Systematic Reviews and Meta-analyses of the Procedure-specific Risks of Thrombosis and Bleeding in General Abdominal, Colorectal, Upper Gastrointestinal, and Hepatopancreatobiliary Surgery.

OBJECTIVE: To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery. BACKGROUND: The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain. METHODS: We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty. RESULTS: After eligibility screening, 285 studies (8,048,635 patients) reporting on 40 general abdominal, 36 colorectal, 15 upper gastrointestinal, and 24 hepatopancreatobiliary surgery procedures proved eligible. Evidence certainty proved generally moderate or low for VTE and low or very low for bleeding requiring reintervention. The risk of VTE varied substantially among procedures: in general abdominal surgery from a median of <0.1% in laparoscopic cholecystectomy to a median of 3.7% in open small bowel resection, in colorectal from 0.3% in minimally invasive sigmoid colectomy to 10.0% in emergency open total proctocolectomy, and in upper gastrointestinal/hepatopancreatobiliary from 0.2% in laparoscopic sleeve gastrectomy to 6.8% in open distal pancreatectomy for cancer. CONCLUSIONS: VTE thromboprophylaxis provides net benefit through VTE reduction with a small increase in bleeding in some procedures (eg, open colectomy and open pancreaticoduodenectomy), whereas the opposite is true in others (eg, laparoscopic cholecystectomy and elective groin hernia repairs). In many procedures, thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding.

Pasireotide Versus Octreotide in Preventing Complications After Simultaneous Pancreas-Kidney Transplantation.

In elective pancreatic surgery, somatostatin-analogues pasireotide and octreotide are variably used to reduce postoperative complications, but knowledge on their role in pancreas transplantation is limited. This study compared pasireotide and octreotide for their association with complications after simultaneous pancreas-kidney transplantation (SPK). This retrospective study included consecutive patients undergoing SPK's from July 2013 to July 2022. Between July 2013 and April 2020, octreotide was administered 0.1 mg s.c. once daily and between May 2020 and July 2022 pasireotide was administered 0.9 mg twice daily, both until third postoperative day. Complications within 90 days postoperatively were collected, and reoperation rate and Comprehensive Complication index (CCI) ≥ 33.7 (morbidity equal to one reoperation) were used as primary outcomes. Of the 213 patients undergoing SPK, 150 patients received octreotide and 63 pasireotide. Baseline characteristics were comparable. Reoperation rate was 25.3% (n = 38) and 17.5% (n = 11) (p = 0.213) and rate of CCI ≥ 33.7 was 40.7% (n = 61) and 30.2% (n = 19) (p = 0.148) in octreotide and pasireotide groups, respectively. When adjusted with donor BMI, pancreas donor risk index, and donor sex, receiving pasireotide translated into OR 0.49 (95% CI: 0.25-0.96 p = 0.037) for CCI ≥ 33.7. Pasireotide was independently associated with lower postoperative morbidity within 90 days of SPK compared to octreotide.

Systematic reviews of observational studies of Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS): introduction and methodology.

BACKGROUND: Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on the incidence of VTE and bleeding in the absence of prophylaxis. These baseline risks vary widely between procedures, but their magnitude is uncertain. Systematic reviews addressing baseline risks are scarce, needed, and require innovations in methodology. Indeed, systematic summaries of these baseline risk estimates exist neither in general nor gynecologic surgery. We will fill this knowledge gap by performing a series of systematic reviews and meta-analyses of the procedure-specific and patient risk factor stratified risk estimates in general and gynecologic surgeries. METHODS: We will perform comprehensive literature searches for observational studies in general and gynecologic surgery reporting symptomatic VTE or bleeding estimates. Pairs of methodologically trained reviewers will independently assess the studies for eligibility, evaluate the risk of bias by using an instrument developed for this review, and extract data. We will perform meta-analyses and modeling studies to adjust the reported risk estimates for the use of thromboprophylaxis and length of follow up. We will derive the estimates of risk from the median estimates of studies rated at the lowest risk of bias. The primary outcomes are the risk estimates of symptomatic VTE and major bleeding at 4 weeks post-operatively for each procedure stratified by patient risk factors. We will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate evidence certainty. DISCUSSION: This series of systematic reviews, modeling studies, and meta-analyses will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding in general and gynecologic surgeries. Our work advances the standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at the best estimates of risk (including modeling of the timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the GRADE approach. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021234119.

TKTL1 as a Prognostic Marker in Pancreatic Ductal Adenocarcinoma and Its Correlation with FDG-PET-CT.

INTRODUCTION: Glucose metabolism in cancer cells differs from noncancerous cells. The expression of transketolase-like protein 1 (TKTL1), a key enzyme in the glucose metabolism of cancer cells, predicts poor prognosis in several cancer types. We studied TKTL1 as a prognostic tool and whether TKTL1 expression correlates with 18F-FDG-PET-CT among patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: This retrospective study examined two PDAC patient cohorts: 168 patients operated on at Helsinki University Hospital between 2001 and 2011, and 20 patients with FDG-PET-CT results available from the Auria Biobank. We used immunohistochemistry for TKTL1 expression, combining results with clinicopathological data. RESULTS: Five-year disease-specific survival (DSS) was slightly but not significantly better in patients with a high versus low TKTL1 expression, with DSS of 28.0 versus 17.3%, respectively (p = 0.123). TKTL1 served as a marker of a better prognosis in patients over 65 years old (p = 0.012) and among those with TNM class M1 (p = 0.018), stage IV disease (p = 0.027), or perivascular invasion (p = 0.008). CONCLUSIONS: Our study shows that TKTL1 cannot be used as a prognostic factor in PDAC with the exception of elderly patients and those with advanced disease. The correlation of TKTL1 with 18F-FDG-PET-CT requires further study in a larger patient cohort.

High TKTL1 expression as a sign of poor prognosis in colorectal cancer with synchronous rather than metachronous liver metastases.

Colorectal cancer (CRC) is the third most common cancer in the world. More than half of all affected patients develop liver metastases during the course of the disease, and over half experience recurrence despite radical primary surgery. Transketolase-like protein 1 (TKTL1) is a key enzyme in the glucose metabolism of cancer cells, and its expression in tumor tissue was previously shown to indicate a poor prognosis in colorectal cancer. In this study, we investigated the prognostic significance of TKTL1 in 111 patients with surgically resected colorectal liver metastases, with a minimum follow-up time of 10.3 years. TKTL1 expression was examined in tissue samples of both primary tumors and liver metastases, and compared to clinicopathological parameters, disease-free survival, and overall survival. We show that a high expression of TKTL1 in primary tumor tissue associated with poor disease-free survival in patients with synchronous liver metastases (P = .026, Kaplan-Meier log-rank test), but with better disease-free survival in patients with metachronous metastases, although not statistically significantly (P = .073). We found similar tendencies for TKTL1 expression in liver metastases. Thus, TKTL1 could serve as a candidate marker to identify patients who benefit from liver resection or who need more aggressive perioperative chemotherapy.

Transketolase-Like Protein 1 and Glucose Transporter 1 in Gastric Cancer.

BACKGROUND: The glucose metabolism of cancer cells differs from that of noncancerous cells. Transketolase-like protein 1 (TKTL1) and glucose transporter 1 (GLUT1) both play a role in this process. These biochemical tumor markers are overexpressed in several types of human cancer. OBJECTIVE: We sought to determine if TKTL1 and/or GLUT1 expression predicts prognosis in gastric cancer. METHODS: In this retrospective study, we selected 284 patients who underwent surgery for gastric cancer at the Helsinki University Hospital. We used immunohistochemistry to assess the expression of TKTL1 and GLUT1, combined with clinicopathological data. RESULTS: Positive expression of TKTL1 was associated with positive expression of GLUT1, age over 65 years, male gender, advanced stage (II-IV), and advanced tumors (T2-T4). Patients with a positive expression of TKTL1 had a poorer prognosis than those with no expression (p = 0.042, Breslow test). GLUT1 positivity was associated with higher age and with the intestinal type of gastric cancer but did not carry any prognostic value. CONCLUSION: In conclusion, our study showed that positive expression of TKTL1 correlates with a poor prognosis in gastric cancer.

Transketolase-like protein 1 expression predicts poor prognosis in colorectal cancer.

BACKGROUND: Transketolase-like protein 1 (TKTL1) is an isoform of tranketolase, a key protein in a cancer cell's glucose metabolism that causes rapid cell growth and controls the non-oxidative part of the pentose phosphate pathway (PPP). Its overexpression occurs in several human cancer types. Our purpose was to study whether TKTL1 expression in colorectal cancer tissue associates with these patients' prognosis. METHODS: We collected retrospectively patient data and tissue samples from 840 colorectal cancer patients treated at Helsinki University Hospital, then stained tumor tissue microarrays for TKTL1 by immunohistochemistry, and compared immunohistochemical tissue expression with clinico-pathological parameters and survival. RESULTS: High expression of TKTL1 associated with high Dukes stage, non-mucinous adenocarcinoma, and left-sided disease. Patients with high TKTL1 expression had poorer prognosis than those with low expression, with a 5-year disease-specific survival of 55.7% vs. 62.7%. CONCLUSION: We show that high TKTL1 in tumor tissue can lead to poor survival in colorectal cancer. TKTL1 thus can serve as a candidate marker for identifying patients at risk of recurrent disease.