disabling surgical procedure associated with high postoperative mortality and morbidity, although it is often the only solution for advanced cases. The judicious selection of patients who can benefit from such extensive surgery is compulsory. Our study suggests that the gynecological origin of the tumor and PPE are key factors in postoperative complications.

Factors influencing the pathological quality of the surgical specimen in rectal cancer - a retrospective single-centre study.

AIM: The pathologist's role in the multidisciplinary treatment of rectal cancer is to evaluate and stage the tumor according to the latest standards, as well as indicate the quality of the surgical act. This study aims to evaluate circumferential and distal resection margins as well as quality of mesorectal resection and correlate them with different clinical, pathological and therapeutic factors. PATIENTS, MATERIALS AND METHODS: Four hundred ninety-eight patients treated radically for mid and low rectal cancer within one Clinic of Oncological Surgery in Iasi, Romania, were included in this study. RESULTS: The distal resection margin showed significant correlations with the type of surgical intervention, chemotherapy in the neoadjuvant treatment plan and pathological node staging. The circumferential resection margin depended mostly on pathological node staging and the length of the interval between neoadjuvant treatment and surgery. Finally, the aspect of the mesorectum varied according to neoadjuvant treatment and the type of surgical intervention performed. CONCLUSIONS: The study reached its aim in providing important data for the expected outcome of the specimen after curative treatment for rectal cancer.

Diffuse malignant peritoneal mesothelioma: long-term survival with complete cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC).

BACKGROUND: Prognosis of diffuse malignant peritoneal mesothelioma (DMPM) has been recently improved by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). As with other peritoneal surface malignancies, the survival benefit is maximal when a complete surgical cytoreduction is achieved, but additional factors predicting long-term outcome are still poorly understood. We sought to investigate outcome and prognostic factors in patients with DMPM treated by complete cytoreduction and HIPEC. METHODS: From a prospective database, we selected 108 patients with DMPM undergoing complete cytoreduction (residual tumour nodules ≤2.5 mm) and closed-abdomen HIPEC with cisplatin and doxorubicin or mitomycin-C. Twenty-seven patient-, tumour- and treatment-related variables were assessed by multivariate analysis with respect to overall (OS) and progression-free (PFS) survival. A panel of immunohistochemical markers was tested. RESULTS: Operative mortality was 1.9% and major morbidity 38.9%. Median follow-up was 48.8 months (95% confidence interval (CI) 37.1-60.6). Median OS and PFS were 63.2 months (95%CI 29.6-96.7) and 25.1 months (95%CI 5.1-45.1). The survival curve reached a plateau after 7 years, representing 19 actual survivors of 39 patients (43.6%) with potential follow-up ≥7 years. Cytokeratin 5/6, calretinin, Wilms tumour-1 (WT-1), podoplanin and epithelial growth factor receptor (EGFR) were mostly positive. At multivariate analysis, epithelial histological subtype, negative lymph-nodes, ≤10% Ki67-positive cells correlated with both increased OS and PFS. Positive podoplanin correlated to increased PFS. CONCLUSIONS: After complete cytoreduction and HIPEC, prognosis of DMPM is primarily dependent on pathologic and biologic features. Patients with DMPM surviving ≥7 years appeared to be cured. Cure rate was 43.6%. Proliferative index and podoplanin may be used for prognostic stratification.

The importance of the learning curve and surveillance of surgical performance in peritoneal surface malignancy programs.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are complex procedures with a very steep a learning curve (LC). This study evaluates the LC of CRS and HIPEC in a single-center experience of peritoneal surface malignancies (PSMs). Approximately 140 to 150 cases were necessary for the acquisition of competence in CRS and HIPEC with adequate radicality and acceptable safety. Eighty to 100 cases were necessary to assure short-term prognostic gains in rare PSMs. This article highlights how LC and continuous monitoring of surgical performance is critical in evaluating the credibility of emerging and already established PSM centers.