A 58-year-old man living in Sichuan, China was transferred to this hospital because of dizziness accompanied by vomiting and diarrhea.
The patient, who had lived and worked in a city in China for a long time, was admitted to the neurology department of our hospital due to "left eyelid ptosis accompanied by diplopia for 20 days". When episodes of bilateral pupils were found to be anisoperiotic, and the right eye was sensitive to direct and indirect light reflection, while the left eye was missing direct and indirect light reflection. Tumor marker: FER 312.8ng/ml. MRI scan of the head was performed two days later. The results showed that the left top wall of the nasopharynx, the sphenoid bone, the occipital bone slope, and the left cavernous sinus were irregular and flaky-like. Left pharyngeal recess disappeared.
The patient had developed upper respiratory tract infection within 1 month. He was been found to have hypertension more than a year ago, with a maximum systolic blood pressure of 160 + mmHg. After regular medication, his blood pressure had been controlled in the normal range. He denies hepatitis, tuberculosis or other infectious diseases and had no known allergies. He quit smoking and drinking more than a year ago. He was married and had one son.
During the next 2 days, the patient underwent "endoscopic intranasal lesion resection", and then the biopsy of the nasopharyngeal mass was performed. The endoscopic lesion resection specimens were found in the tissues submitted for examination, and heterotype cell mass with necrosis was found, and malignant tumor was considered. Immunohistochemical results combined with the morphology of HE sections, pathological diagnosis: biopsy specimens showed non-keratous carcinoma with necrosis. Comprehensive examination of the patient considered diagnosis: non-keratosis nasopharyngeal carcinoma invading intracranial with cervical lymph node and cervical spine metastasis.
The patient received the first cycle of TPF (Docetaxel 120mg d1 ivgtt + cisplatin 40mg D1-d3 ivgtt + 5-Fu 0.9g D1-D5 intravenous infusion for 8 hours, q3w) at the oncology department of our hospital on the 6th day after endoscopic resection for intranasal lesions. MRI of nasopharynx and neck (plain scan + enhancement) was performed on the third day after admission to the oncology department. It was reported that after nasopharyngeal space occupying resection, soft tissue signal shadow appeared in the left side of nasopharynx, parietal wall and left posterior nostril.. It was reported that the above findings in the left lateral and lateral pterygoid muscles, sphenoid bone, parietal bone and left cavernous sinus, pterygopalatine fossa and pituitary fossa were considered to be tumor infiltration. Multiple lymph nodes in the neck, some slightly larger, were reported to be considered metastases pending expulsion. Cervical 4 and 6 vertebral bone metastases are possible. Chest and abdominal CT showed no signs of distant metastasis. WBC 4.89*10^9/L and N# 1.3*10^9/L were reexamined on the 5th day after chemotherapy and discharged.
On the eighth day after chemotherapy, the patient developed dizziness without obvious causes, accompanied by instability of standing, body temperature of 38.5 degrees Celsius, nausea, vomiting of stomach contents and diarrhea, yellow watery stool, so he was admitted to the hospital in emergency and treated accordingly. Chest CT was taken the next day in the emergency department. Chronic bronchitis and emphysema were reported. New lesions were found in the lower lobe of the right lung (2022-9-29), which was considered infection. It is reported that the WBC 0.62 * 10 ^ 9 / L, PCT 100 ng/mL, propagated 26 g/L, PLT 32 * 10 ^ 9 / L (other test results are shown in Table 1). On the 8th day after chemotherapy, the patient had granulocytosis accompanied by fever, the highest body temperature was 39℃, accompanied by cough, sputum, shortness of breath, and wet and dry rale could be heard in both lower lungs. The patient was treated with recombinant human granulocyte stimulating factor, symptomatic human blood albumin, recombinant human interleukin-11, platelet elevation capsule, and blood Bigen, and was injected with meropenem 1g q8h continuously. After four days of treatment, the patient's body temperature was 37.3℃, PCT was 44 ng/mL, WBC returned to normal, ALT was 56U/L, slightly increased, and polyene phosphatidylcholine capsules (Yishanfu) were given. On the fifth day of treatment, the patient's body temperature was 36℃, PCT 24ng/mL (lower than before), PLT 67*10^9/L, the patient's body temperature returned to normal, WBC, PLT, PCT were better than before. The patient was voluntarily transferred to the oncology department for follow-up treatment.
Table 1
Variable | Reference Range,Adults | ICU(10 − 9) | ICU(10–12) | On Admission, Infirmary(10–20) | Day (1–12), Hospital in China |
Hematocrit (%) | 40–50 | 36 | 27 | 32 | 38 |
Hemoglobin (g/L) | 130–175 | 130 | 95 | 106 | 124 |
White-cell count (*10^9per L) | 3.5–9.5 | 0.62 | 7.24 | 8.12 | 2.26 |
Differential count (%) | | | | | |
Neutrophils | 40–75 | 59.7 | 93.0 | 69.8 | 56 |
Lymphocytes | 20–50 | 9.9 | 2.9 | 12.7 | 11 |
Monocytes | 3–10 | 13.9 | 3.5 | 15.5 | 24 |
Eosinophils | 0.4-8.0 | 0.0 | 0.0 | 0.9 | 9.0 |
Basophils | 0.0–1.0 | 1.0 | 0.6 | 1.1 | 0.0 |
Platelet count (per L) | 125–350 | 32 | 31 | 472 | 150 |
Smear description | | | | | |
C‑reactive protein (ng/ml) | 0.046 | > 100 | 44.0 | 0.263 | |
Erythrocyte sedimentation rate (mm/hr) | | | | | |
Fibrinogen (g/L) | 1.8–3.5 | 8.5 | 8.1 | | 5.0 |
d‑Dimer (µg/mL) | 0-0.55 | 1.02 | 1.86 | | 0.17 |
Prothrombin time (sec) | 9.8–12.1 | 17.3 | 11.2 | | 12.2 |
Prothrombin‑time international normalized ratio | 0.86–1.15 | 1.65 | 1.03 | | 1.13 |
Potassium (mmol/liter) | | | | | |
Urea nitrogen (mmoL/L ) | 3.1-8.0 | 11.8 | 5.6 | 3.8 | 3.6 |
Creatinine (µmoL/L) | 57–97 | 131 | 58 | 60 | 63 |
Glucose (mg/dl) | | | | | |
Bilirubin ((µmoL/L)) | | | | | |
Total | 0.0–26.0 | | 13.1 | 10.9 | 7.3 |
Direct | 0.0-6.8 | | 6.0 | 3.9 | 2.2 |
Protein (g/L) | | | | | |
Total | 65–85 | 47 | 42 | 60 | 70 |
Albumin | 35–55 | 26 | 24 | 30 | 41 |
Aspartate aminotransferase (U/L) | 15–40 | 27 | 60 | 25 | 27 |
Alanine aminotransferase (U/L) | 9–50 | 19 | 56 | 18 | 22 |
Alkaline phosphatase (U/L) | 45–125 | 38 | 58 | 60 | 85 |
γ‑Glutamyl transferase (U/L) | 10–60 | 19 | 21 | 19 | 15 |
Lipase (U/L) | 13–63 | 13 | | | |
Amylase (U/L) | 35–135 | 20 | | | |
Lactate (mmol/L) | | | | | |
Carcinoembryonic antigen (ng/ml) | | | | | 1.25 |
In the second week after chemotherapy, the patient had repeated diarrhea and severe imbalance of intestinal flora due to the anti-infection meropenem used in the previous period. After the fever was effectively controlled, clinical pharmacists considered that antibacterial drugs could be used for descending treatment. Oncology physicians adopted the suggestion and continued anti-infection treatment with ceftazidime 2g q12h in the following nine days, supplemented by ambroxol and concentrated sodium chloride atomizing expectorant, montmorillite powder, loperamide capsules and compound glutamine capsules to improve gastrointestinal function, and bifidobacterium to regulate intestinal microbiota. The patient was bedridden for a long time, and should be gargled with sodium bicarbonate to prevent secondary fungal and multi-drug resistant bacterial infections. The diarrhea of the patient was better than before, so Loperamide capsules and montmorillonite powder were stopped five days later. A week later, the patient complained that his cough was worse than before in the last two days, which was obvious at night, and occasionally white sticky sputum was coughed up. It was reported that breathing sounds were coarse in both lungs and wet rales could be heard in the right lower lung. It was reported that the blood image was not high and the sputum culture results were negative. Chest CT examination revealed that the lower lobe of the right lung was infected with multiple new cavities, indicating the possibility of lung abscess formation. There were A few new lesions in the posterior and middle segments of the upper lobe of the right lung (Fig. 1. A).
Respiratory doctors consider that the patient has a high possibility of lung abscess. Due to the patient's previous stage of bone marrow suppression, it is necessary to pay attention to the investigation of fungus, tuberculosis, and Nookadella infection. It is necessary to improve the G test, GM test, reexamination of sputum culture, examination of acid-fast bacilli in sputum, feasible bronchoscopy, sputum drainage and examination of NGS of alveolar lavage fluid. The G test, GM test and sputum culture review should be completed for this patient, and the drained sputum should be examined by bronchoscopy and the alveolar lavage fluid for NGS. The doctor changed the antiinfective regimen for the patient's lung abscess to the broad-spectrum antibiotic laxefin. Fibrobronchoscopy, it was reported that bilateral bronchial mucosa was significantly congested, with more white phlegm visible in the lumen, and bronchial inflammation was observed. It was reported that PLT 0.263*10^9/L, WBC 8.03*10^9/L, N# 5.1*10^9/L, fungal spores and mycelia were not found on fungal smears. No acid-fast bacilli were found in the tuberculosis bacilli smear. It was reported that G test 9.5259pg/mL, Gm test: GM < 0.25S/CO. It was reported that the NGS results of the fiberscope lavage fluid in the patient showed that the gram positive bacterium Acidobacteriae was mycobacterium abscess with a homogeneous sequence number of 20. The patient was considered to have bacterial pneumonia with pulmonary abscess (Mycobacterium abscess infection), and the original anti-infective regimen was continued.
After 10 days of anti-infective treatment, the patient's cough and sputum were improved, and there was occasional cough at night, mostly dry cough, and nasal obstruction was improved. Reexamination of chest CT plain scan revealed that infection in the lower lobe of the right lung was more anterior absorption (Fig. 1. B), and a small amount of fluid was reported in the right thoracic cavity, less than before. After one cycle of chemotherapy, the patient was re-examined by head and neck MRI (Fig. 2. B). Compared with head and neck MRI of 10 − 03 (Fig. 2. A), no significant thickening of the nasopharyngeal mucosa was reported. It is reported that the changes in the bone and surrounding soft tissue at the skull base, considering tumor invasion, are smaller than before; It was reported that the lymph nodes of the original neck were slightly enlarged and almost disappeared. The overall condition was assessed as partial remission(Fig. 2. C).
Head and neck MRI (plain scan + enhancement) from October 31 (Fig. 3. B) : Compared with the old film of 2022-10-03 (Fig. 3. A) : (1) no significant thickening of nasopharyngeal mucosa was observed; (2) The changes in the bone and surrounding soft tissue at the skull base, considering the invasion of tumor, were smaller than before; (3) Slightly enlarged lymph nodes in the original neck basically disappeared.
As the patient is currently complicated with bacterial pneumonia and lung abscess, systemic chemotherapy is not available for the time being in anti-infection treatment. It is planned to first control the patient's lesion with local radiotherapy, and at the same time conduct targeted therapy with nituzumab. In the following days, the patient's cough and sputum were significantly improved, and the frequency of cough at night was reduced. It was reported that the PCT was 0.046ng/mL, the WBC was 5.33*10^9/L, and the N# 2.5*10^9/L. The patient's infection was better than before, so the antibacterial drugs were changed to Cefaclor capsules and moxifloxacin. Reexamination of chest CT showed that the lesions in the lower lobe of the right lung were less absorbed than before (Fig. 1. C). The NGS response showed no mycobacterium abscess. Clinical pharmacists suggested that antibiotics could be replaced with moxifloxacin alone for continued treatment, and clinicians accepted the suggestion. Re-examination of chest CT indicated that the lesions in the lower lobe of the right lung were significantly reduced in scope, and a small amount of effusion in the original right thoracic cavity was reduced (Fig. 1. D). It is suggested that anti-infective therapy is effective and anti-infective therapy should be continued.
Chest CT reexamination two months after the diagnosis of lung abscess showed that the lesions in the lower lobe of the right lung were slightly reduced in scope and peripheral exudation decreased (Fig. 1. E). The last chest CT examination showed that the lesions in the lower lobe of the right lung were significantly reduced in scope (Fig. 1. F).
Differential Diagnosis
I am the clinical pharmacist in charge of the patient, and I understand the diagnosis. I will discuss this case from three aspects. First, granulocytosis accompanied by cough, sputum, fever and shortness of breath after cancer chemotherapy. Further drainage of sputum and examination of NGS of alveolar lavage fluid indicated mycobacterium abscess, which was considered to be bacterial pneumonia combined with lung abscess. And then I'm going to talk about this patient's nasopharyngeal malignancy. Finally, I will discuss the patient's secondary malignancy of the cervical lymph nodes.
Bacterial Pneumonia With Mycobacterium Abscess
The differential diagnosis of granulocytosis with fever and shortness of breath was caused by the patient's post-cancer chemotherapy. The patient presented dizziness without obvious inductions, accompanied by unstable standing, body temperature 38.5℃, accompanied by nausea and vomiting of stomach contents for 3 times, accompanied by diarrhea for several times, yellow watery stool, so he was admitted to the hospital in emergency. The first consideration was that the patient developed IV° myelosuppression after the first TDF regimen, causing symptoms such as fever and neutropenia. NGS results of alveolar lavage fluid of subsequent patients showed that the homogeneous sequence number of gram-positive bacterium Acidobacteriae abscessus was 20. The patient was considered to have bacterial pneumonia with pulmonary abscess (infection with Mycobacterium abscess).
Mycobacterium Abscess
The patient's lung sample was cultured with Mycobacterium abscess, a rapidly growing Mycobacterium (RGM). Identification of specific subspecies of isolates may influence treatment; Most isolates of the abscess subspecies and the Bolae subspecies had active inducible macrolide resistance gene (erm), while the Marseille subspecies did not. However, it is difficult to distinguish these subspecies in clinical laboratory, and subspecies identification is often impossible. Our lab hasn't been able to identify the subspecies. The characteristics of drug sensitivity of Mycobacterium abscess subspecies and Bolea subspecies isolates are usually as follows: Clofazimine (90%), Amikacin (90%), cefoxitin (70%), imipenem (50%), Linezolid (23%), tigecycline (no threshold sensitivity was determined, but MIC < 1µg/mL for most isolates), clarithromycin (100% sensitivity in initial in vitro drug sensitivity tests); However, many of these isolates have active inducible macrolide resistance genes (ERMs), so they may be resistant in vivo even if initial in vitro susceptibility tests indicate sensitivity. The characteristics of drug susceptibility of M. abscessus Masai were similar to those of M. abscessus, but most of the isolates did not have active inducible macrolide resistance genes (erm). In combination with the drug catalog of our hospital, the doctor selected cefaclor capsule, which belongs to the second generation cephalosporin with cefoxitin, for oral administration. After 12 days of medication, chest CT showed improvement in the lower lobe of the right lung. Clinical pharmacists highly suspected the presence of anaerobic bacterial infection in the patient's lungs. However, due to the difficulty of cultivating anaerobic bacteria in lung samples, clinical pharmacists believe that empirical anaerobic bacteria coverage can be carried out in combination with the clinical manifestations of patients, especially in patients with lung abscess caused by aspiration suspected of coughing foul-odor sputum. Moxifloxacin covers anaerobic bacteria and is present in high concentrations in the lungs. Clinical pharmacists recommended subsequent replacement of oral moxifloxacin therapy. The clinician adopted the recommendation of the clinical pharmacist and replaced the antibacterial drug with moxifloxacin to continue the treatment.
For the treatment course of lung abscess, the optimal total course of treatment has not yet been determined, and the reported duration of antibacterial drug use ranges from 21 days to 48 days [17]. For this patient, clinical pharmacists and clinicians agreed that continuous antibiotic therapy should be selected until chest imaging examination (preferably CT) showed no lesions or only small stable lesions remained. CT scan of the patient at 2023-1-11 (21 days after diagnosis) indicated that the lesion area had been significantly reduced.
Studies show that immunosuppression is present in 62% of lung abscess cases. However, immunosuppression caused by tumor may increase the formation rate of lung abscess. This case series study highlighted the correlation between RGM lung infection and malignant tumor [18], but there were no patients with nasopharyngeal carcinoma in the study, and nasopharyngeal carcinoma complicated with lung abscess was first reported here. On admission, the blood routine of the patient showed IV° myelosuppression, which was improved 3 days later. The patient was initially admitted to the ICU, and after two weeks chest CT indicated the formation of a lung abscess. Clinical pharmacists believe that patients with bone marrow suppression may be a risk factor for pulmonary abscess.
Patients with pulmonary abscesses should begin empire-based antibiotic therapy quickly to reduce the risk of abscess rupture into the airway/pleural space or involvement of local structures such as blood vessels. In patients with lung abscesses suspected of aspiration, an empiric intravenous antibiotic regimen should penetrate the lung parenchyma and cover strict anaerobic bacteria (e.g., digestive Streptococcus, Prevotella, Bacteroides, Miller Streptococcus) and microaerostreptococcus. The patient had no underlying lung disease and a prior ICU hospitalization history. Misaspiration was highly suspected, and the possibility of primary lung abscess was considered. For this patient, physicians chose the broad-spectrum antibacterial drug latoxefin (covering most of G-, part of G+, enzyme resistant bacteria and part of anaerobic bacteria) for treatment. The choice of latoxefin was also reported in the treatment of a patient with lung cancer secondary lung abscess [15]. Patients with aspiration related lung abscesses usually show clinical improvement within 3–4 days of starting antibiotic therapy, with remission of fever and leukocytosis expected within 7–10 days [16]. After 8 days of use of cefloxacin, the patient's clinical condition was stable, cough and sputum were relieved, which was more consistent with the prognosis of aspiration related lung abscess according to clinical pharmacists. Subsequent clinicians changed the intravenous medication to the oral drug cefaclor capsules. Clinical pharmacists believe that once the fever has subsided and the patient is clinically stable, intravenous medication is generally changed to oral medication, which oral regimen is chosen depending on the detected or suspected causative agent of infection.
Patients with a lung abscess should begin empire-based antibiotic therapy quickly to reduce the risk of the abscess breaking into the airway/pleural space or involving local structures such as blood vessels. In patients with lung abscesses suspected of aspiration, an empiric intravenous antibiotic regimen should penetrate the lung parenchyma and cover strict anaerobic bacteria (e.g., digestive Streptococcus, Prevotella, Bacteroides, Miller Streptococcus) and microaerostreptococcus. The patient had no underlying lung disease and prior ICU admission, so aspiration was highly suspected and primary lung abscess was considered. For the lung abscess of this patient, physicians selected the broad-spectrum antibacterial drug Laxefin (covering most G-, part G+, enzyme resistant bacteria and part of anaerobic bacteria) for treatment. The choice of laxefin was also reported in the treatment of a patient with lung cancer secondary lung abscess [15]. Patients with aspiration related lung abscess usually show improvement of symptoms within 3–4 days after antibiotic treatment, which is manifested as relief of fever and leukocytosis, and fever is expected to return within 7–10 days [16]. The patient's clinical condition was stable 8 days after the use of Latoxefin, and the cough and sputum were relieved, which was more consistent with the prognosis of aspiration related lung abscess according to the clinical pharmacist. Subsequent clinicians took the advice of clinical pharmacists and changed the intravenous drug into the oral drug cefaclor capsules. Clinical pharmacists believe that once the fever has subsided and the patient is clinically stable, intravenous medication is generally changed to oral medication, which oral regimen is chosen depending on the detected or suspected causative agent of infection.
Nasopharyngeal Malignancies
The patient was evaluated as PR by review after first TPF induction chemotherapy, but the patient developed IV° myelosuppression. TAX 324 showed that TPF-induced chemotherapy had significant acute toxicity. During induction chemotherapy, severe myelosuppression presented as grade 3 or 4 neutropenia, febrile neutropenia, and neutropenic infection in 83%, 12%, and 12% of cases, respectively. Due to lung abscess, systemic intravenous chemotherapy was temporarily unavailable for the patient, and local palliative radiotherapy and targeted therapy combined with nituzumab were given priority. The pharmacist reminds the patient that the first administration of nittuzumab should be done on the first day of radiotherapy and before the start of radiotherapy. At each treatment, the nurse will give an infusion of nituzumab mixture in advance, followed by radiotherapy. Nituzumab is a monoclonal antibody that blocks EGFR from binding to its ligand and has anti-angiogenesis, anti-cell proliferation, and pro-apoptotic effects in tumors with overexpression of EGFR. Better results may be obtained when used before radiotherapy. Animal pharmacokinetic data confirmed the highest concentration in tumor tissue 24 hours after administration. Clinical pharmacists also gave the patient medication education on the use of nituzumab, and finally the patient's lesion was evaluated as PR after 20 anti-tumor treatments. The continuation of antitumor therapy during the treatment of lung abscess has been fully evaluated by clinicians and clinical pharmacists. For patients with lung abscess with underlying diseases (such as malignant tumors and immunosuppression), aggressive treatment of the primary disease is also beneficial to the prognosis of lung abscess [4]. The patient had nasopharyngeal cancer, and the antitumor treatment for him was not in conflict with the treatment of lung abscess. The clinical pharmacist also evaluated the interaction of the patient's use of the drug and agreed that the patient could be treated simultaneously for the tumor and lung abscess, and that the patient would benefit from the treatment.
Secondary Malignancy Of Cervical Lymph Nodes
For patients with locally advanced disease, active treatment of the primary tumor is critical because local disease and invasion of adjacent structures are the main causes of complications and death. Regional lymph node involvement and distant metastasis are mainly seen in advanced disease, highly aggressive histological types, or advanced disease. Cervical mass caused by cervical lymph node metastasis is one of the most common complaints of nasopharyngeal carcinoma patients [8]. The risk of lymph node metastasis varies by primary tumor site and multiple factors such as tumor size, histology, tumor depth, and perineural infiltration. Metastatic lymphadenopathy in the posterior cervical triangle is commonly associated with nasopharyngeal carcinoma. When the probability of latent metastasis exceeds 15%-20%, the risk of cervical recurrence is high with prophylactic therapy, outpacing the complications of cervical lymph node dissection and/or radiotherapy. Selective neck management (cervical lymph node dissection or radiotherapy) is generally required.