Case Report: The molecular fingerprint and the clinical implication of an exceptional response to neoadjuvant therapy in a metastatic cardia adenocarcinoma.

Background: Globally, gastric cancer holds the fifth position in terms of prevalence among malignant tumors and is the fourth leading cause of cancer-related mortality. Particular attention should be paid to cardia adenocarcinoma (CA) due to its increasing incidence and poor prognosis. Diagnosis of CA frequently occurs in advanced stages because of its late symptoms. In such cases, neoadjuvant chemotherapy is the primary treatment option. The response to chemotherapy depends on multiple variables including the tumor's molecular profile, the patient's performance status, and the feasibility of using targeted therapy. Patients exhibiting an exceptional response, defined as a complete response to medical therapy lasting more than 1 year, or a partial response or stable disease lasting more than 2 years, are rarely described. This case report presents one of the longest-lasting exceptional responses to chemotherapy in metastatic cardia adenocarcinoma and discusses its clinical implications. Case presentation: A 49-year-old male patient presented with cardia adenocarcinoma (human epidermal growth factor receptor 2 negative, mismatch repair proficient) and liver metastases. Molecular profiling identified a pathogenic mutation in the TP53 gene (R123W; Arg123Trp) as the sole alteration found. Five months after initiating the neoadjuvant chemotherapy with fluorouracil-leucovorin-oxaliplatin-docetaxel, the patient achieved a complete clinical response. The molecular profile was compared with others previously documented in an international data portal, revealing a similar pattern. At 4 years and 3 months from diagnosis, the exceptional response was still confirmed. The patient underwent a cumulative number of 33 cycles of chemotherapy, leading to chemotherapy-induced liver damage. Conclusions: Exceptional responses to neoadjuvant chemotherapy in cardia adenocarcinomas are rarely reported. The documentation of exceptional responses to cancer therapies should be included in large data repositories to explore the molecular fingerprint of these tumors. In such cases, the clinical implications of long-term chemotherapy should always be taken into account.

Treatment of oligo-metastatic pancreatic ductal adenocarcinoma to the liver: is there a role for surgery? A narrative review.

Pancreatic ductal adenocarcinoma (PDAC) is a prognostically unfavorable malignancy that presents with distant metastases at the time of diagnosis in half of patients. Even if patients with metastatic PDAC have not been traditionally considered candidates for surgery, an increasing number of researchers have been investigating the efficacy of surgical treatment for patients with liver-only oligometastases from PDAC, showing promising results in extremely selected patients, mainly with metachronous metastases after perioperative chemotherapy. Nevertheless, a standardized definition of oligometastatic disease should be adopted and additional investigations focusing on the role of perioperative chemotherapy and tumor biology are warranted to reliably assess the role of resection for PDAC metastatic to the liver.

Emerging Prognostic Markers in Patients Undergoing Liver Resection for Hepatocellular Carcinoma: A Narrative Review.

In patients with hepatocellular carcinoma (HCC), liver resection is potentially curative. Nevertheless, post-operative recurrence is common, occurring in up to 70% of patients. Factors traditionally recognized to predict recurrence and survival after liver resection for HCC include pathologic factors (i.e., microvascular and capsular invasion) and an increase in alpha-fetoprotein level. During the past decade, many new markers have been reported to correlate with prognosis after resection of HCC: liquid biopsy markers, gene signatures, inflammation markers, and other biomarkers, including PIVKA-II, immune checkpoint molecules, and proteins in urinary exosomes. However, not all of these new markers are readily available in clinical practice, and their reproducibility is unclear. Liquid biopsy is a powerful and established tool for predicting long-term outcomes after resection of HCC; the main limitation of liquid biopsy is represented by the cost related to its technical implementation. Numerous patterns of genetic expression capable of predicting survival after curative-intent hepatectomy for HCC have been identified, but published findings regarding these markers are heterogenous. Inflammation markers in the form of prognostic nutritional index and different blood cell ratios seem more easily reproducible and more affordable on a large scale than other emerging markers. To select the most effective treatment for patients with HCC, it is crucial that the scientific community validate new predictive markers for recurrence and survival after resection that are reliable and widely reproducible. More reports from Western countries are necessary to corroborate the evidence.

Right hepatectomy compared with left hepatectomy for resectable Klatskin tumor: A systematic review across tumor types.

BACKGROUND: The prognosis of Klatskin tumors is poor, and radical surgery with disease-free surgical margins (R0) represents the treatment capable of ensuring the best long-term outcomes. In patients with Klatskin tumors, both right hepatectomy and left hepatectomy might achieve R0 surgical margins. This systematic review concentrated on a comparative investigation between left hepatectomy and right hepatectomy, aiming to furnish clinical evidence and to aid in surgical decision-making for Klatskin tumor depending on its spread within the bile duct tree. METHODS: The eligible articles in the study were obtained from PubMed, Medline, and Scopus databases, following the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis, and they were categorized according to the type of Klatskin tumor treated with right hepatectomy or left hepatectomy. The studies that analyzed the outcomes related to the 2 surgical techniques without focusing on the type of Klatskin tumor were included in a separate paragraph and table. RESULTS: In total, 21 studies were included. Four studies reported outcomes of right hepatectomy or left hepatectomy for Klatskin type I/II tumor, 2 for Klatskin type II/IV tumor, 2 for Klatskin type III tumor, and 2 for Klatskin type IV. Eleven studies included the outcomes of right hepatectomy and left hepatectomy for hilar cholangiocarcinoma without specifying the type of Klatskin tumor. Although long-term oncologic outcomes seem comparable between right hepatectomy and left hepatectomy when achieving R0 resection for Klatskin type III/IV tumors, there may exist a marginal oncologic edge and reduced complication rates favoring left hepatectomy in individuals with Klatskin type I/II tumors. DISCUSSION: Right hepatectomy traditionally has played a central role in treating Klatskin tumor, but recent studies have questioned its oncologic efficacy and surgical risks. Currently, there is a lack of evidence regarding the ideal surgical approach for each type of Klatskin tumor, and surgical strategy relies heavily on the individual surgeon's experience and technical skills. The management of Klatskin tumors necessitates specialized hepatobiliary surgical centers capable of conducting major hepatectomy with thorough lymphadenectomy, biliary, and vascular reconstructions. There is a need for studies with larger sample sizes to achieve a wide consensus about the superiority of one surgical technique over the other in cases in which both right hepatectomy and left hepatectomy can achieve an R0 margin.

Splenic abscess with spontaneous gastrosplenic fistula: case report and review of the literature.

Gastrosplenic fistula (GSF) is an unusual event that might occur in patients with various gastric or splenic diseases. While GSF related to gastric and splenic malignancies is well-documented in the literature, cases of GSF due to a splenic abscess are extremely rare. We experienced the case of a 49-year-old man with a medical history of tricuspid cardiac valve replacement for infective endocarditis who presented with a sudden onset of anemia and melena. With the assistance of imaging and endoscopy, a primary splenic abscess complicated by spontaneous GSF was diagnosed. A prompt splenectomy with partial gastrectomy was performed. GSF is a serious occurrence associated with a high risk of morbidity and mortality. The early recognition of GSF related to a splenic abscess is crucial to prevent major complications. Surgical resection with splenectomy and partial gastrectomy is frequently preferred for the treatment of large abscesses with GSF.

The Impact of KRAS Mutational Status on Long-Term Survival following Liver Resection for Hilar Cholangiocarcinoma.

KRAS mutation is reportedly associated with poor prognosis in patients with different cancer types. However, mutational data on hilar cholangiocarcinoma are few and controversial. The aim of this study was to evaluate the rate of KRAS mutations in a single-center homogeneous population resected for hilar cholangiocarcinoma and the subsequent impact on prognosis. KRAS mutation status was evaluated in 54 patients undergoing major hepatectomy combined with resection of the main biliary confluence and regional lymphadenectomy for hilar cholangiocarcinoma between 2001 and 2019. Among these 54 patients, 12 (22.2%) had a KRAS mutation. KRAS mutation was not related with pathologic characteristics of the tumor. Five-year overall survival (OS) in patients with KRAS mutation was significantly lower than that observed in patients with KRAS wild type (0 vs. 49.2%, respectively; p = 0.003). In the multivariable analysis; independent predictors of poor OS were KRAS mutation (HR = 5.384; p = 0.003) and lymph node metastases (HR = 2.805; p = 0.023). The results of our study suggested that KRAS mutation in hilar cholangiocarcinoma was not rarely observed. KRAS mutation was an independent strong predictor of poor OS. KRAS mutation analysis should be included in the routine pathologic evaluation of resected hilar cholangiocarcinoma in order to better stratify prognosis.

Native Nephrectomy in Patients With Autosomal Dominant Polycystic Kidney Disease Evaluated for Kidney Transplantation.

Native nephrectomy (NN) in patients with autosomal dominant polycystic kidney disease (ADPKD) is indicated in cases of recurrent urinary tract infections and hematuria, neoplastic degeneration, and encumbrance. Timing, indication, and surgical approach of NN depends on the symptoms or policy of the center. The aim of our study is to evaluate our experience. In our retrospective study, we included 130 patients with a diagnosis of ADPKD from 530 patients evaluated for renal transplantation from 2011 to 2017. We analyzed the etiologic indication, the timing, and the complications of NN. In our cohort, 53 patients underwent open NN, 85% pre-kidney transplantation (KT), 13% post-KT, and only 1 case simultaneous with KT. In the pre-KT group, indications included: major indication was encumbrance in the. In the post-KT group, the major indication was infection followed by encumbrance, which developed after KT. Complications were: 3 cases of bleeding (1 required relaparotomy, 2 evolved into hematoma and radiological derange); 1 iatrogenic iliac artery injury, which was contextually repaired, and 5 cases of incisional hernia. At 35 ± 7.2 months follow-up, patients' survival was 96%; 1 patient died at the induction of anesthesia and 1 patient from sepsis after double NN and removal of nonfunctional transplanted kidney. NN is not without complications and should be performed when clearly indicated. In our experience, we preferred to perform NN before KT.