Naldemedine-induced opioid withdrawal syndrome with severe psychiatric symptoms in an advanced cervical cancer patient without brain metastasis

Objective Naldemedine, an oral peripheral μ-opioid receptor antagonist, was developed for the treatment of constipation, a side effect of opioid use. Naldemedine is not generally recognized as causing opioid withdrawal in which associated symptoms affecting the central nervous system. Method From the series of cancer patients undergoing symptom management, we report a case treated with naldemedine for constipation in relation to the use of opioids for cancer pain and who displayed severe psychological symptoms associated with withdrawal immediately after the use of naldemedine. Results The patient was a 36-year-old woman diagnosed with cervical cancer Stage IIB, PS3. When the patient, who was using oxycodone hydrochloride hydrate (80 mg/day) for ileal pain, was started on naldemedine for constipation, she complained of sweating after just 5 min and hallucinations after 1 h. The patient also displayed physical/behavioral abnormalities such as diarrhea and hyperactivity, and psychological abnormalities such as aggression toward staff. Despite the psychiatric symptoms worsening over time, there were no abnormalities in terms of blood biochemical data, and no brain metastasis was observed on MRI. Based on the Clinical Opiate Withdrawal Scale, these symptoms were judged to indicate opioid withdrawal. Naldemedine was discontinued due to naldemedine-related opioid withdrawal syndrome and, thereafter, the psychiatric symptoms diminished, with no recurrence of similar symptoms observed to date. Significance of results If mental and behavioral abnormalities occur in patients receiving naldemedine, it is necessary to consider the possibility of opioid withdrawal syndrome as a differential diagnosis.

Development and Feasibility of a Patient-Derived Training Simulator for Image-Guided Adaptive Brachytherapy of Locally Advanced Cervical Cancers

Background Image-guided adaptive brachytherapy (IGABT) plays a pivotal role in definitive radiotherapy of cervical cancer. Although the combination of a tandem and ovoid applicator with interstitial needles (IC/IS brachytherapy) is an efficient IGABT technique for bulky irregular-shaped tumors, training opportunities for IC/IS brachytherapy remain limited. Thus, we developed a training simulator for IC/IS brachytherapy for locally advanced cervical cancer and tested its feasibility. Methods The training simulator combined a patient-derived soft silicone tumor phantom with an acrylic tube mimicking the vagina. The tumor phantom was modeled on a cervical cancer patient treated with IGABT at our institute between 2012–2020, through detailed inspection of their three-dimensional (3D) high-risk clinical target volume (HR-CTV) at the first brachytherapy session. A true-scale tumor phantom was created from the HR-CTV data using 3D-printing. The feasibility of the training simulator was investigated by comparing treatment plans between the following six sessions (sessions #1–#3, with a Fletcher-Suit Asian Pacific applicator; #4–#6, with a Venezia applicator): in sessions #1 and #4, an expert inserted a tandem and ovoids (T&O); in sessions #2 and #5, a resident inserted a T&O plus four needles; and in sessions #3 and #6, an expert inserted a T&O plus four needles. At each session, the highest possible dose was prescribed to the HR-CTV while keeping the D2cc of the rectum and bladder (derived from the model case) below 6 and 7.6 Gy, respectively. Results The training simulator was developed using the HR-CTV data of a FIGO stage IIIB tumor (68 ⋅ 49 ⋅ 45 mm) selected from one of 495 candidates. The feasibility tests with a Fletcher-Suit Asian Pacific applicator resulted in HR-CTV D90 of 4.23, 5.69, and 6.70 Gy for sessions #1, #2, and #3, respectively. With a Venezia applicator, HR-CTV D90 was 4.16, 6.20, and 6.45 Gy for sessions #4, #5, and #6, respectively. Conclusions The tumor phantom was a good representation that resulted in various HR-CTV D90 doses depending on the physician’s experience and applicator type. Further evaluation of the training simulator is warranted to confirm its educational value for IC/IS brachytherapy for locally advanced cervical cancer.

Case Report: A Case Report and Literature Review on Severe Bullous Skin Reaction Induced by anti-PD-1 Immunotherapy in a Cervical Cancer Patient

Background: Anti-programmed cell death protein 1 (PD-1) has been successfully used in carcinomas treatment. However, it causes significant adverse effects (AEs), including cutaneous reactions, particularly the life-threatening severe bullous skin reactions (SBSR) and toxic epidermal necrolysis (TEN).Case summary: Herein, we described for the first time a case report of SBSR induced by anti-PD-1 therapy in a cervical cancer patient. In addition, we revised existing literature on anti-PD-1 induced cutaneous reactions. We reported a cervical cancer patient who was treated with four successive cycles of Sintilimab and Toripalimab injections and developed systemic rashes, bullae, and epidermal desquamation, which worsened and led to infection, eventually causing death after being unresponsive to aggressive treatments.Conclusion: Anti-PD-1 antibodies commonly cause skin toxicity effects, some of which may be deadly. Therefore, healthcare providers should observe early symptoms and administer proper treatment to prevent aggravation of symptoms.

Cervical Cancer Metastasis and Recurrence Risk Prediction Based on Deep Convolutional Neural Network

Background: Evaluating the risk of metastasis and recurrence of a cervical cancer patient is critical for appropriate adjuvant therapy. However, current risk assessment models usually involve the testing of tens to thousands of genes from patients’ tissue samples, which is expensive and time-consuming. Therefore, computer-aided diagnosis and prognosis prediction based on hematoxylin and eosin (H&E) pathological images have received much attention recently. Objective: The prognosis of whether patients will have metastasis and recurrence can support accurate treatment for patients in advance and help reduce patient loss. It is also important for guiding treatment after surgery to be able to quickly and accurately predict the risk of metastasis and recurrence of a cervical cancer patient. Method: To address this problem, we propose a hybrid method. Transfer learning is used to extract features, and it is combined with traditional machine learning in order to analyze and determine whether or not patients have the risks of metastasis and recurrence. First, the proposed model retrieved relevant patches using a color-based method from Hamp;E pathological images, which were then subjected to image preprocessing steps such as image normalization and color homogenization. Based on the labeled patched images, the Xception model with good classification performance was selected, and deep features of patched pathological images were automatically extracted with transfer learning. After that, the extracted features were combined to train a random forest model to predict the label of a new patched image. Finally, a majority voting method was developed to predict the metastasis and recurrence risk of a patient based on the predictions of patched images from the whole-slide H&E image. Results and Conclusion: In our experiment, the proposed model yielded an area under the receiver operating characteristic curve of 0.82 for the whole-slide image. The experimental results showed that the high-level features extracted by the deep convolutional neural network from the whole-slide image could be used to predict the risk of recurrence and metastasis after surgical resection and help identify patients who might receive additional benefit from adjuvant therapy.

Comparison of mental burden across different types of cancer patients in Nepal: a special focus on cervical cancer patients

PurposeThe purpose of the study is to assess the differential impact of gender and cancer sites on mental burden across different types of cancer and control patients.Design/methodology/approachThe paper is based on a primary survey undertaken in 2015–2016 of 600 cancer and 200 control patients across five hospitals of Nepal. The data was analyzed using propensity score matching methods and treatment effect weighting estimators.FindingsThe authors find that of all the types of patients covered under this study, cervical cancer patients suffered from a greater intensity of anxiety and lack of functional wellbeing. On an average, all other female, male cancer patients, and control patients experience significantly lower intensity of mental burden in the range of 1.83, 2.63 and 3.31, respectively when compared to patients of cervical cancer. The results are robust across all the four treatment effect estimators and through all the measures of mental burden. The implications of suffering from cervical cancer, as a unique gynecological cancer was studied in-depth. An effect size analysis pointed out to the dysfunctional familial relationship as additional causes of concern for cervical cancer patients.Originality/valueAn important finding that emerged is that female cancer patients especially those who have cervical cancer should be given special attention because they appear to be the most vulnerable group. Further work is needed to delineate the reasons behind a cervical cancer patient facing higher amount of stress.

Long Term Assessment for Delayed Toxicities of Radiotherapy for Cervical Cancer Patient with Systemic Lupus Erythematosus

Using Radiation in patients with systemic lupus erythematosus (SLE), especially if discoid lesions are present within the radiation field, is associated with modest increase in the risk of acute and delayed toxicity. Thus, its use is relatively contraindicated. Here-in we describe a patient with active SLE and grade 4 renal dysfunction who presented with locally advanced cervical cancer Radiologically stage IIB (by CT and MRI), was treated with radiotherapy alone using intensity modulated radiotherapy (IMRT) in 2008. Patient did not experience any grade 3 or 4 acute toxicities which were reported before. Over the last ten years of follow up she did not experience any delayed toxicity, which supports the patient adapted radiotherapy with novel radiation therapy techniques. Keywords: Pelvic radiotherapy, SLE, Acute and late toxicity