TAS-102 (trifluridine/tipiracil) plus bevacizumab versus TAS-102 alone as salvage treatment options for metastatic colorectal cancer in routine clinical practice.

Introduction: Both regimens of TAS-102 (trifluridine/tipiracil) with and without bevacizumab are considered standard options for salvage treatment in patients with refractory metastatic colorectal cancer. Materials and methods: This analysis included patients with metastatic colorectal cancer who received either TAS-102 plus bevacizumab or TAS-102 alone between July 2022 and November 2023 at Samsung Medical Center. We evaluated the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety profile of both regimens. Results: In total, 139 patients were included in this analysis. Median age was 60.8 years, and median number of previous lines of therapy was four (range: 2.45-6.55). More than half of the subjects (56.8%) had RAS mutations and 92.9% received previous anti-VEGF therapy. 83 (59.7%) patients received the combination of TAS-102 and bevacizumab and 56 (40.3%) received TAS-102 alone. The number of patients with prior regorafenib treatment was 14 in the TAS-102 with bevacizumab group and 5 in the TAS-102 alone group. The disease control rate was 51.8% in the combination group and 32.1% in the TAS-102 alone group. The median PFS was 3.3 months (95% CI, 2.7-6.6) in the combination group and 2.5 months (95% CI, 2.0-3.8) in the TAS-102 alone group (HR, 0.56; 95% CI, 0.38-0.82; p=0.003). The median OS in these two groups was 10.8 months (95% CI, 8.4-NA) and 6.0 months (95% CI, 4.8-9.8), respectively (HR, 0.62; 95% CI, 0.40-0.97, p=0.033). In the exploratory analysis of TAS-102 + Bev group, patients with the KRAS G12 mutation had inferior OS compared to those without the mutation (HR, 2.01, 95% CI, 1.04-3.90, p=0.035). Commonly observed adverse events were hematologic-related, including neutropenia, anemia, and thrombocytopenia, as well as nausea. While any grade neutropenia was observed at similar frequencies in the two groups (57.8% and 57.1%), grade 3 or higher neutropenia was more frequent in the combination group than the TAS-102 alone group (31.3% vs. 17.9%). Among patients who received subsequent anticancer therapy after treatment failure, 74.1% received regorafenib. Conclusions: The combination of TAS-102 and bevacizumab resulted in a better survival outcome than TAS-102 monotherapy, consistent with previous studies. This analysis supports the use of the combination of TAS-102 and bevacizumab as the best therapeutic option for patients with refractory metastatic colorectal cancer in clinical practice.

Fruquintinib in refractory metastatic colorectal cancer: a multicenter real-world study.

BACKGROUND: Fruquintinib has been approved by the Food and Drug Administration for refractory metastatic colorectal cancer (mCRC). In clinical practice, fruquintinib is sometimes used in combination with other drugs, but its efficacy and safety are still unknown. In this study, we present a comprehensive analysis of the real-world treatment modalities involving fruquintinib in late-line settings for mCRC across six centers in China. PATIENTS AND METHODS: Patients with refractory mCRC who received fruquintinib treatment in six centers in China between 1 January 2021 and 31 June 2022 were included in this study. Patients were categorized into two cohorts: the monotherapy group (treated solely with fruquintinib) and the combined group (received fruquintinib combined with chemotherapy and/or anti-programmed cell death protein 1 antibodies). Demographic, clinical, survival, and safety data were retrospectively analyzed. The study was registered at clinicaltrials.gov as NCT06202417. RESULTS: A total of 520 patients were included in this study. The median follow-up time was 9.7 months. The disease control rate was 64.8%. The median progression-free survival was 5.0 months and the median overall survival was 11.4 months. Of them, 387 (74.4%) were treated with fruquintinib alone, while 133 (25.6%) were administered fruquintinib plus chemotherapy and/or anti-programmed cell death protein 1 antibodies, respectively. Adverse events were reported by 91.3% (457/520) of patients. The rate of grade 3 or 4 toxicity was 42.4% (237/520). No treatment-related death occurred. CONCLUSION: Fruquintinib, either as a standalone treatment or in combination with other medications, demonstrates substantial efficacy and favorable tolerability in refractory mCRC patients.

Feasibility of endoscopic resection for superficial laryngopharyngeal cancer after radiotherapy.

BACKGROUND AND AIM: We aimed to elucidate the feasibility of endoscopic resection (ER) for salvage and metachronous lesions following chemoradiotherapy (CRT) and radiotherapy (RT) for laryngopharyngeal cancer. METHODS: Consecutive patients who underwent ER for superficial laryngopharyngeal cancer between March 2005 and September 2022 were retrospectively reviewed and stratified into salvage (16 patients, 16 lesions), metachronous (18 patients, 27 lesions), and naïve RT (217 patients, 306 lesions) groups. Salvage lesions were residual or local recurrent after CRT, and metachronous lesions were second primary lesions in the irradiated field following complete response. Short-term outcomes were evaluated, including R0 resection, en bloc resection, procedure time, adverse events, local recurrence rate, and clinical course. RESULTS: The en bloc resection rates were 88%, 93%, and 88%; R0 resection rates were 50%, 52%, and 56%; procedure times were 25, 27, and 25 min, in the salvage, metachronous, and naïve RT groups, none of which were significantly different among the three groups. Although adverse event rates tended to be higher in the salvage and metachronous groups than in the naïve RT group, the differences were not significant (18%, 15%, and 8%). The cumulative local recurrence rates at 2 years were 21%, 13%, and 6%, significantly higher in the salvage group than in the naïve RT group. The local control rates with ER alone were 94%, 93%, and 97%; none were significantly different among the three groups. CONCLUSION: ER for salvage and metachronous superficial lesions can be safely performed, suggesting its acceptability as a minimally invasive treatment.

Acupuncture for Meige syndrome: A case report.

INTRODUCTION: Meige syndrome (MS) is a cranial dystonia disorder characterized by blepharospasm and oromandibular dystonia. Current treatments include botulinum toxin therapy, oral medications, and surgical interventions. Here, we present a case that the patient's symptoms improved significantly after treatment with acupuncture. CASE DESCRIPTION: A 72-year-old woman came to our acupuncture clinic with eyelid twitching and jaw muscle tension. She described being diagnosed with MS two years ago due to the same symptoms, and her symptoms gradually worsened over the past six months. After 4 weeks of acupuncture treatment, the patient's MS symptoms improved significantly. CONCLUSION: Acupuncture may be a potentially salvage treatment option for MS.

Clinical significance of positive resection margin for patients with rectal neuroendocrine tumors within 20 mm following initial endoscopic resection: A multi-center study.

BACKGROUND: The incidence of rectal neuroendocrine tumors (RNETs) has witnessed a significant surge, with a notable proportion being amenable to endoscopic removal. However, the clinical significance of positive resection margin for RNETs patients following endoscopic resection remain unknown, resulting in a lack of consensus regarding the appropriateness of implementing salvage treatment. METHODS: In this large, multicenter, retrospective cohort study, we analyzed the medical records of individuals who underwent endoscopic resection for RNETs and classified them into two groups: the positive resection margin and the negative resection margin group. The overall survival (OS) and disease-free survival (DFS) were compared among two group. The independent variables were identified using univariate and multivariate logistic regression analyses to predict positive resection margin. Then, the model was established to predict the patients with positive resection margin using multivariate logistic regression. RESULTS: 181 RNETs patients (34.3 %) represented positive margin after endoscopic resection. Following a median follow-up period of 72 months, tumor recurrence manifested in 12 out of 527 patients (2.2 %) and the presence of positive resection margin was associated with worse DFS. Independent factors correlating with positive resection margin included endoscopic resection method choice, RNETs located in the low rectum, NLR >4.44 and tumor size exceeding 14.89 mm. A prediction model was therefore established with high predictive accuracy and excellent clinical applicability determined by calibration curves and DCA curve. Among RNETs patients with positive margin following endoscopic resection, implementing salvage treatment was beneficial for improving DFS and salvage endoscopic resection offer equal efficiency compared with salvage radical resection. CONCLUSIONS: Positive resection margin following endoscopic resection may indicate negative prognosis. Salvage treatment can improve the prognosis of RNETs patients with positive resection margin. Notably, salvage local resection exhibited similar efficacy compared with radical surgery in term of survival benefit.

Salvage radiotherapy for locoregional recurrence of esophageal cancer after surgery.

OBJECTIVE: There is no consensus on the optimal treatment for patients with locoregional recurrence of esophageal cancer after surgery. The objective of this study was to investigate the outcomes and prognostic factors associated with salvage radiotherapy in patients with locoregional recurrence of esophageal cancer after surgery. METHODS: We reviewed 80 patients with locoregional recurrence of esophageal cancer after surgery who were treated with radiotherapy. The median dose was 60 Gy, and 29 patients (36%) received elective nodal irradiation. Fifty-three patients (66%) received concurrent chemotherapy (mostly 5-fluorouracil and cisplatin) during radiotherapy. Overall survival, progression-free survival and in-field recurrence rate were assessed. RESULTS: The median follow-up period was 17 months. Two-year overall survival, progression-free survival and in-field recurrence rate were 50.3%, 23.5% and 41.3%, respectively. On multivariate analysis, a maximum diameter of locoregional recurrence lesions <30 mm was associated with higher overall survival (P = 0.044). Disease-free interval between surgery and locoregional recurrence >14 months was associated with higher PFS (P = 0.003). Late grade 3 toxicities occurred in three patients (3.8%). No grade 4 or higher toxicity was observed. CONCLUSIONS: Salvage radiotherapy demonstrated efficacy in achieving in-field control with acceptable toxicity. However, the high rate of out-of-field metastases led to poor progression-free survival and overall survival, particularly in cases involving large lesions and a short disease-free interval. A prospective study is warranted to establish a treatment strategy, particularly considering the combined use of effective anti-cancer drugs.

Stem Cell Mobilization Performed with Different Doses of Cytarabine in Plasma Cell Myeloma Patients Relapsing after Previous Autologous Hematopoietic Cell Transplantation-A Multicenter Report by the Polish Myeloma Study Group.

Salvage autologous hematopoietic cell transplantation (auto-HCT) may be used to treat relapse of plasma cell myeloma occurring after previous auto-HCT. When an insufficient number of hematopoietic stem cells have been stored from the initial harvest, remobilization is necessary. Here, we aimed to analyze the efficacy and safety of different doses of cytarabine (total 800 vs. 1600 vs. 2400 mg/m2) for remobilization. Sixty-five patients, 55% male, with a median age at remobilization 63 years, were included. Remobilization was performed with cytarabine_800 in 7, cytarabine_1600 in 36, and cytarabine_2400 in 22 patients. Plerixafor rescue was used in 25% of patients receiving cytarabine_1600 and 27% of those receiving cytarabine_2400. Patients administered cytarabine_800 were not rescued with plerixafor. Remobilization was successful in 80% of patients (57% cytarabine_800; 86% cytarabine_1600; 77% cytarabine_2400; p = 0.199). The yield of collected CD34+ cells did not differ between the different cytarabine doses (p = 0.495). Patients receiving cytarabine_2400 were at the highest risk of developing severe cytopenias, requiring blood product support, or having blood-stream infections. One patient died of septic shock after cytarabine_2400. In summary, remobilization with cytarabine is feasible in most patients. All doses of cytarabine allow for successful remobilization. Cytarabine_2400 is associated with higher toxicity; therefore, lower doses (800 or 1600 mg/m2) seem to be preferable.

The safety and efficacy outcomes of Minnelide given alone or in combination with paclitaxel in advanced gastric cancer: A phase I trial.

Minnelide is a water-soluble disodium salt variant of triptolide, an HSP70 inhibitor that can prevent tumor progression and induce apoptosis. Maximum tolerated dose (MTD), safety, and antitumor activity of Minnelide alone and its combination with paclitaxel were evaluated in this open-label, single-center, dose-escalation phase I study (NCT05566834) in patients who were previously treated for advanced gastric cancer (AGC). Minnelide was administered orally using a 3 + 3 dose-escalation design as monotherapy (Regimen A), and in combination with paclitaxel (Regimen B & C). Our results show that no patients experienced dose limiting toxicity (DLT) in the combination group (Regimen B& C) while 2 patients experienced DLT from the Regimen A group (n = 11) (Minnelide 1.5 mg). The MTD was Minnelide 1.25 mg once daily for 21days Q4 weeks as monotherapy. The most common Grade ≥3 AEs were neutropenia (19.4 %) and abdominal pain (11.1 %). In Regimen C, 71.5 % achieved either a partial response or a stable disease with the median PFS of 4.5 months, and the median OS of 10.7 months. The combination of Minnelide plus paclitaxel as salvage treatment in AGC patients showed meaningful clinical activity with a manageable safety profile. Based on these encouraging results, a phase II study is being initiated to test the effectiveness of the combination regimen in patients with advanced gastric cancer.

Multidisciplinary and Tailored Treatment of Locally Advanced Breast Cancer in Progression during Neoadjuvant Chemotherapy: Case Report.

Locally advanced breast cancer (LABC) is a complex disease that requires a multidisciplinary approach. Neoadjuvant chemotherapy (NAC) is usually performed in order to achieve loco-regional radical resection; although its importance in the multidisciplinary approach to LABC is well recognized, a small number of patients show Progressive Disease (PD). No standard salvage treatment (ST) has been defined and different strategies can be adopted, such as second-line systemic therapies, radiation therapy, and surgery. Herein, a case of LABC in PD during NAC is reported with a literature review, with the aim of highlighting the importance of a tailored multidisciplinary treatment for each patient.

Contact X-ray brachytherapy (CXB) as a salvage treatment for rectal cancer patients who developed local tumor re-growth after watch-and-wait approach.

Purpose: A watch-and-wait approach is an alternative to surgery for rectal cancer patients who have achieved a clinical complete response (cCR) following neoadjuvant (chemo)radiotherapy. However, approximately 25-38% of patients experience subsequent local tumor re-growth that requires salvage surgery. We evaluated the effectiveness of contact X-ray brachytherapy (CXB) as an alternative method of salvage therapy for those patients who were either unfit for or refused surgery. Oncological outcomes, tolerability, and feasibility of subsequent surgery for local treatment failure following CXB were reported. Material and methods: From 2009-2021, all patients treated with CXB as salvage therapy for local rectal cancer re-growth after watch-and-wait approach at our center were analyzed. Results: Contact X-ray brachytherapy as a salvage treatment (range, 90-110 Gy) was offered to 56 patients who experienced tumor re-growth following (chemo)radiation and watch-and-wait protocol. Median age was 76 (IQR = 66-83) years. Most patients (82%) had early-stage re-growth (ycT1/ycT2, ycN0), and 18% had more advanced stages (ycT3/ycT4, ycN0). After a median of 37-month follow-up (IQR = 19-53), 48% of patients who had early-stage re-growth achieved a sustained complete remission after CXB compared with 20% of those who had more advanced tumor stages. Disease-free and overall survivals for the whole cohort were 69% and 100% at 1-year, 51% and 82% at 3-year, and 51% and 65% at 5-years. CXB effectively controlled local re-growth-related symptoms. Mild post-CXB side effects occurred in 18% of cases. All (100%) eight patients who developed further local relapse, and 29% of those who had residual disease post-CXB salvage were successfully managed with subsequent surgery. Conclusions: Contact X-ray brachytherapy offers a new treatment option for patients in this situation whose other therapy options are not suitable for or refused initial surgery. Early local tumor re-growth responded best with minimal treatment-related toxicity and excellent symptom control. Disease-free and overall survival rates were acceptable, and delaying surgical salvage for local re-growth did not compromise patients' eventual long-term outcomes.

Salvage Androgen Deprivation Therapy as Potential Treatment for Recurrence after Robot-Assisted Radical Prostatectomy.

BACKGROUND: The efficacy of intermittent androgen deprivation therapy (ADT) for biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP) is unknown, and its usefulness in Japanese practice needs to be investigated. METHODS: We conducted a retrospective analysis of 85 patients who underwent RARP and were selected for intermittent ADT for postoperative recurrence at Kanazawa University Hospital between 2009 and 2019. Intermittent ADT was administered for 2 years. If prostate-specific antigen levels increased post-treatment, intermittent ADT was reinitiated. The median follow-up period was 47 months. RESULTS: The 73 patients had completed the initial course of ADT, and 12 were under initial ADT. The 5-year castration-resistant prostate-cancer-free survival rates, cancer-specific survival, and overall survival were 92.7%, 98.3%, and 94.7%, respectively. A subgroup analysis of 69 patients who completed intermittent ADT was conducted to evaluate the BCR rate following initial ADT. The 5-year BCR-free survival rate was 53.2%. Multivariate analysis identified testosterone ≤ 0.03 ng/mL during ADT as the sole predictor of BCR after ADT. CONCLUSIONS: Salvage intermittent ADT may be an effective treatment option for BCR after RARP. In addition, it would be useful to confirm strong testosterone suppression as a criterion for transition to intermittent therapy.

Necrotizing Parasagittal Meningioma in Patient with Systemic Lupus Erythematosus after Treatments with Methotrexate and Hydroxychloroquine.

Objective Meningiomas are the most common extra-axial tumors of the central nervous system. Meningiomas are particularly problematic when they invade deep or vital structures, causing the tumors to be inoperable. Nonsurgical adjunctive or salvage treatments to shrink a meningioma with multiple recurrences, located in deep-seated area or surgically unfit area, remain underexplored. The authors report a rare case of a spontaneously necrotic meningioma (World Health Organization [WHO] grade I) in a patient with systemic lupus erythematosus on chronic methotrexate and hydroxychloroquine. Case Study A 29-year-old female with systemic lupus erythematosus had been treated with methotrexate and hydroxychloroquine for 7 years. She presented with episodes of seizures and hemiparesis. Neuroimaging revealed a possible necrotic meningioma in the left parietal parasagittal area. Subsequent intraoperative findings showed lytic tissue of the tumor, and by histopathology results the tumor was classified as WHO grade I with massive necrosis. After craniotomy with tumor removal, the patient's motor function fully recovered without recurrent seizures. Discussions Necrotizing of small and benign meningioma is rarely found but otherwise interesting. The cause of this phenomenon is not yet understood thoroughly. In this case, we suspected various possible causes such as vasculitis interrupting blood supply, use of immunosuppressive drugs such as hydroxychloroquine or methotrexate, or, less likely, latent infections in the immunocompromised patient. Despite the lack of more evidence supports, this finding encourages further study of nonsurgical or salvage treatment of inoperable meningioma, so sequalae after refractory recurrences of meningioma can be prevented, and patient treatment outcomes can be improved.

Nadir prostate-specific antigen after salvage cryotherapy as a potential prognostic factor for oncologic outcomes.

PURPOSE: To report oncologic outcomes of patients undergoing salvage cryotherapy (SCT) for local recurrence of prostate cancer (PCa) and to establish a nadir PSA (nPSA) value that best defines long-term oncologic success. METHODS: Retrospective study of men who underwent SCT for local recurrence of PCa between 2008 and 2020. SCT was performed in men with biochemical recurrence (BCR), after primary treatment and with biopsy-proven PCa local recurrence. Survival analysis with Kaplan-Meier and Cox models was performed. We determined the optimal cutoff nPSA value after SCT that best classifies patients depending on prognosis. RESULTS: Seventy-seven men who underwent SCT were included. Survival analysis showed a 5-year biochemical recurrence-free survival (BRFS), androgen deprivation therapy-free survival (AFS), and metastasis-free survival (MFS) after SCT of 48.4%, 62% and 81.3% respectively. On multivariable analysis for perioperative variables associated with BCR, initial ISUP, pre-SCT PSA, pre-SCT prostate volume and post-SCT nPSA emerged as variables associated with BCR. The cutoff analysis revealed an nPSA < 0.5 ng/ml to be the optimal threshold that best defines success after SCT. 5-year BRFS for patients achieving an nPSA < 0.5 vs nPSA ≥ 0.5 was 64% and 9.5% respectively (p < 0.001). 5-year AFS for men with nPSA < 0.5 vs ≥ 0.5 was 81.2% and 12.2% (p < 0.001). Improved 5-year MFS for patients who achieved nPSA < 0.5 was also obtained (89.6% vs 60%, p = 0.003). CONCLUSION: SCT is a feasible rescue alternative for the local recurrence of PCa. Achieving an nPSA < 0.5 ng/ml after SCT is associated with higher long-term BRFS, AFS and MFS rates.

Outcomes in patients with multiple myeloma receiving salvage treatment after BCMA-specific CAR-T therapy: A retrospective analysis of LEGEND-2.

Chimeric antigen receptor T-cell (CAR-T) therapy targeting B-cell maturation antigen (BCMA) has shown profound efficacy and manageable toxicity in patients with relapsed/refractory multiple myeloma (RRMM). However, determining the best course of treatment for post-CAR-T therapy relapse remains a significant challenge. We conducted a retrospective analysis of patients from the phase I LEGEND-2 study (NCT03090659) enrolled at the Xi'an site, analysing the first salvage line of therapy and outcomes in patients with RRMM who progressed after receiving LCAR-B38M CAR-T therapy. Of 45 eligible patients, 34 (76%) had progressive disease (PD). Overall response rate (ORR) to salvage treatment was 50.0%. Median progression-free survival (PFS) after starting salvage treatment was 16.3 months. Median PFS of patients receiving proteasome inhibitor (PI)-based combination therapy was longer (28.2 months) than that of patients receiving a second BCMA CAR-T (including LCAR-B38M; 3.9 months, p = 0.0022) or chemotherapy (1.67 months, p = 0.0001). All patients with extramedullary disease at baseline (n = 11) progressed after CAR-T therapy; ORR to salvage therapy was 25.0% and median PFS was 9.7 months. In conclusion, salvage therapy in patients with PD after receiving LCAR-B38M CAR-T cells produced moderate efficacy, with better outcomes for PI-based salvage regimens.

Salvage vesiculectomy for local prostate cancer recurrence: surgical technique and early post-operative outcomes.

PURPOSE: Isolated recurrence in remnants of the seminal vesicles (SV) after treatment of primary prostate cancer (PCa) has become a more frequent entity with the widespread use of more sensitive next-generation imaging modalities. Salvage vesiculectomy is hypothesized to be a worthwhile management option in these patients. The primary goal of this study is to describe the surgical technique of this new treatment option. Secondary outcomes are peri- and post-operative complications and early oncological outcomes. METHODS: Retrospective multicenter study, including 108 patients with solitary recurrence in the SV treated between January 2009 and June 2022, was performed. Patients with local recurrences outside the SVs or with metastatic disease were excluded. Both SVs were resected using a robot-assisted or an open approach. In selected cases, a concomitant lymphadenectomy was performed. RESULTS: Overall, 31 patients (29%) reported complications, all but one grade 1 to 3 on the Clavien-Dindo Scale. A median PSA decrease of 2.07 ng/ml (IQR: 0.80-4.33, p < 0.001), translating into a median PSA reduction of 92% (IQR: 59-98%) was observed. At a median follow-up of 14 months, freedom from secondary treatment was 54%. Lymphadenectomy had a significant influence on PSA reduction (p = 0.018). CONCLUSION: Salvage vesiculectomy for PCa recurrence limited to the SV is a safe procedure with excellent PSA response and is a potential curative treatment in a subset of patients. A concomitant lymphadenectomy can best be performed in all patients that did not underwent one at primary treatment.

Holmium laser enucleation of the prostate as a secondary surgery following prostatic urethral lift.

Introduction: Prostatic urethral lift is a treatment option for benign prostatic hyperplasia, yet information on surgeries following this procedure is scarce. Case presentation: A 71-year-old man with persistent urinary retention following prostatic urethral lift underwent a secondary holmium laser enucleation of the prostate. The morcellation procedure, complicated by the presence of implants from the previous surgery, broke the morcellator blade. The fragmented blade was successfully retrieved without any organ damage. Postoperatively, the patient encountered no complications and showed improvement in his urinary symptoms. Conclusion: This case highlights the potential risk of device breakage when a secondary surgery, specifically the morcellation process, is performed following prostatic urethral lift. Care must be taken to prevent interaction between the implants and the morcellator. Our case demonstrates the efficacy of holmium laser enucleation of the prostate as a salvage surgical intervention for patients in whom prostatic urethral lift has failed.

Efficacy of Pyrotinib With/Without Trastuzumab in Treatment-Refractory, HER2-Positive Metastatic Colorectal Cancer: Result From a Prospective Observational Study.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is a promising therapeutic target in metastatic colorectal cancer (mCRC). This study was to evaluate the efficacy and safety of pyrotinib alone or pyrotinib with trastuzumab in patients with HER2-positive mCRC. PATIENTS AND METHODS: In this prospective observational study, patients with HER2 positive, Ras Sarcoma Viral Oncogene Homolog (RAS) wild type mCRC who received at least one standard treatment of palliative chemotherapy were enrolled. Patients were treated with oral pyrotinib alone or pyrotinib with trastuzumab. The primary endpoint was progression free survival (PFS), and the secondary endpoints were overall survival (OS), confirmed objective response rate (ORR), and safety. This trial is registered with chitcr.org, number ChiCTR2100046381. RESULTS: From February 15, 2021, to January 10, 2023, 32 patients were enrolled in this study. Twenty (62.5%) patients were treated with pyrotinib, while 12 (37.5%) received pyrotinib and trastuzumab. As of June 24, 2023, with a median follow-up of 11.0 months, the median PFS was 5.7 months (95%CI 4.5-10.2), while OS was not evaluable (NE), ORR and disease control rate (DCR were 34.4% and 87.5%. Patients' PFS in the pyrotinib plus trastuzumab subgroup and pyrotinib monotherapy group were 8.6 and 5.5 months, OS was not evaluable (NE) and 10.9 months, ORR was 50.0% and 25.0%, respectively. Most treatment-related adverse events (TRAEs) were grade 1-2, diarrhea was the most frequent TRAE (81.3%, 26/32). Grade 3 TRAEs occurred in 11 patients: 9 for diarrhea, 1 for nausea, and 1 for oral mucositis. CONCLUSION: Pyrotinib with or without trastuzumab showed promising anti-tumor activity and acceptable toxicities in treatment-refractory, HER2-positive mCRC.

Hybrid endoscopic submucosal dissection as a salvage option for difficult colorectal conventional endoscopic submucosal dissection.

BACKGROUND: When total submucosal dissection is difficult to achieve during conventional colorectal endoscopic submucosal dissection (C-ESD), the lesion can be resected by final snaring through salvage hybrid ESD (SH-ESD). This study aimed to examine the outcomes of SH-ESD and identify its indications that could achieve en bloc resection. METHODS: We recruited 1039 consecutive patients with colorectal lesions that underwent ESD at Hiroshima University Hospital between January 2015 and December 2020. C-ESD was attempted thoroughly in 924 lesions (C-ESD group, including 9 lesions in which ESD was discontinued), and SH-ESD was performed owing to some difficulties in 115 lesions (SH-ESD group). Risk factors for incomplete resection by SH-ESD and ESD discontinuation were evaluated using multivariate analysis. The outcomes were compared between cases with remaining undissected submucosa of < 20 mm in diameter in the SH-ESD and C-ESD groups, using propensity score matching. RESULTS: Multivariate analysis revealed that a procedure time > 80 min and remaining undissected submucosa ≥ 20 mm in diameter were significant risk factors for incomplete resection after SH-ESD and ESD discontinuation. By propensity score matching analysis, procedure time was significantly shorter in the SH-ESD group with remaining undissected submucosa < 20 mm in diameter than in the C-ESD group (71 min vs. 90 min, p = 0.0053), although no significant difference was found in the en bloc resection rate (94% vs. 87%, p = 0.0914). CONCLUSION: SH-ESD can be an alternative surgical method when conventional ESD is difficult to continue in cases in which the remaining undissected submucosa is < 20 mm in diameter.

The use of basic fibroblast growth factor to treat intractable Bell's palsy administered via transcanal endoscopic ear surgery.

PURPOSE: Facial nerve decompression surgery is an invasive procedure which has hitherto been the main option for patients with severe intractable Bell's palsy which is resistant to drug treatment. We have developed a new salvage treatment for such patients by using minimally invasive transcanal endoscopic ear surgery (TEES) to deliver the biological regenerative agent, basic fibroblast growth factor (bFGF), to the damaged facial nerve. MATERIALS AND METHODS: An endoscopic salvage treatment group was studied prospectively and was made up of severe intractable Bell's palsy patients who did not respond to high dose steroid treatment and had an ENoG value of 5 % or less. This surgery group was retrospectively compared to a similar control group who had received high dose steroid only. RESULTS: Complete recovery to House-Brackmann (HB) Grade I was achieved by 44.8 % of the endoscopic salvage treatment group which was significantly higher than the 21.2 % of the control group at one-year follow up. Patients with an ENoG value of 1 % to 5 % exhibited a significantly higher complete recovery rate of 71.4 % in the endoscopic salvage treatment group than the 28.6 % of the control group. In addition, no complications were observed including hearing loss. CONCLUSIONS: bFGF delivered via TEES shows considerable promise as a new salvage treatment of severe intractable Bell's palsy that is resistant to high dose steroid treatment without the risks presented by facial nerve decompression surgery.