Observation Safely Reduces the Use of the Computerized Tomography in Medium-to-Low-Risk Patients with Suspected Acute Appendicitis: Results of a Randomized Controlled Trial.

Objectives-The objective was to compare the effectiveness of observation in standard-of-care computed tomography (CT) in adult patients with suspected acute appendicitis (AA). Methods-Patients with clinically suspected AA and inconclusive diagnosis after primary clinical examination, laboratory examination, and transabdominal ultrasound (TUS) were eligible for the study, and they were randomized (1:1) to parallel groups: observation-group patients were observed for 8-12 h and then, repeated clinical and laboratory examinations and TUS were performed; CT group (control group) patients underwent abdominopelvic CT scan. The study utilized Statistical Analysis System 9.2 for data analysis, including tests, logistic regression, ROC analysis, and significance evaluation. Patients were enrolled in the study at Vilnius University Hospital Santaros Klinikos in Lithuania between December 2018 and June 2021. Results-A total of 160 patients (59 men, 101 women), with a mean age of 33.7 ± 14.71, were included, with 80 patients in each group. Observation resulted in a reduced likelihood of a CT scan compared with the CT group (36.3% vs. 100% p < 0.05). One diagnostic laparoscopy was performed in the observation group; there were no cases of negative appendectomy (NA) in the CT group. Both conditional CT and observation pathways resulted in high sensitivity and specificity (97.7% and 94.6% vs. 96.7% and 95.8%). Conclusions-Observation including the repeated evaluation of laboratory results and TUS significantly reduces the number of CT scans without increasing NA numbers or the number of complicated cases.

[Retracted] Sulforaphane sensitizes human cholangiocarcinoma to cisplatin via the downregulation of anti­apoptotic proteins.

Following the publication of the above article and a corrigendum that was published in October 2023 to address the issue of misplaced control ß­actin western blots comparing between Figs. 3 and 4A (doi: 10.3892/or.2023.8646), an attentive reader drew to the authors' attention that the first author had apparently made additional unreported corrections to the revised version of Fig. 4 presented in the corrigendum. Although these image discrepancies did not alter the study's primary conclusions, they were such that they did cast doubt on the data's integrity. Consequently, the authors have decided to retract the paper and the Editor of Oncology Reports has agreed to the authors' request. The authors deeply regret any confusion or inconvenience this retraction may cause, and offer their sincere apologies to the Editor of Oncology Reports and the readership. [Oncology Reports 37: 3660­3666, 2017; DOI: 10.3892/or.2017.5622].

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.

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.

[Corrigendum] Sulforaphane sensitizes human cholangiocarcinoma to cisplatin via the downregulation of anti­apoptotic proteins.

Following the publication of this article, an interested reader drew to the authors' attention that, in Figs. 3 and 4A on p. 3664, the respective ß­actin controls for the cell lines TFK­1 and HuCCT­1 appeared to have mixed up, comparing the western blots between the two figures. After re­examining their data, the authors have realized that the control blots in Fig. 4A were inadvertently presented the wrong way around. The corrected version of Fig. 4, showing the correctly presented western blotting data in Fig. 4A, is shown on the next page. Note that this error did not grossly affect the results or the conclusions reported in this paper. The authors sincerely apologize for the error that was introduced during the preparation of this figure, and thank the Editor of Oncology Reports for allowing them the opportunity to publish a corrigendum. Furthermore, they regret any inconvenience caused to the readership. [Oncology Reports 37: 3660­3666, 2017; DOI: 10.3892/or.2017.5622].

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.

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.

Impact of the Interval Between Neoadjuvant Chemotherapy and Gastrectomy on Short- and Long-Term Outcomes for Patients with Advanced Gastric Cancer.

BACKGROUND: The optimal time between neoadjuvant chemotherapy (NAC) and gastrectomy for gastric cancer (GC) remains unknown. This study aimed to investigate the association between the time-to-surgery (TTS) interval and the major pathologic response (mPR). METHODS: In this study, 280 consecutive GC patients who underwent NAC followed by gastrectomy between 2014 and 2018 were retrospectively analyzed by the use of prospectively collected databases from three major GC treatment centers in Lithuania and Estonia. Based on TTS, they were grouped into three interval categories: the early-surgery group (ESG: ≤ 30 days; n = 70), the standard-surgery group (SSG: 31-43 days; n = 138), and the delayed-surgery group (DSG: ≥ 44 days, n = 72). The primary outcome of the study was the mPR rate. The secondary end points were postoperative morbidity, mortality, oncologic safety (measured as the number of resected lymph nodes and radicality), and long-term outcomes. RESULTS: The mPR rate for the ESG group (32.9%) was significantly higher than for the SSG group (20.3%) or the DSG group (16.7%) (p = 0.047). Furthermore, after adjustment for patient, tumor, and treatment characteristics, the odds for achievement of mPR were twofold higher for the patients undergoing early surgery (odds ratio [OR] 2.09; 95% conflidence interval [CI] 1.01-4.34; p = 0.047). Overall morbidity, severe complications, 30-day mortality, R0 resection, and retrieval of at least 15 lymph nodes rates were similar across the study groups. In addition, the long-term outcomes did not differ between the study groups. CONCLUSIONS: This study suggests that an interval of more than 30 days between the end of NAC and gastrectomy is associated with a higher mPR rate, the same oncologic safety of surgery, and similar morbidity and mortality.

Short- and long-term outcomes of surgery for colorectal and non-colorectal liver metastasis: a report from a single center in the Baltic country.

BACKGROUND: The liver is a major target organ for metastases of various types of cancers. Surgery is a well-established option for colorectal liver metastases (CRLM). Regarding the improved surgical and anesthetic techniques, the safety of liver resection has increased. Consequently, the interest in the surgical management of non-colorectal liver metastases (non-CRLM) has gained significant attention. Therefore, this study was designed to investigate the surgical treatment outcomes for non-CRLM and to compare it with an outcome of CRLM in a tertiary care center in the Baltic country-Lithuania. METHODS: We retrospectively analyzed data from all patients who underwent liver resection for CRLM or non-CRLM between 2010 and 2017 in a tertiary care center-Vilnius University hospital Santaros Clinics. Demographic and metastasis characteristics, as well as disease-free and overall survival, were compared between the study groups. RESULTS: In total, 149 patients were included in the study. Patients in the CRLM group were older (63.2 ± 1.01 vs 54.1 ± 1.8 years, p < 0.001) and mainly predominant by males. Overall postoperative morbidity rate (16.3% vs 9.8%, p = 0.402) and major complications rate (10% vs 7.8%, p = 0.704) after liver resection for CRLM and non-CRLM was similar. Kaplan-Meier analysis showed higher disease-free survival in the CRLM group with 89.4% vs 76.5% and 64.9% vs 31.4% survival rates at 1 and 3 years, respectively (p = 0.042), although overall survival was not different between the CRLM and non-CRLM groups with 89.4% vs 78.4% and 72.0% vs 46.1% survival rates at 1 and 3 years, respectively (p = 0.300). CONCLUSIONS: In this study, we confirmed comparable short- and long-term outcomes after liver resection for CRLM and non-CRLM. Surgical resection should be encouraged as an option in well-selected patients with non-CRLM.

Does a retrorectal tumour remain a challenge for surgeons?

Background: Retrorectal tumours are lesions with a wide range of histological differentiation that are often diagnostic and clinical challenges due to their rare occurrence. Many cases of this pathology are treated in regional hospitals, which results in serious complications because physicians fail to recognize this pathology. We present our experience in treating these tumours. Methods: A retrospective analysis of a prospectively maintained database was performed using the Vilnius University Hospital Santaros Clinics patient database. Thirty-five cases were identified. Results: Occurrence of retrorectal tumours was higher in women than in men and accounted for 82.86% and 17.14%, respectively. Computer tomography and magnetic resonance imaging were the main methods used to confirm diagnosis and plan surgical treatment. We have used a laparotomy, perineal or combined approach for tumour extirpation. The laparotomy approach was the most used, followed by perineal extirpation. The most common histological type was cystic hamartoma, accounting for 20% of cases. In 80% of cases, the histological findings greatly varied. Hospital stays varied from 3 to 21 days with a mean of 11.6 ± 5.83 days. The postoperative complication rate was 17.14% and was present in six cases. Overall survival was 85.17%, with an average follow-up period of 71.83 months. There were no recurrent tumours diagnosed during follow-up. Conclusion: Retrorectal tumours are a very rare pathology with high histological heterogeneity and problematic diagnostics. Patients should be referred to a tertiary centre that has experience and diagnostic capabilities for the best diagnostic and treatment options.

Laparoscopically assisted colonoscopic polypectomy - viable option for curative surgery in elderly patients.

INTRODUCTION: Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most frequent cause of cancer-related death in the world. CRC screening programs have been widely introduced worldwide, allowing for early detection and removal of precancerous lesions and avoiding major surgical intervention. However, not all polyps are suitable for conventional and advanced colonoscopic polypectomy. Thus, laparoscopically assisted colonoscopic polypectomy (LACP) was introduced to clinical practice as a method of choice for these polyps and adenomas. AIM: To overlook our experience in laparoscopically assisted colonoscopic polypectomies and evaluate effectiveness and quality of the procedure. MATERIAL AND METHODS: A retrospective analysis of a prospectively maintained database was performed. using the Vilnius University Hospital Santariskiu Klinikos patient database for the period from 2010 to 2016, resulting in 21 cases in which LACP was performed. All procedures were performed using combined laparoscopy and videocolonoscopy techniques. Morphology of adenomas was classified according to the Paris classification during the procedure. Creation of the database was approved by the Lithuanian Bioethics committee. RESULTS: Twenty-two adenomas were removed from 21 patients, aged 65.33 ±8.9. There was no difference between male and female age, but occurrence of adenomas in females was 2-fold higher. The majority of removed lesions were localized in the cecum and mean size was 27.2 ±11.1 mm. The morphology of adenomas was distributed equally between 0-Is, 0-Ip, and 0-IIa, except one, which belonged to 0-III. Histological analysis revealed that tubulovillous adenoma occurrence was 1.4 times higher than tubulous adenoma. There was only one postoperative complication - bleeding from the adenoma resection site, which was managed by conservative means. One patient developed G2 adenocarcinoma at the polyp resection site and was referred for radical surgery. CONCLUSIONS: The LACP is a safe procedure with minimal risk to the elderly patient. Patient follow-up is essential for detection of recurrence.

Sulforaphane sensitizes human cholangiocarcinoma to cisplatin via the downregulation of anti-apoptotic proteins.

Cholangiocarcinoma (CCC) is an aggressive malignancy with poor therapeutic options and pronounced chemotherapy resistance. The bioactive broccoli substance, sulforaphane (SFN), is a promising new therapeutic option since it has been found to induce therapeutic effects in both experimental and epidemiological studies in various tumor entities. Thus, the present study was designed to assess the effect of SFN on cisplatin sensitivity in CCC. Human HuCCT-1 and TFK-1 cells, representing intrahepatic and extrahepatic CCC, respectively, were treated with cisplatin and SFN. Viability, the platinated DNA content, and apoptosis were assessed using both MTT assay and flow cytometry, while western blotting was used to analyze the expression of proteins involved in apoptosis and DNA damage. Whereas cisplatin was largely ineffective, SFN only therapy significantly decreased the viability of both CCC cell lines. The combination of SFN with cisplatin increased cisplatin cytotoxicity, which was particularly pronounced relatively early at 36 h after treatment. Apoptosis, which was reflected by the cleavage of caspase-3 and PARP, was significantly enhanced. Notably, only cisplatin was found to induce the expression of proteins involved in the DNA damage response; however, the presence of SFN appeared to enable otherwise cisplatin-resistant cells to undergo apoptosis. Due to the fact that SFN did not enhance the DNA platination levels upon cisplatin treatment, SFN may have exerted its activity via the inhibition of the anti-apoptotic proteins Bcl-2 and XIAP, as we observed. Data presented in the present study clearly demonstrated that SFN significantly decreased the drug resistance to cisplatin in human CCC. This highlights dietary co-treatment as a viable new treatment option for CCC.

Giant Bauhin valve adenoma and laparoscopically assisted colonoscopic polypectomy.

Nowadays colonoscopic polypectomy has become a routine procedure, which is performed daily. Almost every colorectal benign tumor can be removed endoscopically, although there are some problematic adenomas which are either large in size or difficult to approach. In the past two decades laparoscopically assisted colonoscopic polypectomy has become established in the endoscopic world, which reduced the need of operations for those patients with lesions that are large or hard to approach. The first laparoscopically monitored colonoscopic polypectomy was performed by Franklin in 1991, and reported publicly in 1993. We present a case report of a patient who was diagnosed with Bauhin valve giant adenoma and underwent laparoscopically assisted polypectomy.