Fluorescent ICG angiography in laparoscopic rectal resection - a randomized controlled trial. Preliminary report.

Introduction: Anastomotic leakage is one of the most dangerous complications after rectal surgery. It can cause systemic complications, reduce the quality of life and worsen the results of oncological treatment. One of the causes of anastomotic leak is insufficient blood supply to the anastomosis. Intraoperative infrared angiography with indocyanine green (ICG) is expected to improve the assessment of intestinal perfusion and thus prevent anastomotic leakage. Aim: To present the results of the use of ICG intraoperative angiography during rectal surgery in the prevention of anastomotic leakage. Material and methods: The study included 76 patients undergoing rectal cancer surgery. Patients were randomized to 2 groups: Group I - 41 patients with ICG intraoperative angiography; and Group II - 35 patients without ICG imaging. Anastomotic leak, length of hospitalization, and complication rate were compared. Results: Group I patients received intravenous ICG before the anastomosis. Average time of intestinal wall contrasting was 42 s (22-65 s). Average ICG procedure time was 4 min (3.2% of total time of surgery). Three (7.3%) patients after angiography revealed intestinal ischemia requiring widened resection. No anastomotic leak was found post-operatively, and no side effects were observed after administration of ICG. In group II, 3 (8.6%) anastomotic leakages were diagnosed, 2 of which required reoperation. Conclusions: Intraoperative angiography with ICG in near-infrared light is a safe and effective method of assessing intestinal perfusion. ICG angiography may change the surgical plan and reduce the risk of anastomotic leakage. It is necessary to continue the study until the assumed number of patients is reached.

Creating an Innovative Artificial Intelligence-Based Technology (TCRact) for Designing and Optimizing T Cell Receptors for Use in Cancer Immunotherapies: Protocol for an Observational Trial.

BACKGROUND: Cancer continues to be the leading cause of mortality in high-income countries, necessitating the development of more precise and effective treatment modalities. Immunotherapy, specifically adoptive cell transfer of T cell receptor (TCR)-engineered T cells (TCR-T therapy), has shown promise in engaging the immune system for cancer treatment. One of the biggest challenges in the development of TCR-T therapies is the proper prediction of the pairing between TCRs and peptide-human leukocyte antigen (pHLAs). Modern computational immunology, using artificial intelligence (AI)-based platforms, provides the means to optimize the speed and accuracy of TCR screening and discovery. OBJECTIVE: This study proposes an observational clinical trial protocol to collect patient samples and generate a database of pHLA:TCR sequences to aid the development of an AI-based platform for efficient selection of specific TCRs. METHODS: The multicenter observational study, involving 8 participating hospitals, aims to enroll patients diagnosed with stage II, III, or IV colorectal cancer adenocarcinoma. RESULTS: Patient recruitment has recently been completed, with 100 participants enrolled. Primary tumor tissue and peripheral blood samples have been obtained, and peripheral blood mononuclear cells have been isolated and cryopreserved. Nucleic acid extraction (DNA and RNA) has been performed in 86 cases. Additionally, 57 samples underwent whole exome sequencing to determine the presence of somatic mutations and RNA sequencing for gene expression profiling. CONCLUSIONS: The results of this study may have a significant impact on the treatment of patients with colorectal cancer. The comprehensive database of pHLA:TCR sequences generated through this observational clinical trial will facilitate the development of the AI-based platform for TCR selection. The results obtained thus far demonstrate successful patient recruitment and sample collection, laying the foundation for further analysis and the development of an innovative tool to expedite and enhance TCR selection for precision cancer treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT04994093; https://clinicaltrials.gov/ct2/show/NCT04994093. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45872.

Can the POLARS tool accurately predict low anterior resection syndrome in rectal cancer patients undergoing laparoscopic resection?

Introduction: Radical rectal cancer resection can lead to a long-term bowel function impairment known as low anterior resection syndrome (LARS). It remains unclear how to determine which patients are at a higher risk of developing LARS post-surgery. The POLARS tool was designed to predict the onset and severity of LARS in rectal cancer patients after surgery. The study aimed to assess the accuracy of POLARS in predicting the onset of LARS. Material and methods: A total of 66 rectal cancer patients treated laparoscopically between January 2016 and December 2017 were included in this retrospective study. Using POLARS, the predictive value for the occurrence of LARS was documented. During an average 17-month follow-up period, the bowel function of the patients was assessed using the dedicated LARS questionnaire. The predicted and actual scores were then compared. Results: Study participants included 36 women (54.5%) and 30 men (45.5%), with a mean age of 62.55 years (standard deviation: 10.2; range: 37-81). The mean predicted score according to POLARS was 24.5 (i.e. category "minor LARS"), and the mean actual score in the follow-up period was 16.42 ("no LARS" category). In only 39% of patients, the predicted LARS category was the same as the actual LARS category assessed by the questionnaire. Worse bowel function than reported at follow-up was predicted in 75% of all mispredictions. Conclusions: POLARS did not prove to be accurate in predicting the risk and severity of LARS in these patients, although the average numbers appear promising. Further evaluation of the POLARS tool using a larger cohort is needed.

Panoramic colonoscopy in colorectal cancer screening - a randomized controlled trial.

INTRODUCTION: Colonoscopy is considered the gold standard for colorectal cancer screening. Panoramic colonoscopy offers better visualization to decrease the adenoma miss rate. AIM: To assess the influence of 330° panoramic view colonoscopy on adenoma and polyp detection rate, cecal intubation time, and examiner's comfort. MATERIAL AND METHODS: The study enrolled 421 patients aged 18-80 years who were eligible for colonoscopy screening. Patients with prior abdominal surgery, inflammatory bowel disease or after colorectal resections were excluded from the study. Patients were randomized to either standard frontal view (SFV) (Olympus Evis Exera III 190 CF-HQ190L) or the panoramic view colonoscopy (PVC) (FUSE CDVL slim c38). The study was approved by the local bioethics committee and registered at ClinicalTrial.gov (NCT02929381). RESULTS: There were 214 patients examined with SFV and 207 with PVC. The mean age of patients was 64 ±12.26 years. The two groups were comparable. The median cecal intubation time was 234 s with SFV vs. 311 s with PVC (p < 0.001). There were no significant differences in CIR or withdrawal time. PVC made it possible to discover more diverticula in the ascending colon (p = 0.009). PDR with SFV was 34.6% and 40.1% with PVC (p = 0.242). A higher number of polyps was found in the transverse colon in the PVC group (p = 0.006). ADR and advanced ADR (aADR) in both groups were similar (26.4% vs. 27.1% and 14, 2% vs. 13.9%). CONCLUSIONS: Colonoscopy with wide-angle endoscopes lasts longer and allows for the detection of more polyps and diverticula without affecting ADR and aADR. Our study did not reveal the superiority of wide-angle colonoscopy in colorectal cancer screening.

Quality of life in patients after laparoscopic cholecystectomy due to gallstone disease - evaluation of long-term postoperative results.

<b>Introduction:</b> Currently, the standard treatment of gallstone disease is laparoscopic cholecystectomy. Considering its availability, reduction of postoperative pain and shortened stay in the hospital, a constant upward trend in the number of such procedures is observed. However, about one third of patients undergoing such treatment report pain and dyspeptic disorders following the surgery. The assessment of the quality of life of patients undergoing laparoscopic cholecystectomy, based on standardized questionnaires, should be one of the elements allowing for the assessment of the impact of the applied treatment on patients' lives. </br></br> <b>Aim:</b> The aim of this retrospective study is to evaluate the impact of laparoscopic cholecystectomy on the quality of life of patients operated in one center. </br></br> <b>Materials and methods:</b> The study has been carried out retrospectively with the use of a GIQLI questionnaire completed online by the patients 6 months after undergoing laparoscopic cholecystectomy. The study included patients over 18 years of age who have not experienced any complications within the perioperative period and did not require open surgery. The study group has been divided into two subgroups depending on the presence of symptoms of acute gallstone disease in the pre-operative period. </br></br> <b>Results: </b>The study group consisted of 205 patients (53 men, 152 women, aged 19 to 87, with an average of 54.3). The subgroup with an asymptomatic gallstone disease (dyspeptic disorders, without biliary colic) consisted of 47 patients (18 men, 29 women, aged 19-87). Symptomatic gallstone disease occurred in 158 people (35 men, 123 women aged 22 to 81). There have been certain statistically significant differences in the post-operative health condition between the group of patients with symptoms of gallstone disease and the asymptomatic patients. 94.3% of symptomatic patients concluded that their condition has improved and 5.7% that it remained unchanged. Among asymptomatic patients, only 53.2% of patients stated that they felt better post-surgery, 44.7% reported no changes (p < 0.001). There have been no significant differences in the overall QIQLI scores between these subgroups, although symptomatic patients assessed their social functioning better (8.9 ±1.5 vs 8.11 ±2.08, p = 0.004). There have been certain differences between men and women in the assessment of the quality of life in the context of the presence of key symptoms (M: 28.87 ±4.23, F: 26.77 ±5.0, p = 0.007). </br></br> <b> Conclusion:</b> The patients with a symptomatic gallstone disease report they feel better after laparoscopic cholecystectomy as compared to the group of asymptomatic patients. The overall QOL score measured by the GIQLI form does not depend on the presence of symptoms in the preoperative period. Men benefited more from surgery as regards key symptoms.

Preoperative radiotherapy and local excision of rectal cancer: Long-term results of a randomised study.

BACKGROUND AND PURPOSE: It is uncertain whether local control is acceptable after preoperative radiotherapy and local excision (LE). An optimal preoperative dose/fractionation schedule has not yet been established. MATERIAL AND METHODS: In a phase III study, patients with cT1-2N0M0 or borderline cT2/T3N0M0 < 4 cm rectal adenocarcinomas were randomised to receive either 5 × 5 Gy plus 1 × 4 Gy boost or chemoradiation: 50.4 Gy in 28 fractions plus 3 × 1.8 Gy boost and 5-fluorouracil with leucovorin bolus. LE was performed 6-8 weeks later. Patients with ypT0-1R0 disease were observed. Completion total mesorectal excision (CTME) was recommended for poor responders, i.e. ypT1R1/ypT2-3. RESULTS: Of 61 randomised patients, 10 were excluded leaving 51 for analysis; 29 in the short-course group and 22 in the chemoradiation group. YpT0-1R0 was observed in 66% of patients in the short-course group and in 86% in the chemoradiation group, p = 0.11. CTME was performed only in 46% of patients with ypT1R1/ypT2-3. The median follow-up was 8.7 years. Local recurrence incidences and overall survival at 10 years were respectively for the short-course group vs. the chemoradiation group 35% vs. 5%, p = 0.036 and 47% vs. 86%, p = 0.009. In total, local recurrence at 10 years was 79% for ypT1R1/T2-3 without CTME. CONCLUSIONS: This trial suggests that in the LE setting, both local recurrence and survival are worse after short-course radiotherapy than after chemoradiation. Because of the risk of bias, a confirmatory study is desirable. Lack of CTME is associated with an unacceptably high local recurrence rate.

Underexpression of LATS1 TSG in colorectal cancer is associated with promoter hypermethylation.

AIM: To investigate large tumor suppressor 1 (LATS1) expression, promoter hypermethylation, and microsatellite instability in colorectal cancer (CRC). METHODS: RNA was isolated from tumor tissue of 142 CRC patients and 40 colon mucosal biopsies of healthy controls. After reverse transcription, quantitative polymerase chain reaction (PCR) was performed, and LATS1 expression was normalized to expression of the ACTB and RPL32 housekeeping genes. To analyze hypermethylation, genomic DNA was isolated from 44 tumor CRC biopsies, and methylation-specific PCR was performed. Microsatellite instability (MSI) status was checked with PCR using BAT26, BAT25, and BAT40 markers in the genomic DNA of 84 CRC patients, followed by denaturing gel electrophoresis. RESULTS: Decreased LATS1 expression was found in 127/142 (89.4%) CRC cases with the average ratio of the LATS1 level 10.33 ± 32.64 in CRC patients vs 32.85 ± 33.56 in healthy controls. The lowest expression was found in Dukes' B stage tumors and G1 (well-differentiated) cells. Hypermethylation of the LATS1 promoter was present in 25/44 (57%) CRC cases analyzed. LATS1 promoter hypermethylation was strongly associated with decreased gene expression; methylated cases showed 162× lower expression of LATS1 than unmethylated cases. Although high-grade MSI (mutation in all three markers) was found in 14/84 (17%) cases and low-grade MSI (mutation in 1-2 markers) was found in 30/84 (36%) cases, we found no association with LATS1 expression. CONCLUSION: Decreased expression of LATS1 in CRC was associated with promoter hypermethylation, but not MSI status. Such reduced expression may promote progression of CRC.

Preoperative radiotherapy and local excision of rectal cancer with immediate radical re-operation for poor responders: a prospective multicentre study.

PURPOSE: To assess local control after preoperative radiation and local excision and to determine an optimal radiotherapy regimen. METHODS: Eighty-nine patients with G1-2 rectal adenocarcinoma <3-4 cm; unfavourable cT1N0 (23.6%), cT2N0 (62.9%) or borderline cT2/cT3N0 (13.5%) received 5 × 5 Gy plus 4 Gy boost (71.9%) or 55.8 Gy in 31 fractions with 5-FU and leucovorin (28.1%). Local excision (traditional technique 56.2%, transanal endoscopic microsurgery 41.6%, Kraske procedure 2.2%) was performed 6-8 weeks later. If patients were downstaged to ypT0-1 without unfavourable factors (good responders), this was deemed definitive treatment. Immediate conversion to radical surgery was recommended for remaining patients. RESULTS: Good response to radiation was seen in 67.2% of patients in the short-course group and in 80.0% in the chemoradiation group, p = 0.30. Local recurrence at 2 years (median follow-up) in good responders was 11.8% in the short-course group and 6.2% in the chemoradiation group, p = 0.53. In the total group, a lower rate of local recurrence at 2 years was observed in elderly patients (>69 years, median value) when compared to the younger patients; 8.3% vs. 27.7%, Cox analysis hazard ratio 0.232, p = 0.016. A total of 18 patients initially managed with local excision required conversion to abdominal surgery but either refused it or were unfit. In this group, local recurrence at 2 years was 37.1%. CONCLUSIONS: This study suggests an acceptable local recurrence rate after preoperative radiotherapy and local excision of small, radiosensitive tumours in elderly patients.

Enterocolic lymphocytic phlebitis: an unusual cause of abdominal complaints.

Enterocolic lymphocytic phlebitis (ELP) is a rare disease of unknown etiology involving most often the intramural and mesenteric small and medium-sized veins of the gastrointestinal tract. The diagnosis of the disorder is based on the histopathological examination of a surgical specimen as endoscopically obtained diagnostic material is usually too superficial. Clinical manifestation of ELP most frequently is characterized by acute symptoms, such as acute abdomen, signs suggesting acute appendicitis, gastrointestinal hemorrhage, sometimes it manifests as chronic gastrointestinal complaints. We report, to our knowledge for the first time in Poland, a case of ELP with clinical symptoms pointing to acute appendicitis, on laparoscopy manifesting as a tumorous mass in the colonic wall with an unchanged appendix.

Randomized clinical trial on preoperative radiotherapy 25 Gy in rectal cancer--treatment results at 5-year follow-up.

PURPOSE: The purpose of this study was to establish the influence of time interval between preoperative hyperfractionated radiotherapy (5 × 5 Gy) and surgery on long-term overall survival (5 years) and recurrence rate in patients with locally advanced rectal cancer operated on according to total mesorectal excision technique. METHODS: The treatment group comprised 154 patients with locally advanced rectal cancer who were operated on between 1999 and 2006 in the 1st Department of General Surgery, Jagiellonian University, Cracow, Poland. The data on survival has been systematically collected until 31st of December 2010. In addition, the following aspects were analyzed: the significance of time interval between the end of radiotherapy and surgical treatment and its influence on downsizing, downstaging, rate of curative resections, and sphincter-sparing procedures. Patients were qualified to preoperative radiotherapy 5 × 5 Gy and then randomly assigned to subgroups with different time intervals between radiotherapy and surgery: one subgroup consisted of 77 patients operated on 7-10 days after the end of irradiation, and the second subgroup consisted of 77 patients operated on after 4-5 weeks. Both groups were homogenous in sex, age, cancer stage and localization, distal and circumferential resection margins, and number of resected lymph nodes. RESULTS: The 5-year survival rate in patients operated on 7-10 days after irradiation was 63%, whereas in those operated on after 4-5 weeks, it was 73%-the difference was not statistically significant (log rank, p = 0.24). A statistically significant increase in 5-year survival rate was observed only in patients with downstaging after radiotherapy-90% in comparison with 60% in patients without response to neoadjuvant treatment (log rank, p = 0.004). Recurrence was diagnosed in 13.2% of patients. A lower rate of systemic recurrence was observed in patients operated on 4-5 weeks after the end of irradiation (2.8% vs. 12.3% in the subgroup with a shorter interval, p = 0.035). No differences in local recurrence rates were observed in both subgroups of irradiated patients (p = 0.119). The longer time interval between radiotherapy and surgery resulted in higher downstaging rate (44.2% vs. 13% in patients with a shorter interval, p = 0.0001) although it did not increase the rate of sphincter-saving procedures (p = 0.627) and curative resections (p = 0.132). CONCLUSIONS: 1. Improved 5-year survival rate is observed only in patients with downstaging after preoperative irradiation dose of 25 Gy. 2. Longer time interval after preoperative radiotherapy 25 Gy does not improve the rate of sphincter-saving procedures and curative resections (R0) despite higher downstaging rate observed in this regimen.

Preoperative radiotherapy and local excision of rectal cancer with immediate radical re-operation for poor responders.

BACKGROUND AND PURPOSE: To report an early analysis of prospective study exploring preoperative radiotherapy and local excision in rectal cancer. MATERIALS AND METHODS: Mucosa at tumour edges was tattooed. Patients with cT1-3N0 tumour <3-4 cm were treated with either 5x5Gy+4Gy boost (N=31) or chemoradiation (50.4Gy+5.4Gy boost, 1.8Gy per fraction+5-fluorouracyl and leucovorin; N=13). Thirteen patients from the short-course group were unfit for chemotherapy. The interval from radiation to full-thickness local excision was 6 weeks. The protocol called for conversion to a transabdominal surgery in case of ypT2-3 disease or positive margin. RESULTS: The postoperative complications requiring hospitalization were recorded in 9% of patients. The rate of pathological complete response was 41%. The rate of patients requiring conversion was 34%; however, 18% actually underwent conversion and the remaining 16% refused or were unfit. During the 14 months of median follow-up, local recurrence was detected in 7% of patients and all underwent salvage surgery. Of 19 patients in whom initially anterior resection was likely, 16% had abdominoperineal resection performed for a conversion or as a rescue procedure. CONCLUSION: Our study suggests that the short-course radiation prior to local excision is a treatment option for high-risk patients.

The impact of immunostimulating nutrition on infectious complications after upper gastrointestinal surgery: a prospective, randomized, clinical trial.

BACKGROUND AND AIM: Immunomodulating nutrition is supposed to reduce the number of complications and lengthen of hospital stay during the postoperative period in patients after major gastrointestinal surgery. The aim of the study was to assess the clinical effect of immunostimulatory enteral and parenteral nutrition in patients undergoing resection for gastrointestinal cancer in the group of well-nourished patients. MATERIAL AND METHODS: Between June 1, 2001, and December 31, 2005, a group of 214 well-nourished patients was initially assessed (150 men, 64 women, mean age 61.2 years) to participate in the study. Nine patients were subsequently excluded and the remaining 205 subjects were randomly assigned in a 2 x 2 factorial design into 4 study groups, ie, standard enteral nutrition (n = 53), immunomodulating enteral nutrition (n = 52), standard parenteral nutrition (n = 49), and immunomodulating enteral nutrition (n = 51). The study was designed to test the hypothesis that immunonutrition and enteral nutrition would reduce the incidence of infectious complications after upper gastrointestinal surgery; the secondary objective of the study was to evaluate the effect of nutritional intervention on overall morbidity and mortality rates, and hospital stay. The study was registered in the Clinical Trials Database-number NCT 00558155. RESULTS: The overall morbidity rate was 33% and the incidence of individual complications was comparable between all groups. Infectious complications occurred in 26 of 102 patients given standard diets and in 22 of 103 patients receiving immunomodulatory formulas (odds ratio 0.81; 95% CI, 0.43-1.50). There were no significant differences between infectious complications in patients using parenteral nutrition (22 of 100 patients) and parenteral formulas (26 of 105, odds ratio 1.14; 95% CI, 0.61-2.14). Neither immunostimulating formulas nor enteral feeding significantly affected secondary outcome measures, including overall morbidity and mortality rates, and hospital stay. CONCLUSIONS: Our study failed to demonstrate any clear advantage of routine postoperative immunonutrition in patients undergoing elective upper gastrointestinal surgery. Both enteral and parenteral treatment options showed similar efficacy, tolerance, and effects on protein synthesis. Parenteral nutrition composed according to contemporary rules showed similar efficiency to enteral nutrition. However, because of its cost-efficiency, enteral therapy should be considered as the treatment of choice in all patients requiring nutritional therapy.

The role and value of endorectal ultrasonography in diagnosing T1 rectal tumors.

Rectal carcinoma in 50% to 60% of cases is localized in the rectum and, if diagnosed early can be locally excised. The authors evaluated the diagnostic accuracy of the preoperative endorectal ultrasonography (ERUS) in the staging of rectal tumors and the usefulness of the method to assess patients' suitability for local excision. In the retrospective analysis, we analyzed 29 patients with rectal cancer. The depth of invasion into the rectal wall was assessed by ERUS and all patients were qualified for tumor excision with transanal endoscopic microsurgery (TEM). We analyzed overall accuracy of ERUS and the effectiveness of treatment. In the analyzed group, diagnostic accuracy of ERUS in assessing T1 carcinomas was 89.2%, sensitivity 92.3% and specificity 50%. Local excision with TEM was deemed to be curative in 86.2% patients with rectal tumors detected by ERUS. ERUS is an accurate method of preoperative assessment of T1 and T2 carcinomas and its diagnostic accuracy is sufficient to qualify patients for anal-saving operations.

[Radiofrequency ablation of the primary and secondary liver malignancies]. / Zastosowanie termoablacji (RFA--radiofrequency thermal ablation) w leczeniu pierwotnych i wtórnych nowotworów zlosliwych watroby.

For primary liver tumors and selected cases of colorectal liver metastases, surgical resection with preserved oncological margins of healthy tissue has been a method of choice. The criteria that decide about qualifying the patients to surgical resections include the number of nodules, size, localization, infiltrations to vessels or neighboring organs, liver functions, and patient's general condition. In fact, these criteria confine the number of performed resections to 5-25% of cases. These low rates encourage the search for the effective methods of primary and secondary liver tumors destruction with low complication rates. The authors review the results of radiofrequency thermal ablation (RFA) used to treat hepatocellular carcinoma and colorectal metastases in 65 patients, who underwent 178 RFA procedures (143 percutaneous and 35 during laparotomy). Positive response (regression, fibrosis or stabilized disease) to RFA was obtained from 60% of cases, and 3 (1.7%) patients developed bowel perforation. RFA is recommended as effective method with low rates of complications to be used for palliative treatment of unresectable primary and secondary liver malignancies.

[Perioperative infections in implantative surgery. Patogenesis and prevention]. / Zakazenia w chirurgii implantacyjnej. Patogeneza i zapobieganie.

The last decades have been witnessing rapid development of the implantation surgery. The use of artificial materials to replace damaged tissues has become more and more popular. One of the complications of these procedures is graft infection. The presence of foreign body can impair local host defence on the tissue level and reduce the number of contaminating microorganisms necessary for infection to 104-105. The most common pathogens responsible for graft infections are S. epidermidis, S. aureus and other Gram + and Gram - bacteria. The sources of infection are numerous and include patients, operative, and personnel factors. Graft-related infections are hazardous to the patients and can have even fatal consequences. Due to the limited effectiveness of applied methods to treat graft infections, more attention should be paid to prophylactic measures. These should cover all range of problems related to hospital work organisation, adequate sanitary and epidemiological conditions in the hospital wards and operating theatres as well as the use of local and systemic perioperative antibiotic prophylaxis.