Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) for Gastric Cancer Peritoneal Metastases: Results from the Lithuanian PIPAC Program.

BACKGROUND: Peritoneal metastases (PM) of gastric cancer (GC) are considered a terminal condition, with reported median survival ranging from 2 to 9 months. Standard treatment typically involves systemic chemotherapy alone or combined with targeted therapy or immunotherapy, though efficacy is limited. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has emerged as a novel technique for treating GC PM, although it remains an experimental treatment under investigation. This study aimed to summarize the outcomes of GC PM treatment with PIPAC from the Lithuanian PIPAC program. METHODS: All patients who underwent PIPAC for GC PM at Vilnius University Hospital Santaros Klinikos between 2015 and 2022 were included in this retrospective study. The safety of PIPAC was assessed by postoperative complications according to the Clavien-Dindo classification. Efficacy was evaluated based on the peritoneal carcinomatosis index (PCI), ascites dynamics throughout the treatment, and long-term outcomes. RESULTS: In total, 32 patients underwent 71 PIPAC procedures. Intraoperative and postoperative morbidity related to PIPAC occurred after three (4.2%) procedures. Following PIPAC, there was a tendency towards a decrease in median PCI from 10 (Q1 3; Q3 13) to 7 (Q1 2; Q3 12), p = 0.75, and a decrease in median ascites volume from 1300 mL (Q1 500; Q3 3600) at the first PIPAC to 700 mL (Q1 250; Q3 4750) at the last PIPAC, p = 0.56; however, these differences were not statistically significant. The median overall survival after PM diagnosis was 12.5 months (95% CI 10-17), and the median survival after the first PIPAC procedure was 5 months (95% CI 4-10). CONCLUSIONS: PIPAC is a safe and feasible treatment option for GC PM; however, well-designed prospective studies are needed to fully assess its efficacy.

Primary Liver Perivascular Epithelioid Cell Tumor (PEComa): Case Report and Literature Review.

A primary liver perivascular epithelioid cell tumor (PEComa) is an extremely rare entity. In this article, we present a case report with a review of the literature on the patients diagnosed with primary liver PEComa and an elaboration of diagnostic and treatment modalities. A systematic literature search was conducted using the terms "perivascular epithelioid cell tumor", "PEComa", "liver", and "hepatic". All articles describing patients diagnosed with primary liver PEComa were included. We identified a total of 224 patients of primary liver PEComa from 75 articles and a case from the present study with a significant preponderance of females (ratio 4:1) and with a mean age of 45.3 ± 12.1 years. Most of the patients (114 out of 224, 50.9%) were asymptomatic. A total of 183 (81.3%) patients underwent surgical hepatic resection at the time of diagnosis, while 19 (8.4%) underwent surveillance. Recurrence and metastases were detected in seven (3.1%) and six (2.7%) patients, respectively. In conclusion, surgical resection remains the cornerstone of therapy; however, the presence of nonspecific imaging features makes it difficult to reach a definite diagnosis preoperatively. Therefore, a multidisciplinary approach should be the gold standard in selecting the treatment modality.

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.

Self-Locking Polymeric Clips Are Safe for the Closure of Appendiceal Stump in Laparoscopic Appendectomy.

Background: Closure of the appendix stump is critical to avoid serious postoperative complications. There are a number of options, but the best one has not been identified yet. The purpose of this study is to evaluate the outcomes of appendiceal stump closure using self-locking polymeric clips and endoloops. Methods: A retrospective analysis of the prospectively maintained database of patients with acute appendicitis was performed. Patient demographic details and surgical characteristics, including the duration of hospital stay, postoperative complications, and also the cost of the appendix stump closure, were recorded. Patients were divided into two groups according to the appendix stump closure method: the clips group if it was closed with self-locking polymeric clips and the loops group if Vicryl or PDS loops were used. Statistical analysis was performed using Pearson's chi-squared test, Wilcoxon rank sum (Mann-Whitney U) test, and Fisher's exact test in R statistical software package version 4.2.1. Results: 515 patients were included in the study from June 2016 to April 2021. There were no significant differences in terms of demographics (p-value in comparison of groups' sex > 0.99, age p-value 0.16), postoperative complications (p-value > 0.99), histological findings (p-value 0.27), or length of hospital stays (p-value 0.18) between the two patient groups (clips group, N = 454 and loops group, N = 61). The price of operation while using different appendiceal stump closures is significantly different. In a laparoscopic appendectomy, one stump closure with self-locking clips costs 7.69 €, with Vicryl loops-91.35 €, with PDS loops-96.51 €, and with a stapler-514.50 €. Conclusions: Self-locking polymeric clips can be used for the safe and effective closure of an appendiceal stump. There were no significant differences in the postoperative time (30 days) or complication rates among patients in both (clips and loops) groups. Thus, this might be a technique to reduce expenses while maintaining good postoperative results after laparoscopic appendectomy.

Aberrant pancreas adenocarcinoma in the stomach: A case report and literature review.

RATIONALE: Aberrant pancreatic tissue in the gastrointestinal tract is a relatively common finding. However, malignant transformation is extremely rare. Herein, we report a case of ectopic pancreatic ductal adenocarcinoma in the stomach wall. PATIENT CONCERNS: A 38 year old male presented with nausea, bloating, abdominal distention and weight loss for 4 months. DIAGNOSES: Endoscopy of upper gastrointestinal tract was performed twice with 2 months interval and a stenotic pyloric part was observed with a suspected submucosal lesion. It was sampled both times, however the pathology findings of the mucosal biopsies were unremarkable with no identifiable neoplastic structures. CT scan and MRI was performed and showed a thickened pyloric wall with a submucosal lesion 15 × 15 mm in diameter. Blood levels of tumor markers carcinoembrionic antigen and carbohydrate antigen 19-9 were within a normal range. INTERVENTIONS: Pyloric stenosis progressed and the patient underwent a Billroth type I distal gastric resection with D2 lymphadenectomy. Pathologic examination revealed a well differentiated ductal adenocarcinoma arising in the heterotopic pancreatic tissue (Heinrich type III). The resection margins and lymph nodes were free of tumor. The patient received adjuvant chemotherapy with 6 courses of XELOX. OUTCOMES: No disease recurrence is reported in 12 months follow-up. LESSONS: Aberrant pancreatic ductal adenocarcinoma in the stomach is a rare finding, however this pathology should be included in the differential diagnosis of gastric submucosal lesion causing pyloric stenosis.

Suspected and Confirmed Acute Appendicitis During the COVID-19 Pandemic: First and Second Quarantines-a Prospective Study.

Purpose: COVID-19 posed an unprecedented modern global healthcare crisis affecting both elective and urgent surgeries. The aim of this study is to evaluate the difference in the presentation of acute appendicitis (AA) before and during the COVID-19 era, the first and second quarantines. Methods: We performed a prospective study from December 2018 to May 2021. Two cohorts were analysed, one with patients who presented to the emergency department (ED) with suspected AA and the second with confirmed AA. Both cohorts were divided into four groups: before COVID-19, during the first quarantine, between the first and second quarantine, and during the second quarantine. Data such as demographics, the time to first contact with the healthcare provider and time to operation, laboratory tests, clinical stage of AA, length of stay, and COVID-19 status were collected. A total of 469 patients were enrolled. Results: A total of 209 patients were male (45%) and 260 were female (55%), with the median age being 33 years (24-45). In the first cohort of suspected AA, there was no difference in sex; however, more older patients presented to the ED during the first quarantine (41 years) compared with other groups (28.5, 36, and 32.5 years), p < 0.000. Before the pandemic, there was a shorter duration of symptoms to first contact with the healthcare provider (13 h) compared with other groups, p = 0.001. In the second cohort of confirmed AA, there was a shorter period of time to operation from first symptoms before the pandemic (22 h) compared with other groups (30, 35, 30.5 h), p < 0.000. There were more complicated gangrenous, perforated appendicitis or periappendicular abscess in Group 2 and 3 (26, 22 and 10%, and 26, 22 and 2%, respectively) compared with Group 1 (20, 4 and 3%) and Group 4 (22, 12, and 2%), p = 0.009. Hospital stay was longer during the first quarantine (3 days) compared with other groups (2 days), p = 0.009. Six patients were COVID-19 positive: one from Group 3 and five from Group 4 (p > 0.05). Conclusions: Our study suggests that during the first quarantine of the COVID-19 pandemic, there was delayed presentation to the ED with suspected AA and there was a greater proportion of complicated appendicitis and longer hospitalization in confirmed cases as well.

Magnetic resonance imaging reduces the rate of unnecessary operations in pregnant patients with suspected acute appendicitis: a retrospective study.

PURPOSE: This is a retrospective single-institution study performed to compare the rate of unnecessary operations in pregnant women with suspected acute appendicitis with and without the use of MRI. METHODS: The study subjects were all pregnant women with suspected acute appendicitis admitted to a tertiary institution from January 2012 to December 2019. If acute appendicitis was not excluded clinically and by ultrasound (US), laparoscopies were performed until May 2017 (US-only group). MRI was added as a diagnostic tool when US was inconclusive from May 2017 (US + MRI group). Surgery was considered unnecessary when no inflamed appendix was found. The rate of unnecessary surgery, postoperative complications, length of stay were analyzed. RESULTS: Seventy-six women were included in the study; 38 women in the US-only group and 38 women in the US + MRI group. There were no differences in admission characteristics between the groups. One of 38 women (2.6%) underwent unnecessary surgery in the US + MRI group vs. 10 of 38 (26.3%) in the US-only group (P = 0.007). The patients in the US + MRI group were significantly less likely to undergo a diagnostic operation than in the US-only group (5.26% vs. 55.3%, respectively; P < 0.001) and their hospital stay was significantly shorter (0.74 ± 1.64 days vs. 3.7 ± 3.0 days, respectively; P < 0.001). The obstetric outcomes were not different between the groups. MRI had a sensitivity of 83.3% and specificity of 100% in the series. CONCLUSION: The rate of unnecessary surgery was significantly reduced in pregnant women, who underwent MRI after inconclusive transabdominal US.