Long-Term Impact of D2 Lymphadenectomy during Gastrectomy for Cancer: Individual Patient Data Meta-Analysis and Restricted Mean Survival Time Estimation.

BACKGROUND: Debate exists concerning the impact of D2 vs. D1 lymphadenectomy on long-term oncological outcomes after gastrectomy for cancer. METHODS: PubMed, MEDLINE, Scopus, and Web of Science were searched and randomized controlled trials (RCTs) analyzing the effect of D2 vs. D1 on survival were included. Overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) were assessed. Restricted mean survival time difference (RMSTD) and 95% confidence intervals (CI) were used as effect size measures. RESULTS: Five RCTs (1653 patients) were included. Overall, 805 (48.7%) underwent D2 lymphadenectomy. The RMSTD OS analysis shows that at 60-month follow-up, D2 patients lived 1.8 months (95% CI -4.2, 0.7; p = 0.14) longer on average compared to D1 patients. Similarly, 60-month CSS (1.2 months, 95% CI -3.9, 5.7; p = 0.72) and DFS (0.8 months, 95% CI -1.7, 3.4; p = 0.53) tended to be improved for D2 vs. D1 lymphadenectomy. CONCLUSIONS: Compared to D1, D2 lymphadenectomy is associated with a clinical trend toward improved OS, CSS, and DFS at 60-month follow-up.

Surgical management of hydatid cyst disease of the liver: An improvement from our previous experience?

BACKGROUND: Hydatid liver disease remains an important issue in endemic areas, which may require immediate surgery. Although laparoscopic surgery is on the rise, the presence of certain complications may require conversion to the open approach. AIM: To compare the results of laparoscopic treatment and the open approach in the context of a 12-year single institution experience, and to perform a further comparison between results from the current study and those from a previous study. METHODS: Between January 2009 and December 2020, 247 patients underwent surgery for hydatic disease of the liver in our department. Of the 247 patients, 70 underwent laparoscopic treatment. A retrospective analysis between the two groups was performed, as well as a comparison between current and previous laparoscopic experience (1999-2008). RESULTS: There were statistically significant differences between the laparoscopic and open approaches regarding the cyst dimension, location, and presence of cystobiliary fistula. There were no intraoperative complications in the laparoscopic group. The cutoff value for the cyst size regarding the presence of cystobiliary fistula was 6.85 cm (P = 0.001). CONCLUSION: Laparoscopic surgery still plays an important role in the treatment of hydatid disease of the liver, with an increase in its usage over the course of years that has shown benefits regarding the postoperative recovery with a decreased rate of intraoperative complications. Although experienced surgeons can perform laparoscopic surgery in the most difficult conditions, there are some selection criteria that need to be maintained for higher quality results.

Specific Septic Complications after Rectal Cancer Surgery: A Critical Multicentre Study.

The postoperative septic complications in gastrointestinal surgery impact immediate as well as long-term outcomes, which lead to reinterventions and additional costs. The authors presented the experience of three surgery clinics in Romania regarding the specific septic complications occurring in patients operated on for rectal cancer. The study group comprised 2674 patients who underwent surgery over a 5-year period (2017-2021). Neoplasms of the middle and lower rectum (76%) were the majority. There were 85% rectal resections and 15% abdominoperineal excisions of the rectum. In total, 68.54% of patients were operated on laparoscopically, and 31.46% received open surgery. Without taking wound infections into account, 97 (3.67%) patients had abdominal-pelvic septic complications. The aim was to evaluate the causes of the complications. The percentage of suppurations after surgery of the rectum treated by radiochemotherapy was considerably higher than after surgery of the non-radiated upper rectum. The fatality rate was 5.15%. The risk of fistulas was significantly associated with the preoperative treatment, tumour position and type of intervention. Sex, age, TNM stage or grade were not significant at 0.05 the threshold. The risk of fistulas is reduced with low anterior resection, but the gravity of these complications is higher in the lower rectum compared with the superior rectum. Preoperative radiochemotherapy is a contributing factor to septic complications.

A novel step-by-step training program for transanal endoscopic surgery.

BACKGROUND: The objective of our study is to develop an effective training platform for transanal endoscopic surgery and to validate a step-by-step training program for learning the basic skills necessary for this approach. METHODS: We have designed a two-part study: an experimental study (with the aim to design the training platform and the training exercises - on synthetic and biological material) and a prospective analytical study, in order to validate the training program by enrolling as participants general surgery residents and specialists, without previous experience in transanal endoscopic interventions. The performance of the participants was assessed based on the time of completion, as well as the quality of the execution. RESULTS: We have developed three different diameter platforms (5 cm, 7.5 and 10 cm), that can be used with both the TEO and TAMIS platforms; specific exercises were developed to train different surgical skills like manipulation of tissue, cutting, dissection and suturing. Forty participants were enrolled for the validation of the proposed training program (12 young residents, 16 senior residents and 12 specialist surgeons). A statistically significant improvement of the performance time, from round to round, was observed for all participants in all exercises. The time of completion for the exercises, considering the correct technical execution, was the shortest for more experienced surgeons: specialist surgeons, followed by senior residents and young residents. The biological material exercises, that closely recreate intraoperative conditions and had more strict technical requirements, were difficult to be performed by young residents; better completion rates were seen in senior residents, while all the participants in the specialist surgeons group have completed these exercises. CONCLUSIONS: Our training program is an effective simulation based educational model for recreating intraoperative conditions particular to transanal endoscopic surgery. The proposed step-by-step training program has demonstrated to be useful in developing the important basic skills needed for transanal endoscopic surgery and assured the progress of all the participants, regardless of their surgical experience.

The Multifaceted Role and Regulation of Nlrp3 Inflammasome in Colitis-Associated Colo-Rectal Cancer: A Systematic Review.

Colitis-associated colo-rectal cancer remains the leading cause of mortality in inflammatory bowel diseases, with inflammation remaining one of the bridging points between the two pathologies. The NLRP3 inflammasome complex plays an important role in innate immunity; however, its misregulation can be responsible for the apparition of various pathologies such as ulcerative colitis. Our review focuses on the potential pathways of upregulation or downregulation of the NLRP3 complex, in addition to evaluating its role in the current clinical setting. Eighteen studies highlighted the potential pathways of NLRP3 complex regulation as well as its role in the metastatic process in colo-rectal cancer, with promising results. Further research is, however, needed in order to validate the results in a clinical setting.

Residents Can Do It! A Training Program in Laparoscopic Liver Surgery for General Surgery Residents.

INTRODUCTION: Laparoscopic liver resections (LLRs) constitute an area of surgery that has been kept away from residents in their hands-on training. The aim of our study is to assess the feasibility and the value of a didactic "step-by-step" program for LLR performed by residents using the swine training model. METHODS: From May 2018 to November 2019, three hands-on workshops were held. The protocol involved the performance of cholecystectomy, liver mobilization, minor and major hepatectomies. The participants' performance results in terms of operative time, blood loss, conversion, trainers' intervention, and intraoperative mortality, were recorded. The first workshop was comprised of 30 residents who previously participated in laparoscopic surgery workshops. In the second workshop, after six residents dropped out due to residency completion, the findings for the remaining 24 residents were compared to those for 24 junior-attending surgeons who did not follow the protocol and had not performed LLR previously, and to another 24 residents in a third workshop, who had not taken the training program before but followed the protocol. RESULTS: All residents fully completed the surgical procedures. Trained residents achieved better operative times and less blood loss compared to junior-attending surgeons (p < 0.017), however, the remaining parameters were comparable. When compared to non-trained residents, those who underwent training achieved significantly better results only in operative times (p < 0.001). CONCLUSION: A continuous LLR "step-by-step" training program on swine for residents is feasible and the "step-by-step" protocol is a valuable tool for a proper surgical education.

Do Patient Delay and Diagnostic Delay Influence Long Term Survival in Patients with Gastric Cancer?

BACKGROUND AND AIMS: Gastric cancer is one of the most common malignancies, with an aggressive evolution and a poor long-term prognosis. No screening program is available in Europe for this pathology; therefore, the delay from the appearance of the first symptom until the initiation of treatment might influence the prognosis of gastric cancer patients. We aimed to investigate the impact on the prognosis of the delay in the presentation and diagnosis in patients with gastric adenocarcinoma. METHODS: Our study is a retrospective, single-center, observational cohort study, based on patients diagnosed with gastric adenocarcinoma and operated in our institution between 2013 and 2021. We have defined patient delay as the time from the onset of symptoms to the first encounter with a health care provider and diagnosis delay as the time from the first consultation with a health care provider to the establishment of the final diagnosis. RESULTS: A total of 671 patients were included in our study. The survival rate at 5 years was 55% for the patients operated with curative intent and 7.4% for the patients operated with palliative intent. Patient delay and diagnosis delay were not correlated with the overall survival. A lower survival was observed for patients admitted through transfer (p<0.001) or the emergency department (p<0.001). No statistically significant relationship was identified between patient delay or diagnosis delay and the age, gender or area of origin of patients. Patients that experienced melena or hematemesis had a shorter patient delay, with a highly significant statistical relationship (p<0.01). Patients that experienced nausea, epigastric pain, palpable epigastric tumor mass or anorexia also had a highly significant statistical relationship between the symptoms and the patient delay interval. CONCLUSIONS: The overall survival is not influenced by the patient delay or diagnosis delay. An earlier presentation was correlated with some specific exhibited symptoms: upper gastro-intestinal bleeding, abdominal pain, palpable epigastric tumor, nausea.

Trends in Minimally Invasive Approaches for Liver Resections-A Systematic Review.

BACKGROUND: SILS (single incision laparoscopic surgery) and NOTES (natural orifice transluminal endoscopic surgery) are considered breakthroughs in minimally invasive surgery, the first consisting in the surgeon working via a single entrance site and the second via a natural orifice (e.g., oral cavity). METHODS: Since 2000 until 2022, the original articles published in the online databases were analyzed. Eligible studies included information about the current therapy of patients with liver surgical pathology and how the two new techniques improve the surgical approach. RESULTS: A total of 798 studies were identified. By applying the exclusion criteria, nine studies remained to be included in the review. Two out of nine studies examined the NOTES approach in liver surgery, whereas the other seven focused on the SILS technique. The age of the patients ranged between 24 and 83 years. Liver resections for hepatocellular carcinoma or colorectal metastases were undertaken and biliary or hydatid cysts were removed. The mean procedure time was 95 to 205 min and the average diameter of the lesions was 5 cm. CONCLUSIONS: When practiced by multidisciplinary teams, transvaginal liver resection is feasible and safe. The goals of SILS and NOTES are to be less intrusive, more easily tolerated and aesthetic.

Impact of the COVID-19 pandemic on the training of general surgery residents: Surgical training and the COVID-19 pandemic.

Background: The educational process of young doctors should be a topic of high interest, since it is central to preparing the new generations of healthcare providers. The COVID-19 pandemic has affected the medical system on multiple levels, including medical education. Methods: We conducted a descriptive survey study, designed to reflect the impact of the pandemic on the training of general surgery residents. Two questionnaires were delivered to general surgery residents at two different periods: one in the pre-COVID-19 era (December 2019) and one in the COVID-19 era (December 2020). Data were gathered on participants' characteristics, current clinical practice and knowledge, extracurricular activities, and involvement in the management of COVID-19 cases. Results: We registered 33 responses in the pre-COVID-19 era and 45 responses in the COVID-19 era. Most participants felt that the pandemic significantly affected their training in classic and laparoscopic surgery. The number of days per week that the residents were active in the operating room and the possibility of training in laparoscopic surgery outside the hospital decreased significantly in the COVID-19 era. Most participants consider they have not gained sufficient knowledge to practice laparoscopic surgery or to assure their employment in another hospital after finishing their residency program. Conclusion: The pandemic reduced the hands-on activities of general surgery residents, while training in laparoscopy was deficient both before and during the pandemic. New training methods should be sought and used in order to adapt the educational system to the current context.

Perioperative Management of Patients with Pancreatic Cancer - the ERAS Protocols.

Background: Pancreatic cancer represents the fifth leading cause of death in industrialized countries. The prognosis is reserved, surgical resection being the only curative treatment, but the complications associated bear important impact on the patients survival, prognosis, and quality of life. The ERAS protocols come to meet these shortcomings for enhanced recovery after major pancreatic resections. Material and method: A systematic review was performed following the guidelines outlined by The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Original articles published in the online databases Pubmed (Medline), Embase and Cochrane since 2017 until 2022 were screened after using specific keywords. Results: A total of 252 studies was obtained by searching through online databases. Following the exclusion criteria, we included 7 studies in the systematic review. Conclusions: The ERAS protocols are safe to be applied in the common practice. They are efficient in the perioperative management of patients undergoing pancreatic resections. They can further decrease hospitalization stay, promote better recovery of gastrointestinal function, and speed up postoperative recovery.

Pancreatic Adenocarcinoma Associated to Intraductal Papillary Mucinous Neoplasia: Histopathological Particularities and Clinical Implications.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic tumor, known for an aggressive evolution. Intraductal papillary mucinous neoplasm (IPMN) is a rare pancreatic tumor, considered a premalignant lesion with the possibility of carcinogenesis towards PDAC. The clinical, surgical and histopathological particularities of the association between PDAC and IPMN are yet unknown, further research being needed. Methods: We have conducted a retrospective descriptive study, on a nine-year period (2012-2020), with the aim of comparing the characteristics of patients that underwent curative surgical interventions for solitary PDAC and PDAC associated to IPMN. Results: Fifteen patients with PDAC associated with IPMN (Group 1) and 386 patients with solitary PDAC (Group 2) were included in our study. Group 1 had a younger average age (61.8 years) compared to Group 2 (63.89 years). Total pancreatectomy was more frequently performed for Group 1 than Group 2 (33.33% vs 12.43%). Group 1 had a higher percentage of cases with positive perineural, perilymphatic and perivascular invasion. Group 1 registered a worse overall survival, as well as a worse short-time survival compared to Group 2. Conclusions: PDAC associated to IPMN registers distinct epidemiological, clinical and histopathological characteristics compared to solitary PDAC.

Emergency Pancreatoduodenectomy: A Non-Trauma Center Case Series.

(1) Background: Emergency pancreatoduodenectomy (EPD) is a rare procedure, especially in non-trauma centers. Pancreatoduodenectomy is a challenging intervention, that has even higher risks in emergency settings. However, EPD can be a life-saving procedure in selected cases. (2) Methods: Our study is a single-center prospective consecutive case series, on patients that underwent emergency pancreatoduodenectomies in our surgical department between January 2014 to May 2021. (3) Results: In the 7-year period, 4 cases were operated in emergency settings, out of the 615 patients who underwent PD (0.65%). All patients were male, with ages between 44 and 65. Uncontrollable bleeding was the indication for surgery in 3 cases, while a complex postoperative complication was the reason for surgery in one other case. In three cases, a classical Whipple procedure was performed, and only one case had a pylorus-preserving pancreatoduodenectomy. The in-hospital mortality rate was 25% and the morbidity rate was 50%; the two patients that registered complications also needed reinterventions. The patients who were discharged had a good long-term survival. (4) Conclusion: EPD is a challenging procedure, rare encountered in non-traumatic cases, that can be a life-saving intervention in well-selected cases, offering good long-term survival.

The Role of IL-22 in Wound Healing. Potential Implications in Clinical Practice.

Wound healing is a complex process that is mediated and influenced by several cytokines, chemokines, and growth factors. Interleukin-22 (IL-22) is a cytokine that plays a critical role in tissue regeneration. Our study is a systematic review that addressed the implications of IL-22 in the healing of wounds caused by external factors. Thirteen studies were included in our review, most of them being experimental studies. Three clinical studies underlined the potential role of IL-22 in day-to-day clinical practice. IL-22 plays a central role in wound healing, stimulating the proliferation, migration, and differentiation of the cells involved in tissue repair. However, overexpression of IL-22 can cause negative effects, such as keloid scars or peritoneal adhesions. The results of the presented studies are promising, but further research that validates the roles of IL-22 in clinical practice and analyzes its potential implication in surgical healing is welcomed.

Preventing Breast Cancer-Related Lymphedema: Feasibility of Axillary Reverse Mapping Technique.

INTRODUCTION: Our study aimed to determine the feasibility of axillary reverse mapping (ARM) technique, the identification rate of ARM nodes and their metastatic involvement, as well as to identify the factors that influence the identification and metastatic involvement. MATERIAL AND METHODS: In total, 30 breast cancer patients scheduled for axillary lymph node dissection were enrolled in our study. The lymphatic nodes that drain the arm were identified by injecting 1 mL of blue dye in the ipsilateral upper arm; then, the ARM nodes were resected along with the other lymph nodes and sent for histological evaluation. RESULTS: Identification of ARM node was successful in 18 patients (60%) and 22.22% of the identified ARM lymph nodes had metastatic involvement. Patients with identified ARM nodes had a significant lower BMI and a statistically significant relationship between axillary lymph node status and ARM node metastases was proven. Most of ARM lymph nodes (96.3%) were found above the intercostobrachial nerve, under the axillary vein and lateral to the thoracodorsal bundle. CONCLUSIONS: The ARM procedure is easy to reproduce but might not be appropriate for patients with a high BMI. The rate of metastatic involvement of ARM nodes is significant and no factor can predict it, showing that the preservation of these nodes cannot be considered.

Is There a Role for Surgery in BCLC B Hepatocellular Carcinoma?

Intermediate stage hepatocarcinoma, classified b Barcelona Clinic Liver Cancer (BCLC) comprises a large number of patients, with diverse characteristics, being defined by multiple tumours, preserved liver function and good performance status. The recommended treatment for this stage is transarterial chemoembolization (TACE), but there are a few studies that discuss the role of surgery in this stage. We report a case of a 59-year-old woman diagnosed with BCLC B hepatocarcinoma (two tumours of 34 and 25 mm, in liver segments 5 and 6) who was successfully treated with surgical resection. This patient had additional risk factors like morbid obesity, clinically significant portal hypertension, and thrombocytopenia. Despite these characteristics, the evolution was favourable. In conclusion, we believe that surgery has an important role in the treatment of well-selected BCLC B patients and a good preoperative assessment of the patient can minimize the perioperative risk.

Synchronous Pancreatic Tumours: Intraductal Papillary Mucinous Neoplasm with Pancreatic Ductal Adenocarcinoma and Neuroendocrine Tumour: A Case Presentation and Review of Literature.

Synchronous tumours of the pancreas are rare encounters, with few reported cases. Thus, new information can be brought about the diagnosis, proper management, and prognosis of cases. We believe that the presentation of this case can help to establish relevant conclusions. We report the case of a 54-year-old man, with the preoperative diagnosis of a cephalic intraductal papillary mucinous neoplasm (IPMN), who underwent a planned cephalic pancreatoduodenectomy with completion to total pancreatectomy based on the intraoperative extemporaneous histopathological examination of the resection margin. The final histopathological diagnosis was cephalic IPMN associated with invasive ductal adenocarcinoma (PDAC) and a small well-differentiated neuroendocrine tumour (NET) in the tail of the pancreas. No recurrence was detected in the 3 years of follow-up. We conducted a review of the literature to illustrate the particularities of the presented case; it identified 4 articles about the association of PDAC and NET and 8 articles regarding the association of IPMN with NET. Only 2 patients had a histopathological diagnosis of three synchronous tumours (IPMN, PDAC, and NET). We present a rare case of three synchronous pancreatic tumours, with a favourable evolution after a total pancreatectomy, only two other similar cases being reported in medical literature.

Neutrophils-to-lymphocytes, lymphocytes to-monocytes and platelets-to-lymphocytes ratios - predictive biomarkers for response to neoadjuvant chemotherapy in breast cancer.

PURPOSE: Several biomarkers have been reported to correlate with neoadjuvant chemotherapy response. Our aim was to establish the correlation between neutrophils-to-lymphocytes (NLR), lymphocytes-to-monocytes (LMR), and platelets-to-lymphocytes ratios (PLR) and the Miller Payne grade (MPG) and Residual Cancer Burden Score (RCB), as indicators to response to chemotherapy. METHODS: Data were retrospectively collected from the First Surgical Clinic database between January 2016 and December 2018. RESULTS: 96 patients were included in the study. The multivariate regression analysis showed a statistical correlation between oestrogen (ER) and progesterone receptor (PR) status, Ki67 over 15%, and tumour infiltrating lymphocytes (TILs) and MPG and RCB. For the three studied ratios, p value was statistical not significative. ROC curve showed a cut-off value of 2.7 NLR, for which correlation with the pathological complete response to chemotherapy (pCR) was significative (p=0.03). CONCLUSIONS: Our findings suggest that NLR can be a predictive biomarker for pCR. Further studies, on larger sample size, are necessary to establish the correlation with MPG and RCB.

Can Tumor-Infiltrating Lymphocytes (TILs) Be a Predictive Factor for Lymph Nodes Status in Both Early Stage and Locally Advanced Breast Cancer?

The status of axillary lymph nodes is an important prognostic factor in the outcome of breast cancer tumors. New trials changed the attitude towards axillary clearance. In the era of development of new immune therapies for breast cancer, it is important to identify a biomarker that can predict lymph node status. Tumor-infiltrating lymphocytes (TILs) are a valuable indicator of the immune microenvironment that plays the central role in new anticancer drugs. Although the correlation between TILs and response to chemotherapy was established by previous studies, our retrospective study investigated the correlation between TILs and lymph node status. We analyzed data on 172 patients. According to stage, patients were divided in two groups: patients who underwent primary surgical treatment (breast-conserving or mastectomy and sentinel lymph node (SLN) biopsy +/- axillary clearance in conformity with lymph node status) and patients who received chemotherapy prior to surgical treatment (breast-conserving or mastectomy + axillary clearance). We showed a good inverse correlation between TILs and lymph nodes status for both early stage and locally advanced breast cancers. Moreover, TILs are a predictor for positive lymph nodes in the axilla in patients undergoing axillary clearance after SLN biopsy, with no statistical difference between the intrinsic or histological subtype of breast cancers. We also obtained a significant correlation between TILs and response to chemotherapy with no significative difference according to histological subtype. Although further data have still to be gathered before meeting the criteria for clinical utility, this study demonstrates that TILs are one of the most accredited forthcoming biomarkers for breast cancer (BC) patients.