NOVA2 regulates the properties of liver cancer stem cells and lenvatinib resistance in hepatocellular carcinoma via the Wnt pathway.

Background: The regulation of cancer stem cells (CSCs) is influenced by RNA-binding proteins (RBPs). The present study sought to investigate the role of NOVA2 in the processes of self-renewal, carcinogenesis, and lenvatinib resistance in liver CSCs. Methods: Neuro-oncological ventral antigen 2 (NOVA2) expression in liver CSCs was examined by real-time polymerase chain reaction (PCR). In vitro experiments were used to assess the effects of NOVA2 on liver CSC expansion and lenvatinib resistance. Results: In our study, the expression of the RBP NOVA2 was higher in CSCs. NOVA2 also increased the capacity for self-renewal and carcinogenesis of the liver CSCs via the Wnt pathway. Further, suppressing the Wnt pathway leads to desensitization of the hepatocellular carcinoma (HCC) cells that overexpress NOVA2 to apoptosis caused by lenvatinib. Analyzing patient data confirmed reduced levels of NOVA2 and therefore we speculate that NOVA2 may serve as a potential indicator for response to lenvatinib in patients with HCC. Methyltransferase-like 3 (METTL3) and YTH N6-methyladenosine RNA-binding protein 1 (YTHDF1)-dependent N6-methyladenosine (m6A) methylation were linked to upregulation of NOVA2 in HCC. Furthermore, it was shown that the expression of METTL3 was elevated in cellular models of type 2 diabetes mellitus (T2DM). Conclusions: NOVA2 is involved in the process of liver CSC self-renewal and carcinogenesis. In addition, NOVA2 expression may help identify patients with a higher chance of benefiting from lenvatinib treatment and can be a promising therapeutic target for HCC.

Identification of a prognostic disulfidptosis-related gene signature in hepatocellular cancer.

Background: Disulfidptosis regulate various biological processes in cancer. However, there is limited research on the genes related to disulfidptosis in predicting the prognosis of hepatocellular carcinoma (HCC). We aimed to develop a reliable disulfidptosis-related gene signature, which will characterize different HCC subtypes and predict their prognosis. Methods: The Cancer Genome Atlas (TCGA)-HCC dataset, comprising RNA sequencing data and clinical information, was obtained from the TCGA database. The crucial disulfidptosis-related genes were selected for bioinformatic analysis in HCC. HCC tumor classification was established through a consistent cluster analysis. The prognosis and immune-cell infiltration were investigated in association with a disulfidptosis-related HCC model. Results: In TCGA-HCC patients, a total of 3,621 prognostic genes and 30 key prognostic disulfidptosis-related genes were identified. Using key prognostic disulfidptosis-related genes, TCGA-HCC patients were categorized into low- and high-risk clusters. The upregulated differentially expressed genes (DEGs) in high-risk cluster 1 (C1) could significantly impact cell cycle, DNA replication, and the p53 signaling pathway, whereas the pathways associated with the downregulated DEGs in high-risk C1 could significantly impact metabolism of xenobiotics by cytochrome P450, the PPAR signaling pathway, and tyrosine metabolism. Furthermore, the immune activity of the high-risk C1 group was different to that of the low-risk cluster 2 (C2) group. The 13 disulfidptosis-related genes were finally screened using least absolute shrinkage and selection operator (LASSO) regression analysis, including ANP32E, BOP1, RPN1, SLC7A11, PPIH, PCBP2, ME1, PRDX1, FLNC, INF2, MYH11, LRPPRC, and HNRNPM. Conclusions: The genes related to disulfidptosis are closely associated with tumor classification and immunity in patients with HCC. This is the first gene signature related to disulfidptosis demonstrated a strong predictive performance for the prognosis of HCC, which provide new perspectives for the diagnosis and treatment of HCC.

Concomitant or antecedent intraductal papillary mucinous neoplasm is not a prognostic factor in resected pancreatic cancer.

Background: Intraductal papillary mucinous neoplasm (IPMN)-associated pancreatic cancer is becoming a common subtype of pancreatic cancer found in resected specimens. The prognostic of this subtype is still under evaluation. The study aims to evaluate the prognosis of IPMN-associated pancreatic adenocarcinoma compared to the conventional pancreatic adenocarcinoma. Methods: In this study, patients with resected pancreatic neoplasms and IPMN treated at Hospital Israelita Albert Einstein, from January 2016 to December 2020, were analyzed. Overall survival (OS) was estimated using the Kaplan-Meier method, and correlations between the variables of interest and the disease specific OS was assessed by multivariate analysis. Results: Of 187 patients undergoing resection for pancreatic adenocarcinoma or IPMN, 125 (67%) had pancreatic adenocarcinoma, 33 (18%) had IPMN-associated pancreatic adenocarcinoma, and 29 (16%) had IPMN. Resected IPMN was associated with long-term OS for most of the patients. Similar OS was identified in this study in upfront resected pancreatic cancer associated or not with IPMN. No statistical differences in median OS were identified between resected pancreatic adenocarcinoma and IPMN-associated pancreatic adenocarcinoma (48 vs. 44 months, P=0.44). Size of the tumor [hazard ratio (HR), 1.33], resected stage III (HR, 1.31), perineural invasion (HR, 1.58), lymphovascular invasion (HR, 1.44), positive lymph nodes (HR, 1.34), and neoadjuvant treatment (HR, 1.70) were associated with worse outcomes. Conclusions: Our findings confirm that resected pancreatic cancer has a poor prognosis and IPMN-associated pancreatic adenocarcinoma has the same prognosis as a conventional pancreatic adenocarcinoma. More than half of the cases of IPMN-associated adenocarcinoma already had positive lymph nodes. The impact of neoadjuvant treatment in this group of patients should be investigated in larger cohorts.

IS THERE A ROLE FOR BILIODIGESTIVE BYPASS SURGERY IN TREATING CHOLESTASIS IN ADVANCED PANCREATIC CANCER?

BACKGROUND: The unresectable pancreatic head tumors develop obstructive jaundice and cholestasis during follow-up. Cholestasis is associated with complications and treatment options are endoscopic stenting (ES) and biliary bypass surgery (BBS). AIMS: The aim of the current study was to compare the safety and efficacy of biliary bypass surgery (BBS) and endoscopic stenting (ES) for cholestasis in advanced pancreas cancer. METHODS: This is a retrospective cohort of patients with cholestasis and unresectable or metastatic pancreas cancer, treated with BBS or ES. Short and long-term outcomes were evaluated. We considered the need for hospital readmission due to biliary complications as treatment failure. RESULTS: A total of 93 patients (BBS=43; ES=50) were included in the study. BBS was associated with a higher demand for postoperative intensive care (37 vs.10%; p=0.002, p<0.050), longer intensive care unit stay (1.44 standard deviation±2.47 vs. 0.66±2.24 days; p=0.004, p<0.050), and longer length of hospital stay (7.95±2.99 vs. 4.29±5.50 days; p<0.001, p<0.050). BBS had a higher risk for procedure-related complications (23 vs. 8%; p=0.049, p<0.050). There was no difference in overall survival between BBS and ES (p=0.089, p>0.050). ES was independently associated with a higher risk for treatment failure than BBS on multivariate analysis (hazard ratio 3.97; p=0.009, p<0.050). CONCLUSIONS: BBS is associated with longer efficacy than ES for treating cholestasis in advanced pancreatic cancer. However, the BBS is associated with prolonged intensive care unit and hospital stays and higher demand for intensive care.

Obesity and Colorectal Cancer: A Narrative Review.

Background and Objectives: Cancer is a multicausal disease, and environmental, cultural, socioeconomic, lifestyle, and genetic factors can influence the risk of developing cancer. Colorectal cancer (CRC) stands as the third most common cancer globally. Some countries have observed a rise in the incidence of CRC, especially among young people. This increase is associated with lifestyle changes over the last few decades, including changes in diet patterns, a sedentary lifestyle, and obesity. Currently, obesity and overweight account for approximately 39% of the world's population and increase the risk of overall mortality of certain cancer types. This study aims to conduct a literature review examining the association between obesity and CRC. Materials and Methods: This narrative review explored the pathophysiological mechanisms, treatment strategies, and challenges related to obesity and CRC. Results: Several studies have established a clear causal relationship between obesity and CRC, showing that individuals with morbid obesity are at a higher risk of developing colorectal cancer. The adipose tissue, particularly the visceral, secretes proinflammatory cytokines, such as TNF-alpha, interleukin-6, and C-reactive protein. Chronic inflammation is closely linked to cancer initiation and progression, with a complex interplay of molecular mechanisms underlying this association. Obesity can complicate the treatment of CRC due to several factors, reducing the therapeutic effectiveness and increasing the risk for adverse events during treatment. Dietary modification, calorie restriction, and other types of weight-control strategies can reduce the risk of CRC development and improve treatment outcomes. Conclusions: Obesity is intricately linked to CRC development and progression, making it a crucial target for intervention, whether through diet therapy, physical exercises, medical therapy, or bariatric surgery.

Disparities in esophageal cancer care: a population-based study.

BACKGROUND: Vulnerable populations potentially have a worse prognosis for cancer. The present study aimed to identify individual and municipal characteristics of access to health, including education, use of health insurance, gross domestic product per capita (GDPpc), and urban aspects, which could impact the prognosis of patients with esophageal cancer. METHODS: Data on urban concentration, administrative hierarchy, GDPpc, individual patient characteristics, and access to healthcare were collected from national and state public databases spanning between 2013 and 2022. The study included cities in the state of Sao Paulo, Brazil. Independent variables such as GDPpc, urban concentration, municipal administrative hierarchy, health insurance status, education level, and individual cancer and patient characteristics were evaluated against the outcomes of overall survival (OS), likelihood of undergoing surgical treatment, and time-to-treatment initiation. RESULTS: A total of 9280 patients with esophageal cancer (85% squamous cell carcinoma and 15% adenocarcinoma) treated in 42 cities were included in the study. In univariate analysis, higher education (hazard ratio [HR] = 0.6; P < .001), female gender (HR = 0.85; P < .001), and having private health insurance (HR = 0.65; P < .001) were identified as protective factors for OS in esophageal cancer. After adjusting for other variables in multivariate analysis, higher education (HR = 0.77; P = .009), female gender (HR = 0.82; P < .001), and private insurance (HR = 0.65; P < .001) remained protective factors. GDPpc was not associated with OS. Urban concentration and hierarchy influenced the likelihood of receiving surgical treatment. Patients from high urban concentrations had shorter time-to-treatment initiation intervals. CONCLUSION: Populations at risk, particularly those with limited access to education and healthcare, face a worse prognosis for esophageal cancer.

The role of living donor liver transplantation in treating intrahepatic cholangiocarcinoma.

Introduction: Intrahepatic cholangiocarcinoma (iCC) is the liver's second most common neoplasm. Until now, surgery is the only curative option, but only 35% of the cases are considered resectable at the diagnosis, with a post-resection survival of around 30%. Advancements in surgical techniques and perioperative care related to liver transplantation (LT) have facilitated the expansion of indications for hepatic neoplasms. Method: This study is a comprehensive review of the global experience in living donor LT (LDLT) for treating iCC and describes our first case of LDLT for an unresectable iCC. Results: While exploring LT for intrahepatic cholangiocarcinoma dates to the 1990s, the initial outcomes were discouraging, marked by poor survival and high recurrence rates. Nevertheless, contemporary perspectives underscore a reinvigorated emphasis on extending the frontiers of LT indications within the context of the "oncologic era." The insights gleaned from examining explants, wherein incidental iCC was categorized as hepatocellular carcinoma in the preoperative period, have demonstrated comparable survival rates to small hepatocellular carcinoma. These findings substantiate the potential viability of LT as a curative alternative for iCC. Another investigated scenario pertains to "unresectable tumors with favorable biological behavior," LT presents a theoretical advantage by providing free margins without the concern of a small future liver remnant. The constraint of organ shortage persists, particularly in nations with low donation rates. LDLT emerges as a viable and secure alternative for treating iCC. Conclusion: LDLT is an excellent option for augmenting the graft pool, particularly in carefully selected patients.

Robot-assisted transanal minimally invasive surgery for the treatment of rectal adenocarcinoma.

This is a video vignette of a 57-year-old asymptomatic female patient. The patient underwent a screening colonoscopy which revealed a 10 mm scar in the rectum. Biopsy resulted in a well-differentiated tubular adenocarcinoma. Computed tomography and pelvic magnetic resonance imaging confirmed tumor characteristics without distant or lymph nodal metastasis. A minimally invasive robotic transanal resection using the Da Vinci Xi platform was performed, achieving full-thickness lesion excision with uneventful recovery. Histopathology revealed intramucosal adenocarcinoma with free margins. Local resection is advocated for selected T1 lesions and demands a thorough preoperative assessment. Robotic-assisted surgery presents a valuable alternative for early rectal adenocarcinoma management.

Temporary abdominal closure in oncological patients: Surgical characteristics and implications.

BACKGROUND AND OBJECTIVES: In critically ill patients, temporary abdominal closure (TAC) is utilized for conditions like abdominal compartment syndrome risk, gross abdominal contamination, and intestinal loop viability doubts. TAC techniques aim to safeguard abdominal contents, drain intraperitoneal fluids, and minimize fascia and skin damage. Our goal is to outline clinical characteristics and surgical outcomes in oncological patients undergoing peritoneostomy. METHODS: Patients undergoing TAC with vacuum therapy at a tertiary oncological center were studied, with data sourced from an institutional database. RESULTS: Forty-seven patients (54.3% female), with an average age of 63.1 ± 12.3 years, were included in the study. The primary tumor site was predominantly gastrointestinal (78.2%). Patients presented systemic signs of chronic disease, reflected by a mean body mass index of 18.2 ± 7.6 kg/m², hemoglobin level of 9.2 ± 1.8 g/dL, and albumin level of 2.3 ± 0.6 g/dL. Additionally, most patients had a low-performance status (53% Eastern Cooperative Oncology Group 1/2, 44.8% Karnofsky score ≤80, and 61.2% Charlson Comorbidity Index ≥6). Emergency surgical complications were the main reasons for initial surgery (68%), with the majority attributed to fecal peritonitis (65.9%). Only 14.8% of patients achieved complete abdominal closure with an average of 24.8 days until closure. The in-hospital mortality rate was 85.2%. CONCLUSION: TAC is an alternative for oncological patients with surgical complications, but it carries a high mortality rate due to the compromised conditions of the patients.

THE VALUE OF PREOPERATIVE PROGNOSTIC NUTRITIONAL INDEX IN GASTRIC CANCER AFTER CURATIVE RESECTION.

BACKGROUND: Predicting short- and long-term outcomes of oncological therapies is crucial for developing effective treatment strategies. Malnutrition and the host immune status significantly affect outcomes in major surgeries. AIMS: To assess the value of preoperative prognostic nutritional index (PNI) in predicting outcomes in gastric cancer patients. METHODS: A retrospective cohort analysis was conducted on patients undergoing curative-intent surgery for gastric adenocarcinoma between 2009 and 2020. PNI was calculated as follows: PNI=(10 x albumin [g/dL])+(0.005 x lymphocytes [nº/mm3]). The optimal cutoff value was determined by the receiver operating characteristic curve (PNI cutoff=52), and patients were grouped into low and high PNI. RESULTS: Of the 529 patients included, 315 (59.5%) were classified as a low-PNI group (PNI<52) and 214 (40.5%) as a high-PNI group (PNI≥52). Older age (p=0.050), male sex (p=0.003), American Society of Anesthesiologists score (ASA) III/IV (p=0.001), lower hemoglobin level (p<0.001), lower body mass index (p=0.001), higher neutrophil-lymphocyte ratio (p<0.001), D1 lymphadenectomy, advanced pT stage, pN+ and more advanced pTNM stage were related to low-PNI patient. Furthermore, 30-day (1.4 vs. 4.8%; p=0.036) and 90-day (3.3 vs. 10.5%; p=0.002) mortality rates were higher in low-PNI compared to high-PNI group. Disease-free and overall survival were worse in low-PNI patients compared to high-PNI (p<0.001 for both). ASA III/IV score, low-PNI, pT3/T4, and pN+ were independent risk factors for worse survival. CONCLUSIONS: Preoperative PNI can predict short- and long-term outcomes of patients with gastric cancer after curative gastrectomy. Low PNI is an independent factor related to worse disease-free and overall survival.

Brazil-TNT: A Randomized Phase 2 Trial of Neoadjuvant Chemoradiation Followed by FOLFIRINOX Versus Chemoradiation for Stage II/III Rectal Cancer.

BACKGROUND: Neoadjuvant radiation and oxaliplatin-based systemic therapy (total neoadjuvant therapy-TNT) have been shown to increase response and organ-preservation rates in localized rectal cancer. However, trials have been heterogeneous regarding treatment protocols and few have used a watch-and-wait (WW) approach for complete responders. This trial evaluates if conventional long-term chemoradiation followed by consolidation of FOLFIRINOX increases complete response rates and the number of patients managed by WW. METHODS: This was a pragmatic randomized phase II trial conducted in 2 Cancer Centers in Brazil that included patients with T3+ or N+ rectal adenocarcinoma. After completing a long-course 54 Gy chemoradiation with capecitabine patients were randomized 1:1 to 4 cycles of mFOLFIRINOX (Oxaliplatin 85, irinotecan 150, 5-FU 2400)-TNT-arm-or to the control arm, that did not include further neoadjuvant treatment. All patients were re-staged with dedicated pelvic magnetic resonance imaging and sigmoidoscopy 12 weeks after the end of radiation. Patients with a clinical complete response were followed using a WW protocol. The primary endpoint was complete response: clinical complete response (cCR) or pathological response (pCR). RESULTS: Between April 2021 and June 2023, 55 patients were randomized to TNT and 53 to the control arm. Tumors were 74% stage 3, median distance from the anal verge was 6 cm, 63% had an at-risk circumferential margin, and 33% an involved sphincter. The rates of cCR + pCR were (31%) for TNT versus (17%) for controls (odds ratio 2.19, CI 95% 0.8-6.22 P = .091) and rates of WW were 16% and 9% (P = ns). Median follow-up was 8.1 months and recurrence rates were 16% versus 21% for TNT and controls (P = ns). CONCLUSIONS: TNT with consolidation FOLFIRINOX is feasible and has high response rates, consistent with the current literature for TNT. This trial was supported by a grant from the Brazilian Government (PROADI-SUS - NUP 25000.164382/2020-81).

STAPLED FASCIAL CLOSURE VS. CONTINUOUS HAND-SEWN SUTURE: EXPERIMENTAL STUDY OF THE ABDOMINAL WALL ON PORCINE MODEL AND HUMAN CADAVER.

BACKGROUND: One of the primary complications associated with large incisions in abdominal surgery is the increased risk of fascial closure rupture and incisional hernia development. The choice of the fascial closure method and closing with minimal tension and trauma is crucial for optimal results, emphasizing the importance of uniform pressure along the suture line to withstand intra-abdominal pressure. AIMS: To evaluate the resistance to pressure and tension of stapled and sutured hand-sewn fascial closure in the abdominal wall. METHODS: Nine abdominal wall flaps from human cadavers and 12 pigs were used for the experimentation. An abdominal defect was induced after the resection of the abdominal wall and the creation of a flap in the cadaveric model and after performing a midline incision in the porcine models. The models were randomized into three groups. Group 1 was treated with a one-layer hand-sewn small bite suture, Group 2 was treated with a two-layer hand-sewn small bite suture, and Group 3 was treated with a two-layer stapled closure. Tension measurements were assessed in cadaveric models, and intra-abdominal pressure was measured in porcine models. RESULTS: In the human cadaveric model, the median threshold for fascial rupture was 300N (300-350) in Group 1, 400N (350-500) in Group 2, and 350N (300-380) in Group 3. Statistical comparisons revealed non-significant differences between Group 1 and Group 2 (p=0.072, p>0.05), Group 1 and Group 3 (p=0.346, p>0.05), and Group 2 and Group 3 (p=0.184, p>0.05). For porcine subjects, Group 1 showed a median pressure of 80 mmHg (85-105), Group 2 had a median of 92.5 mmHg (65-95), and Group 3 had a median of 102.5 mmHg (80-135). Statistical comparisons indicated non-significant differences between Group 1 and Group 2 (p=0.243, p>0.05), Group 1 and Group 3 (p=0.468, p>0.05), and Group 2 and Group 3 (p=0.083, p>0.05). CONCLUSIONS: Stapled and conventional suturing resist similar pressure and tension thresholds.

Choledocoduodenal Biliary Bypass for Recurrent Choledocholithiasis in a Patient with Gastric Bypass: An Old Trick to Solve a Modern Problem.

Bariatric patients are at risk for developing biliary stones. Choledocholithiasis poses a significant challenge in Roux-en-Y gastric bypass patients due to anatomical changes, complicating the treatment. We present a case of a 71-year-old female with recurrent choledocholithiasis post-bariatric surgery. After failed endoscopic attempts, a biliodigestive bypass with choledocoduodenal anastomosis was performed successfully using the Da Vinci robotic platform. This technique offers a single anastomosis, excluding the duodenum from transit, preventing food reflux. The patient had an uneventful recovery with no recurrence after 1 year. The choledocoduodenal anastomosis is a viable option for biliary diversion in patients with challenging endoscopic access post-gastric bypass, offering favorable outcomes.

Prognosis value of heat-shock proteins in esophageal and esophagogastric cancer: A systematic review and meta-analysis.

BACKGROUND: Heat shock proteins (HSPs) are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overexpressed in many cancers. The prognostic significance of HSPs and their regulatory factors, such as heat shock factor 1 (HSF1) and CHIP, are poorly understood. AIM: To investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric cancer. METHODS: A systematic review was conducted in accordance with PRISMA recommendations (PROSPERO: CRD42022370653), on Embase, PubMed, Cochrane, and LILACS. Cohort, case-control, and cross-sectional studies of patients with esophagus or esophagogastric cancer were included. HSP-positive patients were compared with HSP-negative, and the endpoints analyzed were lymph node metastasis, tumor depth, distant metastasis, and overall survival (OS). HSPs were stratified according to the HSP family, and the summary risk difference (RD) was calculated using a random-effect model. RESULTS: The final selection comprised 27 studies, including esophageal squamous cell carcinoma (21), esophagogastric adenocarcinoma (5), and mixed neoplasms (1). The pooled sample size was 3465 patients. HSP40 and 60 were associated with a higher 3-year OS [HSP40: RD = 0.22; 95% confidence interval (CI): 0.09-0.35; HSP60: RD = 0.33; 95%CI: 0.17-0.50], while HSF1 was associated with a poor 3-year OS (RD = -0.22; 95%CI: -0.32 to -0.12). The other HSP families were not associated with long-term survival. HSF1 was associated with a higher probability of lymph node metastasis (RD = -0.16; 95%CI: -0.29 to -0.04). HSP40 was associated with a lower probability of lymph node dissemination (RD = 0.18; 95%CI: 0.03-0.33). The expression of other HSP families was not significantly related to tumor depth and lymph node or distant metastasis. CONCLUSION: The expression levels of certain families of HSP, such as HSP40 and 60 and HSF1, are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.

Does Tri-Staple™ technology reduce the risk of anastomotic leakage in colorectal surgery? A propensity score matching analysis.

BACKGROUND AND OBJECTIVES: This study evaluates the Tri-Staple™ technology in colorectal anastomosis. METHODS: Patients who underwent rectosigmoidectomy between 2016 and 2022 were retrospectively evaluated and divided into two groups: EEA™ (EEA) or Tri-Staple™ (Tri-EEA). The groups were matched for age, sex, American Society of Anesthesiologists (ASA), and neoadjuvant radiotherapy using propensity score matching (PSM). RESULT: Three hundred and thirty-six patients were included (228 EEA; 108 Tri-EEA). The groups were similar in sex, age, and neoadjuvant therapy. The Tri-EEA group had fewer patients with ASA III/IV scores (7% vs. 33%; p < 0.001). The Tri-EEA group had a lower incidence of leakage (4% vs. 11%; p = 0.023), reoperations (4% vs. 12%; p = 0.016), and severe complications (6% vs. 14%; p = 0.026). There was no difference in complications, mortality, readmission, and length of stay. After PSM, 108 patients in the EEA group were compared with 108 in the Tri-EEA group. The covariates sex, age, neoadjuvant radiotherapy, and ASA were balanced, and the risk of leakage (4% vs. 12%; p = 0.04), reoperation (4% vs. 14%; p = 0.014), and severe complications (6% vs. 15%; p = 0.041) remained lower in the Tri-EEA group. CONCLUSION: Tri-Staple™ reduces the risk of leakage in colorectal anastomosis. However, this study provides only insights, and further research is warranted to confirm these findings.

Liver transplantation as an alternative for the treatment of perihilar cholangiocarcinoma: A critical review.

BACKGROUND: Perihilar cholangiocarcinoma (phCCC) is a dismal malignancy. There is no consensus regarding the best treatment for patients with unresectable phCCC. The present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical practice. DATA SOURCES: The search was conducted in PubMed, Embase, Cochrane, and LILACS. The related references were searched manually. Inclusion criteria were: reports in English or Portuguese literature that a) patients with confirmed diagnosis of phCCC; b) patients treated with a curative intent; c) patients with the outcomes of liver resection and liver transplantation. Case reports, reviews, letters, editorials, conference abstracts and papers with full-text unavailability were excluded from the analysis. RESULTS: Most of the current literature is based on observational retrospective studies with low grades of evidence. Liver resection has better long-term outcomes than systemic chemotherapy or palliation therapy and liver transplantation is a good alternative for selected patients with unresectable phCCC. All candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahepatic diseases. As a general rule, patients presenting with a tumor having a longitudinal size > 3 cm or extending below the cystic duct, lymph node disease, confirmed extrahepatic dissemination; intraoperatively diagnosed metastatic disease; a history of other malignancies within the last five years, and did not complete chemoradiation regimen and were medically unfit should not be considered for transplantation. Some of these criteria should be individually assessed. Liver transplantation or resection should only be considered in highly experienced hepatobiliary centers, and any decision-making must be based on a multidisciplinary evaluation. CONCLUSIONS: phCCC is a complex condition with high morbidity. Surgical therapies, including hepatectomy and liver transplantation, are the best option for better long-term disease-free survival.

O valor do índice nutricional prognóstico pré-operatório no câncer gástrico após ressecção curativa / The value of preoperative prognostic nutritional index in gastric cancer after curative resection

ABSTRACT BACKGROUND: Predicting short- and long-term outcomes of oncological therapies is crucial for developing effective treatment strategies. Malnutrition and the host immune status significantly affect outcomes in major surgeries. AIMS: To assess the value of preoperative prognostic nutritional index (PNI) in predicting outcomes in gastric cancer patients. METHODS: A retrospective cohort analysis was conducted on patients undergoing curative-intent surgery for gastric adenocarcinoma between 2009 and 2020. PNI was calculated as follows: PNI=(10 x albumin [g/dL])+(0.005 x lymphocytes [nº/mm3]). The optimal cutoff value was determined by the receiver operating characteristic curve (PNI cutoff=52), and patients were grouped into low and high PNI. RESULTS: Of the 529 patients included, 315 (59.5%) were classified as a low-PNI group (PNI<52) and 214 (40.5%) as a high-PNI group (PNI≥52). Older age (p=0.050), male sex (p=0.003), American Society of Anesthesiologists score (ASA) III/IV (p=0.001), lower hemoglobin level (p<0.001), lower body mass index (p=0.001), higher neutrophil-lymphocyte ratio (p<0.001), D1 lymphadenectomy, advanced pT stage, pN+ and more advanced pTNM stage were related to low-PNI patient. Furthermore, 30-day (1.4 vs. 4.8%; p=0.036) and 90-day (3.3 vs. 10.5%; p=0.002) mortality rates were higher in low-PNI compared to high-PNI group. Disease-free and overall survival were worse in low-PNI patients compared to high-PNI (p<0.001 for both). ASA III/IV score, low-PNI, pT3/T4, and pN+ were independent risk factors for worse survival. CONCLUSIONS: Preoperative PNI can predict short- and long-term outcomes of patients with gastric cancer after curative gastrectomy. Low PNI is an independent factor related to worse disease-free and overall survival.

RESUMO RACIONAL: Estimar os desfechos de curto e longo prazo das terapias contra o câncer é crucial para o desenvolvimento de estratégias de tratamento eficazes. A desnutrição e o estado imunológico do hospedeiro afetam significativamente os desfechos em cirurgias de grande porte. OBJETIVOS: Avaliar o valor do índice nutricional prognóstico pré-operatório (INP) na predição de desfechos em pacientes com câncer gástrico. MÉTODOS: Foi realizada uma análise de coorte retrospectiva de pacientes submetidos à cirurgia com intenção curativa para adenocarcinoma gástrico entre 2009 e 2020. O INP foi calculado da seguinte forma: INP=(10 x albumina [g/dL])+(0.005 x linfócitos [nº/mm3]). O valor de corte ideal foi determinado pela curva característica de operação do receptor (ponto de corte do INP=52), e os pacientes foram agrupados em INP baixo ou alto. RESULTADOS: Dos 529 pacientes incluídos, 315 (59,5%) foram classificados como grupo de baixo INP (INP<52) e 214 (40,5%) como grupo de alto INP (INP>52). Idade mais avançada (p=0,050), sexo masculino (p=0,003), escore da Sociedade Americana de Anestesiologistas (ASA) III/IV (p=0,001), menor nível de hemoglobina (p<0,001), menor índice de massa corpórea (p=0,001), maior relação neutrófilos-linfócitos (p<0,001), linfadenectomia D1, estágio pT avançado, pN+ e estágio pTNM mais avançado foram relacionados ao paciente com baixo INP. Além disso, as taxas de mortalidade em 30 dias (1,4 vs. 4,8%; p=0,036) e em 90 dias (3,3 vs. 10,5%; p=0,002) foram maiores no grupo com baixo PNI em comparação ao grupo com alto INP. A sobrevida livre de doença e a sobrevida global foram piores em pacientes com baixo INP em comparação com pacientes com alto INP (p<0,001 para ambos). Escore ASA III/IV, baixo INP, pT3/T4 e pN+ foram fatores de risco independentes para pior sobrevida. CONCLUSÕES: O INP pré-operatório pode predizer desfechos de curto e longo prazo de pacientes com câncer gástrico após gastrectomia curativa. Baixo INP é um fator independente relacionado a piores sobrevida livre de doença e sobrevida global.

MANAGEMENT OF SYMPTOMS RECURRENCE AFTER MYOTOMY FOR ACHALASIA. A PRACTICAL APPROACH.

BACKGROUND: Achalasia is an esophageal motility disorder, and myotomy is one of the most used treatment techniques. However, symptom persistence or recurrence occurs in 9 to 20% of cases. AIMS: This study aims to provide a practical approach for managing the recurrence or persistence of achalasia symptoms after myotomy. METHODS: A critical review was performed to gather evidence for a rational approach for managing the recurrence or persistence of achalasia symptoms after myotomy. RESULTS: To properly manage an achalasia patient with significant symptoms after myotomy, such as dysphagia, regurgitation, thoracic pain, and weight loss, it is necessary to classify symptoms, stratify severity, perform appropriate tests, and define a treatment strategy. A systematic differential diagnosis workup is essential to cover the main etiologies of symptoms recurrence or persistence after myotomy. Upper digestive endoscopy and dynamic digital radiography are the main tests that can be applied for investigation. The treatment options include endoscopic dilation, peroral endoscopic myotomy, redo surgery, and esophagectomy, and the decision should be based on the patient's individual characteristics. CONCLUSIONS: A good clinical evaluation and the use of proper tests jointly with a rational assessment, are essential for the management of symptoms recurrence or persistence after achalasia myotomy.