e-ISSN: 2722-3558 Sriwijaya Journal of Surgery [SJS] https://sriwijayasurgery.
Serum Calcium as a Preoperative Surrogate of Tumour Burden in Stage i Breast Carcinoma: A Cross-Sectional Surgical-Oncology Study Feizal Faturahman1*.
Mulawan Umar2.
Theodorus3 1Department of Surgery.
Faculty of Medicine.
Universitas Sriwijaya.
Palembang.
Indonesia 2Department of Oncology Surgery.
Faculty of Medicine.
Universitas Sriwijaya.
Palembang.
Indonesia 3Department of Pharmacology.
Faculty of Medicine.
Universitas Sriwijaya.
Palembang.
Indonesia
ARTICLE INFO
ABSTRACT
Keywords:
Introduction: Stage i breast carcinoma dominates surgical-oncology practice in Indonesian referral hospitals.
Tumour-secreted PTHrP and dysregulated calcium signalling link tumour mass to systemic calcium, yet routinely available serum calcium is rarely quantified as a preoperative surrogate of tumour burden.
Breast carcinoma Serum calcium Surgical oncology Stage i Tumour burden Methods: In this cross-sectional study, 35 women with Stage i breast carcinoma at Dr.
Mohammad Hoesin General Hospital Palembang underwent preoperative serum calcium measurement.
Tumour size was dichotomised (O5 cm vs >5 c.
Associations were tested by Spearman correlation and the MannAeWhitney U test.
serum calcium was assessed as a classifier of large tumours by ROC analysis, with multivariable logistic regression, effect sizes and 95% confidence intervals (CI).
*Corresponding author:
Feizal Faturahman E-mail address:
Feizal.
Faturahman99@gmail.
All authors have reviewed and approved the final version of the manuscript.
https://doi.
org/10.
37275/sjs.
Results: Mean serum calcium was 9.
34 A 0.
82 mg/dL, and 27 patients .
1%) had tumours >5 cm.
Calcium was higher in tumours >5 cm .
76 mg/dL.
95% CI 9.
28Ae9.
than O5 cm .
54 A 0.
37 mg/dL.
95% CI
23Ae8.
, a difference of 1.
04 mg/dL .
% CI 0.
66Ae1.
Cohen d = 1.
MannAeWhitney U = 0.
p < 0.
r = 0.
Calcium correlated with size (Spearman rho = 0.
p < 0.
and discriminated tumours >5 cm .
rea under the curve 1.
cut-off 8.
95 mg/dL.
sensitivity and specificity 100%).
Immunohistochemical subtype was the only independent predictor .
djusted odds ratio 71.
95% CI 2.
95Ae1728.
p = 0.
Conclusion: Preoperative serum calcium rose in proportion to tumour size in Stage i breast carcinoma, acting as a low-cost surrogate of tumour burden that may aid risk stratification in resource-limited centres, pending Introduction geographic and financial barriers to care, and diagnostic Breast cancer is the most frequently diagnosed delay together drive a profound stage migration, so that malignancy among women worldwide.
In 2022 an surgical caseloads are dominated by tumours exceeding 3 million new cases were recorded globally, and modelling projects the annual burden to surpass Indonesian series the median diameter of advanced three million cases by 2040, with the steepest relative tumours reached 5.
5 cm.
In such a population, where increases occurring in transitioning economies such as neoadjuvant therapy, the extent of resection and axillary Indonesia.
1Ae3 A defining characteristic of breast cancer management must all be calibrated to tumour burden, presentation in Indonesian tertiary referral hospitals is inexpensive and reproducible markers of that burden the predominance of locally advanced (Stage .
carry disproportionate clinical value.
Low uptake, limited public awareness.
Surgery remains the cornerstone of locoregional Stage i breast carcinoma managed at a tertiary control in Stage i breast carcinoma.
Large cohort surgical-oncology referral centre, and to evaluate the characterisation of tumour size underpins decisions on operability, breast conservation versus mastectomy, and the sequencing of systemic therapy, with breastconserving surgery plus radiotherapy yielding survival identifying patients with large (>5 c.
tumour burden.
Methods Study design and setting at least equivalent to mastectomy when tumour burden This analytical observational study used a cross- is correctly assessed.
Primary tumour size therefore sectional design and is reported in accordance with the remains a fundamental surgical determinant rather STROBE statement for observational research.
The study was conducted in the Department of Surgery and independent prognostic weight even in node-positive the Department of Oncology Surgery.
Faculty of 6Ae9 Medicine.
Universitas Sriwijaya/Dr.
Mohammad Hoesin A growing body of mechanistic work links calcium General Hospital.
Palembang, the principal tertiary biology to breast cancer progression.
The calcium- referral centre for South Sumatra.
Indonesia.
sensing receptor is over-expressed in breast tumours Participants and eligibility and correlates positively with tumour size irrespective of invasive breast carcinoma clinically staged as Stage i .
ocally advance.
according to the eighth-edition migration and chemoresistance.
and tumour-secreted AJCC/UICC TNM system were eligible.
Inclusion criteria were age 18 years or older, a tissue diagnosis of invasive osteoclastic bone resorption, releasing calcium into the carcinoma with available immunohistochemistry, and STIM1 store-operated Orai1 hormone-related These Consecutive women with histologically confirmed biological rationale for the clinical observation that Patients with primary hyperparathyroidism, chronic larger, more advanced tumours are accompanied by higher circulating calcium.
10Ae13 concurrent second malignancy, or recent calcium or Despite this mechanistic foundation, few surgical- vitamin D supplementation that could confound serum oncology series Ai and almost none from Indonesia Ai calcium interpretation were excluded.
Sampling was have quantified the relationship between routinely performed by consecutive .
sampling until the available serum calcium and primary tumour size in required sample size was met.
operable Stage i disease using effect sizes, confidence intervals and a defined diagnostic cut-off.
Most prior work has emphasised calcium as a risk or prognostic factor in cohorts from high-income settings rather than as a pragmatic, preoperative surrogate of tumour burden in the resource-limited surgical theatre.
14,15
Sample size The minimum sample size was derived from the twomean hypothesis-testing formula with a two-sided significance level () of 0.
05 and power .
using the difference in serum calcium between tumoursize groups reported in prior work.
this yielded a To our knowledge, this is among the first Indonesian minimum of 30 participants.
Thirty-six patients were surgical-oncology studies to characterise preoperative enrolled and 35 had complete data for analysis, serum calcium as a low-cost surrogate of primary exceeding the a priori requirement.
tumour burden in Stage i breast carcinoma, complete effect-size receiver-operating- characteristic analysis and multivariable adjustment for molecular subtype and demographic factors.
Accordingly, the aim of this study was to determine the association between preoperative serum calcium concentration and primary tumour size in patients with Surgical and oncological context All patients were managed within a standardised surgical-oncology After staging, candidates for upfront surgery underwent modified radical mastectomy with level IAeII axillary lymph-node downstaging received neoadjuvant systemic therapy Statistical analysis before definitive surgery, consistent with contemporary Data were analysed with SPSS.
Continuous variables guidelines for locally advanced disease.
The operative are summarised as mean A standard deviation and principles applied uniformly were: patient supine with median .
categorical variables as frequency and the ipsilateral arm abducted under general anaesthesia.
Normality was assessed with the ShapiroAe an elliptical skin incision encompassing the nippleAe Wilk test.
because serum calcium departed from areola complex and any involved skin.
raising of normality within tumour-size groups, between-group superior and inferior skin flaps.
en-bloc removal of the comparison used the MannAeWhitney U test, and the breast with the pectoral fascia.
oncological clearance of rank-biserial correlation r (|Z|/OoN) together with Cohen axillary levels I and II with preservation of the long d quantified effect size.
The Spearman rank correlation thoracic and thoracodorsal neurovascular bundles.
assessed the monotonic relationship between serum and closed-suction drainage of the axilla and chest-wall flap.
The present study focused on the characteristic analysis evaluated serum calcium as a preoperative biomarker assessment that informs this classifier of tumours >5 cm, with the area under the pathway rather than on operative outcomes.
curve, a bootstrap 95% confidence interval, and the Serum calcium measurement Youden-optimal cut-off reported.
Multivariable binary Venous blood .
Ae5 mL) was collected preoperatively into plain .
o-anticoagulan.
vacutainer tubes after standard aseptic preparation, allowed to clot for 20Ae30 minutes, and centrifuged at 2500Ae3000 rpm to separate Total i cresolphthalein-complexone method against a known Receiver-operating- logistic regression modelled predictors of large tumour burden, adjusting for age, residence, occupation and molecular subtype, with adjusted odds ratios and 95% confidence intervals.
A two-sided p-value below 0.
denoted statistical significance, and exact p-values are reported to three decimal places.
Ethics calcium standard, with low, normal and high quality- This study obtained ethical clearance from the control sera analysed in each run.
Serum calcium was Health Research Ethics Committee of Dr.
Mohammad categorised as below 8.
5 mg/dL .
, 8.
5Ae11 Hoesin Central General Hospital.
Palembang.
The study mg/dL .
, and above 11 mg/dL .
was conducted in accordance with the Declaration of Pathological assessment Helsinki, and written informed consent was obtained Primary tumour size was recorded as the greatest dimension of the target lesion and dichotomised as O5 cm or >5 cm in accordance with the T-category thresholds of the TNM system.
Molecular subtype was receptor, progesterone receptor.
HER2 and Ki-67 and classified as Luminal A.
Luminal B or HER2-enriched.
Histological diagnosis followed the 2019 World Health Organization classification of breast tumours.
Patient and tumour characteristics Of 36 women enrolled, 35 had complete data and constituted the analytical cohort.
All were female, with a mean age of 50.
6 A 10.
9 years .
range 32Ae.
, and 16 patients .
7%) were older than 50 years.
Luminal B was the predominant molecular subtype .
HER2-enriched disease .
, 8.
6%).
Reflecting the referral The primary outcome, defined a priori, was the Results patients, 60.
0%), followed by Luminal A .
, 31.
4%) and Outcomes from all participants.
pattern of locally advanced disease, 27 patients .
presented with primary tumours larger than 5 cm and concentration and primary tumour-size category (O5 cm only 8 .
9%) with tumours of 5 cm or smaller.
The vs >5 c.
Secondary outcomes were the discriminative patient and tumour characteristics are summarised in performance of serum calcium for identifying tumours Table 1.
>5 cm and the association of serum calcium and tumour size with molecular subtype.
Table 1.
Patient demographics and tumour characteristics (N = .
Characteristic Value, n (%) or as stated Age, years Ai mean A SD 6 A 10.
Age, years Ai median .
Ae.
Age group Ai 30Ae40 years 6 .
Age group Ai 41Ae50 years 13 .
Age group Ai >50 years 16 .
Sex Ai female 35 .
Residence Ai within city 19 .
Residence Ai outside city 16 .
Molecular subtype Ai Luminal A 11 .
Molecular subtype Ai Luminal B 21 .
Molecular subtype Ai HER2-enriched 3 .
Primary tumour size Ai O5 cm 8 .
Primary tumour size Ai >5 cm 27 .
Serum calcium Ai <8.
5 mg/dL .
Serum calcium Ai 8.
5Ae11 mg/dL .
Serum calcium Ai >11 mg/dL .
Serum calcium, mg/dL Ai mean A SD 34 A 0.
Notes: SD, standard deviation.
Percentages are of evaluable patients (N = .
Distribution of serum calcium serum calcium of 9.
58 A 0.
76 mg/dL .
% CI 9.
28Ae9.
Mean preoperative serum calcium was 9.
34 A 0.
compared with 8.
54 A 0.
37 mg/dL .
% CI 8.
23Ae8.
in mg/dL .
0Ae12.
As shown in Table patients with tumours O5 cm Ai a mean difference of 1, thirty patients .
7%) were normocalcaemic .
5Ae11 04 mg/dL .
% CI 0.
66Ae1.
The effect was very mg/dL), three .
6%) were hypocalcaemic (<8.
5 mg/dL), large (Cohen d = 1.
, and because serum calcium was and two .
7%) were frankly hypercalcaemic (>11 non-normally distributed within groups (ShapiroAeWilk p mg/dL).
Thus the majority of patients maintained < 0.
, the MannAeWhitney U test was applied, calcium concentrations within or near the reference demonstrating complete rank separation (U = 0.
Z =
interval, with overt hypercalcaemia confined to the Oe4.
264, p < 0.
with a large rank-biserial effect size highest tumour-burden extreme.
= 0.
The monotonic association was confirmed by Serum calcium and primary tumour size Serum calcium differed markedly between tumoursize groups.
Patients with tumours >5 cm had a mean Spearman correlation .
ho = 0.
731, p < 0.
These comparisons are detailed in Table 2 and depicted in Figure 1.
Figure 1.
Preoperative serum calcium by primary tumour size category.
Boxes show median and interquartile range.
diamonds denote group means.
points are individual patients.
Serum calcium was significantly higher in tumours >5 cm (MannAeWhitney U = 0.
p < 0.
r = 0.
Table 2.
Serum calcium by primary tumour size and intergroup comparison.
Parameter Tumour O5 cm Tumour >5 cm Comparison Ai Mean A SD, mg/dL 54 A 0.
58 A 0.
Ai 95% CI of mean, mg/dL 23Ae8.
28Ae9.
Ai Median .
, mg/dL 75 .
00Ae8.
00Ae12.
Ai Mean difference .
% CI), mg/dL 04 .
66Ae1.
p < 0.
Effect size (Cohen .
Very large MannAeWhitney U.
U = 0.
Z =
Oe4.
p < 0.
Rank-biserial r Large Spearman rho .
alcium vs siz.
p < 0.
Notes: CI, confidence interval.
Between-group comparison by MannAeWhitney U test.
exact p-values to three decimals.
Diagnostic performance of serum calcium detailed in Table 3 and illustrated by the receiver- On receiver-operating-characteristic analysis, serum operating-characteristic curve in Figure 2.
This perfect calcium discriminated tumours >5 cm with an area separation reflects the complete absence of overlap in under the curve of 1.
% CI 1.
000Ae1.
The serum calcium between the two tumour-size groups in Youden-optimal cut-off was 8.
95 mg/dL, at which this sample and is interpreted with appropriate caution sensitivity, specificity, positive and negative predictive given the modest, single-centre design.
values, and overall accuracy were each 100%, as Figure 2.
Receiver-operating-characteristic curve for preoperative serum calcium identifying primary tumours >5 cm.
The Youden-optimal cut-off .
95 mg/dL) is marked.
area under the curve = 1.
% CI 1.
000Ae1.
Table 3.
Diagnostic performance of serum calcium for identifying tumours >5 cm.
Diagnostic metric Value Area under the ROC curve 000 .
% CI 1.
000Ae1.
Optimal cut-off (Youde.
95 mg/dL Sensitivity Specificity Positive predictive value Negative predictive value Overall accuracy Notes: ROC, receiver-operating-characteristic.
The perfect discrimination reflects complete rank separation in this modest, single-centre sample and requires external validation.
Predictors of large tumour burden .
, residence .
djusted OR 0.
95% CI 0.
03Ae4.
In multivariable logistic regression adjusting for age, p = 0.
and occupation .
djusted OR 1.
95% CI
55Ae3.
p = 0.
were not significant.
The very wide confidence interval for subtype indicates small-sample independent predictor of a tumour >5 cm .
djusted odds instability and is interpreted cautiously.
The full model 95% CI 2.
95Ae1728.
Wald = 6.
is presented in Table 4 and visualised as a forest plot in Age .
djusted OR 1.
95% CI 0.
92Ae1.
Figure 3.
Figure 3.
Forest plot of adjusted odds ratios from multivariable logistic regression for the outcome of primary tumour >5 cm.
Immunohistochemical subtype .
was the only independent predictor .
= 0.
the dashed line marks the null (OR = .
Table 4.
Multivariable logistic regression Ai predictors of primary tumour >5 cm.
Predictor Adjusted OR 95% CI Wald p-value Age .
er yea.
92Ae1.
Residence .
utside cit.
03Ae4.
Occupation 55Ae3.
IHC subtype .
igher grad.
95Ae1728 Notes: OR, odds ratio.
CI, confidence interval.
IHC, immunohistochemistry.
The wide CI for IHC subtype reflects smallsample quasi-separation and is interpreted with caution.
Serum molecular subtype Serum likewise increased across subtypes (Z = Oe3.
596, p < The graded relationship between subtype, tumour size and serum calcium is shown in Figure 4 (MannAe and is consistent with the more aggressive biology of Whitney p = 0.
, rising from Luminal A through non-luminal tumours.
Luminal B to HER2-enriched disease, and tumour size Figure 4.
Preoperative serum calcium across immunohistochemical molecular subtypes.
Bars show group means with 95% confidence intervals.
points are individual patients.
Serum calcium rose from Luminal A to HER2-enriched disease (MannAeWhitney p = 0.
Discussion In a tertiary Indonesian centre where most In this cross-sectional surgical-oncology study of 35 patients present with tumours exceeding 5 cm, a women with Stage i breast carcinoma, preoperative preoperative serum calcium concentration in the upper serum calcium rose in close proportion to primary part of the reference range Ai or frank hypercalcaemia tumour size.
Patients with tumours larger than 5 cm Ai may serve as an early, low-cost signal of substantial had serum calcium concentrations approximately 1.
tumour burden, prompting expedited multidisciplinary mg/dL higher than those with smaller tumours, a review, consideration of neoadjuvant systemic therapy difference that was both statistically robust (MannAe for downstaging, and heightened vigilance for skeletal Whitney p < 0.
and clinically large (Cohen d = 1.
Unlike advanced imaging or molecular Spearman rho = 0.
Serum calcium classified large- assays, serum calcium is available in virtually every burden tumours with excellent discrimination at a cut- Indonesian hospital laboratory at negligible cost, an advantage of particular importance in resource-limited mg/dL, inexpensive laboratory test as a candidate preoperative surrogate of tumour burden.
surgical practice.
6,8,9
The clinical implications extend to perioperative These findings align closely with the international Hypercalcaemia of malignancy, though present literature on calcium and breast cancer.
In a landmark in only a minority of our patients, is a recognised cross-sectional study of 555 untreated women, tumour determinant of tumour burden and carries risks of volume correlated positively with serum calcium, and dehydration, renal impairment and cardiac dysrhythmia pooled prospective data have linked circulating calcium that are directly relevant to the surgical patient.
with breast tumour behaviour.
Our mean difference and Recognising an elevated serum calcium preoperatively effect size are concordant with, and arguably more allows correction and optimisation before anaesthesia, pronounced than, these reports Ai plausibly because integrating the biomarker into both oncological and our cohort was deliberately confined to locally advanced operative decision-making.
17Ae19 tumour-burden-driven mobilisation is most pronounced.
10,14
Several features of the Indonesian and broader Asian context deserve emphasis.
The high proportion of large The biological plausibility of the association is well tumours in our series mirrors reports from other Tumour-secreted parathyroid hormone- Indonesian referral centres, where diagnostic delay and limited screening produce advanced-stage presentation.
stimulating osteoclastic bone resorption and renal In this epidemiological setting, the discriminative calcium reabsorption.
its expression scales with tumour performance of serum calcium may be amplified mass and predicts both bone metastasis and shorter precisely because the spectrum of tumour burden is Larger tumours therefore generate a greater shifted towards its upper extreme, increasing the humoral calcaemic stimulus.
In parallel, the calcium- separation between size groups.
4,5,20
sensing receptor is over-expressed in breast tumours in The graded behaviour of serum calcium across proportion to tumour size irrespective of subtype, and molecular subtype invites a mechanistic reading.
HER2-
store-operated calcium entry through STIM1 and Orai1 enriched and high-proliferation tumours exhibit greater sustains the proliferative and migratory phenotype of store-operated calcium entry and calcium-sensing- breast cancer cells.
Our observation, illustrated in receptor activity, both of which have been linked Figure 4, that serum calcium and tumour size both experimentally to enhanced migration and to disordered increased across molecular subtypes from Luminal A to calcium handling.
The convergence of higher subtype HER2-enriched disease, is consistent with this subtype- grade, larger size and higher circulating calcium in our dependent calcium signalling and with the more cohort is therefore unlikely to be coincidental, although aggressive growth kinetics of non-luminal tumours.
11Ae the small number of HER2-enriched cases warrants 13,16 caution and dedicated study.
11,12,21
From a surgical-oncology standpoint, the principal It is important to interpret the perfect diagnostic value of these data lies in risk stratification before separation observed here within its statistical context.
Complete rank separation, an area under the curve of function and cardiac rhythm before anaesthesia, and for 000 and a MannAeWhitney U of zero arise because no early involvement of medical oncology where humoral patient with a small tumour had a serum calcium reaching the value of any patient with a large tumour in calcium-vitamin D axis is itself biologically active in this particular sample.
While internally consistent, such breast cancer, underscoring that calcium measurement perfect separation is characteristic of modest, single- carries information beyond a single electrolyte value.
centre datasets and dichotomised outcomes and will Embedding a simple calcium threshold into preoperative checklists could therefore improve both oncological heterogeneous cohorts.
The cut-off of 8.
95 mg/dL triage and operative safety simultaneously, an efficiency should thus be regarded as hypothesis-generating that is attractive in high-volume, resource-limited rather than as a validated clinical threshold.
14,22
surgical units.
19,25
The Our results sit comfortably within the wider evidence The graded rise of serum calcium across Luminal A, that circulating calcium tracks tumour aggressiveness Luminal B and HER2-enriched subtypes adds a across solid tumours.
Pooled prospective data in breast biological coherence that extends beyond size alone.
cancer associate higher circulating calcium with adverse Non-luminal tumours are characterised by higher tumour behaviour, and cohort studies in prostate and proliferative indices and greater dependence on calcium- colorectal cancer show serum calcium tracking tumour driven signalling, and their tendency towards both These larger size and higher circulating calcium in our cohort observations parallel the determinants of breast cancer is consistent with subtype-specific differences in store- survival, in which tumour size and biology jointly shape operated calcium entry and calcium-sensing-receptor The consistency of these independent datasets activity reported experimentally, against a background strengthens the inference that the calciumAetumour-size in which calcium and vitamin D biology modulate breast relationship is real rather than an artefact of our cancer behaviour.
Although the small number of HER2-
14,19,21,23
enriched cases precludes firm conclusions, this pattern The translational appeal of serum calcium lies in its suggests that serum calcium may capture not only the integration into an existing surgical workflow rather quantity but also, in part, the biological character of the than in its replacement of established staging tools.
tumour Ai a hypothesis that merits dedicated, subtype- Preoperative blood chemistry is obtained as a matter of stratified investigation.
11,12,26
routine before mastectomy or axillary Positioned against the prevailing Indonesian health- reading the calcium value through an oncological lens system reality, the case for a calcium-based triage signal adds no incremental cost or patient burden.
In a future becomes stronger still.
National survival from breast predictive model, serum calcium could be combined cancer remains substantially lower than in high-income with clinical tumour size, nodal status and molecular settings, a gap driven in large part by advanced-stage, subtype to yield a composite, low-resource estimate of large-tumour presentation rather than by inferior tumour burden that flags patients for accelerated surgical technique.
Tools that shorten the interval from neoadjuvant pathways and heightened surveillance for first surgical contact to definitive, burden-appropriate the bone-tropic spread to which large, biologically treatment Ai including objective monitoring of response aggressive tumours are prone.
Such a model would be to neoadjuvant therapy Ai therefore have plausible especially valuable where access to magnetic resonance survival relevance.
A serum calcium result, returned imaging or genomic assays is constrained, as is common within hours and at trivial cost, could function as one across much of the Indonesian archipelago.
6,8,24
such tool, complementing rather than competing with There is also a perioperative-medicine dimension to these findings.
Because the two patients with frank examination and imaging in the staging 5,9,27 This study should be read as an early, hypothesis- burden, an elevated preoperative calcium can act as a generating step rather than as definitive evidence.
Its trigger for focused assessment of hydration, renal contribution is to translate a robust body of laboratory and epidemiological work on calcium and breast cancer proportion to primary tumour size, with a mean into a concrete, surgically actionable observation drawn difference of 1.
04 mg/dL .
% CI 0.
66Ae1.
between from a real Indonesian operative population, and to do tumours above and below 5 cm and a strong rank so with explicit effect sizes, confidence intervals and a correlation (Spearman rho = 0.
p < 0.
Serum cut-off.
calcium Ai an inexpensive, universally available test Ai therefore behaves as a useful surrogate of tumour albumin-corrected and ionised calcium, tumour size burden in locally advanced breast cancer and may aid modelled as a continuous variable, and linkage to operative and survival outcomes Ai extending the inexpensive-biomarker paradigm already explored for resource-limited settings.
Given the single-centre design other serum analytes in locally advanced disease Ai a and small sample, these findings should be confirmed in design that would establish whether the striking larger, prospectively followed, multicentre cohorts that incorporate albumin-corrected The natural calcium, continuous representative and rigorously followed population.
14,22,28
tumour-size modelling and oncological outcomes before This study addresses a genuine gap by quantifying a serum calcium is adopted as a routine preoperative low-cost population dominated by locally advanced disease.
The analysis was strengthened by the reporting of effect sizes and 95% confidence intervals alongside exact p-values.
References