Iatrogenic Dissemination Of initially Resectable Lung Cancer After Transthoracic Fine-needle Biopsy : who is to Be Blamed?


 Background: Percutaneous fine-needle biopsy is a well-established procedure for the diagnosis of lung lesions. However, tumor dissemination after transthoracic biopsy is potentially unpreventable.For radiographical malignant localized tumors, the optimal choice (a timely surgery or preoperative biopsy) is debatable.Case Presentation: A 57-year-old male patient was admitted due to a radiographical malignant but initially resectable lung tumor in the chest images. Although lobectomy, instead of biopsy, was recommended by the multidisciplinary consultation team, the patient declared that he would ask for compensation if the pulmonary lesion was benign. He developed pleural and pericardial effusion about 9 months after the first biopsy, which failed to yield a definite diagnosis.Chest tube drainage revealed malignant tumor cells. Finally, unresectable stage Ⅳ primary lung adenocarcinoma was confirmed by another biopsy. Therefore, chemotherapy plus targeted agents was administered.The patient was lost to follow up 1 month later.Conclusions: A timely resection rather than biopsy of the lung lesion suspicious for cancer should be considered when appropriate. In addition,how to avoid the negative effect of patient-physician relationship in medical decision making warrants further ethical and clinical studies.


Background
Fine needle aspiration biopsy is a useful procedure for the diagnosis of lung cancer. However, controversy still remains as to whether it should be employed in patients with undiagnosed and operable lesions suspicious for lung cancer. A potential complication of computed tomography (CT)-guided transthoracic ne-needle biopsy is the dissemination of tumor cells along the needle track, resulting in pleural and chest wall metastasis [1,2]. In thoery, a timely operationrather than preoperative biopsy for pahtological diagnosis seems reasonable for selected patients.
Physicians could explain what should be done and the patients could freely express their opinions regarding treatment choice. Nevertheless, surgical decision-making is sometimes inevitably hampered by a few absurd reasons including the quality of patient-physician relationship and the personality of the patients. For example, a timely resection of the initially localized tumor would be suspended or cancelled if the patient distrusts the physician. Thus, in addition to identifying reliable and the optimal individualizedmanagement options, it is crucial to improve the patient-physician relationship. To the best of our knowledge, the negative effect of patient-physician con ict on medical decision is not uncommon in the real-world settings. Who is to be blamed?
Herein we presented a case of pleural dissemination of initially resectable lung adenocarcinoma after percutaneous ne-needle biopsy, followed by a brief literature review regarding the usefulness and potential risks of transthoracic biopsy.

Case presentation
The clinical data of the patient was presented anonymously for privacy concern. A 57-year-old male patient was admitted on April 4, 2016 because of cough for about 1 month, without fever, hemoptysis, hoarseness, chest distress, thorcalgia, dorsalgia, or signi cant weight loss. The physical examination showed nothing abnormal. The serum carcinoembryonic antigen, neuron-speci c enolase, squamous cell carcinoma antigen, and cytokeratin-19 fragment were all in normal range. Further chest CT revealed a pulmonary lesion in the left upper lobe, measuring 43 mm× 19 mm in size (Fig. 1A). It was in suspicious of lung cancerdue to the obvious spiculation margin and pleural tag signs. Distal metastasis was excluded by preoperative work-up including abdomen CT, cranial magnetic resonance and bone emission CT. Based on these ndings, the case was staged as cT2bN0M0 ( A) according to the 8th edition of tumor node metastasis staging system for lung cancer [3].
After a multidisciplinary consultation, uniportal thoracoscopic lobectomy and mediastinal lymph node sampling was recommended. The patient was informed that the lung tumor was probably malignancy, and biopsy was correlated with the potential risk of tumor dissemination. Nevertheless, the patient declared that he would ask for reimbursement from the physicians after the operation if the lesion turned out to be benign. Surgery was therefore cancelled. However, a CT-guided percutaneous core biopsy with an 18-gauge cutting needle failed to yield a pathological diagnosis of lung cancer. The alternative management including a second biopsy and intensive follow up were introduced. Then the patient was discharged from the hospital.
During the follow up, his CT on June 13, 2016 showed that the pulmonary lesion was slightly enlarged (Fig. 1B). But the physicians still did not perform surgery because of the fear of patient-physician con ict.
The patient was readmitted about 9 months after the rst transthoracic biopsy on January 9, 2017 due to gradually aggravated chest tightness. Unfortunately, the pleural and pericardial perfusion was indicated ( Fig. 1C), and malignant cells were detected in the pleural effusion after chest tube drainage. The second CT-guided biopsy revealed the pathological diagnosis of lung adenocarcinoma (cT4NxM1a, A). Systemic chemotherapy plus targeted agents was conducted accordingly. Thereafter, the patient was transferred to another hospital after the rst cycle of anti-tumor treatment.

Discussion And Conclusions
The present report aimed to improve both clinicians and patients' understanding of the risk of CT-guided biopsy, as well as the importance role of patient-physician relationship in medical decision making.
The radiographical features of pulmonary nodules including short axis, contour, concavity, texture, location, ssure attachment, lobulation; while spiculation can be used with size-based measures to enhance prediction accuracy and to reduce false-positives [4]. Positron Emission Tomography-CT (PET-CT) plays an important role in the diagnosis, staging, response assessment and follow-upfor non-small cell lung cancer (NSCLC)patients [5]. The diagnostic accuracy of contrast-enhanced CT and PET-CT is 0.58 and 0.9 respectively in identifying malignant solitary pulmonary nodules (diameter range 8-30 mm) [6].
In addition to the radiological images, percutaneous ne-needle biopsy is widely used for cytological diagnosis of bronchogenic carcinoma. We searched PubMed, Web of Science, Scopus, Embase and Google Scholar for relevant reports up to January 2020. Key words and MeSH terms in title or abstract including "biopsy" or "puncture" or "CT-guided" and "pulmonary" or "lung" were used. No restriction was made regarding the publication language. Finally a total of 15 studies indicating the performance of CTguided transthoracic needle biopsy were summarized in Table 1.The diagnostic accuracy of CT-guided aspiration biopsy of large nodules (>1.5 cm) and small nodules (≤1.5 cm) was 96% and 74%, respectively [7].In addition, the diagnostic accuracy of CT-guided needle biopsy was signi cantly improved for large (> 10 mm) lesion size and short (< or = 40 mm) needle path length [9]. Factors such as the acquisition of two or fewer specimens, lesions in the lower lobe, malignant lesions, and lesions measuring ≤ 1.0 cm or ≥ 3.1 cm signi cantly increased the rate of diagnostic failure [10]. Core biopsy is a preferred method as it gives a higher percentage of representative samples than ne-needle aspiration biopsy [12].Furthermore, the major complication rates for core biopsy and ne needle aspiration were 5.7 % and 4.4 %, respectively. Smaller nodule diameter, larger needle diameter and increased traversed lung parenchyma were risk factors for complications [22].Based on the available evidence, CT-guided percutaneous lung biopsy for pulmonary nodules is afeasible and e cient diagnostic method.
However, dissemination of cancer cells along needle track can make a potentially resectable localized lung cancer to be unresectable. Previous reports of lung tumor dissemination or implantation after biopsy were summarized in Table 2.The largest reported sample from Japan indicated that the incidence of tumor seeding at the site of the puncture route after ne-needle biopsy was about 0.06% [34]; whereas the interval between the initiation of biopsy and the diagnosis of implantation/metastasis was reported to be 4-13 months [26,30,36]. Therefore, post-biopsy radiographic examination was necessary.Furthermore, transthoracic ne-needle biopsy should not be performed in patients with sub-pleural pure solid nodules who were suspected of having NSCLC [40]. Other studies showed that CT-guided lung biopsy with a coaxial needle did not seem to cause pleural dissemination or pleural recurrence [35,41]; whereas visceral pleural invasion was responsible for tumor relapse.
On the other hand, chest wall implantation of lung adenocarcinoma at the drainage tube site has also been reported [43]. To prevent such tumor seeding at the time of thoracotomy, the pleural cavity should be washed out routinely with a massive volume of saline prior to closure of the chest wall. Despite the reports of malignant spread along the needle track, preoperative biopsy does not affect the survival in stage I NSCLC patients [44]. In addition, subcutaneous implantation of tumor cells along the needle track has also been reported in bladder, urethra, and prostate, adrenal, pancreatic, thyroid, parathyroid, and hepatocellularcarcinoma [28,[45][46][47][48][49][50][51][52]. Therefore, percutaneous ne-needle biopsy of the suspicious malignant lesions as indicated in radiographical images should not be performed indiscriminately but be reserved.
Moreover, the patient-physician trust is the foundation of clinical practice. The incidence of patientreported regret over the decision to major abdominal and thoracic operations is 37% [53]. The factors most often associated with regret include type of surgery, disease-speci c quality of life [54], decisional con ict and lower satisfaction with the decision, adverse physical health outcomes, and greater anxiety levels [55].
Furthermore, healthcare workplace violence is an underreported problem that has been largely ignored. Deterioration of patient-physician relationship had worsened and the violence against the healthcare workers emerged as a visible risk to reasonable decision-making [56]. One of the most prominent forces driving patient-physician mistrust is a patient perception of injustice within the medical sphere due to knowledge imbalances and con icts of interest. The mistrust leads to attacks against physicians [57]. A cross-sectional survey indicated that 34.4% of healthcare workers reported verbal or physical violence in the preceding 12 months, along with 13.5% of physical assault [58]. A meta-analysis showed that the prevalence of healthcare workplace violence is especially high in Asian and North American countries [59]. On the contrary, patients are also afraid that an important diagnosis will be missed or delayed through laziness, or incompetence of the physicians [60]. Moral, regulatory and legal responses are needed to restore the patient-physician trust. Generally speaking, surgical decision-making is impaired by time constraints, uncertainty, complexity, decision fatigue, hypothetical-deductive reasoning and bias. Integration of arti cial intelligence with surgical decision-making has the potential to diminish overtreatment [61].
For the present case, a timely minimally invasive lobectomy was recommended on his rst admission after multidisciplinary evaluation. However, the physicians intentionally gave upthe operation to avoid potential patient-physician con ict, as the patient declared that he would demand compensation if the lesion turned out to be benign. In the real-world settings, some doctors do not know how to face the complex relationship with their patients. Meanwhile,the fear of violence impairs the decision-making deliberately. Therefore, the choice of treatment is only partly provided based on the publishedo cial guidelines and consensus recommendations.
In summary, tumor implantation or dissemination after ne-needle biopsy is somewhatinevitable and unpreventable. A timely operation should always be considered for radiographicalmalignantandresectable lung lesions, providing that the potential patient-physician con ict could be avoided e ciently.

List Of Abbreviations
CT, computed tomography; MRI, magnetic resonance imaging; PET-CT, Positron Emission Tomography-Computed Tomography; NSCLC, non-small-cell lung cancer Declarations Ethics approval and consent to participate This report was approved by the Institutional Review Board of Xuzhou Central Hospital, and written informed consent was obtained from the patient.

Consent for publication
Written informed consent was obtained from the patient for publication of this report and any accompanying images.

Availability of data and materials
The data of the present case is available from the corresponding author on reasonable request.

Competing interests
The authors declare that they have no competing interests.

Funding
Not applicable.
Authors' contributions MZ performed the surgery and wrote this paper. YYL contributed to the preparation of the gures and tables. All authors contributed to preparation of the paper and to the perioperative treatment of the patient. All authors approved the nal manuscript.

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