Serum procalcitonin improves diagnosis of infectious complications after CRS/HIPEC.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) improve the survival of selected patients with peritoneal metastasis. A major cause of treatment-related morbidity after CRS/HIPEC is infection and sepsis. HIPEC alters the diagnostic sensitivity and specificity of blood and serum markers and therefore has an impact on early diagnosis of postoperative complications. This study aimed to assess the sensitivity and specificity of blood and serum markers after CRS/HIPEC. METHODS: Patients from two centers, operated between 2009 and 2017, were enrolled in this study. Perioperative blood samples were analyzed for white blood cells (WBC), C-reactive protein (CRP), and procalcitonin (PCT); postoperative complications were graded according to Clavien-Dindo and infectious complications according to CDC criteria. RESULTS: Overall, n=248 patients were included with peritoneal metastasis from different primary tumors treated by CRS/HIPEC. Depending on the applied HIPEC protocol, patients presented a suppressed WBC response to infection. In addition, a secondary and unspecific CRP elevation in absence of an underlining infection, and pronounced after prolonged perfusion for more than 60 min. PCT was identified as a highly specific - although less sensitive - marker to diagnose infectious complications after CRS/HIPEC. DISCUSSION/CONCLUSION: Sensitivity and specificity of WBC counts and CRP values to diagnose postoperative infection are limited in the context of HIPEC. PCT is helpful to specify suspected infection. Overall, diagnosis of postoperative complications remains a clinical diagnosis, requiring surgical expertise and experience.

Mutations of RAS/RAF Proto-oncogenes Impair Survival After Cytoreductive Surgery and HIPEC for Peritoneal Metastasis of Colorectal Origin.

BACKGROUND: Adequate selection of patients with peritoneal metastasis (PM) for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remains critical for successful long-term outcomes. Factors reflecting tumor biology are currently poorly represented in the selection process. The prognostic relevance of RAS/RAF mutations in patients with PM remains unclear. METHODS: Survival data of patients with colorectal PM operated in 6 European tertiary centers were retrospectively collected and predictive factors for survival identified by Cox regression analyses. A simple point-based risk score was developed to allow patient selection and outcome prediction. RESULTS: Data of 524 patients with a median age of 59 years and a median peritoneal cancer index of 7 (interquartile range: 3-12) were collected. A complete resection was possible in 505 patients; overall morbidity and 90-day mortality were 50.9% and 2.1%, respectively. PCI [hazard ratio (HR): 1.08], N1 stage (HR: 2.15), N2 stage (HR: 2.57), G3 stage (HR: 1.80) as well as KRAS (HR: 1.46) and BRAF (HR: 3.97) mutations were found to significantly impair survival after CRS/HIPEC on multivariate analyses. Mutations of RAS/RAF impaired survival independently of targeted treatment against EGFR. Consequently, a simple point-based risk score termed BIOSCOPE (BIOlogical Score of COlorectal PEritoneal metastasis) based on PCI, N-, G-, and RAS/RAF status was developed, which showed good discrimination [development area under the curve (AUC) = 0.72, validation AUC = 0.70], calibration (P = 0.401) and allowed categorization of patients into 4 groups with strongly divergent survival outcomes. CONCLUSION: RAS/RAF mutations impair survival after CRS/HIPEC. The novel BIOSCOPE score reflects tumor biology, adequately stratifies long-term outcomes, and improves patient assessment and selection.

Increase of papillary thyroid microcarcinoma and a plea for restrictive treatment: A retrospective study of 1,391 prospective documented patients.

BACKGROUND: The incidence of papillary thyroid microcarcinomas (PMCs) has increased sharply and therefore the lack of consensus for treatment has become a clinical dilemma. Our aim was to evaluate a less-radical approach. METHODS: This study includes 1,391 patients with PMC treated at a single surgical referral center in the endemic goiter area in Austria. Data, including long-term follow-up examinations with a median follow-up time of 7 years, were collected from the institutional surgery database. RESULTS: Of the 1,391 patients, 947 (68.1%) had a near-total or total thyroidectomy; 1,090 patients (78.3%) had no lymphadenectomy, and 1,136 patients (81.7%) did not receive radioiodine treatment. Twenty-one patients (1.5%) underwent reoperation, 5 because of lymph node recurrence (0.4%), 16 with clinically benign recurrence, including 4 cases of another PMC. There were no recurrences in the thyroid bed and no disease-related deaths. Risk factors for lymph node recurrences were nonincidental finding, nodal metastases at presentation, young age, aggregate tumor size, and subcapsular tumor localization. Multifocality, sex, maximum tumor size, and the extent of surgery were not relevant factors. CONCLUSION: Nodal recurrence is rare and reoperation cured all patients. Micrometastases are not of clinical relevance. The postoperative findings of most PMCs suggest that, even if multifocal, a limited approach without completion thyroidectomy, lymphadenectomy and radioiodine treatment is sufficient. In case of pre- or intraoperative clinically suspected nodal metastases or postoperatively diagnosed risk factors we propose the standard radical procedure. Routine preoperative cervical lymph node sonography is advisable before any thyroid surgery.

Can a surgeon predict the risk of postoperative hypoparathyroidism during thyroid surgery? A prospective study on self-assessment by experts.

BACKGROUND: Thyroid surgery can cause postoperative hypocalcemia (POH) and permanent hypoparathyroidism (PEH). Surgeons implicitly assess the risk and adapt their surgical strategy accordingly. METHODS: The outcome of this intraoperative decision-making process (the surgeons' ability to predict the risk of POH and PEH on a numerical rating scale and their actual incidence) was studied prospectively in 2,558 consecutive thyroid operations. RESULTS: POH and PEH occurred in 723 and 64 patients, respectively. In multivariate analysis, the surgeons' risk assessment score was an independent predictive factor for both complications (P < .05). Surgeons' differed significantly (P = .015) in their rates of POH but not of PEH (P = .062). Six and 3 (of 9) surgeons correctly predicted an increased risk of PEH and POH (adjusted odds ratios 1.67 to 2.21 and 1.47 to 12.73), respectively. CONCLUSION: The risk for hypoparathyroidism can be estimated, but surgeons differ substantially in this ability and in the extent to which this implicit knowledge is translated into lower complication rates.

Hashimoto's thyroiditis affects symptom load and quality of life unrelated to hypothyroidism: a prospective case-control study in women undergoing thyroidectomy for benign goiter.

BACKGROUND: Hashimoto's thyroiditis (HT) is a common disease, and is the most prevalent cause of hypothyroidism. Symptoms and diseases associated with HT are considered to be caused by hypothyroidism. We hypothesized that higher antithyroperoxidase (anti-TPO) antibody levels would be associated with an increased symptom load and a decreased quality of life in a female euthyroid patient collective. METHODS: In a prospective cohort study 426 consecutive euthyroid female patients undergoing thyroid surgery for benign thyroid disease were included. Main outcome measures were preoperative anti-TPO levels, a symptom questionnaire and the SF-36 questionnaire, and lymphocytic infiltration of the thyroid tissue as evaluated by histology. RESULTS: Histology revealed HT in 28/426 (6.6%) subjects. To maximize the sum of the predictive values, a cut-off point for anti-TPO of 121.0 IU/mL was calculated (sensitivity 93.3% [95% confidence interval: 77.9%-99.0%]; specificity 94.7% [95% confidence interval: 92.0%-96.7%]) to predict the presence of histological signs of HT. The mean number of reported symptoms was significantly higher in patients with anti-TPO levels >121.0 IU/mL than in the other group (6.7 ± 2.5 vs. 4.1 ± 2.8; p < 0.001). There were no differences in preoperative thyroid-stimulating hormone levels (1.7 ± 1.3 vs. 1.5 ± 1.4 µU/mL, respectively; p = 0.155). Chronic fatigue, dry hair, chronic irritability, chronic nervousness, a history of breast cancer and early miscarriage, and lower quality-of-life levels were significantly associated with anti-TPO levels exceeding the cut-off point (p < 0.05). CONCLUSIONS: Women with HT suffer from a high symptom load. Hypothyroidism is only a contributing factor to the development of associated conditions.

Normal parathyroid hormone levels do not exclude permanent hypoparathyroidism after thyroidectomy.

BACKGROUND: Permanent hypoparathyroidism has become the most common and the most severe complication after thyroid surgery. In our experience, some patients suffer from permanent hypocalcemia and related symptoms despite normal parathyroid hormone (PTH) values after thyroid surgery. The aim of this work was to present a series of such patients with long-term hypocalcemia and normal PTH values to evaluate to what extent parathyroid function was impaired by thyroidectomy, and determine whether irregularities of bone and calcium metabolism were associated with this phenomenon. METHODS: We present a series of eight patients with normal PTH and subnormal calcium levels at follow-up 2 months after thyroid surgery. Outcome parameters were intra- and postoperative PTH and calcium kinetics, and the following markers of calcium and bone metabolism at long-term follow-up: serum calcium, total serum albumin, ionized calcium, magnesium, PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, urinary calcium, urinary creatinine, osteocalcin, c-terminal telopeptide of type I collagen, and alkaline phosphatase. RESULTS: All patients had normal calcium and PTH levels at the start of the operation. The intraoperative decline in PTH was >90%; the trough (3.3% of preoperative value) was reached 3 hours after surgery. Patients underwent complete determination of bone metabolism parameters during long-term follow-up 13.8 ± 2.4 months after surgery. Hypocalcemia was found in all eight patients, as well as PTH levels within the normal range. In three patients (3/8 = 37.5%), none of the other parameters was altered. In the remaining five patients, only isolated abnormalities in bone and calcium metabolism parameters were found (i.e., alterations in urinary calcium, thyrotropin, 25-hydroxyvitamin D, osteocalcin, and c-terminal telopeptide of type I collagen). CONCLUSIONS: An intraoperative injury to the parathyroid glands or their vascularization is the likely contributing factor to the development of permanent hypocalcemia with normal PTH values after thyroid surgery. The remaining parathyroid tissue is subject to a maximum stimulus by hypocalcemia and, therefore, is able to maintain PTH values in the normal range. These are still too low to re-establish normal serum calcium levels. In these patients, the term "hypoparathyroidism" might be replaced with "parathyroid insufficiency."

Intra- and postoperative parathyroid hormone-kinetics do not advocate for autotransplantation of discolored parathyroid glands during thyroidectomy.

BACKGROUND: Thyroidectomy continues to pose the risk of typical complications, including postoperative hypocalcemia and permanent hypoparathyroidism. The strategic decision on how to preserve parathyroid hormone (PTH) secretion relies on assessing the viability of the parathyroid glands (PGs). The aim of this study was to assess parathyroid discoloration as an indicator for loss of parathyroid function. METHODS: The prospective study included 29 patients (24 women, 5 men; age 53.2 ± 13.0 years) who underwent near-total or total thyroidectomy. An intra- and postoperative PTH and calcium monitoring was performed. The intraoperative situs of the PGs was documented by a study protocol. The patients were grouped in three categories: group A, 12 patients with four visualized and normally colored PGs; group B, 13 patients with four visualized and three or four discolored PGs; group C, 4 patients who had undergone autotransplantation of two PGs. RESULTS: Compared to group A, groups B and C showed sharper intraoperative PTH declines. PTH values recovered more quickly in group B than in group C. However, no significant differences in PTH kinetics were found in the general linear model for repeated measures (p = 0.132). However, a significantly higher incidence of protracted hypocalcemia-related symptoms for more than 14 postoperative days was found for group C (50.0%) than for groups A (0%) and B (0%; p = 0.011). None of the patients developed permanent hypoparathyroidism. CONCLUSIONS: The function of discolored PGs is only transiently impaired and recovers within a short time after surgery. Our observations do not support autotransplantation as a generally applicable first-line intervention for discolored PGs in the absence of other criteria for autotransplantation.