Radiotherapy is a definitive treatment for early-stage cervical cancer; however, a subset of this disease recurs locally, necessitating establishment of predictive biomarkers and treatment strategies. To address this issue, we performed gene panel-based sequencing of 18 stage IB cervical cancers treated with definitive radiotherapy, including two cases of local recurrence, followed by in vitro and in silico analyses. Simultaneous mutations in KRAS and SMAD4 (KRASmt/SMAD4mt) were detected only in a local recurrence case, indicating potential association of this mutation signature with radioresistance. In isogenic cell-based experiments, a combination of activating KRAS mutation and SMAD4 deficiency led to X-ray resistance, whereas either of these factors alone did not. Analysis of genomic data from 55,308 cancers showed a significant trend toward co-occurrence of mutations in KRAS and SMAD4. Gene Set Enrichment Analysis of the Cancer Cell Line Encyclopedia dataset suggested upregulation of the pathways involved in epithelial mesenchymal transition and inflammatory responses in KRASmt/SMAD4mt cancer cells. Notably, irradiation with therapeutic carbon ions led to robust killing of X-ray-resistant KRASmt/SMAD4mt cancer cells. These data indicate that the KRASmt/SMAD4mt signature is a potential predictor of radioresistance, and that carbon ion radiotherapy is a potential option to treat early-stage cervical cancers with the KRASmt/SMAD4mt signature.

The elevation of the serum squamous cell carcinoma (SCC) antigen unrelated to disease progression occurs during the follow-up of patients with cervical cancer treated with radiotherapy. Although known empirically, the incidence and characteristics of this non-cancer specific elevation in SCC remain unclear. Here, we examined the post-treatment kinetics of SCC in 143 consecutive patients with squamous cell carcinoma of the cervix treated with definitive radiotherapy; in all patients, progression-free disease status was confirmed by periodic monitoring for at least 36 months (median, 61 months). We found that the 5-year cumulative incidence of post-treatment SCC elevation was unexpectedly high at 37.3% (59/143 patients), and that 59.3% (35/59) of event-positive patients experienced multiple events. The median peak SCC level for a given event was 2.0 ng/mL (interquartile range, 1.7–2.9 ng/mL). The multivariate analysis showed that renal dysfunction was associated significantly with a greater incidence of SCC elevation (p = 0.046). In addition, the 5-year cumulative incidence of SCC elevation was significantly greater in patients with renal dysfunction than in those without (54.8% vs. 32.9%, respectively; hazard ratio, 2.1 [95% confidence interval, 1.1–4.2]; p = 0.028). These data will be useful for monitoring cervical cancer patients treated with radiotherapy.

Laparoscopic hysterectomy is widely performed in obese patients in Japan; however few studies have reported on laparoscopic surgery in patients with severe obesity (body mass index [BMI] > 35 kg/m 2 ). Here, we share our experience of performing laparoscopic hysterectomy for endometrial carcinoma in a patient with severe obesity and a giant thyroid tumor. Our patient was a 69-year-old woman (height 151 cm, weight 104 kg [BMI 45 kg/m 2 ]) with a history of hypertension, diabetes mellitus, and hyperlipidemia and appendectomy, who presented with endometrial cancer and a thyroid tumor.Endometrial biopsy findings revealed carcinosarcoma and magnetic resonance imaging showed an endometrial tumor without myometrial or cervical stromal invasion, with uterine adnexal metastasis. Computed tomography revealed a giant thyroid tumor in the left lobe (82 mm) with bronchial compression, but no lymphadenopathy. Fine needle aspiration cytology revealed a benign thyroid tumor. Because of severe obesity and a giant thyroid tumor, we performed laparoscopic hysterectomy and concomitant thyroidectomy. We initially performed thyroidectomy under general anesthesia using tracheal intubation (tube diameter: 6 mm) in the supine position, followed by laparoscopic hysterectomy using tracheal intubation (tube diameter: 7 mm) with the patient placed in the Trendelenburg position. After the surgery, the patient was admitted in the intensive care unit for only one day, and after an uneventful course, was discharged on day 5 postoperatively. Adjuvant chemotherapy for endometrial cancer was initiated at 1 month postoperatively. This report highlights that laparoscopic hysterectomy can reduce perioperative complications and enable prompt initiation of adjuvant chemotherapy in patients with severe obesity. Thus, obesity and comorbidities are not contraindications for laparoscopic surgery.

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