We investigated whether early circulating tumor DNA (ctDNA) changes, measured using digital PCR (dPCR), can predict later chemotherapy responses in esophageal squamous cell cancer (ESCC). We compared the dynamics of ctDNA and tumor volumes during chemotherapy in 42 ESCC. The accuracy of predictions of later chemotherapy responses were evaluated by the ratio of the variant allele frequency (VAF) of ctDNA (post-/pre-ctDNA) and the total tumor volume (post-/pre-volume) before and after an initial chemotherapy cycle using a receiver-operating characteristic curve analysis. Total positive and negative objective responses (ORs) were defined as either >50% or ≤50% reductions, respectively, in the total tumor volume at the end of first-line chemotherapy. Mutation screening of 43 tumors from 42 patients revealed 96 mutations. The pretreatment dPCR-ctDNA data were informative in 38 patients, using 70 selected mutations (1–3 per patient). The areas under the curve (AUCs) for the post-/pre-volume and post-/pre-ctDNA levels used in predicting the total OR were 0.85 and 0.88, respectively. The optimal cutoff value of post-/pre-ctDNA was 0.13. In 20 patients with post-/pre-volume ≥50%, the total OR could be predicted by the post-/pre-ctDNA with high accuracy; the AUC by post-/pre-ctDNA was higher than that by post-/pre-volume (0.85 vs 0.76, respectively). Patients with low post-/pre-ctDNA (n = 18) had a significantly better overall survival rate than those with high post-/pre-ctDNA (n = 20; P = 0.03). Early ctDNA changes after an initial cycle of chemotherapy predict later responses to treatment with high accuracy in ESCC patients.
Situs inversus totalis (SIT) is a rare congenital condition in which the abdominal and thoracic organs are on the opposite sides to their normal anatomic positions. Reports of laparoscopic surgery for colorectal cancer with SIT are very few. Due to the mirror-image transposition of organs and vascular abnormalities, laparoscopic surgery for patients with SIT is technically complicated. Therefore, it has been reported as easier for left-handed surgeons. This report presents that operative procedures can be conducted as usual by changing the positions of the operator and assistants, even if the operator is right-handed. A 71-year-old woman visited our hospital with a 2-month history of hematochezia. Colonoscopy revealed an ulcerative tumor in the sigmoid colon and biopsy confirmed well-differentiated adenocarcinoma. Laparoscopic sigmoidectomy radical lymphadenectomy was performed. The operating time was 189 minutes and blood loss was 13 mL. The patient was discharged on postoperative day 7, without any complications. We report that complicated surgical procedures for patients with SIT can be simplified by changing viewpoints. Due to the altered anatomy in SIT, the positions of the operator and assistants are very important. Location of the pelvis is almost the same as in orthotopic patients, by moving the operator from the left side to the right side of the patient. Changing the position of the operator to the right side seems to be effective for patients with SIT during pelvic procedures.
Background Circulating tumour DNA (ctDNA) is known as a tumour-specific personalised biomarker, but the mutation-selection criteria from heterogeneous tumours remain a challenge. Methods We conducted multiregional sequencing of 42 specimens from 14 colorectal tumours of 12 patients, including two double-cancer cases, to identify mutational heterogeneity to develop personalised ctDNA assays using 175 plasma samples. Results “Founder” mutations, defined as a mutation that is present in all regions of the tumour in a binary manner (i.e., present or absent), were identified in 12/14 tumours. In contrast, “truncal” mutations, which are the first mutation that occurs prior to the divergence of branches in the phylogenetic tree using variant allele frequency (VAF) as continuous variables, were identified in 12/14 tumours. Two tumours without founder and truncal mutations were hypermutators. Most founder and truncal mutations exhibited higher VAFs than “non-founder” and “branch” mutations, resulting in a high chance to be detected in ctDNA. In post-operative long-term observation for 10/12 patients, early relapse prediction, treatment efficacy and non-relapse corroboration were achievable from frequent ctDNA monitoring. Conclusions A single biopsy is sufficient to develop custom dPCR probes for monitoring tumour burden in most CRC patients. However, it may not be effective for those with hypermutated tumours.
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