Anastomotic dehiscence remains a major complication in surgery of the large bowel, and studies on the healing sequence of experimental anastomoses are necessary to define underlying mechanisms and find ways to improve surgical outcome, particularly in high-risk situations. For the quantitative description of anastomotic repair, both mechanical and biochemical parameters are employed, each with their own limitations. Mechanical parameters, either bursting pressure or breaking strength, only reflect growing anastomotic strength as long as disruption occurs within the anastomotic area, which is less than one week after surgery for the bursting pressure and probably up to two weeks for the breaking strength. The biochemical description of anastomotic repair has been limited to behavior of collagen, as represented by its rather unique constituent amino acid hydroxyproline. Conclusions based on collagen concentrations--per unit weight--should be considered with caution since they may change as a consequence of changes in noncollagenous substances. In this respect, collagen content, per unit length, is probably a better parameter to describe anastomotic collagen levels. Few investigations have addressed the quality of collagen (e.g., crosslinking or type). Since, at this time, no distinct correlations have been demonstrated between development of mechanical strength or occurrence of leakage and collagen levels in the healing anastomosis, attention should not be restricted to a description of the quantity of collagen present: the quality of anastomotic collagen should be investigated, perhaps even more so.

IntroductionThe presence of circulating tumor cells (CTC) is an independent prognostic factor for progression-free survival and breast cancer-related death (BRD) for patients with metastatic breast cancer beginning a new line of systemic therapy. The current study was undertaken to explore whether the presence of CTC at the time of diagnosis was associated with recurrence-free survival (RFS) and BRD.MethodsIn a prospective single center study, CTC were enumerated with the CellSearch system in 30 ml of peripheral blood of 602 patients before undergoing surgery for breast cancer. There were 97 patients with a benign tumor, 101 did not meet the inclusion criteria of which there were 48 patients with DCIS, leaving 404 stage I to III patients. Patients were stratified into unfavorable (CTC ≥1) and favorable (CTC = 0) prognostic groups.Results≥1 CTC in 30 ml blood was detected in 15 (15%) benign tumors, in 9 DCIS (19%), in 28 (16%) stage I, 32 (18%) stage II and in 16 (31%) patients with stage III. In stage I to III patients 76 (19%) had ≥1 CTC of whom 16 (21.1%) developed a recurrence. In 328 patients with 0 CTC 38 (11.6%) developed a recurrence. Four-year RFS was 88.4% for favorable CTC and 78.9% for unfavorable CTC (P = 0.038). A total of 25 patients died of breast cancer-related causes and 11 (44%) had ≥1 CTC. BRD was 4.3% for favorable and 14.5% for unfavorable CTC (P = 0.001). In multivariate analysis ≥1 CTC was associated with distant disease-free survival, but not for overall recurrence-free survival. CTC, progesterone receptor and N-stage were independent predictors of BRD in multivariate analysis.ConclusionsPresence of CTC in breast cancer patients before undergoing surgery with curative intent is associated with an increased risk for breast cancer-related death.

Background and purpose — Tenosynovial giant cell tumors (TGCT) are rare, benign tumors, arising in synovial lining of joints, tendon sheaths, or bursae. 2 types are distinguished: localized, either digits or extremity, and diffuse lesions. Current TGCT incidence is based on 1 single US-county study in 1980, with an incidence of 9 and 2 per million person-years in localized (including digits) and diffuse TGCT, respectively. We aim to determine nationwide and worldwide incidence rates (IR) in TGCT affecting digits, localized-extremity TGCT and diffuse-type TGCT.Material and methods — Over a 5-year period, the Dutch Pathology Registry (PALGA) identified 4,503 pathology reports on TGCT. Reports affecting digits were solely used for IR calculations. Reports affecting extremities were clinically evaluated. Dutch IRs were converted to world population IRs.Results — 2,815 (68%) digits, 933 (23%) localized-extremity and 390 (9%) diffuse-type TGCT were identified. Dutch IR in digits, localized-extremity, and diffuse-type TGCT was 34, 11 and 5 per million person-years, respectively. All 3 groups showed a female predilection and highest number of new cases in age category 40–59 years. The knee joint was most often affected: localized-extremity (46%) and diffuse-type (64%) TGCT, mostly treated with open resection: localized (65%) and diffuse (49%). Reoperation rate due to local recurrence for localized-extremity was 9%, and diffuse TGCT 23%.Interpretation — This first nationwide study and detailed analyses of IRs in TGCT estimated a worldwide IR in digits, localized-extremity and diffuse TGCT of 29, 10, and 4 per million person-years, respectively. Recurrence rate in diffuse type is 2.6 times higher, compared with localized extremity. TGCT is still considered a rare disease; however, it is more common than previously understood.

Background Upfront cytoreductive surgery with HIPEC (CRS-HIPEC) is the standard treatment for isolated resectable colorectal peritoneal metastases (PM) in the Netherlands. This study investigates whether addition of perioperative systemic therapy to CRS-HIPEC improves oncological outcomes. Methods This open-label, parallel-group, phase II-III, randomised, superiority study is performed in nine Dutch tertiary referral centres. Eligible patients are adults who have a good performance status, histologically or cytologically proven resectable PM of a colorectal adenocarcinoma, no systemic colorectal metastases, no systemic therapy for colorectal cancer within six months prior to enrolment, and no previous CRS-HIPEC. Eligible patients are randomised (1:1) to perioperative systemic therapy and CRS-HIPEC (experimental arm) or upfront CRS-HIPEC alone (control arm) by using central randomisation software with minimisation stratified by a peritoneal cancer index of 0–10 or 11–20, metachronous or synchronous PM, previous systemic therapy for colorectal cancer, and HIPEC with oxaliplatin or mitomycin C. At the treating physician’s discretion, perioperative systemic therapy consists of either four 3-weekly neoadjuvant and adjuvant cycles of capecitabine with oxaliplatin (CAPOX), six 2-weekly neoadjuvant and adjuvant cycles of 5-fluorouracil/leucovorin with oxaliplatin (FOLFOX), or six 2-weekly neoadjuvant cycles of 5-fluorouracil/leucovorin with irinotecan (FOLFIRI) followed by four 3-weekly (capecitabine) or six 2-weekly (5-fluorouracil/leucovorin) adjuvant cycles of fluoropyrimidine monotherapy. Bevacizumab is added to the first three (CAPOX) or four (FOLFOX/FOLFIRI) neoadjuvant cycles. The first 80 patients are enrolled in a phase II study to explore the feasibility of accrual and the feasibility, safety, and tolerance of perioperative systemic therapy. If predefined criteria of feasibility and safety are met, the study continues as a phase III study with 3-year overall survival as primary endpoint. A total of 358 patients is needed to detect the hypothesised 15% increase in 3-year overall survival (control arm 50%; experimental arm 65%). Secondary endpoints are surgical characteristics, major postoperative morbidity, progression-free survival, disease-free survival, health-related quality of life, costs, major systemic therapy related toxicity, and objective radiological and histopathological response rates. Discussion This is the first randomised study that prospectively compares oncological outcomes of perioperative systemic therapy and CRS-HIPEC with upfront CRS-HIPEC alone for isolated resectable colorectal PM. Trial registration Clinicaltrials.gov/ NCT02758951 , NTR/ NTR6301 , ISRCTN/ ISRCTN15977568 , EudraCT/ 2016–001865-99 .

Background. Preoperative staging of patients with colorectal carcinoma (CRC) has the potential benefit of altering treatment options when metastases are present. The clinical value of chest computed tomography (CT) in staging remains unclear. Materials and Methods. All patients who undergo colorectal surgery in our hospital are prospectively registered, including patient, treatment, and histopathological characteristics; outcome; and follow-up. Since January 2007, routine preoperative staging CT of chest and abdomen for patients with CRC has been performed as part of our regional guidelines. In this observational cohort study, an analysis on outcome was done after inclusion of 200 consecutive patients. Results. Synchronous metastases were present in 60 patients (30%). Staging chest CT revealed pulmonary metastases in 6 patients, with 1 false positive finding. In 50 patients indeterminate lesions were seen on chest CT (25%). These were diagnosed during follow-up as true metastases (n = 8), bronchus carcinoma (n = 2), benign lesions (n = 25), and remaining unknown (n = 15). Ultimately, synchronous pulmonary metastases were diagnosed in 13 patients (7%), in 6 patients confined to the lung (3%). In none of the patients the treatment plan for the primary tumor was changed based on the staging chest CT. Conclusion. The low incidence of pulmonary metastases and minimal consequences for the treatment plan limits the clinical value of routine staging chest CT before operation.It has several disadvantages such as costs, radiation exposure, and prolonged uncertainty because of the frequent finding of indeterminate lesions. Based on this study, a routine staging chest CT in CRC patients is not advocated.