A Case of a Metastatic Pancreatic Neuroendocrine Tumor: A Surgical Conundrum Wrapped in Functionality's Embrace.

This case study reports a rare case of a non-functioning metastatic pancreatic neuroendocrine tumor (pNET) transforming into a functioning pNET. A 59-year-old male, previously treated with distal pancreatectomy, splenectomy, lymph node dissection, liver metastasectomy, and pharmacotherapy, presented with weakness, hypoglycemia, and daily episodes of watery diarrhea. A functioning neuroendocrine liver metastasis expressing insulin and gastrin was identified. Surgical intervention, including left lateral hepatectomy and microwave ablation of multiple intrahepatic lesions, resulted in symptom resolution and uneventful recovery. However, metastatic liver disease re-emerged seven months post-surgery, necessitating chemotherapy. This case highlights the importance of vigilance for symptom development in non-functioning pNETs, signaling potential disease relapse and phenotype transformation, and suggests surgical treatment as a viable option in select cases.

Transverse colon diverticulitis mimicking acute appendicitis.

Diverticulitis in a solitary transverse colon diverticulum is uncommon, with only a handful of cases documented in the literature. There are various clinical manifestations of the disease, which make clinical and radiological diagnosis rather challenging. Herein, we present a case of a premenopausal female patient in her late 40s who presented to the emergency department, complaining of right lower quadrant abdominal pain, nausea, anorexia and fever. Following clinical, biochemical and radiological tests, the patient was prepared for surgical operation, with the presumed diagnosis of acute appendicitis. An appendicectomy was planned via a McBurney incision. Notably, no inflammation of the appendix was discovered. However, on further exploration, an inflammatory mass was identified in the transverse colon, which was subsequently excised and sent for histological examination. The histology results confirmed the presence of a ruptured solitary transverse colon diverticulum, accompanied by an adjacent mesenteric abscess. The patient's postoperative recovery was uneventful.

Clinical and Oncological Impact of the Toll-like Receptor-3 and -4 in Esophageal and Gastro-esophageal Junction Adenocarcinoma.

BACKGROUND/AIM: Esophageal and gastro-esophageal junction cancer is a major cause of cancer-related mortality, with poor prognosis. Toll-like receptors (TLRs) play a significant role in the innate immune system; their increased expression has been associated with esophageal adenocarcinoma. This study aimed to determine the association between TLR-3 and TLR-4 expression with clinical and oncological outcomes of patients that underwent esophagectomy for cancer. PATIENTS AND METHODS: This is a retrospective analysis of prospectively collected data from consecutive patients within a 2-year period. Primary endpoints of the study were the assessment of the expression of TLR-3 and TLR-4 in primary tumors as well as in metastatic lymph nodes. Secondary endpoints were the correlation of TLR-3 and TLR-4 values with the clinical, pathological, and oncological outcomes. RESULTS: A significantly higher expression of TLR-3 and TLR-4 in primary tumors and metastatic-lymph nodes was observed. There was a significant association between TLR-3 expression and T-stage, as well as TLR-4 expression and grade of differentiation in the primary site. Additionally, metastatic-lymph node TLR-4 expression was significantly correlated with N-stage. A strong correlation between TLR-4 expression and overall or progression-free survival rates was detected. CONCLUSION: This study found a significantly increased TLR expression in malignant tissue/metastatic lymph nodes, as well as a significant positive correlation between TLRs and worse clinical outcomes. TLRs have a pivotal role in the inflammation pathway in the esophagus and during esophageal carcinogenesis. This study highlights the need for further investigation into TLR-mediated signaling pathways and their potential role as diagnostic and therapeutic targets.

All you need to know about gastrinoma today | Gastrinoma and Zollinger-Ellison syndrome: A thorough update.

Zollinger-Ellison syndrome (ZES) is a distinct syndrome characterized by hyperchlorhydria-induced peptic ulcer disease and chronic diarrhea. It is the result of a gastrin-excess state caused by a duodenal or pancreatic neuroendocrine tumor referred to as gastrinoma. This gastrin-secreting neuroendocrine tumor is usually sporadic in nature, or part of multiple endocrine neoplasia type 1 syndrome. The high rate of malignancy associated with gastrinomas substantiates the need for early diagnosis. In order to diagnose ZES with laboratory tests, patients under antacid medication are required to stay off proton pump inhibitors for at least one week and H2 receptor antagonists for 48 h. Fasting serum gastrin level measurement serves as an initial and fundamental diagnostic test, boasting a sensitivity of 99%. Gastrinoma patients will present with a gastrin level greater than 100 pg/mL, while a serum gastrin level higher than 1000 pg/mL, in the presence of gastric pH <2, is considered diagnostic. Since more common causes of hypergastrinemia exist in the setting of hypochlorhydria, ruling those out should precede ZES consideration. Such causes include atrophic gastritis, Helicobacter pylori (H. pylori)-associated pangastritis, renal failure, vagotomy, gastric outlet obstruction and retained antrum syndrome. The secretin stimulation test and the calcium gluconate injection test represent classic adjuvant diagnostic techniques, while alternative approaches are currently being introduced and evaluated. Specifically, the secretin stimulation test aids in differentiating ZES cases from other hypergastrinemic states. Its principle is based on secretin stimulation of gastrinoma cells to secrete gastrin, while inhibiting normal G cells. The rapid intravenous infusion of 4 µg/kg secretin over 1 min is followed by gastrin level evaluation at specific intervals post-infusion. Localization of the primary tumor and its metastases is the next diagnostic step when gastrinoma-associated ZES is either suspected or biochemically confirmed. Endoscopic ultrasound has showcased sensitivity as high as 83% for pancreatic gastrinomas and is considered the primary modality in such cases, although its tumor detection rates are substantially lower in duodenal lesions. Gallium-68 radiotracers, especially DOTATOC with positron emission tomography, are currently setting the standard in tumor localization, enhancing traditional imaging techniques and showcasing high sensitivity and specificity. Although gastrinomas have been reported in various anatomic locations, the vast majority arise in a specific site named the "gastrinoma triangle", involving parts of the duodenum, pancreas and extra-hepatic biliary system. Proton pump inhibitors serve as the cornerstone of symptomatic ZES treatment. Surgery is routinely performed in localized sporadic ZES, irrespective of imaging results. ZES in multiple endocrine neoplasia type 1 requires work-up for evaluation and treatment of hyperparathyroidism, while surgery might be an option for selected cases. In cases of advanced and metastatic disease, there is a variety of potential treatments, ranging for somatostatin analogs to chemotherapeutic drugs, liver-directed therapies and liver transplantation, while neither hepatic metastases, nor locally invasive disease necessarily preclude surgical management. This article thoroughly and critically reviews available literature and provides an extensive and multidimensional overview of ZES, along with current controversies regarding management of this disease.

The Prognostic Role of GLIM Criteria in Postoperative Outcomes after Upper Gastrointestinal Cancer Surgery: A Meta-Analysis of Observational Studies.

Oncologic patients often suffer from malnutrition, which might negatively affect treatment outcomes. Global Leadership Initiative on Malnutrition (GLIM)-based malnutrition is associated with short- and long-term outcomes in cancer patients. The aim of the current meta-analysis was to determine the impact of GLIM-defined malnutrition on postoperative complications and survival in esophageal and gastric cancer patients. A systematic search was conducted to identify studies published until February 2022 that assessed the association between GLIM criteria and short- and long-term outcomes in esophageal and gastric cancer patients. We included seven observational studies reporting on a total of 3662 patients with esophageal and gastric cancer. GLIM-defined malnutrition was associated with increased overall complications (pooled HR 2.58, 95% CI 1.45-4.59, p = 0.001). Malnutrition was significantly associated with decreased overall survival (pooled HR 1.63, 95% CI 1.18-1.84, p = 0.003) as well as with decreased disease-free survival (pooled HR 1.78, 95% CI 1.36-2.33, p < 0.0001). GLIM-based malnutrition was associated with an increased risk for developing postoperative complications and impaired survival of esophageal and gastric cancer patients. Our findings support the use of GLIM criteria in clinical practice as a relatively simple and reliable tool for assessing the nutritional status of oncologic patients.

Tissue classification and diagnosis of colorectal cancer histopathology images using deep learning algorithms. Is the time ripe for clinical practice implementation?

Colorectal cancer is one of the most prevalent types of cancer, with histopathologic examination of biopsied tissue samples remaining the gold standard for diagnosis. During the past years, artificial intelligence (AI) has steadily found its way into the field of medicine and pathology, especially with the introduction of whole slide imaging (WSI). The main outcome of interest was the composite balanced accuracy (ACC) as well as the F1 score. The average reported ACC from the collected studies was 95.8 ±3.8%. Reported F1 scores reached as high as 0.975, with an average of 89.7 ±9.8%, indicating that existing deep learning algorithms can achieve in silico distinction between malignant and benign. Overall, the available state-of-the-art algorithms are non-inferior to pathologists for image analysis and classification tasks. However, due to their inherent uniqueness in their training and lack of widely accepted external validation datasets, their generalization potential is still limited.

The Expression Patterns and Implications of MALAT1, MANCR, PSMA3-AS1 and miR-101 in Esophageal Adenocarcinoma.

Esophageal adenocarcinoma (EAC) is a malignant tumor with poorly understood molecular mechanisms. This study endeavors to elucidate how the long non-coding RNAs (lncRNAs) MALAT1, MANCR and PSMA3-AS1, as well as the microRNA miR-101, exhibit specific expression patterns in the pathogenesis and prognosis of EAC. A total of 50 EAC tissue samples (tumors and lymph nodes) and a control group comprising 26 healthy individuals were recruited. The samples underwent quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses. The relative expression levels of MALAT1, MANCR, PSMA3-AS1, and miR-101 were ascertained and correlated with various clinicopathological parameters including TNM staging, tumor characteristics (size and grade of the tumor) lymphatic invasion, disease-free (DFS) and overall survival (OS) of EAC patients. Quantitative analyses revealed that MALAT1 and MANCR were significantly upregulated in EAC tumors and positive lymph nodes when compared to control tissues (p < 0.05). Such dysregulations correlated positively with advanced lymphatic metastases and a higher N stage. DFS in the subgroup of patients with negative lymph nodes was higher in the setting of low-MANCR-expression patients compared to patients with high MANCR expression (p = 0.02). Conversely, miR-101 displayed a significant downregulation in EAC tumors and positive lymph nodes (p < 0.05), and correlated negatively with advanced tumor stage, lymphatic invasion and the grade of the tumor (p = 0.006). Also, patients with low miR-101 expression showed a tendency towards inferior overall survival. PSMA3-AS1 did not demonstrate statistically significant alterations (p > 0.05). This study reveals MALAT1, MANCR, and miR-101 as putative molecular markers for prognostic evaluation in EAC and suggests their involvement in EAC progression.

Surgical management in hepatocellular carcinoma with portal vein tumour thrombosis: is this the end of the road or a chance to expand the criteria for resectability?

Portal vein thrombosis is a common complication associated with malignancies such as hepatocellular carcinoma, with a dismal and negative impact on prognosis. A thorough literature search in Pubmed and Google Scholar, under the terms 'hepatocellular carcinoma AND portal vein thrombosis', regarding the surgical management of portal vein thrombosis was conducted by the authors, and the associated results are presented in this narrative review. Precise classification of portal vein thrombosis and identification of subgroups of patients that will benefit from surgery is of paramount importance. Evolution of novel surgical techniques in liver resection and associated low morbidity and mortality rates in specialized hepatobiliary centres worldwide have been linked with promising results from the adoption of surgical management in these patients, when compared to systemic chemotherapy or arterial chemoembolization management that has traditionally been followed in such cases.

The impact of surgery delay on survival of resectable pancreatic cancer: A systematic review of observational studies.

BACKGROUND: Pancreatic cancer is considered a lethal disease and the only potentially curative option is R0 excision. The aim of this study was to investigate whether the waiting time interval from diagnosis to surgical treatment affects overall survival in patients who undergo curative-intent surgery for pancreatic cancer. METHODS: Search in Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases was conducted from inception until April 2022. RESULTS: Overall, 10 studies were included that enrolled 181,344 patients. The dominating cut-off time point was 4 weeks in studies which utilized a biphasic waiting time pattern. In addition, prolonged waiting time interval was associated with decreased overall survival in 3 studies, whereas it demonstrated a favorable effect on overall survival in 2 studies and no impact on survival in 5 studies. CONCLUSION: The great diversity that was observed regarding the impact of surgery delay on survival underlines the lack of knowledge about biologic pathways of pancreatic cancer. Novel imaging studies and molecular "fingerprints" in combination to time-to-treatment standardization in the design of future randomized trials could lead to the recognition of patients that could benefit from a timely resection.

Primary Synovial Sarcoma of the Kidney: Diagnostic Approach and Therapeutic Modalities for a Rare Nosological Entity.

Synovial sarcoma (SS) is a rare mesenchymal entity that represents 5-10% among soft tissue sarcomas (STS). Primary renal synovial sarcoma (PRSS) is an uncommon, rapidly growing tumor, with potential metastatic dissemination. The main prognostic factors of PRSS include tumor size and histologic grade, while translocation t (X; 18) (p11.2; q11.2) (fusion of SYT gene -chromosome 18- with SSX genes (1, 2 or 4)-chromosome X) is the most common pathognomonic sign. Aggressive surgical resection of the tumor along with concomitant regional lymphadenectomy is the treatment of choice for PRSS, while additional en bloc resection of the adjacent affected organs is often performed. To date, the role of preoperative or postoperative chemotherapy remains equivocal. The prognosis of patients with PRSS is poor, as the 5-year survival rate is only 20-30% and further deteriorates when a high mitotic activity is detected. Local recurrence even after complete R0 surgical excision remains the most frequent cause of death. The aim of this review was to meticulously discuss clinical features, histogenesis, and morphological and immunochemical findings of PRSS, while the role of current diagnostic and therapeutic management of this aggressive neoplasm was emphasized.

Radiation-Induced Esophageal Cancer: Investigating the Pathogenesis, Management, and Prognosis.

One of the most serious late side effects of irradiation is the promotion of tumorigenesis. Radiation-induced esophageal cancer (RIEC) can arise in a previously irradiated field, mostly in patients previously irradiated for thoracic malignancies such as breast cancer, Hodgkin and non-Hodgkin lymphomas, head and neck cancers, lung cancer, or previous esophageal cancer. RIEC is rare and accounts for less than 1% of all carcinomas of the esophagus. There are little data available in the current literature regarding pathogenesis, diagnosis, treatment, and outcome of esophageal cancer developed in a previously irradiated field. RIEC seems to represent a biologically aggressive disease with a poor prognosis. Although it is difficult to perform radical surgery on a previously irradiated field, R0 resection remains the mainstay of treatment. The use of neoadjuvant and adjuvant chemoradiotherapy remains very helpful in RIEC, similarly to conventional esophageal cancer protocols. The aim of this article is to elucidate this rare but challenging entity.

Surgical management of familial pancreatic cancer: a systematic review of the literature.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the third most common cause of cancer-related mortality. The fact that the vast majority of patients with PDAC are diagnosed at an advanced stage highlights the need of early diagnosis. As hereditary factors are associated with approximately 5% of all PDAC cases, a screening programme to these high-risk individuals (HRI) has been proposed. The aim of screening methods is to identify selected group of patients with morphological abnormalities at an early stage, in order to be treated promptly. In this study, we evaluate the surgical outcomes and the appropriateness of pancreatic resection in HRIs who were selected for screening. METHODS: A systematic literature search of the PubMed, Embase, and Cochrane databases was performed. The clinicopathological features were recorded and evaluated. RESULTS: Six studies were selected for data collection. A total number of 77 patients were identified. Twenty-one patients had a germline mutation, with CDKN2A being the most prominent one (15.6%). Distal pancreatectomy was the most common surgical procedure (42.8%), followed by pancreaticoduodenectomy (33.8%). The mean disease-free survival was 23.6 months and tumour recurrence occurred in 9 patients (11.7%). Disease-specific mortality was 17.8%, while overall mortality was 19.5%. The most frequently reported postoperative diagnosis was PDAC (28 cases, 38.9%), followed by IPMN (23 cases, 31.9%), whereas high-grade PanIN lesions were found in 13 patients (18.1%). CONCLUSION: High-risk individuals for pancreatic cancer, who are eventually operated may have a relatively uneventful postoperative course, however the oncological outcomes are comparable to the general population.

Postoperative sepsis after colorectal surgery: a prospective single-center observational study and review of the literature.

Introduction: Postoperative sepsis represents a significant problem in colorectal surgery patients. Aim: To identify the etiology as well as the risk factors associated with the development of postoperative sepsis, based on prospective data of patients undergoing colorectal surgery at a single large-volume institution. Material and methods: Between November 2019 and February 2021, 141 patients underwent an elective operation for colorectal cancer at a tertiary hospital center. The following variables were recorded for each patient: age, gender, American Society of Anesthesiologists Classification (ASA class), duration of surgery, surgical approach, comorbidities (diabetes, cardiovascular disease, respiratory disease). Univariate analysis was performed using χ2 tests for categorical variables. Results: A total of 69 males and 72 females were enrolled. Postoperative sepsis was diagnosed in 18 (12.77%) cases, with anastomotic leakage being the most frequent cause (3.55%). There was no statistically significant difference in the presence of sepsis among patients when gender, surgical approach, duration of surgery, and respiratory disease were taken into account. Sixty-nine patients were > 65 years old, with sepsis being statistically significant in this group (p = 0.034). Furthermore, patients with ASA class ≤ 2 developed postoperative sepsis less frequently than patients with advanced ASA scores (p = 0.008). Diabetes and cardiovascular disease also reach statistical significance; sepsis was more frequent in this group of patients (p = 0.013 and p = 0.009, respectively). Conclusions: Following colorectal cancer procedures, postoperative sepsis was significantly more common among patients over 65 years old, ASA score > 2, and also with associated comorbidities such as diabetes and cardiovascular disease.

Bochdalek hernias in the adult population: a systematic review of the literature.

BACKGROUND: Bochdalek hernia (BH) is characterized by the protrusion of viscera into thorax through the posterolateral section of the diaphragm. The aim of this study was to systematically review current literature concerning Bochdalek hernias in adults and elucidate their clinical characteristics and preferable treatment approach. METHODS: A search of PubMed and Cochrane bibliographical databases for studies regarding BHs was conducted (last search: 31st March 2021). RESULTS: Predefined inclusion criteria were met by 173 articles and concerned collectively 192 patients (50.5% males) with a mean age of 45.41 ± 20.26 years. Abdominal pain (62.0%) and pulmonary symptoms (41.1%) were the predominant symptomatology of included cases. BHs protruded mainly through the left side of the diaphragm (70.7%), with large intestine (42.7%) and stomach (37.1%) being the most commonly herniated abdominal organs. Most patients (53.8%) underwent an open surgical approach, while abdominal approach was preferred (64.8%). to the thoracic one. Thirty-day postoperative complication were encountered at 21.5% of patients, while 30-day mortality reached 4.4%. CONCLUSION: BH is an extremely rare type of congenital diaphragmatic hernia. It rarely concerns adults, and it manifests with vague gastrointestinal or pulmonary symptoms. Surgical approach is the preferred method for their management with open procedures being preferable at emergency cases, while minimal invasive approach necessitates experienced centers. Further research is needed in order to clarify their true incidence and optimal therapeutic strategy.

Growth of Intestinal Neomucosa on Pedicled Gastric Wall Flap, a Novel Technique in an Animal Model.

Background: Short bowel syndrome (SBS) remains an unsolved issue in modern medicine. Numerous experimental surgical techniques have been proposed in the attempt to increase the intestinal absorptive capacity.Materials and Methods: Ten female Landrace pigs, divided in two groups of 5 (A and B), were explored through a midline incision. A spindle-shaped vascularized full-thickness gastric wall flap (GWF) consisting of part of the major curvature with the gastroepiploic arch preserved was de-epithelialized and then placed as a "patch" to cover an antimesenteric border defect of either a nonfunctional blind intestinal loop (group A) or a functional intestinal loop of the gastrointestinal tract (group B). A spindle-shaped curved, rigid, low density polyethylene (LDPE) splint was sutured on the external surface of the patch in order to prevent shrinkage of GWF and collapse of the intestinal wall in group A.Results: There was a decrease of both dimensions of the patch. Microscopically a thin layer of columnar epithelial cells covered the center of the patch, evolving in shorter, blunt, poorly developed villi with increasing maturation laterally. The patch surface was covered by nearly 90%. In the three animals that died prematurely the coverage of GWF was negligent or suboptimal directly dependent on the length of survival.Conclusions: The hereby-described patching technique demonstrated the growth of intestinal neomucosa on the GWF. The capability of the stomach to provide large flaps and the advantages of the use of native tissues render this animal model valuable for the future research in the field.

Revision of Roux-en-Y Gastric Bypass for Inadequate Weight Loss or Weight Regain.

Inadequate weight loss or weight regain after Roux-en-Y gastric bypass (RYGBP) occurs in more than a quarter of patients for various reasons. Available remedying treatment options include endoscopic and surgical techniques for revision of the gastric pouch and the gastro-jejunal anastomosis, conversion of standard to distal gastric bypass (DRYGBP) or the conversion of RYGBP to biliopancreatic diversion (BPD) or duodenal switch (DS). There is quite a variability concerning the technical simplicity, safety, and effectiveness of these techniques and the small number of patients in the numerous single-center reports precludes any meaningful comparisons. This review aimed to describe all available methods and present the advantages and disadvantages of each of them, to facilitate, rather than guide, the decision of the average bariatric surgeon who encounters such a patient.

Immunotherapy for gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): a 2021 update.

Neuroendocrine neoplasms (NENs) are a group of heterogeneous malignancies, arising from the neuroendocrine system. These neoplasms are divided into two distinct groups, the low-proliferating, well-differentiated neuroendocrine tumors (NETs), and the highly-proliferating, poorly-differentiated neuroendocrine carcinomas (NECs). Recent data demonstrate that the incidence of gastroenteropancreatic (GEP) neuroendocrine neoplasms, GEP-NETs and GEP-NECs, has increased exponentially over the last three decades. Although surgical resection is considered the best treatment modality, patients with GEP-NETs often present with advanced disease at diagnosis associated with a 5-year survival rate of 57% for well-differentiated tumors, and only 5.2% for small-cell tumors. Immunotherapy is a novel treatment approach, which has demonstrated effective and promising therapeutic results against several types of cancers. In the present study, we review the current ongoing clinical trials and to evaluate the efficacy of immunotherapy in GEP-NENs. Furthermore, we analyze the importance of tumor genetic profiling and its clinical implications in immunotherapy response.

Chyle leak after major pancreatic surgery. Is this an underestimated complication? A narrative review of the literature.

PURPOSE: Postoperative chyle leak, termed 'chylous ascites', is a rare complication with a reported frequency of only one in 20464 abdominal operations. The purpose of this study was to summarize the available scientific data reviewing the most relevant studies for this type of postoperative complication after pancreatic surgery, highlighting at the same time the necessity for pancreatic surgeons to retain a high level of clinical suspicion for the early diagnosis and its therapeutic management. METHODS: A thorough literature search in Pubmed and Google Scholar, under the terms' chylous ascites OR chyle leak AND pancreas OR pancreatic', since the year of inception until 19th of February 2021 was conducted by the authors and the associated results are presented in this narrative review. RESULTS: Chyle leak is a rare complication following pancreatic surgery. Patients may suffer from exudative enteropathy and malnutrition leading to repeated infections and impaired wound healing or even death secondary to sepsis. Several studies have highlighted the issue of increased hospital stay, while others failed to reach statistical significance as far as hospital stay or survival are concerned. Researchers found that patients with diffuse chyle leak tended to have a worse 3-year survival rate (18.8%), which can be attributed to postoperative complications and early demise due to immunosuppression associated with the leak, or delayed adjuvant chemotherapy Conclusion: Further clinical research is needed to enhance prevention, diagnosis, treatment and long-term prognosis of this relevant surgical problem that shows trends of increase due to the great number of major operations which are performed nowadays.

A personalized approach to pancreatic ductal adenocarcinoma and its application in surgical practice.

Pancreatic duct adenocarcinoma is an aggressive tumor which constitutes the fourth leading cause of cancer-related mortality in the USA. Despite the fact that surgery is an integral part of treatment, 5-year survival rates remain unfavorable, partly because of the complex genetic background, delayed diagnosis and also the absence of effective therapeutic approaches. To optimize surgery's results in recent years, the use of patients' genetic profile has been implemented through classification into subtypes; subtypes based on mutations which could efficiently lead oncologists to the path of targeted novel neoadjuvant regimens. This approach aims to achieve the most effective selection of patients undergoing surgery, to increase the number of potentially resectable tumors and also control micro-metastases, aiming to extend overall survival.