Prognostic factors and risk-stratification model of recurrent or metastatic head and neck squamous cell carcinoma treated with cetuximab containing regimen.

BACKGROUND: In recent years, the addition of cetuximab to chemotherapy has improved treatment outcomes for patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). In this study, we present the real-world survival data of R/M HNSCC patients who received cetuximab-containing regimens from thirteen medical centers in Taiwan, as well as a three-level risk stratification model for this patient population. METHODS: This study enrolled R/M HNSCC patients from thirteen medical centers in Taiwan who received cetuximab-containing regimens from January 1, 2017 to June 6, 2022. The cases were divided into a training cohort and a validation cohort based on the start of treatment. Overall survival (OS) was evaluated in both cohorts and exploratory analysis was performed to identify associated adverse clinical and laboratory factors. The results of the exploratory analysis were used to construct a three-level risk stratification prediction model for OS. RESULTS: A total of 1434 patients with R/M HNSCC were enrolled in this study and received cetuximab-containing regimens. The overall population had a median OS of 8.57 months (95% CI: 8.07 - 9.08). Multivariate analysis of the training cohort identified poor ECOG performance status, heavy alcohol consumption, and prior adjuvant CCRT or lack of prior RT as adverse prognostic factors. Comparison of laboratory data between patients with OS≦6 and OS > 6 also revealed unfavorable factors, including increased white blood cell count, decreased hemoglobin level, increased platelet count, increased absolute neutrophil count, decreased absolute lymphocyte count, and increased neutrophil-to-lymphocyte ratio. Using forward prediction, a three-level risk stratification prediction model was constructed using the variables of ECOG performance status, alcohol consumption, skin metastasis, modality of radiation therapy, hemoglobin level, and neutrophil-to-lymphocyte ratio. The median OS in the low-risk, intermediate-risk, and high-risk groups were 12.02 months (95% CI 10.44-13.61), 7.5 months (95% CI 7.33-8.17), and 4.01 months (95% CI 3.94-4.08), respectively, with a log-rank test p-value < 0.001. CONCLUSION: This study presents a three-level risk stratification model with strong prediction ability for OS in R/M HNSCC patients who received cetuximab-containing regimens. The results are based on real-world data and may provide valuable information for clinicians in treatment planning and future drug development.

Treatment outcomes of cetuximab-containing regimen in locoregional recurrent and distant metastatic head and neck squamous cell carcinoma.

BACKGROUND: Recurrent/ metastatic squamous cell carcinoma of head and neck (R/M SCCNH) is still a difficult-to-treat disease with poor clinical outcomes and limited treatment choices. In view of locoregional recurrent versus distant metastatic SCCHN, the therapeutic efficacy of cetuximab-containing regimen and relevant prognostic factors for these two groups may be different. Thus, the aim of this study was to explore the treatment outcomes of cetuximab-containing regimen in locoregional recurrent and distant metastatic SCCHN groups, and to identify clinical factors correlated with better survival outcomes. METHODS: From 2016 to 2020, patients with R/M SCCHN who received cetuximab-containing regimen in our institute were enrolled in this study. Clinical outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were evaluated in both locoregional recurrence and distant metastasis groups. Exploratory analysis were conducted to investigate major clinical features associated with better outcomes. RESULTS: A total of 107 patients with locoregional recurrent SCCHN (N = 66) and distant metastatic SCCNH (N = 41) who received cetuximab-containing regimen were enrolled in this retrospective study. Patients with oral cavity cancer and patients with disease recurrence within 6 months after radiation therapy were significantly increased in locoregional recurrence group. The median OS (15.6 vs. 9.7 months, P = 0.004) and PFS (5.8 months vs. 4.2 months, P = 0.008) were longer in locoregional recurrence group than in distant metastasis group. In multivariate analysis of clinical features, locoregional recurrence was still an important risk factor associated with better OS (Hazzard ratio (HR) 0.64, p = 0.06) and PFS (HR 0.67, p = 0.075). In addition, a trend of favorable disease control rate (DCR; 62.5% vs. 45.0%, p = 0.056) was noted in locoregional recurrence group. In locoregional recurrence group, prior salvage surgery was associated with longer OS (HR = 0.24, P = 0.008) and PFS (HR = 0.30, P = 0.005). CONCLUSION: SCCHN with locoregional recurrence is associated with better disease control and survival outcomes comparing to distant metastatic SCCHN when treated with cetuximab-containing regimen. Salvage surgery for locoregional recurrence may further improves clinical outcome.

Nitric Oxide Mobilizes Intracellular Zn2+ via the GC/cGMP/PKG Signaling Pathway and Stimulates Adipocyte Differentiation.

Plasma and tissue zinc ion levels are associated with the development of obesity. Previous studies have suggested that zinc ions may regulate adipocyte metabolism and that nitric oxide (NO) plays a pivotal role in the regulation of adipocyte physiology. Our previous study showed that chronic NO deficiency causes a significant decrease in adipose tissue mass in rats. Studies also suggested that zinc ions play an important modulatory role in regulating NO function. This study aims to explore the role of zinc ions in NO-regulated adipocyte differentiation. We hypothesized that NO could increase intracellular Zn2+ level and then stimulate adipocyte differentiation. ZnCl2 and the NO donor, NONOate, were used to explore the effects of Zn2+ and NO on adipocyte differentiation. Regulatory mechanisms of NO on intracellular Zn2+ mobilization were determined by detection. Then, Zn2+-selective chelator TPEN was used to clarify the role of intracellular Zn2+ on NO-regulated adipocyte differentiation. Furthermore, the relationship between adipocyte size, Zn2+ level, and NOS expression in human subcutaneous fat tissue was elucidated. Results showed that both ZnCl2 and NO stimulated adipocyte differentiation in a dose-dependent manner. NO stimulated intracellular Zn2+ mobilization in adipocytes through the guanylate cyclase (GC)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) pathway, and NO-stimulated adipocyte differentiation was Zn2+-dependent. In human subcutaneous adipose tissue, adipocyte size was negatively correlated with expression of eNOS. In conclusion, NO treatment stimulates intracellular Zn2+ mobilization through the GC/cGMP/PKG pathway, subsequently stimulating adipocyte differentiation.

YC-1 alleviates bone loss in ovariectomized rats by inhibiting bone resorption and inducing extrinsic apoptosis in osteoclasts.

Osteoporosis is a major health problem in postmenopausal women and the elderly that leads to fractures associated with substantial morbidity and mortality. Current osteoporosis therapies have significant drawbacks, and the risk of fragility fractures has not yet been eliminated. There remains an unmet need for a broader range of therapeutics. Previous studies have shown that YC-1 has important regulatory functions in the cardiovascular and nervous systems. Many of the YC-1 effector molecules in platelets, smooth muscle cells and neurons, such as cGMP and µ-calpain, also have important functions in osteoclasts. In this study, we explored the effects of YC-1 on bone remodeling and determined the potential of YC-1 as a treatment for postmenopausal osteoporosis. Micro-computed tomography of lumbar vertebrae showed that YC-1 significantly improved trabecular bone microarchitecture in ovariectomized rats compared with sham-operated rats. YC-1 also significantly reversed the increases in serum bone resorption and formation in these rats, as measured by enzyme immunoassays for serum CTX-1 and P1NP, respectively. Actin ring and pit formation assays and TRAP staining analysis showed that YC-1 inhibited osteoclast activity and survival. YC-1 induced extrinsic apoptosis in osteoclasts by activating caspase-3 and caspase-8. In osteoclasts, YC-1 stimulated µ-calpain activity and inhibited Src activity. Our findings provide proof-of-concept for YC-1 as a novel antiresorptive treatment strategy for postmenopausal osteoporosis, confirming an important role of nitric oxide/cGMP/protein kinase G signaling in bone.

Intraportal injection of insulin-producing cells generated from human bone marrow mesenchymal stem cells decreases blood glucose level in diabetic rats.

We studied the process of trans-differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) into insulin-producing cells. Streptozotocin (STZ)-induced diabetic rat model was used to study the effect of portal vein transplantation of these insulin-producing cells on blood sugar levels. The BM-MSCs were differentiated into insulin-producing cells under defined conditions. Real-time PCR, immunocytochemistry and glucose challenge were used to evaluate in vitro differentiation. Flow cytometry showed that hBM-MSCs were strongly positive for CD44, CD105 and CD73 and negative for hematopoietic markers CD34, CD38 and CD45. Differentiated cells expressed C-peptide as well as ß-cells specific genes and hormones. Glucose stimulation increased C-peptide secretion in these cells. The insulin-producing, differentiated cells were transplanted into the portal vein of STZ-induced diabetic rats using a Port-A catheter. The insulin-producing cells were localized in the liver of the recipient rat and expressed human C-peptide. Blood glucose levels were reduced in diabetic rats transplanted with insulin-producing cells. We concluded that hBM-MSCs could be trans-differentiated into insulin-producing cells in vitro. Portal vein transplantation of insulin-producing cells alleviated hyperglycemia in diabetic rats.

Paclitaxel-Ifosfamide-based Therapy as Salvage Treatment in Platinum-resistant Recurrent/Metastatic Head and Neck Cancer.

BACKGROUND: Treatment options are limited, and the prognosis is poor for patients with platinum-resistant recurrent metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). This study evaluated the efficacy and safety of a paclitaxel and ifosfamide (TI) regimen in patients with R/M HNSCC whose disease had progressed following platinum-based therapy. PATIENTS AND METHODS: In this retrospective study, we included 53 patients with R/M HNSCC who underwent at least one cycle of TI-based therapy, post platinum failure, between February 2020 and August 2023. Some patients received the TI regimen in combination with immunotherapy and/or cetuximab. Key metrics assessed included the objective response rate (ORR), disease control rate, and progression-free as well as overall survival. RESULTS: The study observed an ORR of 15.8% and a disease control rate of 36.8%. The median progression-free survival for the entire cohort was 3.3 months, and the median overall survival was 9.6 months. Notably, the combination of TI with immunotherapy yielded a higher ORR of 30.8%, compared to 14.3% with TI alone. The most prevalent grade 1-2 adverse events were anemia (81%), weight loss (68%) and hypernatremia (55%). CONCLUSION: The TI-based regimen demonstrated favorable efficacy and safety profile in treating R/M HNSCC. Enhanced outcomes may be attainable when combining it with immunotherapy. This study suggests that TI-based therapy could serve as a potential salvage option for this specific patient group.

Wharton's jelly of the umbilical cord serves as a natural biomaterial to promote osteogenesis.

Various factors can contribute to bone damage or loss, presenting challenges for bone regeneration. Our study explores the potential clinical applications of two processed forms of Wharton's jelly of the human umbilical cord for treating bone loss. Wharton's jelly from fresh umbilical cords underwent two distinct processes: (1) frozen Wharton's jelly (WJF), preserved with cryoprotective agents, and (2) decellularized Wharton's jelly matrix (WJD), prepared only via lyophilization without cryoprotectants. Both WJD and WJF are rich in collagen, hyaluronan, and polysaccharide proteins. Notably, WJD exhibited a porous structure lacking nuclei from human umbilical cord mesenchymal stem cells, unlike WJF. In direct contact experiments, WJD stimulated osteoblast migration, enhanced osteoblast maturation, and promoted calcium deposition for bone formation when administered to cultured rat osteoblasts. Furthermore, in transwell co-culture experiments, both WJD and WJF increased the rat osteoblast expression of RUNX2 and OPN genes, elevated alkaline phosphatase levels, and enhanced extracellular calcium precipitation, indicating their role in osteoblast maturation and new bone formation. Hyaluronic acid, one of the ingredients from WJD and WJF, was identified as a key component triggering osteogenesis. In vivo experiments involved creating circular bone defects in the calvarias of rats, where WJD and WJF were separately implanted and monitored over five months using micro-computerized tomography. Our results demonstrated that both WJD and WJF enhanced angiogenesis, collagen formation, osteoblast maturation, and bone growth within the bone defects. In summary, WJD and WJF, natural biomaterials with biocompatibility and nontoxicity, act not only as effective scaffolds but also promote osteoblast adhesion and differentiation, and accelerate osteogenesis.

Clinical outcomes of cetuximab-based treatment for distant metastatic head and neck squamous cell carcinoma: A real-world study using Taiwan Head Neck Society registry database.

BACKGROUND: For R/M HNSCC, the differences in prognosis and treatment options between distant metastasis (DM) and locoregional recurrence, especially in the DM group, remain unclear. METHODS: From the Taiwan Head Neck Society registry database, patients who were diagnosed with R/M HNSCC and received cetuximab-based frontline therapy were collected for analysis. RESULTS: Among the enrolled patients, 59.3% (491/827) belonged to the DM group. The DM group had less primary site of oral cavity, less betel nut chewing, higher lactate dehydrogenase (LDH) levels, and higher LDH/albumin ratio compared with the non-DM group. For the patients with primary site of oral cavity and current smokers, DM coexisted with poorer outcomes. In the DM group, EXTREME-like regimen was more suitable for older patients, those with elevated LDH, and those with higher LDH/albumin ratio than TPExtreme-like regimen. CONCLUSION: DM coexisted with poorer prognosis in certain groups. LDH-associated biomarkers may aid treatment options for DM patients.

Tumor-associated tissue eosinophilia promotes angiogenesis and metastasis in head and neck squamous cell carcinoma.

Eosinophils are terminally differentiated leukocytes that participate in the process of chronic inflammation and allergy and are able to release multiple cytokines into the surrounding tissue environment. Tumor-associated tissue eosinophilia (TATE) is the presence of eosinophils in the tumor or in the neighboring stroma and has been observed in various types of cancer. In head and neck squamous cell carcinoma (HNSCC), the clinical relevance of TATE has not been concluded yet because of the inconsistent results in different studies. In our study, we focus on the prognostic effects of TATE on HNSCC and how TATE can influence tumor behavior and tumor microenvironment. We first showed that in both the TCGA-HNSC cohort and our cohort of patients with HNSCC who had received curative surgery, TATE is correlated with worse overall survival. To investigate the underlying mechanism of how TATE leads to poor clinical outcomes, we showed that activated eosinophils produce a variety of cytokines and chemokines, and activated TATE-derived culture medium promotes tumor migration mainly through CCL2. We also showed that eosinophils are capable of inducing angiogenesis and that HNSCC samples enriched with TATE are highly correlated with tumor angiogenesis. Furthermore, HNSCC enriched with TATE had more aggressive pathological features, including regional lymph node metastasis, perineural invasion, lymphovascular invasion, and tumor growth. Lastly, we showed that HNSCC enriched with TATE is associated with immunosuppressive tumor microenvironment. Taken together, our results suggest that TATE promotes cancer metastasis and angiogenesis which results in a poor clinical outcomes in HNSCC.

Elevated PD-L1 Expression and Microsatellite Instability in Elderly Patients With Gastric Cancer.

Immunotherapy in combination with chemotherapy is the current treatment of choice for frontline programmed cell death ligand 1 (PD-L1)-positive gastric cancer. However, the best treatment strategy remains an unmet medical need for elderly or fragile patients with gastric cancer. Previous studies have revealed that PD-L1 expression, Epstein-Barr virus association, and microsatellite instability-high (MSI-H) are the potential predictive biomarkers for immunotherapy use in gastric cancer. In this study, we showed that PD-L1 expression, tumor mutation burden, and the proportion of MSI-H were significantly elevated in elderly patients with gastric cancer who were older than 70 years compared with patients younger than 70 years from analysis of The Cancer Genome Atlas gastric adenocarcinoma cohort [≥70/<70: MSI-H: 26.8%/15.0%, P =0.003; tumor mutation burden: 6.7/5.1 Mut/Mb, P =0.0004; PD-L1 mRNA: 5.6/3.9 counts per million mapped reads, P =0.005]. In our real-world study, 416 gastric cancer patients were analyzed and showed similar results (≥70/<70: MSI-H: 12.5%/6.6%, P =0.041; combined positive score ≥1: 38.1%/21.5%, P <0.001). We also evaluated 16 elderly patients with gastric cancer treated with immunotherapy and revealed an objective response of 43.8%, a median overall survival of 14.8 months, and a median progression-free survival of 7.0 months. Our research showed that a durable clinical response could be expected when treating elderly patients with gastric cancer with immunotherapy, and this approach is worth further study.

Transplantation of insulin-producing cells from umbilical cord mesenchymal stem cells for the treatment of streptozotocin-induced diabetic rats.

BACKGROUND: Although diabetes mellitus (DM) can be treated with islet transplantation, a scarcity of donors limits the utility of this technique. This study investigated whether human mesenchymal stem cells (MSCs) from umbilical cord could be induced efficiently to differentiate into insulin-producing cells. Secondly, we evaluated the effect of portal vein transplantation of these differentiated cells in the treatment of streptozotocin-induced diabetes in rats. METHODS: MSCs from human umbilical cord were induced in three stages to differentiate into insulin-producing cells and evaluated by immunocytochemistry, reverse transcriptase, and real-time PCR, and ELISA. Differentiated cells were transplanted into the liver of diabetic rats using a Port-A catheter via the portal vein. Blood glucose levels were monitored weekly. RESULTS: Human nuclei and C-peptide were detected in the rat liver by immunohistochemistry. Pancreatic ß-cell development-related genes were expressed in the differentiated cells. C-peptide release was increased after glucose challenge in vitro. Furthermore, after transplantation of differentiated cells into the diabetic rats, blood sugar level decreased. Insulin-producing cells containing human C-peptide and human nuclei were located in the liver. CONCLUSION: Thus, a Port-A catheter can be used to transplant differentiated insulin-producing cells from human MSCs into the portal vein to alleviate hyperglycemia among diabetic rats.

Diagnostic and therapeutic dilemmas in periampullary lesions.

BACKGROUND/AIMS: Periampullary lesions often present diagnostic and therapeutic dilemmas. This study is to clarify the justification of pancreaticoduodenectomy for the resectable periampullary lesion without histological confirmation of malignancy. METHODOLOGY: Clinical data for periampullary lesions with presumed malignancy were retrieved from our prospectively-collected computer database. The surgical risks and test performance characteristics in diagnosis were determined. RESULTS: There were 636 patients undergoing pancreaticoduodenectomy, including 572 with malignancy and 64 (10.1% false positive rate) with benign lesions. No resection was attempted for 32 patients, but 8 (25% false negative rate) eventually turned out to be malignant. Our data showed a sensitivity of 98.6% (572/580), a specificity of 27% (24/88) and an accuracy of 89.2% (596/668) in detecting periampullary malignancy. The surgical risks after pancreaticoduodenectomy were significantly lower in the benign group, with 28.1% morbidity (vs. 43.7% in the malignant group), no pancreatic leakage (vs. 11.5% in malignant group) and no surgical mortality (vs. 7.3% in the malignant group). CONCLUSIONS: Pancreaticoduodenectomy is justified for a periampullary lesion without histological confirmation whenever malignancy is suspected. Moreover, a nihilistic approach could be associated with a significant false negative rate (25%) if left unresected and might preclude a patient with periampullary malignancy from cure.

Reappraisal of pancreatic adenocarcinoma undergoing pancreaticoduodenectomy.

BACKGROUND/AIMS: This study is to reappraise the clinical presentations, surgical and survival outcomes of pancreatic head adenocarcinoma. METHODOLOGY: Data of pancreatic head adenocarcinomas undergoing pancreaticoduodenectomy were reappraised and compared between period 1 (1984-1996) and period 2 (1997-2009). RESULTS: Surgical mortality was 3.6% in period 2 and 5.0% in period 2. The surgical morbidity was 35.7% in period 1, 35.3% in period 2. Pancreatic leakage was significantly lower (3.4%) in pancreaticogastrostomy group, as compared to 11.7% in pancreaticojejunostomy. There was 57.5% positive lymph node involvement and 77.4% perineural invasion. More patients underwent adjuvant or palliative chemotherapy in period 2 (42.2%) than in period 1 (14.8%). The 5-year survival for resected pancreatic head adenocarcinoma was 3.7% in period 1 and 11.1% in period 2. The 5-year survival after curative resection in period 1 was significantly lower than that in period 2 (4.2% vs. 14.7%). CONCLUSIONS: Although surgical mortality has significantly decreased recently, pancreaticoduodenectomy continues to be a complex and technically-demanding procedure with high and unchanged surgical morbidity. The poor survival outcome of pancreatic head adenocarcinoma might be a combined reflection of difficulty in early detection, aggressive biological behavior of tumor itself and complex surgical anatomy for resection.

Efficacy of cetuximab-containing regimens in the treatment of recurrent/metastatic head and neck cancer after progression to immune checkpoint inhibitors.

BACKGROUND: The antiepidermal growth factor receptor (EGFR) monoclonal antibody cetuximab and immune checkpoint inhibitors (ICIs) are the current front-line treatment for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, understanding of the efficacy of cetuximab-containing regimens in patients who fail ICI treatments is limited. In this study, we present the efficacy of cetuximab-based regimens in heavily pretreated R/M HNSCC patients after progression to ICIs. METHODS: This was a retrospective study that analyzed patients diagnosed with R/M HNSCC who progressed after ICIs and then received their first-time cetuximab-based regimens at Taipei Veterans General Hospital from January 2017 to December 2020. The response rate, overall survival, and progression-free survival were measured. RESULTS: A total of 28 patients were included in this study. Most patients had received pembrolizumab as an ICI. The median duration of cetuximab-based regimens prescribed was 4.5 months. The objective response rate (ORR) was 32.1% (95% confidence interval [CI], 17.9%-50.6%), and the disease control rate (DCR) was 53.6% (95% CI, 42.4%-76.4%). The median overall survival and median progression-free survival were 9.1 months (95% CI, 1.3-16.8) and 2.9 months (95% CI, 2.2-3.5), respectively. The incidence of cetuximab-related adverse events was reported as 39.2%. CONCLUSION: A cetuximab-based regimen is still an effective and tolerable treatment for R/M HNSCC after progression on ICIs. Future prospective studies are needed to identify better treatments for previously ICI-treated or heavily treated R/M HNSCC patients.

Anatomic study of the axillary nerve in a Chinese cadaveric population: correlation of the course of the nerve with proximal humeral fixation with intramedullary nail or external skeletal fixation.

INTRODUCTION: The axillary nerve can be injured during external skeletal fixation with Schanz screws or proximal locking screws of intramedullary nails. Being aware of the axillary nerve's anatomic relationship to the proximal humerus is vital for avoiding complications. METHODS: We investigated the relationship of the axillary nerve to surrounding bony landmarks by studying 88 axillary nerves in 44 embalmed cadaveric adult Chinese males. These measurements were then compared with the results from a similar study among Caucasians using the same reference points. RESULTS: We identified three significantly different parameters between our Chinese and the previously studied Caucasian subjects (P ≤ 0.05): the distances from the superior aspect of the humeral head to the axillary nerve (D1) (5.2 ± 0.7 vs. 6.09 ± 0.65 cm, respectively); surgical neck to axillary nerve (D2) (2.0 ± 0.7 vs. 1.72 ± 0.84 cm); and humeral length (D3) (29.0 ± 2.2 vs. 35.25 ± 5.7 cm). The D1 distance ranged from 4.0 to 6.7 cm; the D2 distance ranged from 1.0 to 4.1 cm; and the entire humeral length (D3) ranged from 23.3 to 33.3 cm. Iatrogenic injury to the axillary nerve could be reduced by placing pins and screws in proper directions using portable C-arm fluoroscopic guidance, drill-guided protective systems, and a mini-open-incision with muscle spreading and drill protective systems directly placed on the bone. CONCLUSION: Because of physical variability among individual patients and populations, surgeons should consider the possible courses of the axillary nerve when treating proximal humeral fractures.

Combination of pembrolizumab and lenvatinib is a potential treatment option for heavily pretreated recurrent and metastatic head and neck cancer.

BACKGROUND: Immunotherapy has become the current standard of care for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). One potential approach to improve immunotherapy efficacy is to combine pembrolizumab, an anti-PD-1 agent, with lenvatinib, a potent multikinase inhibitor. In this study, we presented our up-to-date experience with pembrolizumab/lenvatinib combination therapy in heavily pretreated R/M HNSCC. METHODS: Patients who had R/M HNSCC, were ineligible for curative treatment, progressed after at least two lines of systemic treatment and had received pembrolizumab/lenvatinib combination therapy were enrolled in this study. The primary endpoint was the objective response rate. The secondary endpoints included the disease control rate, overall survival, progression-free survival, and the duration of response. RESULTS: A total of 14 patients were enrolled in this study. All the patients had received at least two lines of systemic treatment and radiation therapy, and 71% of patients had failed previous anti-PD-1 treatment. The objective response rate of pembrolizumab/lenvatinib combination therapy was 28.6% (95% confidence interval [CI], 5.0%-52.2%). The disease control rate was 42.9% (95% CI, 17.0%-68.8%). The overall survival and progression-free survival were 6.2 months (95% CI, 2.9-9.6) and 4.6 months (95% CI, 0.05-0.9.2), respectively. Of those who had failed previous anti-PD-1 therapy, partial responses were observed in two patients. All the patients with partial responses were in the tumor proportion score <50 and combined positive score 1 to 19 groups. CONCLUSION: Our study provided up-to-date evidence that pembrolizumab/lenvatinib combination therapy achieved objective responses in both heavily pretreated and anti-PD-1 refractory R/M HNSCC patients. This study supported the use of pembrolizumab/lenvatinib combination therapy in R/M HNSCC patients without standard of care.

Diabetes Is the Most Critical Risk Factor of Adverse Complications After Peritoneal Dialysis Catheter Placement.

Introduction: Peritoneal dialysis (PD) is a kind of renal replacement therapy for end-stage renal disease (ESRD). While PD has many advantages, various complications may arise. Methods: This retrospective study analyzed the complications of ESRD patients who received PD catheter implantation in a single medical center within 15 years. Results: This study collected 707 patients. In the first 14 days after PD implantation, 54 patients experienced bleeding complications, while 47 patients experienced wound infection. Among all complications, catheter-related infections were the most common complication 14 days after PD implantation (incidence: 38.8%). A total of 323 patients experienced PD catheter removal, of which 162 patients were due to infection, while 96 were intentional due to kidney transplantation. Excluding those whose catheters were removed due to transplantation, the median survival of the PD catheter was 4.1 years; among them, patients without diabetes mellitus (DM) were 7.4 years and patients with DM were 2.5 years (p < 0.001). Further, 50% probability of surviving was beyond 3.5 years in DM patients with HbA1CC < 7 and 1.6 years in DM patients with HbA1C <7 (p ≥ 0.001). Conclusions: Catheter-related infections were the most common complications following PD catheter implantation. DM, especially with HbA1C ≥7, significantly impacted on the catheter-related infection and the survival probability of the PD catheter.

Surgical Intervention Strategies of Necrotizing Pancreatitis With Abdominal Compartment Syndrome.

OBJECTIVE: Acute pancreatitis can usually recover after conservative treatment. Five to 10 percent of acute pancreatitis may proceed into peripancreatic fluid collection and necrosis development, called necrotizing pancreatitis (NP), which has a high mortality rate. If it is accompanied by the occurrence of abdominal compartment syndrome (ACS) and does not respond to medical therapy, surgical intervention is indicated. METHODS: We analyzed our experience of surgical intervention strategies for NP patients with medically irreversible ACS from January 1, 2004, to December 31, 2018. RESULTS: Of the 47 NP patients with ACS, mean Ranson score was 6.5, mean Acute Physiology and Chronic Health Evaluation II score was 22.2, and Modified computed tomography severity index score was all 8 or greater. The mean total postoperative hospital length of stay was 80.2 days, of which the mean intensive care unit length of stay was 16.6 days. The overall complication rate was 31.9%. The mortality rate was 8.5%. Among the 47 patients, only fungemia was significantly associated with mortality incidence. CONCLUSIONS: The combination of multiple drainage tube placement, feeding jejunostomy, and ileostomy at the same time were effective surgical intervention strategies for NP patients with ACS, which brought a lower mortality rate.

Effect of Primary Tumor Location on Postmetastasectomy Survival in Patients with Colorectal Cancer Liver Metastasis.

BACKGROUND: The effects of primary tumor location on colorectal liver metastasis (CRLM) and post-hepatic-metastasectomy overall survival (OS) are controversial. This study evaluated the difference in post-hepatic-metastasectomy OS among right-sided colon, left-sided colon, and rectal cancer groups. METHODS: In total, 381 patients who underwent curative-intent CRLM resection were enrolled. Patients were grouped based on the primary tumor location (right-sided, left-sided, and rectum). The Kaplan-Meier analysis and log-rank test were performed for survival analysis. The univariate and multivariate analyses of clinical and pathological factors were performed using the Cox proportional hazards model. RESULTS: Significant OS difference was noted among the three groups (log-rank, p = 0.014). The multivariate analysis revealed a 32% lower death risk in left-sided colon cancer compared with right-sided colon cancer (hazard ratio [HR] 0.68, p = 0.042), whereas no OS difference was noted between the rectal cancer and right-sided colon cancer groups. The left- versus right-sided OS advantage was noted only in the KRAS wild-type subgroup (HR 0.46, p = 0.002), and a rectal versus right-sided OS disadvantage was noted in the KRAS mutant subgroup (HR 1.78, p = 0.03). CONCLUSIONS: The CRLM post-hepatic-metastasectomy OS was superior in left-sided colon cancer than in right-sided colon cancer and was similar in rectal and right-sided colon cancer. The OS difference in different primary tumor locations is dependent on KRAS mutation status, with a decreased left- versus right-sided death risk noted only in KRAS wild-type colon cancer and an increased rectal versus right-sided death risk noted only in KRAS mutant colon cancer.

Preemptive light sedation in intensive care unit may reduce pulmonary complications in geriatrics receiving pancreaticoduodenectomy.

BACKGROUND: Patients undergoing pancreaticoduodenectomy (PD) for periampullary lesions are usually elderly with a high risk of postoperative morbidity and mortality. This retrospective cohort study investigated whether postoperative preemptive light sedation aids in recovery of elderly patients following PD. METHODS: Ninety-nine geriatric patients undergoing PD at one hospital were enrolled from 2009 to 2018. Patients in the sedation group received mechanical ventilation support and preemptively light sedation with fentanyl and propofol or dexmedetomidine in the first 5 days postoperatively in the intensive care unit (ICU). Patients in the control group underwent early extubation and received morphine for pain control but no postoperative sedatives in the ordinary ward. Patients in the two groups were matched 1:1 using propensity scoring. The postoperative complication rate, surgical mortality, and postoperative hospital length of stay (LOS) were recorded. We also tested inflammation in an immortal human bronchial epithelial cell line. RESULTS: After 1:1 matching, 40 patients in the sedation group were compared with 40 patients in the control group. The sedation group had a significantly lower pulmonary complication rate and fewer patients with postoperative gastroparesis. Both groups had similar postoperative hospital LOS and identical surgical mortality rates. Patients in the sedation group had significantly better postoperative quality of life, including less pain and less heartbeat variation. In vitro cell experiments supported the above clinical observations, showing that adequate use of sedatives could significantly elevate the cell viability rate, protect cells from damage, decrease interleukin-6 production, and reduce inflammation. CONCLUSION: Postoperative preemptive light sedation in the ICU in geriatric patients following PD may not only reduce the rates of postoperative pulmonary complications and gastroparesis but also improve postoperative quality of life without prolonging the postoperative hospital LOS.