Short- and long-term outcome differences between patients undergoing left and right colon cancer surgery: cohort study.

PURPOSE: Since the literature currently provides controversial data on the postoperative outcomes following right and left hemicolectomies, we carried out this study to examine the short- and long-term treatment outcomes. METHODS: This study included consecutive patients who underwent right or left-sided colonic resections from year 2014 to 2018 and then they were followed up. The short-term outcomes such as postoperative morbidity and mortality according to Clavien-Dindo score, duration of hospital stay, and 90-day readmission rate were evaluated as well as long-term outcomes of overall survival and disease-free survival. Multivariable Cox regression analysis was performed of overall and progression-free survival. RESULTS: In total, 1107 patients with colon tumors were included in the study, 525 patients with right-sided tumors (RCC) and 582 cases with tumors in the left part of the colon (LCC). RCC group patients were older (P < 0.001), with a higher ASA score (P < 0.001), and with more cardiovascular comorbidities (P < 0.001). No differences were observed between groups in terms of postoperative outcomes such as morbidity and mortality, except 90-day readmission which was more frequent in the RCC group. Upon histopathological analysis, the RCC group's patients had more removed lymph nodes (29 ± 14 vs 20 ± 11, P = 0.001) and more locally progressed (pT3-4) tumors (85.4% versus 73.4%, P = 0.001). Significantly greater 5-year overall survival and disease-free survival (P = 0.001) were observed for patients in the LCC group, according to univariate Kaplan-Meier analysis. CONCLUSIONS: Patients with right-sided colon cancer were older and had more advanced disease. Short-term surgical outcomes were similar, but patients in the LCC group resulted in better long-term outcomes.

Achieving Textbook Outcomes in Colorectal Cancer Surgery Is Associated with Improved Long-Term Survival: Results of the Multicenter Prospective Cohort Study.

Background: The outcomes of patients with colorectal cancer greatly depend on the quality of their surgical care. However, relying solely on a single quality indicator does not adequately capture the multifaceted nature of modern perioperative care. A new tool-"Textbook Outcome" (TO)-has been suggested to provide a comprehensive evaluation of surgical quality. This study aims to examine how TO affects the long-term outcomes of colorectal cancer patients who are scheduled for surgery. Methods: The data of all patients undergoing elective colorectal cancer resection with primary anastomosis at two major cancer treatment centers in Lithuania-Vilnius University Hospital Santaros Klinikos and National Cancer Institute-between 2014 and 2018 were entered into the prospectively maintained database. The study defined TO as a composite quality indicator that incorporated seven parameters: R0 resection, retrieval of ≥12 lymph nodes, absence of postoperative complications during the intrahospital period, hospital stay duration of fewer than 14 days, no readmission within 90 days after surgery, no reinterventions within 30 days after surgery, and no 30-day mortality. Long-term outcomes between patients who achieved TO and those who did not were compared. Factors associated with failure to achieve TO were identified. Results: Of the 1524 patients included in the study, TO was achieved by 795 (52.2%). Patients with a higher ASA score (III-IV) were identified to have higher odds of failure to achieve TO (OR 1.497, 95% CI 1.203-1.863), while those who underwent minimally invasive surgery had lower odds for similar failure (OR 0.570, 95% CI 0.460-0.706). TO resulted in improved 5-year overall-(80.2% vs. 65.5%, p = 0.001) and disease-free survival (76.6% vs. 62.6%; p = 0.001) rates. Conclusions: Elective colorectal resections result in successful TO for 52.5% of patients. The likelihood of failure to achieve TO is increased in patients with a high ASA score, while minimally invasive surgery is associated with higher TO rates. Patients who fail to achieve successful surgical outcomes experience reduced long-term outcomes.

The Impact of Chemotherapy and Transforming Growth Factor-ß1 in Liver Regeneration after Hepatectomy among Colorectal Cancer Patients.

An ongoing debate surrounds the impact of chemotherapy on post-hepatectomy liver regeneration in patients with colorectal cancer liver metastases (CRLM), with unclear regulatory mechanisms. This study sought to delve into liver regeneration post-resection in CRLM patients, specifically examining the roles of hepatocyte growth factor (HGF) and transforming growth factor ß1 (TGF-ß1). In this longitudinal observational study, 17 patients undergoing major liver resection for CRLM and 17 with benign indications as controls were enrolled. Liver regeneration within 30 postoperative days was assessed via CT, considering clinicopathological characteristics, liver enzymes, liver stiffness by elastography, and the impact of HGF and TGF-ß1 on liver regeneration. The results revealed that the control group exhibited significantly higher mean liver regeneration volume (200 ± 180 mL) within 30 days postoperatively compared to the CRLM group (72 ± 154 mL); p = 0.03. Baseline alkaline phosphatase (AP) and TGF-ß1 blood levels were notably higher in the CRLM group. Immunohistochemical analysis indicated a higher proportion of CRLM patients with high TGF-ß1 expression in liver tissues compared to the control group (p = 0.034). Correlation analysis showed that resected liver volume, baseline plasma HGF, AP, and albumin levels significantly correlated with liver regeneration volume. However, in multivariable analysis, only resected liver volume (ß: 0.31; 95% CI: 0.14-0.47, p = 0.01) remained significant. In conclusion, this study highlights compromised liver regeneration in CRLM patients post-chemotherapy. Additionally, these patients exhibited lower serum TGF-ß1 levels and reduced TGF-ß1 expression in liver tissue, suggesting TGF-ß1 involvement in mechanisms hindering liver regeneration capacity following major resection after chemotherapy.

Neoadjuvant Chemotherapy Followed by Gastrectomy for Cytology-Positive Gastric Cancer without Any Other Non-Curative Factors in a Western Setting: An International Eastern European Cohort Study.

The optimal approach for treating cytology-positive (Cy1) gastric cancer (GC) patients without additional non-curative factors remains uncertain. While neoadjuvant chemotherapy followed by gastrectomy shows promise, its suitability for Western patients is not well supported by existing data. To address this knowledge gap, a cohort study was conducted across four major GC treatment centers in Lithuania, Estonia, and Ukraine. Forty-three consecutive Cy1 GC patients who underwent neoadjuvant chemotherapy between 2016 and 2020 were enrolled. The study evaluated overall survival (OS), progression-free survival (PFS), cytology status conversion, and major pathological response rates, along with the factors influencing these outcomes. All patients underwent surgery post-neoadjuvant chemotherapy, with 53.5% experiencing cytological status conversion and 23.3% achieving a major pathological response. The median OS and PFS were 20 (95% CI: 16-25) and 19 (95% CI: 11-20) months, respectively. Conversion to negative cytology significantly reduced the relative risk of peritoneal progression (RR: 0.11; 95% CI: 0.03-0.47, p = 0.002). The study suggests that neoadjuvant chemotherapy followed by gastrectomy holds promise as a treatment option for Cy1 GC without additional non-curative factors, associating cytology status conversion with improved long-term outcomes and reduced peritoneal relapse risk.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin in combination with FOLFOX chemotherapy as a first-line treatment for gastric cancer patients with peritoneal metastases: single-arm phase II study.

BACKGROUND: Gastric cancer (GC) remains among the most common and most lethal cancers worldwide. Peritoneum is the most common site for distant dissemination. Standard treatment for GC peritoneal metastases (PM) is a systemic therapy, but treatment outcomes remain very poor, with median overall survival ranging between 3-9 months. Thus, novel treatment methods are necessary. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is the most novel technique for intraperitoneal chemotherapy. Some preliminary data suggest PIPAC can achieve improved long-term outcomes in patients with GC PM, especially when used in combination with systemic chemotherapy. However, there is a lack of data from well-design prospective studies that would confirm the efficacy of PIPAC and systemic therapy combination for first-line treatment. METHODS: This study is an investigator-initiated single-arm, phase II trial to investigate the efficacy of PIPAC combined with systemic FOLFOX (5-fluorouracil, oxaliplatin, leucovorin) as a first-line treatment for GC PM. The study is conducted in 2 specialized GC treatment centers in Lithuania. It enrolls GC patients with histologically confirmed PM without prior treatment. The treatment protocol consists of PIPAC with cisplatin (10.5 mg/m2 body surface in 150 mL NaCl 0.9%) and doxorubicin (2.1 mg/m2 in 50 mL NaCl 0.9%) followed by 2 cycles of FOLFOX every 6-7 weeks. In total 3 PIPACs and 6 cycles of FOLFOX will be utilized. The primary outcome of the study is the objective response rate (ORR) according to RECIST v. 1.1 criteria (Eisenhauer et al., Eur J Cancer 45:228-47) in a CT scan performed 7 days after the 4th cycle of FOLFOX. Secondary outcomes include ORR after all experimental treatment, PIPAC characteristics, postoperative morbidity, histological and biochemical response, ascites volume, quality of life, overall survival, and toxicity. DISCUSSION: This study aims to assess PIPAC and FOLFOX combination efficacy for previously untreated GC patients with PM. TRIAL REGISTRATION: NCT05644249. Registered on December 9, 2022.

Effect of home-based prehabilitation on postoperative complications after surgery for gastric cancer: randomized clinical trial.

BACKGROUND: Recent studies have demonstrated that prehabilitation improves patients' physical fitness but its impact on postoperative morbidity remains unclear. This study aimed to assess the effect of personalized, multimodal, semisupervised, home-based prehabilitation on postoperative complications after surgery for gastric cancer. METHODS: This RCT was conducted at two centres in Lithuania. Patients (aged at least18 years) with gastric cancer scheduled to undergo elective primary surgery or surgery after neoadjuvant chemotherapy for gastric cancer were randomized (1 : 1) to prehabilitation or standard care. Prehabilitation included exercise interventions focused on endurance, respiratory muscle strength, stretching, and resistance training as well as nutritional and psychological support. The primary outcome was the proportion of patients with postoperative complications within 90 days after surgery. Secondary outcomes included 90-day mortality rate, physical condition, fitness level, nutritional status, quality of life, anxiety and depression level, and proportion of patients completing neoadjuvant chemotherapy. RESULTS: Between February 2020 and September 2022, 128 participants were randomized to prehabilitation (64) or standard care (64), and 122 (prehabilitation 61, control 61) were analysed. The prehabilitation group had increased physical capacity before the operation compared with baseline (mean 6-min walk test change +31 (95 per cent c.i. 14 to 48) m; P = 0.001). The prehabilitation group had a decreased rate of non-compliance with neoadjuvant treatment (risk ratio (RR) 0.20, 95 per cent c.i. 0.20 to 0.56), a 60 per cent reduction in the number of patients with postoperative complications at 90 days after surgery (RR 0.40, 0.24 to 0.66), and improved quality of life compared with the control group. CONCLUSION: Prehabilitation reduced morbidity in patients who underwent gastrectomy for gastric cancer. REGISTRATION NUMBER: NCT04223401 (http://www.clinicaltrials.gov).

Initial Experience of Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Baltic Country Center.

Background: Peritoneal surface malignancies (PSMs) are a heterogenous group of primary and metastatic cancers affecting the peritoneum. They are associated with poor long-term outcomes. Many centers around the world adopt cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in routine clinical practice for these otherwise condemned patients despite a lack of high-level evidence from randomized control trials. This study aimed to investigate and present our 10-year experience with this controversial method, CRS and HIPEC, for PSM in a single tertiary center in a Baltic country. Methods: Patients who underwent CRS and HIPEC at Vilnius University Hospital Santaros Klinikos between 2011 and 2021 were included in this retrospective study. Overall survival was the primary study outcome. Secondary outcomes included postoperative morbidity and mortality, and local or systemic recurrence rates. Results: Sixty-nine patients who underwent CRS and HIPEC were included in the study. Most patients underwent treatment for peritoneal metastases from colorectal, ovarian, and appendiceal cancers. Six (8.7%) patients received CRS and HIPEC for primary peritoneal neoplasm-pseudomyxoma peritonei. The mean peritoneal carcinomatosis index score was 12 ± 7. Complete cytoreduction was achieved in 62 (89.9%) patients. The mean OS was 39 ± 29 months. The mean survival of patients with PSMs of different origin was as follows: 39 ± 25 (95% CI: 28-50) months for colorectal cancer, 44 ± 31 (95% CI: 30-58) months for ovarian cancer, 32 ± 21 (95% CI: 21-43) months for appendiceal cancer, 422 ± 1 (95% CI: 12-97) months for pseudomyxoma peritonei, and 7 months for gastric cancer. Conclusions: The current study demonstrated the results of the CRS and HIPEC program in a single Baltic country tertiary center. Patients who underwent CRS and HIPEC for PSMs achieved moderate survival rates with acceptable postoperative morbidity and mortality risk.

Prehabilitation in Modern Colorectal Cancer Surgery: A Comprehensive Review.

Colorectal cancer remains the third most prevalent cancer worldwide, exceeding 1.9 million new cases annually. Surgery continues to be the gold standard treatment option. Unfortunately, colorectal cancer surgery carries significant postoperative morbidity and mortality. Moreover, most rectal cancer patients and some patients with locally advanced colon cancer require preoperative neoadjuvant therapy. It improves long-term outcomes but impairs patients' physical fitness and thus further increases surgical risk. Recently, prehabilitation has gained interest as a novel strategy to reduce treatment-related morbidity for patients undergoing colorectal cancer surgery. However, the concept is still in its infancy, and the role of prehabilitation remains controversial. In this comprehensive review, we sum up present evidence on prehabilitation before colorectal cancer surgery. Available studies are very heterogenous in interventions and investigated outcomes. Nonetheless, all trials show at least some positive effects of prehabilitation on patients' physical, nutritional, or psychological status or even reduced postoperative morbidity. Unfortunately, the optimal prehabilitation program remains undetermined; therefore, this concept cannot be widely implemented. Future studies investigating optimal prehabilitation regimens for patients undergoing surgery for colorectal cancer are necessary.

Sulforaphane has an additive anticancer effect to FOLFOX in highly metastatic human colon carcinoma cells.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Patients with CRC may need chemotherapy (CTx) in a neoadjuvant, adjuvant or palliative setting through the course of the disease. Unfortunately, its effect is limited by chemoresistance and chemotoxicity. Novel more effective and non­toxic CTx regimens are needed to further improve CRC treatment outcomes. Thus, the present study was designed to test the hypothesis that non­toxic sulforaphane (SF) is effective against CRC and has additive effects in combination with conventional 5­fluorouracil, oxaliplatin and folinic acid (FOLFOX) CTx in vitro. Highly metastatic human colon cancer cells, CX­1, and fibroblasts were treated with FOLFOX ± SF. Cell viability was assessed using an MTT assay. The level of apoptosis and the expression of apoptotic proteins were measured by TUNEL assay and quantitative PCR analysis. Aldehyde dehydrogenase isoform 1 (ALDH1) and multidrug resistance protein 2 (MRP2) levels were evaluated. The ability of cells to form spheroids was measured in three­dimensional cell culture. SF alone and in combination with FOLFOX effectively decreased the viability of the CX­1 cells, promoted apoptosis within the CX­1 cells, prevented cellular spheroid formation and decreased ALDH1 activity. However, SF promoted MRP2 expression and protein levels. In conclusion, SF together with conventional FOLFOX has additive anticancer effects against highly metastatic human CRC in vitro.

Anastomotic Leak Impact on Long-Term Survival after Right Colectomy for Cancer: A Propensity-Score-Matched Analysis.

Our goal was to assess the impact of anastomotic leaks (ALs) on oncologic outcomes using a case-matched analysis. Patients undergoing right hemicolectomy for cancer between 2014 and 2018 were included. The main variables were the risk factor of anastomotic leak, overall survival and disease-free survival. Propensity score matching was performed according to the patient's age, co-morbidities and TNM staging as well as the type of procedure. Oncologic outcomes were analyzed. We included 488 patients and performed final analysis on 69 patients. The AL rate was 4.71% (23 patients). Intrahospital mortality was significantly higher in the AL group, at 1.3% (6 of 465) vs. 8.7% (2 of 23), p = 0.05. Three-year overall survival (OS) in the non-AL group was higher, although the difference could not be considered significant (71.5% vs. 37.3%, p = 0.082); similarly, the likelihood for impaired 3-year progression-free survival (PFS) was lower, but the difference here could also not be considered significant (69.3% vs. 37.3%, p = 0.106). Age, advanced tumor stage, lymph node metastases and distant metastases were associated with higher probability of death or recurrence of disease. In contrast, minimally invasive surgery was associated with lower probability of death (HR (95% CI): 0.99 (0.14-0.72); p = 0.023) and recurrence of disease (HR (95% CI): 0.94 (0.13-0.68); p = 0.020). In an adjusted Cox regression analysis, AL, age and distant metastases were associated with poor long-term survival. Moreover, AL, age and distant metastases were associated with higher probability of recurrence of disease. Based on our results, AL is a significant factor for worse oncologic outcomes. Simple summary: we aimed to assess patients with anastomotic leaks following right hemicolectomy for cancer. These patients were matched to patients without leaks. Propensity score analysis demonstrated that anastomotic leak was a marker of worse oncologic outcomes.

The Role of Prehabilitation in Modern Esophagogastric Cancer Surgery: A Comprehensive Review.

Esophagogastric cancer is among the most common malignancies worldwide. Surgery with or without neoadjuvant therapy is the only potentially curative treatment option. Although esophagogastric resections remain associated with major surgical trauma and significant postoperative morbidity. Prehabilitation has emerged as a novel strategy to improve clinical outcomes by optimizing physical and psychological status before major surgery through exercise and nutritional and psychological interventions. Current prehabilitation programs may be unimodal, including only one intervention, or multimodal, combining the benefits of different types of interventions. However, it still is an investigational treatment option mostly limited to clinical trials. In this comprehensive review, we summarize the current evidence for the role of prehabilitation in modern esophagogastric cancer surgery. The available studies are very heterogeneous in design, type of interventions, and measured outcomes. Yet, all of them confirm at least some positive effects of prehabilitation in terms of improved physical performance, nutritional status, quality of life, or even reduced postoperative morbidity. However, the optimal interventions for prehabilitation remain unclear; thus, they cannot be standardized and widely adopted. Future studies on multimodal prehabilitation are necessary to develop optimal programs for patients with esophagogastric cancer.

Comprehensive testing of colorectal anastomosis: results of prospective observational cohort study.

BACKGROUND: Anastomotic leakage remains one of the most threatening complications in colorectal surgery. Intraoperative testing of anastomosis may reduce the postoperative anastomotic leakage rates. This study aimed to investigate a novel comprehensive intraoperative colorectal anastomosis testing technique to detect the failure of the anastomosis construction and to reduce the risk of postoperative leak. METHODS: This multi-centre prospective cohort pilot study included 60 patients who underwent colorectal resection with an anastomosis at or below 15 cm from the anal verge. Comprehensive trimodal testing consisted of indocyanine green fluorescence angiography, tension testing, air-leak, and methylene blue leak tests to evaluate the perfusion, tension, and mechanical integrity of the anastomosis. RESULTS: Ten (16.7%) patients developed an anastomotic leakage. Trimodal test was positive in 16 (26.6%) patients and the operative plan was changed for all of them. Diverting ileostomy was performed in 14 (87.5%) patients. However, two (12.5%) patients still developed clinically significant anastomotic leakage (Grade B). Forty-four (73.4%) patients had a negative trimodal test, preventive ileostomy was performed in 19 (43.2%), and five (11.4%) patients had clinically significant anastomotic leakage (Grade B and C). CONCLUSION: Trimodal testing identifies anastomoses with initial technical failure where reinforcement of anastomosis or diversion can lead to an acceptable rate of anastomotic leakage. Identification of well-performed anastomosis could allow a reduction of ileostomy rate by two-fold. However, anastomotic leakage rate remains high in technically well-performed anastomoses.

Current treatment strategies for patients with only peritoneal cytology positive stage IV gastric cancer.

Gastric cancer (GC) is one of the most common malignancies worldwide and surgery remains the only potentially curative treatment option for it. Although a significant proportion of GC patients are found with distant metastases already at the initial diagnosis. Peritoneal dissemination is the most common site of metastases. Positive peritoneal cytology (Cy1) is associated with poor long-term outcomes; thus, these patients are considered as stage IV even if macroscopic carcinomatosis is absent. Currently, there is no clear evidence for the most optimal treatment for this distinct subpopulation of the stage IV cohort. Available strategies vary from palliative chemotherapy to upfront gastrectomy. This comprehensive review summarized current evidence of different treatment strategies for Cy1 GC including roles of surgery, systemic and intraperitoneal chemotherapy.

Short and long-term outcomes of elderly patients undergoing left-sided colorectal resection with primary anastomosis for cancer.

BACKGROUND: The proportion of elderly colorectal cancer (CRC) patients requiring surgery is increasing. Colorectal resection for left-sided cancers is the most controversial as the primary anastomosis or end-colostomy and open or minimally invasive approaches are available. Therefore, this study was conducted to investigate the short- and long-term outcomes in elderly patients after resection with primary anastomosis for left-sided CRC. METHODS: The cohort study included left-sided colorectal cancer patients who underwent resection with primary anastomosis. The participants were divided into non-elderly (≤75 years) and elderly (> 75 years) groups. Short- and long-term postoperative outcomes were investigated. RESULTS: In total 738 (82%) and 162 (18%) patients were allocated to non-elderly and elderly groups, respectively. Minimally invasive surgery (MIS) was less prevalent in the elderly (42.6% vs 52.7%, p = 0.024) and a higher proportion of these suffered severe or lethal complications (15.4% vs 9.8%, p = 0.040). MIS decreased the odds for postoperative complications (OR: 0.41; 95% CI: 0.19-0.89, p = 0.038). The rate of anastomotic leakage was similar (8.5% vs 11.7%, p = 0.201), although, in the case of leakage 21.1% of elderly patients died within 90-days after surgery. Overall- and disease-free survival was impaired in the elderly. MIS increased the odds for long-term survival. CONCLUSIONS: Elderly patients suffer more severe complications after resection with primary anastomosis for left-sided CRC. The risk of anastomotic leakage in the elderly and non-elderly is similar, although, leakages in the elderly seem to be associated with a higher 90-day mortality rate. Minimally invasive surgery is associated with decreased morbidity in the elderly.

Custodiol® Supplemented with Synthetic Human Relaxin Decreases Ischemia-Reperfusion Injury after Porcine Kidney Transplantation.

Objective. Ischemia-reperfusion injury (IRI) is inevitable after kidney transplantation (KT), impairing outcomes. Relaxin-2 (RLX) is a promising insulin-related peptide hormone that protects against renal IRI in rodents, although large animal models are needed before RLX can be tested in a human setting. Methods. In this blinded, randomized, and placebo-controlled experimental study kidneys from 19 donor pigs were retrieved after perfusion with Custodiol® ± RLX (5 or 20 nmol/L) and underwent static cold storage (SCS) for 24 and 48 h, respectively. Subsequently, KT was performed after unilateral right nephrectomy. Study outcomes included markers for kidney function, oxidative stress, lipid peroxidation, and endothelial cell damage. PCR analysis for oxidative stress and apoptosis-related gene panels as well as immunohistochemistry were performed. Results. RLX upregulated SOD2 and NFKB expression to 135% (p = 0.042) and 125% (p = 0.019), respectively, while RIPK1 expression was downregulated to 82% (p = 0.016) of corresponding controls. Further RLX significantly downregulated RIPK1 and MLKL expression and decreased the number of Caspase 3- and MPO-positive cells in grafts after SCS. Conclusions. RLX supplemented Custodiol® significantly decreased IRI via both antioxidant and anti-apoptotic mechanisms. Clinical trials are warranted to implement synthetic human RLX as a novel additive to preservation solutions against IRI.

Gastrectomy impact on the gut microbiome in patients with gastric cancer: A comprehensive review.

Gastric cancer is one of the most common malignancies worldwide and gastrectomy remains the only potentially curative treatment option for this disease. However, the surgery leads to significant physiological and anatomical changes in the gastrointestinal (GI) tract including loss of the gastric barrier, an increase in oxygenation levels in the distal gut, and biliary diversion after gastrectomy. These changes in the GI tract influence the composition of the gut microbiome and thus, host health. Gastrectomy-induced dysbiosis is characterized by increased abundance of typical oral cavity bacteria, an increase in aero-tolerant bacteria (aerobes/facultative anaerobes), and increased abundance of bile acid-transforming bacteria. Furthermore, this dysbiosis is linked to intestinal inflammation, small intestinal bacterial overgrowth, various GI symptoms, and an increased risk of colorectal cancer.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for peritoneal malignancy: initial experience of the first program in the Baltic countries.

BACKGROUND: Peritoneal malignancies include primary and metastatic cancer of the peritoneal cavity. The most common origin for peritoneal metastasis is ovarian, gastric, and colorectal cancers. Irrespective of the origin, peritoneal metastases represent the advanced disease and are associated with poor long-term outcomes. The minimally invasive approach of pressurized intraperitoneal aerosol chemotherapy (PIPAC) allows repeated applications and objective assessment of tumor response by comparing histological samples. This study aimed to investigate the initial experience with PIPAC in the Baltic region. METHODS: All patients who underwent PIPAC at Vilnius University Hospital Santaros Klinikos between 2015 and 2020 were included in this retrospective study. The primary outcome of the study was overall survival (OS) in patients with peritoneal carcinomatosis treated by PIPAC. The secondary outcomes included postoperative morbidity; peritoneal carcinomatosis index (PCI) and ascites reduction after treatment by PIPAC. RESULTS: In total, 15 patients underwent 34 PIPAC procedures. PIPAC-related intraoperative and postoperative morbidity occurred in 3 (8.8%) of 34 procedures. Following PIPAC, the median PCI decreased from 8 (4; 15) to 5 (1; 16) in GC patients, although, the difference failed for significance, p = 0.581. In OC patients, PCI after PIPAC remained stable. Median overall survival after PIPAC procedure was 25 (95% CI 5-44) months. Ovarian cancer patients (22; 95% CI 12-44 months) had significantly higher OS, compared to gastric cancer patients (8; 95% CI 4-16 months), p = 0.018. CONCLUSIONS: PIPAC is safe and feasible for patients with gastric and ovarian cancers peritoneal metastases.

Characteristics of Early-Onset vs Late-Onset Colorectal Cancer: A Review.

Importance: The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer. Observations: Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts. Conclusions and Relevance: The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.

Histologic Lymph Nodes Regression after Preoperative Chemotherapy as Prognostic Factor in Non-metastatic Advanced Gastric Adenocarcinoma.

Background: The study aims to evaluate the lymph node (LN) response to preoperative chemotherapy and its impact on long-term outcomes in advanced gastric cancer (AGC). Methods: Histological specimens retrieved at gastrectomy from patients who received preoperative chemotherapy were evaluated. LN regression was graded by the adapted tumor regression grading system proposed by Becker. Patients were classified as node-negative (lnNEG) in the case of all negative LN without evidence of previous tumor involvement. Patients with LN metastasis were classified as nodal responders (lnR) in case of a regression score 1a-2 was detected in the LN. Nodal non-responders (lnNR) had a regression score of 3 in all of the metastatic nodes. Survival was compared using Kaplan-Meier and Cox regression analysis. Results: Among 87 patients included in the final analysis 29.9 % were lnNEG, 21.8 % were lnR and 48.3 % were lnNR. Kaplan-Meier curves showed a survival benefit for lnR over lnNR (p=0.03), while the survival of lnR and lnNEG patients was similar. Cox regression confirmed nodal response to be associated with decreased odds for death in univariate (HR: 0.33; 95 % CI 0.11-0.96, p=0.04) and multivariable (HR 0.37; 95 CI% 0.14-0.99, p=0.04) analysis. Conclusions: Histologic regression of LN metastasis after preoperative chemotherapy predicts the increased survival of patients with non-metastatic resectable AGC.