Total neoadjuvant therapy in rectal cancer: the evidence and expectations.

Current management of locally advanced rectal cancer achieves high cure rates, distant metastatic spread being the main cause of patients' death. Total neoadjuvant therapy (TNT) employs (chemo)radiotherapy and combined chemotherapy prior to surgery to improve the treatment outcomes. TNT has been shown to reduce significantly distant metastases, increase disease-free survival by 5 - 10% in 3 years, and finally also overall survival (≈ 5% in 7 years). It proved to double the rate of pathologic complete responses, making it an attractive strategy for non-operative management to avoid permanent colostomy in patients with distal tumors. In addition, it endorses adherence to the therapy due to better tolerance and, potentially, shortens its overall duration. A number of questions related to TNT remain currently unresolved including the indications, preferred radiotherapy and chemotherapy regimens, their sequence, timing of surgery, and role of adjuvant therapy. A stratified approach may be the optimal way to go.

MUC13-miRNA-4647 axis in colorectal cancer: Prospects to identifications of risk factors and clinical outcomes.

MUC13, a transmembrane mucin glycoprotein, is overexpressed in colorectal cancer (CRC), however, its regulation and functions are not fully understood. It has been shown that MUC13 protects colonic epithelial cells from apoptosis. Therefore, studying MUC13 and MUC13-regulated pathways may reveal promising therapeutic approaches for CRC treatment. Growing evidence suggests that microRNAs (miRs) are involved in the development and progression of CRC. In the present study, the MUC13-miR-4647 axis was addressed in association with survival of patients. miR-4647 is predicted in silico to bind to the MUC13 gene and was analyzed by RT-qPCR in 187 tumors and their adjacent non-malignant mucosa of patients with CRC. The impact of previously mentioned genes on survival and migration abilities of cancer cells was validated in vitro. Significantly upregulated MUC13 (P=0.02) in was observed tumor tissues compared with non-malignant adjacent mucosa, while miR-4647 (P=0.05) showed an opposite trend. Higher expression levels of MUC13 (log-rank P=0.05) were associated with worse patient's survival. The ectopic overexpression of studied miR resulted in decreased migratory abilities and worse survival of cells. Attenuated MUC13 expression levels confirmed the suppression of colony forming of CRC cells. In summary, the present data suggested the essential role of MUC13-miR-4647 in patients' survival, and this axis may serve as a novel therapeutic target. It is anticipated MUC13 may hold significant potential in the screening, diagnosis and treatment of CRC.

Silver-Based Dressings in the Prevention of the Incisional Surgical Site Infection: A Prospective Multicenter Observational Controlled Trial.

Background: A new silver-based dressing has been designed to reduce surgical sited infections. Patients and Methods: A prospective multicenter observational study was conducted from January 2020 to October 2021. Patients with and without silver-based dressing after surgical incision were observed and their data analyzed. The study aimed to assess the incidence of incisional surgical site infection and primary healing after general surgery procedures. Results: Overall, 218 patients with silver-based (n = 109) and conventional silver-free dressing (n = 109) were analyzed. Surgical site infection (SSI) and primary incision healing were reported in 10 (9.2%) versus 21 (19.3%) (p = 0.037) and in 95 (87.2%) versus 86 (78.9%) (p = 0.107) patients treated with and without silver-based dressing, respectively. Conclusions: Silver-based dressing demonstrated a lower incidence of incisional SSI and improved primary healing in comparison with patients in whom conventional non-silver-based dressing has been used.

Treatment of Malignant Peritoneal Mesothelioma.

Malignant mesothelioma is a highly malignant disease that most often occurs in the pleura of the thoracic cavity, followed by the peritoneum, pericardium, or tinea vaginalis testis. Malignant peritoneal mesothelioma (MPM) accounts for 10-15% of all mesotheliomas. The most significant risk factor for MPM is exposure to asbestos. There is no specific symptomatology, and imaging (computed tomography) and histopathology are crucial for diagnosis. There are no generally accepted guidelines for radical treatment of MPM. Previously, the prognosis of MPM patients was poor, with survival of up to 1 year. However, median survival of patients who are suitable candidates for radical therapy is currently 3-5 years. A combination of cytoreductive surgery (CRS) and hyperthermic perioperative chemotherapy (HIPEC) is recommended in selected patients, while chemotherapy alone has insufficient efficacy. Systemic chemotherapy remains the only treatment option for patients who are unsuitable for CRS and HIPEC. In selected patients scheduled for or currently undergoing CRS and HIPEC, surgery may be performed in combination with systemic chemotherapy in the neoadjuvant or adjuvant setting; however, the benefit is unclear. There are no recommendations for follow-up of MPM patients after radical surgery. Existing guidelines for the pleural form (e.g., those issued by the European Society for Medical Oncology) do not specify the frequency or method of investigation. In the absence of specific serum markers, only CA 125 and mesothelin are generally available. Imaging methods include ultrasonography, computed tomography, and magnetic resonance imaging.

Significance of postoperative follow-up of patients with metastatic colorectal cancer using circulating tumor DNA.

BACKGROUND: One of the most notable applications for circulating tumor DNA (ctDNA) detection in peripheral blood of patients with metastatic colorectal cancer (mCRC) is a long-term postoperative follow-up. Sometimes referred to as a "liquid (re)biopsy" it is a minimally invasive procedure and can be performed repeatedly at relatively short intervals (months or even weeks). The presence of the disease and the actual extent of the tumor burden (tumor mass) within the patient's body can be monitored. This is of particular importance, especially when evaluating radicality of surgical treatment as well as for early detection of disease progression or recurrence. AIM: To confirm the radicality of surgery using ctDNA and compare available methods for detection of recurrence in metastatic colorectal cancer. METHODS: A total of 47 patients with detected ctDNA and indications for resection of mCRC were enrolled in the multicenter study involving three surgical centers. Standard postoperative follow-ups using imaging techniques and the determination of tumor markers were supplemented by ctDNA sampling. In addition to the baseline ctDNA testing prior to surgery, a postoperative observation was conducted by evaluating ctDNA presence up to a week after surgery and subsequently at approximately three-month intervals. The presence of ctDNA was correlated with radicality of surgical treatment and the actual clinical status of the patient. RESULTS: Among the monitored patients, the R0 (curative) resection correlated with postoperative ctDNA negativity in 26 out of 28 cases of surgical procedures (26/28, 93%). In the remaining cases of R0 surgeries that displayed ctDNA, both patients were diagnosed with a recurrence of the disease after 6 months. In 7 patients who underwent an R1 resection, 4 ctDNA positivities (4/7, 57%) were detected after surgery and associated with the confirmation of early disease recurrence (after 3 to 7 months). All 15 patients (15/15, 100%) undergoing R2 resection remained constantly ctDNA positive during the entire follow-up period. In 22 cases of recurrence, ctDNA positivity was detected 22 times (22/22, 100%) compared to 16 positives (16/22, 73%) by imaging methods and 15 cases (15/22, 68%) of elevated tumor markers. CONCLUSION: ctDNA detection in patients with mCRC is a viable tool for early detection of disease recurrence as well as for confirmation of the radicality of surgical treatment.

Strategies to reduce perioperative morbidity in cytoreductive surgery.

BACKGROUND/AIMS: Peritoneal carcinoma has been regarded as a uniformly lethal clinical entity. Cytoreductive surgery and intraperitoneal hyperthermic chemoperfusion (HIPEC) is an aggressive treatment for patients with peritoneal malignancies. While promising, this therapeutic regimen has been associated with significant morbidity, long hospital stay and an increased risk for perioperative mortality. The purpose of this study was to evaluate the possibility to reduce morbidity by use of strategy aiming to reduce inflammatory response associated with cytoreductive surgery plus HIPEC. METHODOLOGY: 241 consecutive patients underwent cytoreductive surgery plus HIPEC during the period of 4 years (1/03-12/06). All patients were managed through multivisceral resection followed by HIPEC using an open technique. Peritonectomy was performed with the goal of total eradication of all visible tumor formations. RESULTS: 276 procedures were performed in 241 patients with 27 re-resections and 4 re-re-resections. Male/female ratio was 134/142. Mean age was 49 years (range 26-82). Optimal cytoreduction defined as CC-0 and CC-1 resection could be reached in 230 cases (83.3%). Complication rate (Feldman scale grade 3/4) and 30-day mortality rate were as follows: 2003: 26.5%, 2% 2004: 20%, 0% 2005: 14%, 1% 2006: 10%, 0%. CONCLUSIONS: The results of this study demonstrate the possibility to reduce the perioperative risk of cytoreductive surgery plus IPHC. The described strategy aiming the reduction of inflammatory response was able to reach a morbidity level which stands in line with other major oncologic operations.

Cytoreductive surgery in the elderly patients--is it feasible?

BACKGROUND/AIMS: Cytoreductive surgery and intraperitoneal hyperthermic chemoperfusion (HIPEC) is an aggressive treatment for patients with peritoneal malignancies. While promising, this therapeutic approach is still associated with significant morbidity and mortality. Surgical risk in elderly patients is even higher, since these people suffer from frequent comorbidities, resulting in poorer performance status. Whether this type of major cancer surgery is feasible in elderly patients is an ongoing question. METHODOLOGY: Retrospective analysis of elderly patients, undergoing cytoreductive surgery during a period of three years in one centre. Criteria of patients' eligibility were peritoneal carcinomatosis of different origin, age > 65 years, good general status, no extra-abdominal extension and no evidence of bowel obstruction. To reduce morbidity of surgical procedure special perioperative management program including intensified warming management, intra-operative fluid restriction, control of hyperglycaemia, increase of the tissue oxygenation, restriction of blood loss and adenosine receptor activation was employed. RESULTS: Between January 2004 and January 2007, 47 cytoreductive interventions have been carried out in 44 patients aged older than 65 years at the Department for Surgical Oncology KKH Hammelburg. Mean age of patients in this group was 71 years (min. 65 years, max 82 years). Mean duration of surgery was 5.3 hours (SD = 1.59; range 3.0 to 8.5 hours). Mean duration of the hospital stay was 19.3 days (SD = 9.55, range 11 to 58 days). The frequency of grade 3 and 4 complications was 17.0%. There was no postoperative death registered within the 30 days after surgery (30-days mortality rate 0%). CONCLUSIONS: Incorporating new strategies to reduce morbidity makes aggressive cytoreduction procedure feasible in the majority of elderly patients. Age and advanced peritoneal malignancy should not preclude patients from the maximal surgical effort.