Volume 102 ·  Issue 39 ·  2022

Hyperalgesia is an occult complication during the treatment of cancer pain, not only related to opioids, but also pertaining to the tumor itself and cancer therapeutic drugs. Yet it is often ignored by clinicians. Patients with cancer pain who were treated with opioids often have sensory abnormalities presented with reduced pain threshold and increased sensitivity to nociceptive stimuli. This phenomenon is clinically called opioid-induced hyperalgesia (OIH). However, due to the complexity of pathogenesis and the lack of clinical diagnostic criteria, the pain management of cancer patients is still facing great challenges. Therefore, this article focuses on the clinical diagnosis, pathogenesis, prevention and treatment of hyperalgesia related to cancer pain treatment, in order to provide a basis for optimal use of opioids in the future.

Nausea and vomiting are common adverse reactions of tumor drug therapy. With the advent of new anti-tumor drugs and antiemetic drugs, and the improvement of domestic drug accessibility, formulating timely, scientific, standardized and reasonable expert consensus on the prevention and treatment of nausea and vomiting related to cancer drug treatment is conducive to ensuring the smooth progress of cancer treatment. This consensus is based on the "Chinese Expert Consensus on the Prevention and Treatment of Nausea and Vomiting Related to Cancer Drug Treatment (2019 Edition)", based on the latest evidence-based medical evidence at home and abroad, combined with domestic clinical practice experience, and was formed by the consensus expert group through repeated discussion and consideration. The contents include consensus formulation methodology, overview of nausea and vomiting, principles for the treatment of nausea and vomiting related to cancer drugs, commonly used antiemetics and application precautions, prevention of nausea and vomiting caused by anti-tumor drugs in adults and children, and management of antiemetics in cancer patients, so as to provide professional guidance for the prevention and treatment of nausea and vomiting related to cancer drug treatment.

Stereotactic electroencephalography (SEEG) is a minimally invasive evaluation method before epilepsy surgery. Stereotactic technique is used to place intracranial electrodes, record intracranial brain electrical activity and direct electrical stimulation to determine the epileptogenic area of patients with focal epilepsy. In recent years, this technique has gradually become popular at home and abroad. In order to standardize SEEG indications, contraindications, design ideas of electrode placement scheme, operation procedures, direct electrical stimulation, result interpretation and other related issues, the consensus writing group invited authoritative experts in this field in China to discuss and form an expert consensus in China. The consensus is that SEEG is mainly used for the preoperative evaluation of drug-refractory epilepsy in which the epileptogenic area cannot be defined after non-invasive evaluation but where focal initiation is highly suspected, or where the epileptogenic area may involve functional areas. According to the results of SEEG, the epileptogenic area can be located more accurately and the surgery can be planned, or the SEEG-guided radiofrequency thermocoagulation damage (SEEG RF-TC) can be directly used as a treatment means for treatment.

To investigated the concept and clinical practice of patient-controlled analgesia (PCA) in the treatment of cancer pain.

Doctors, nurses, pharmacists from the oncology department, pain department, or hospice department were investigated using an electronic questionnaire from December 1 to December 31, 2021. In addition to the basic information, there were 26 questions were collected, including the current situation of cancer pain treatment, the concept of medical staff on PCA treatment of cancer pain and the clinical practice of PCA.

Questionnaires from 2 872 medical staff were collected from 993 hospitals in 30 provincial administrative units. Only 34.8% (955/2 748) of medical staff considered that the satisfaction rate of cancer pain control was over 75%, and 27.9% (548/1 968) of medical staff convinced that the satisfaction rate of breakthrough pain control was less than 50%. 97.1% (2 439/2 513) of medical staff considered that PCA could be effectively used for cancer pain treatment. The proportion of medical staff in secondary and tertiary hospitals who thought that PCA was applicable to cancer pain that could not be effectively alleviated by standardized non-invasive drug administration was 64.6% (319/494) and 69.1% (1 262/1 826) respectively, which was higher than that in primary hospitals [57.0% (110/193)] (P=0.002). In different occupations, the proportion of nurses who convinced PCA treatment of cancer pain increased the risk of addiction and drug overdose was 62.8% (431/686) and 76.1% (522/686), respectively, which was higher than doctors [39.2% (670/1709) and 58.2% (995/1709), respectively] and pharmacists [49.2% (58/118) and 65.3% (77/118), respectively] (allP<0.001). There was no significant difference in type of pump, route of administration, mode of infusion, protocol for PCA administration and selection of common medication in PCA treatment of cancer pain among different hospitals (allP>0.05). The calculation of continuous infusion dose and rescue dose of PCA was not uniform among different hospitals. After initiation of PCA, 71.7% (1 226/1 709) of hospitals had insufficient analgesia and most of them needed to be adjusted for 1-3 times to achieve satisfactory analgesia.

Medical staff have insufficient cognition of PCA treatment of cancer pain and there is a lack of unified guidance in clinical practice. Therefore, it is an urgent need to develop an expert consensus on PCA treatment of cancer pain.

To investigate the effect of CD4-positive T lymphocyte expression rate on the pain control and prognosis of stage Ⅳ non-small cell lung cancer (NSCLC) patients with cancerous pain.

The clinical data of 128 stage Ⅳ NSCLC patients with cancerous pain who were admitted to the Affiliated Cancer Hospital of Zhengzhou University from January to December 2020 were retrospectively analyzed, including 92 males and 36 females, with a male-to-female ratio of 23∶9 and an average age of (56±21) years old. The expression rate of CD4-positive T lymphocytes in peripheral blood was routinely detected on admission, and the expression rate of CD4-positive T lymphocytes ≥45% was defined as the CD4 high expression group, and<45% was defined as the low expression group. The differences in the time required for pain control, the dosage of opioids and the incidence of adverse reactions between the two groups were compared and analyzed. Survival analysis was performed by Kaplan-Meier method, and the overall survival (OS) time and progression-free survival (PFS) time of the two groups were calculated. Cox regression model was used to analyze the influencing factors of patients′ OS time and PFS time.

The median time required for pain control in the high CD4 expression group [M (Q₁, Q₃)] was 18.6 (4.6, 21.5) h, which was lower than that in the low CD4 expression group [28.2 (7.1, 38.9) h] (P=0.012). The dosage of morphine in the CD4 high expression group [M (Q₁, Q₃)] was 88.6 (42.5, 295.0) mg, which was lower than that in the low expression group [145.8 (82.5, 442.5) mg] (P=0.010). There was no significant difference in the incidence of adverse reactions such as nausea and vomiting, constipation, urinary retention, intestinal obstruction, and respiratory depression between the two groups (all P>0.05). The OS time and PFS time in the CD4 high expression group [M (Q₁, Q₃)] were 12.5 (8.1, 13.8) months and 8.5(3.1, 9.4) months, respectively, which were higher than those in the CD4 low expression group [8.6 (4.1, 12.9) months and 6.5 (2.1, 7.9) months, respectively] (allP<0.01). Cox multivariate analysis showed that high expression of CD4 was a protective factor affecting OS (HR=0.876, 95%CI: 1.224-6.641, P=0.004) and PFS (HR=0.675, 95%CI: 1.742-5.930, P=0.031)

The stage Ⅳ NSCLC patients with cancerous pain and high expression of CD4-positive T lymphocytes have shorter pain control time, less morphine dosage, and longer OS and PFS time.

To establish the quality evaluation criteria for out-patient medical records of cancer pain and evaluate the effect of its application.

The evaluation criterion was established based on Delphi method for out-patient medical records of cancer pain in the Affiliated Huai′an No.1 People′s Hospital of Nanjing Medical University. Firstly, the weight of each evaluation indicator was calculated by the method of Attribute Hierarchical Model in combination with technique for order preference by similarity to solution (AHM-TOPSIS), and out-patient medical records of 50 cancer pain patients (group A, 150 records) received in June 2020 were assessed comprehensively. Secondly, the relative closeness (Ci value) between the writing quality and the ideal solution was calculated, as well as the proportion of evaluation indicators which were lack of standardization. Thirdly, the corresponding countermeasures were adapted based on the results of assessment. Finally, another 50 medical records (156 records) received in October 2021 were re-evaluated by the same method, and the differences of quality of medical record and proportion of each evaluation indicator which was lack of standardization before and after the intervention were compared.

A specific criterion which contained integrity of materials required for the medical records, documents of the complaints and medical history of cancer pain, description of the previous medical treatment for cancer pain, regular assessment of cancer pain and its′ document, quantitative assessment and its′ document, comprehensive assessment and its′ document, dynamic assessment and its′ document, reasonable of pain medication, reasonable of the drug usage and dosage, reasonable adjustment of the drug variety or dosage, prevention of adverse reactions of analgesic drugs and its′ document, evaluation and management of adverse reactions of analgesic drugs and its′ document (12 indicators) was established to evaluate the out-patient medical records of cancer pain. The proportion of medical records which Ci≥0.6 was 62.0% (93/150) in group A before the intervention. It was increased to 84.6% (132/156) in group B after the intervention and the difference was statistically significant (P<0.001). Furthermore, the proportions of comprehensive assessment of cancer pain which were lack of standardization, prevention of adverse reaction, quantitative evaluation and dynamic assessment of cancer pain accounted for a higher level, which was 64.0% (96/150), 55.3% (83/150), 54.7% (93/150) and 52.7% (79/150) respectively in group A before the intervention. However, proportions of such records were decreased to 50.6% (79/156), 35.9% (56/156), 32.1% (50/156) and 39.7% (62/156) respectively in group B after the intervention and the differences were statistically significant (allP<0.05).

A specific quality evaluation criterion is established based on Delphi method and AHM-TOPSIS for the out-patient medical records of cancer pain. The quality of medical records has been improved in a certain level after adapting comprehensive evaluation and intervention on the out-patient medical records of cancer pain.

To investigate the impact of the dosage of intraoperative opioids on postoperative survival of pancreatic cancer patients who underwent pancreatectomy.

The clinical data of 95 patients with pancreatic cancer who underwent pancreatectomy at Harbin Medical University Cancer Hospital from September 2013 to August 2018 were retrospectively collected. Dosage of intraoperative opioid medications was converted to fentanyl equivalent dose. Patients were divided into high-dose group (fentanyl consumption ≥2.21 mg, n=46) and low-dose group (fentanyl consumption<2.21 mg,n=49) according to the median intra-operative fentanyl equivalents. The relapse-free survival (RFS) and overall survival (OS) between the two groups were compared. Cox proportional hazards regression model was used to analyze the impact of important covariates on RFS and OS.

RFS of patients in low-dose group at 1, 3 and 5 years was 75.5%, 26.5% and 15.2% respectively. OS of patients in low-dose group at 1, 3 and 5 years was 77.6%, 32.5% and 24.4% respectively. RFS of patients in high-dose group at 1, 3 and 5 years was 76.1%, 23.9% and 12.0% respectively. OS of patients in high-dose group at 1, 3 and 5 years was 76.1%, 37.0% and 15.0%. There was no significant difference in RFS and OS between the two groups (all P>0.05). Multivariate Cox analysis showed that dosage of intraoperative fentanyl was not associated with RFS (HR=1.205, 95%CI: 0.737-1.970, P=0.456) or OS (HR=1.062, 95%CI: 0.634-1.778, P=0.818).

Dosage of intraoperative opioid has no effect on RFS and OS in pancreatic cancer patients undergoing pancreatectomy.

To evaluate the safety and feasibility of robotic-assisted thoracoscopic day surgery for pulmonary nodules.

Clinical data of 523 patients with pulmonary nodule underwent robotic-assisted thoracoscopic surgery in the Department of Thoracic Surgery, Xiangya Hospital, Central South University from January 2021 to June 2022 were retrospectively analyzed, which including 223 males and 300 females, aged from 19 to 72 (54.0±11.7) years. Those patients were divided into the day surgery group (DSG) and inpatient surgery group (ISG) according to perioperative management methods. Propensity score matching (PSM) (1∶2) was performed according to the general baseline information, T stage of the tumor, surgery approach, and tumor position, and a total of 178 patients were finally included. Clinical outcomes of DSG were observed. The differences in incidence of postoperative complications, treatment-related costs and resource consumption between DSG and ISG were compared. Subgroup analysis was performed according to surgery method to evaluate the difference between DSG and ISG in lobectomy and sublobectomy.

In 81 cases DSG, eight patients were transferred to thoracic surgery ward, and the day surgery discharge rate was 90% (73/81). There was no statistically significant difference in incidence of postoperative complications between DSG and ISG (P=0.612). The length of stay after surgery, period of chest draining, average hospital cost, and drug cost of DSG were statistically significant lower than ISG, ((2.19±0.84) vs (4.74±1.81) days, (1.70±0.65) vs (3.45±1.85) days, (6.64±0.74) vs (8.29±0.97)×10⁴ CNY, (0.35±0.07) vs (0.69±0.18)×10⁴ CNY), respectively(all P<0.05). The drainage volume and VAS score at discharge in DSG and ISG group were(220.47±120.02) ml and(242.21±129.96) ml, 1.68±0.79 and 1.64±0.91, respectively, with no statistically significant difference (P>0.05). In subgroup analysis, there was no statistically significant difference in incidence of postoperative complications, drainage volume after surgery and VAS score at discharge between DSG and ISG both for lobectomy and sublobectomy patients. And the results of the length of stay after surgery, period of chest draining, and drug cost in DSG were also significantly lower than ISG (P<0.05).

Robotic-assisted thoracoscopic day surgery for pulmonary nodule is safe and feasible, with the advantage of short length of stay after surgery, short period of chest draining, less average hospital cost and drug cost. There is no difference in incidence of postoperative complications between DSG and ISG.

To observe the lipid metabolism characteristics of tumor-associated macrophages (TAM) after malignant transformation in the glioma micro-environment, and analyze the biological phenotype changes and regulatory mechanisms after inhibiting the lipid metabolism remodeling.

Twelve male Balb/c mice of 6-8 weeks were used in the study. Macrophages (Mφ) were derived from mouse bone marrow, and malignantly transformed macrophages (tMφ₁ and tMφ₂) were cloned from the model of glioma stem cell (GSC) through interaction with Mφ in vivo and in vitro. Intracellular lipid droplet formation and cellular cholesterol content were measured respectively in Mφ, tMφ₁ and tMφ₂. qRT-PCR was performed to detect the genes expression level related with lipid metabolism, including sterol regulatory element binding protein (SREBP), fatty acid synthase (FASN), and 3-hydroxy-3-methylglutarate monoacyl coenzyme A reductase (HMG-CoA). Simvastatin (SIM) was used to analyze the proliferation, immigration and invasiveness ability in tMφ₁ and tMφ₂ after inhibition of the lipid metabolism. Differential expression profiles of miRNAs after SIM treatment were constructed in t-Mφ₁ and bio-informatics analysis was screened and verified for miR449a and its target gene sorting micro-tubule connectin 17 (SNX17) associated with lipid metabolism remodeling. The effect on SNX17 by up-regulated miR-449a were analyzed by qRT-PCR and Western blot, meanwhile, the biological phenotype and cholesterol content were observed after up-regulation of miR449a. Low-density lipoprotein receptor (LDLR) protein levels after SNX17 knockdown and intracellular cholesterol content after LDLR knockdown were detected respectively.

The numbers of intracellular lipid droplet formation in tMφ₁ and tMφ₂ were more than that in Mφ (P<0.001). Likewise, the relative contents of cholesterol (3.89±0.68 and 3.56±0.53), SREBP (4.78±0.60 and 2.84±0.41), FASN (4.65±0.70 and 3.01±0.45), and HMG-CoA (5.74±0.55 and 2.97±0.34) were significantly higher in tMφ₁ and tMφ₂ than those of Mφ (1.01 wel, 1.02 wel and 0.99 wel, respectively) (all P<0.001). The proliferation rates of tMφ₁ and tMφ₂ decreased from (47.06±5.88) % and (45.29±5.64)% to (23.53±4.70)% and (18.74±5.76)%, respectively after treatment with SIM (both P<0.05). The numbers of migrated cells decreased from 1 025±138 and 350±47 to 205±63 and 99±25, respectively (bothP<0.001). And the numbers of invasiveness cells decreased from 919±45 and 527±34 to 220±23 and 114±21, respectively (bothP<0.001). While the relative intracellular cholesterol content decreased to 0.52±0.08 and 0.58±0.07 (bothP<0.05), respectively. MiR-449a was screened from tMφ₁ by SIM, and the target gene was analyzed and verified to be SNX17. SNX17 expression was down-regulated, and the proliferation rate, the number of migration and invasiveness was significantly decreased after miR-449a over-expression (all P<0.05). Low-density lipoprotein receptor (LDLR) expression was down-regulated after knock-down of SNX17, while the cholesterol content was decreased after knock-down of LDLR in tMφ₁ and tMφ₂ (all P<0.05).

Malignantly transformed TAMs undergo lipid metabolism remodeling characterized with enhanced lipid metabolism. MiR-449a regulates the LDLR by targeting SNX17, thereby affecting the lipid metabolism of malignantly transformed macrophages, and subsequently inhibiting its proliferation, migration, and invasion ability. Precise intervention with miR-449a/SNX17/LDLR axis could provide an experimental basis for reversing its tumor-promoting micro-environment remodeled by GSC through metabolic intervention.

Refractor esophageal stenosis after endoscopic submucosal dissection of early esophageal carcinoma is a difficult clinical problem. To verify the effect of endoscopic radial incision combined local triamcinolone injection to treat refractory esophageal stenosis, we retrospectively analyzed 7 patients diagnosed with refractory esophageal stricture after endoscopic mucosal dissection of early esophageal cancer in this study, of whom 4 male and 3 female patients, aged 50-76 years, with the mean age of 63 years. We performed the endoscopic radial incision in the thickness point of the scar stricture and injected the triamcinolone locally. The results showed it was safe and effective. The follow-up showed no esophageal stenosis occured and no adverse reaction such as hemorrhage, perforation, tumor-recurrence and triamcinolone-allergy occured.

This article reported the clinical experience of diagnosis and treatment for two patients with lymphomatosis cerebri. Case 1 was female and aged 53 years old, while case 2 was male and aged 69 years old. Progressive cognitive impairment was the main clinical manifestation in both patients. Brain magnetic resonance imaging (MRI) suggested leukoencephalopathy with patchy or mass enhancement. Cerebral blood flow was reduced on perfusion imaging in one patient. Brain biopsy confirmed diffuse large B-cell lymphoma in both cases. The concentration of interleukin-10 in cerebrospinal fluid (CSF) of two patients was significantly increased, however, the result of CSF flow cytology was negative. The current study suggests that interleukin-10 in CSF is an important biological indicator for the diagnosis of lymphomatosis cerebri, but CSF flow cytometry may not be helpful. Moreover, cerebral hypoperfusion can be present in patients with lymphomatosis cerebri.

Childhood cancer pain is a long-neglected problem. There is a lack of relevant clinical research. Pharmaceutical companies rarely develop preparations separately for this special group during drug development, and often adjust them directly from the treatment plan of adults. At present, the management of childhood cancer-related pain is mainly based on the WHO's 2012 edition of the Guidelines for the Diagnosis and Treatment of Children's Chronic Pain, which deletes the previous recommendation of weak opioids such as tramadol and codeine for children's chronic pain, and emphasizes the direct application of strong opioid morphine when the first-step drugs such as acetaminophen and ibuprofen are not effective. Morphine has a definite analgesic effect and is the "gold standard" for the treatment of acute and chronic severe pain in children. However, for patients who cannot tolerate the adverse reactions of morphine, the current guidelines lack relevant drug recommendations, resulting in a "gap" in pain management. Nalbuphine is a suitable drug to fill this "gap". Nalbuphine is an agonist antagonist of opioid receptors, which agonizes kappa receptors and antagonizes mu receptors. Agonizing kappa receptors makes nalbuphine have a strong analgesic effect, and its antagonistic effect on mu receptors can be used to reverse the adverse reactions of systemic and epidural use of opioids: pruritus, urinary retention or respiratory depression, etc. At the same time, it also leads to its analgesic efficacy is not as good as strong opioids such as morphine, and it has a "ceiling effect", so it is included in the category of intermediate-acting opioids.

Due to the high tolerability of long-term use of methadone, providing adequate pain management is a daunting challenge for this group of patients. Accumulating preclinical and clinical evidence suggests that repeated opioid exposure can catalyze a range of counteranalgesic processes and adverse reactions, including nociceptive sensitization (i.e. hyperalgesia), tolerance, and loss of opioid efficacy. The treatment of acute pain is a particularly intractable problem in patients with methadone maintenance. Previous studies have shown that it is difficult to obtain adequate analgesia even after taking large doses of opioids and non-opioids such as morphine, additional doses of methadone and gabapentin. Hydromorphone, a complete μ-opioid receptor agonist commonly used to treat moderate to severe pain, is considered a promising pharmacotherapeutic strategy to overcome these barriers. In studies of non-opioid tolerance, intravenous administration of 1 to 2 mg hydromorphone was found to provide significant analgesic effects. A recently published buprenorphine-maintained study evaluating the analgesic effect of intravenous hydromorphone provides preliminary evidence that intravenous administration of at least 16 mg of hydromorphone is necessary to maintain clinical pain management in patients with 12 to 16 mg/d sublingual buprenorphine/naloxone. The primary objective of this study was to evaluate the dose effect of hydromorphone compared to placebo in reducing acute pain responses in patients maintaining medium to high doses of oral methadone (80 to 100 mg/d) and to assess concurrent abuse liability for increasing hydromorphone doses, assuming that hydromorphone provides better analgesia than placebo at all time points. This randomized controlled study evaluated the analgesic and abuse propensity effects of escalating doses of acute intravenous hydromorphone versus placebo using a validated experimental pain paradigm, the Quantitative Sensory Test (QST). Patients without chronic pain (n=8) Maintain oral methadone 80~100 mg/d. Participants received 4 intravenous injections over 1 trial day with increasing escalating doses of hydromorphone (32 mg total) or 4 placebo doses over 270 min. Test times are at least 1 week apart. QST and abuse liability measures were performed at baseline and after each injection. There was no statistically significant difference between the hydromorphone and placebo groups in the analgesia index of any QST outcome. Similarly, despite the use of high doses of hydromorphone, there were no statistically significant differences in safety or abuse liability index. The incidence of adverse events was low and the severity of re-reported adverse events was mild.