Clinical benefits of symptom resolution after palliative surgery in advanced cancer: A single-center experience.

BACKGROUND: Palliative surgery (PS) is defined as any surgical procedure aimed at improving quality of life or relieving symptoms caused by an advanced or metastatic cancer. The involvement of patients, caregivers, and other professional figures is crucial for obtaining optimal symptom relief and avoiding complications. This study aims to evaluate the short-term outcome and related factors in patients undergoing PS. PATIENTS AND METHODS: A retrospective analysis was performed in consecutive patients who underwent palliative gastrointestinal surgery at our surgical unit during the period June 2018 to May 2023. Demographic, clinical, pathological and follow-up data were collected from a prospectively maintained department database. The main outcomes were complications, symptoms palliation, symptoms recurrence and return to systemic chemotherapy. Standard statistical analysis was performed. RESULTS: During the study period, 127 patients underwent palliative surgery. The Clavien-Dindo 3-5 complication rate and mortality rate were 19.7 % and 6 %, respectively. The resolution of symptoms was achieved in 109 patients (89 %). Successful symptom palliation was significantly related to the possibility of returning to systemic chemotherapy (SC) (OR 9.30 95 % CI 0.1.83-47.18, p 0.007). The only factor related to survival in multivariate analysis was the return to systemic chemotherapy (HR 0.25 95 % CI 0.15-0.42 0.001). CONCLUSION: PS in selected patients is effective for symptom resolution and improving overall survival, if the result is making anticancer therapy possible. Prospective data collection is in any case warranted in every institution performing PS for the purpose of monitoring appropriateness and quality of surgical care.

IMMUNOREACT 7: Regular aspirin use is associated with immune surveillance activation in colorectal cancer.

BACKGROUND: Long-term daily use of aspirin reduces incidence and mortality due to colorectal cancer (CRC). This study aimed to analyze the effect of aspirin on the tumor microenvironment, systemic immunity, and on the healthy mucosa surrounding cancer. METHODS: Patients with a diagnosis of CRC operated on from 2015 to 2019 were retrospectively analyzed (METACCRE cohort). Expression of mRNA of immune surveillance-related genes (PD-L1, CD80, CD86, HLA I, and HLA II) in CRC primary cells treated with aspirin were extracted from Gene Expression Omnibus-deposited public database (GSE76583). The experiment was replicated in cell lines. The mucosal immune microenvironment of a subgroup of patients participating in the IMMUNOREACT1 (ClinicalTrials.gov NCT04915326) project was analyzed with immunohistochemistry and flow cytometry. RESULTS: In the METACCRE Cohort, 12% of 238 patients analyzed were aspirin users. Nodal metastasis was significantly less frequent (p = .008) and tumor-infiltrating lymphocyte infiltration was higher (p = .02) among aspirin users. In the CRC primary cells and selected cell lines, CD80 mRNA expression was increased following aspirin treatment (p = .001). In the healthy mucosa surrounding rectal cancer, the ratio of CD8/CD3 and epithelial cells expressing CD80 was higher in aspirin users (p = .027 and p = .034, respectively). CONCLUSIONS: These data suggested that regular aspirin use may have an active role in enhancing immunosurveillance against CRC.

IMMUNOREACT 6: weak immune surveillance characterizes early-onset rectal cancer.

BACKGROUND: Colon cancer in young patients is often associated with hereditary syndromes; however, in early-onset rectal cancer, mutations of these genes are rarely observed. The aim of this study was to analyse the features of the local immune microenvironment and the mutational pattern in early-onset rectal cancer. METHODS: Commonly mutated genes were analysed within a rectal cancer series from the University Hospital of Padova. Mutation frequency and immune gene expression in a cohort from The Cancer Genome Atlas ('TCGA') were compared and immune-cell infiltration levels in the healthy rectal mucosa adjacent to rectal cancers were evaluated in the IMMUNOlogical microenvironment in REctal AdenoCarcinoma Treatment 1 and 2 ('IMMUNOREACT') series. RESULTS: In the authors' series, the mutation frequency of BRAF, KRAS, and NRAS, as well as microsatellite instability frequency, were not different between early- and late-onset rectal cancer. In The Cancer Genome Atlas series, among the genes with the most considerable difference in mutation frequency between young and older patients, seven genes are involved in the immune response and CD69, CD3, and CD8ß expression was lower in early-onset rectal cancer. In the IMMUNOlogical microenvironment in REctal AdenoCarcinoma Treatment 1 and 2 series, young patients had a lower rate of CD4+ T cells, but higher T regulator infiltration in the rectal mucosa. CONCLUSION: Early-onset rectal cancer is rarely associated with common hereditary syndromes. The tumour microenvironment is characterized by a high frequency of mutations impairing the local immune surveillance mechanisms and low expression of immune editing-related genes. A constitutively low number of CD4 T cells associated with a high number of T regulators indicates an imbalance in the immune surveillance mechanisms.

IMMUNOREACT 5: female patients with rectal cancer have better immune editing mechanisms than male patients - a cohort study.

BACKGROUND: Studies evaluating sex differences in colorectal cancer (CRC) tumor microenvironment are limited, and no previous study has focused on rectal cancer patients' constitutive immune surveillance mechanisms. The authors aimed to assess gender-related differences in the immune microenvironment of rectal cancer patients. METHODS: A systematic review and meta-analysis were conducted up to 31 May 2021, including studies focusing on gender-related differences in the CRC tumor microenvironment. Data on the mutational profile of rectal cancer were extracted from the Cancer Genome Atlas (TCGA). A subanalysis of the two IMMUNOREACT trials (NCT04915326 and NCT04917263) was performed, aiming to detect gender-related differences in the immune microenvironment of the healthy mucosa in patients with early (IMMUNOREACT 1 cohort) and locally advanced rectal cancer following neoadjuvant therapy (IMMUNOREACT 2 cohort). In the retrospective IMMUNOREACT 1 cohort (therapy naive), the authors enrolled 442 patients (177 female and 265 male), while in the retrospective IMMUNOREACT 2 cohort (patients who had neoadjuvant therapy), we enrolled 264 patients (80 female and 184 male). In the prospective IMMUNOREACT 1 cohort (therapy naive), the authors enrolled 72 patients (26 female and 46 male), while in the prospective IMMUNOREACT 2 cohort (patients who had neoadjuvant therapy), the authors enrolled 105 patients (42 female and 63 male). RESULTS: Seven studies reported PD-L1 expression in the CRC microenvironment, but no significant difference could be identified between the sexes. In the TGCA series, mutations of SYNE1 and RYR2 were significantly more frequent in male patients with rectal cancer. In the IMMUNOREACT 1 cohort, male patients had a higher expression of epithelial cells expressing HLA class I, while female patients had a higher number of activated CD4+Th1 cells. Female patients in the IMMUNOREACT 2 cohort showed a higher infiltration of epithelial cells expressing CD86 and activated cytotoxic T cells (P=0.01). CONCLUSIONS: Male patients have more frequent oncogene mutations associated with a lower expression of T-cell activation genes. In the healthy mucosa of female patients, more Th1 cells and cytotoxic T cells suggest a potentially better immune response to the tumor. Sex should be considered when defining the treatment strategy for rectal cancer patients or designing prognostic scores.

A Potentially Misleading Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) typically presents in patients with a chronic liver disease and rarely develops in healthy liver, especially within an accessory liver lobe. We present a case of a healthy 64-years-old woman who showed a serum alpha-fetoprotein (AFP) value of 226.3 µg/mL during a screening blood test. Past medical history was negative for chronic liver disease or cirrhosis. Intraoperative finding was an ovaloid mass connected with the second hepatic segment by a thin pedicle of hepatic tissue. Lesion was safely resected by laparoscopic approach. Histopathology analysis showed a trabecular hepatocellular carcinoma. After a 6-month follow up, there was no evidence of recurrent disease. This case report showed how serum AFP remains a highly sensitive marker, although the presentation of HCC was unusual. To our knowledge, this is the second case reported in the literature.

Clinical and predictive value of blood lactate levels during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC): a comparative analysis.

Postoperative outcome after cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is strongly related to surgical and anesthesiologic expertise. This study aims to evaluate the clinical significance and prognostic value of lactate levels (LL) measured during CRS-HIPEC on postoperative outcome compared to similar major surgical procedures. Patients who were treated between January and September 2019 at our Institute and met the inclusion criteria were selected. Patients were divided into three groups: group 1: patients who underwent major surgical procedures; group 2: patients who underwent CRS without HIPEC; group 3: patients who underwent CRS with HIPEC. Intraoperative LL were analyzed and correlated with surgical procedure and postoperative outcome. We observed a significant increase of LL during surgical/CRS phase (group 1: p = 0.0001; group 2: p = 0.001; group 3: p = 0.057), rather than during the HIPEC phase in group 3 (p = ns). In patients undergoing CRS and peritonectomies, the mean LL were significantly higher compared to group 1 (p = 0.05). Although not statistically significant, the complication rate was higher in patients with end-CRS lactate values > 2 mMol/l, especially in the group undergoing CRS plus HIPEC. Our pilot study shows that higher LL during peritoneal cancer surgery are expected compared to major surgical procedures. Cytoreductive phase, rather than HIPEC, is related to an increase of LL. The role of LL as an early marker of postoperative complications after CRS-HIPEC should be further verified in properly designed studies.

Complete mesocolic excision versus conventional hemicolectomy in patients with right colon cancer: a systematic review and meta-analysis.

PURPOSE: Complete mesocolic excision (CME) has introduced a promising surgical approach for treatment of right colon cancer. However, benefits of CME are still a matter of debate. We conducted a systematic review and meta-analysis to assess safety and long-term outcomes of CME versus conventional right hemicolectomy (CRH). METHODS: We systematically searched MEDLINE, the Cochrane Database of Systematic Reviews, Scopus, Web of Science, and Embase for retrieving studies comparing CME with CRH in right colon cancer. After data extraction from the included studies, meta-analysis was performed to compare postoperative complications, anastomotic leakage, 30-day mortality, number of lymph node yield, disease-free survival (DFS), and overall survival (OS). RESULTS: Eight studies met the inclusion criteria with a total of 1871 patients enrolled. No difference was observed in postoperative complications (OR 1.13, 95% CI 0.88-1.47, p = 0.34). CME was associated with significantly higher number of lymph nodes retrieved (MD 9.17, CI 4.67-13.68, p < 0.001). CME also improved 3-year OS (OR 1.57, 95% CI 1.17-2.11, p = 0.003), 5-year OS (OR 1.41, 95% CI 1.06-1.89, p = 0.02), and 5-year DFS (OR 1.99, 95% CI 1.29-3.07, p = 0.002). A sub-group analysis for patients with stage III colon cancer showed no significant impact of CME on 3-year and 5-year OS (OR 2.47, 95% CI 0.86-7.06, p = 0.09; OR 1.23, 95% CI 0.78-1.94, p = 0.38). CONCLUSION: Although with limited evidence, CME shows similar postoperative complication rates and an improved survival outcome compared with CRH.

Impact of Age on Short- and Long-Term Outcomes after Pancreatoduodenectomy for Periampullary Neoplasms.

BACKGROUND: Although mortality and morbidity of pancreatoduodenectomy (PD) have improved significantly over the past years, the impact of age for patients undergoing PD is still debated. This study is aimed at analyzing short- and long-term outcomes of PD in elderly patients. METHODS: 124 consecutive patients who have undergone PD for pancreas neoplasms in our center between 2012 and 2017 were analyzed. Patients were divided into two groups: group I (<75 years) and group II (≥75 years). Demographic features and intraoperative and clinical-pathological data were collected. Primary endpoints were perioperative morbidity and mortality; complications were classified according to the Clavien-Dindo Score. Secondary endpoints included feasibility of adjuvant treatment and overall survival rates. RESULTS: A total of 106 patients were included in this study. There were 73 (68.9%) patients in group I and 33 (31.1%) in group II. Perioperative deceases were 4 (3.6%), and postoperative pancreatic fistulas were 34 (32.1%). Significant difference between two groups was demonstrated for the ASA Score (p = 0.004), Karnofsky Score (p = 0.025), preoperative jaundice (p = 0.004), and pulmonary complications (p = 0.034). No significance was shown for diabetes, radicality of resection, stage of disease, operative time, length of stay, postoperative complications according to the Clavien-Dindo Score, postoperative mortality, pancreatic fistula, and reoperation rates. 69.9% of the patients in group I underwent adjuvant treatment vs. 39.4% of the older ones (p = 0.012). Mean overall survival was 28.5 months in group I vs. 22 months in group II (p = 0.909). CONCLUSION: PD can be performed safely in elderly patients. Advanced age should not be an absolute contraindication for PD, even if greater frailty should be considered. The outcome of elderly patients who have undergone PD is similar to that of younger patients, even though adjuvant treatment administration is significantly lower, demonstrating that surgery remains the main therapeutic option.

Double incision laparoscopic cholecystectomy (DILC) with routinary intra-operative cholangiography (IOC) : less trauma, same safety. Report on 30 consecutive non-selected cases.

Laparoscopic approach for cholecystectomy is, actually, the gold standard for gallbladder surgical benign diseases. Single transumbilical incision can further reduce abdominal wall trauma. Two main related issues are still to be enlighten: difficulty in obtaining a clear exposure of the Calot's triangle and routinely use of intra-operative cholangiography (IOC). A standardized technique of double incision laparoscopic cholecystectomy (DILC) with routine IOC is described. Between January and May 2012, 30 consecutive patients scheduled for elective cholecystectomy underwent DILC with IOC. Exclusion criteria were: clinical and/or radiological suspect of gallbladder malignancy/acute cholecystitis (AC)/common duct stones; ASA > 3; previous extensive abdominal surgery. Follow-up was performed at 7, 30 and 60 days postoperatively. Three 5-mm trocars through the umbilicus and one 3-mm subcostally on the right are used, along with a 30° laparoscopic camera. IOC is performed through the 3-mm channel. Median age was 49.5 years (range 24-78); female/male was 21/9. Median BMI was 27.4 (range 16.2-38.9). AC was encountered in five cases (17 %). Synchronous AC and choledocolithiasis occurred in one case (3 %), requiring conversion to laparoscopic choledocolithotomy. Additional ports were required in these latter five patients (17 %). IOC was routinely attempted in all patients, succeeding in 26 (86 %). Median operative 'skin to skin' time was 47.8 min (range 25-75). In the subgroup not receiving IOC, median operative time was 35 min (range 25-45); 51.5 min as median time (range 25-75) was reported for the subgroup undergone the entire planned procedure. No intraoperative complications occurred. Median length of stay was 1.51 days (range 1-5). Postoperative minor complications occurred in three patients (10 %) and wound umbilical infection occurred in one (3.4 %). DILC with the routine use of IOC seems to be repeatable and safe. Even if DILC seems more easily learnt, further studies are needed to address this issue.

Laparoscopic approach to acute abdomen from the Consensus Development Conference of the Società Italiana di Chirurgia Endoscopica e nuove tecnologie (SICE), Associazione Chirurghi Ospedalieri Italiani (ACOI), Società Italiana di Chirurgia (SIC), Società Italiana di Chirurgia d'Urgenza e del Trauma (SICUT), Società Italiana di Chirurgia nell'Ospedalità Privata (SICOP), and the European Association for Endoscopic Surgery (EAES).

BACKGROUND: In January 2010, the SICE (Italian Society of Endoscopic Surgery), under the auspices of the EAES, decided to revisit the clinical recommendations for the role of laparoscopy in abdominal emergencies in adults, with the primary intent being to update the 2006 EAES indications and supplement the existing guidelines on specific diseases. METHODS: Other Italian surgical societies were invited into the Consensus to form a panel of 12 expert surgeons. In order to get a multidisciplinary panel, other stakeholders involved in abdominal emergencies were invited along with a patient's association. In November 2010, the panel met in Rome to discuss each chapter according to the Delphi method, producing key statements with a grade of recommendations followed by commentary to explain the rationale and the level of evidence behind the statements. Thereafter, the statements were presented to the Annual Congress of the EAES in June 2011. RESULTS: A thorough literature review was necessary to assess whether the recommendations issued in 2006 are still current. In many cases new studies allowed us to better clarify some issues (such as for diverticulitis, small bowel obstruction, pancreatitis, hernias, trauma), to confirm the key role of laparoscopy (such as for cholecystitis, gynecological disorders, nonspecific abdominal pain, appendicitis), but occasionally previous strong recommendations have to be challenged after review of recent research (such as for perforated peptic ulcer). CONCLUSIONS: Every surgeon has to develop his or her own approach, taking into account the clinical situation, her/his proficiency (and the experience of the team) with the various techniques, and the specific organizational setting in which she/he is working. This guideline has been developed bearing in mind that every surgeon could use the data reported to support her/his judgment.