Low-power pure-cut hot snare polypectomy for colorectal polyps 10-14 mm in size: a multicenter retrospective study.

BACKGROUND AND AIM: Hot snare excision using electrocautery is widely used for large colorectal polyps (>10 mm); however, adverse events occur due to deep thermal injury. Colorectal polyps measuring 10-14 mm rarely include invasive cancer. Therefore, less invasive therapeutic options for this size category are demanding. We have developed hot snare polypectomy with low-power pure-cut current (LPPC HSP), which is expected to contribute to less deep thermal damage and lower risk of adverse events. This study aimed to evaluate the efficacy and safety of LPPC HSP for 10-14 mm colorectal polyps, compared with conventional endoscopic mucosal resection (EMR). METHODS: In this multicenter, retrospective, observational study, clinical outcomes of EMR and LPPC HSP for 10-14 mm nonpedunculated colorectal polyps between January 2021 and March 2022 were compared using propensity score matching. RESULTS: We identified 203 EMR and 208 LPPC HSP cases. After propensity score matching, the baseline characteristics between the groups were comparable, with 120 pairs. The en bloc and R0 resection rates were not significantly different between EMR and LPPC HSP groups (95.8% vs 97.5%, P = 0.72; 90.0% vs 91.7%, P = 0.82). The rates of delayed bleeding and perforation did not differ between the groups. CONCLUSIONS: Compared with conventional EMR, LPPC HSP showed a similar resection ability without an increase in adverse events. These results suggest that LPPC HSP is a safe and effective treatment for 10-14 mm nonpedunculated colorectal polyps.

Effect of Direct-Acting Antiviral Agents on Gastroesophageal Varices in Patients with Hepatitis C Virus-Related Cirrhosis.

Aim: In patients with hepatitis C virus-related liver cirrhosis (LC) who achieve sustained virological responses (SVRs) through treatment with direct-acting antiviral agents (DAAs), it remains unclear whether there are improvements in gastroesophageal varices (GEVs) and portal hypertension. We investigated changes in liver function and GEVs that occurred after DAA therapy. Materials and Methods: We evaluated the medical records of 195 patients with hepatitis C virus-related LC who received DAAs. A total of 171 patients achieved SVRs, among whom 36 had GEVs before or after receiving DAA therapy. The liver function, fibrosis, and GEVs were re-evaluated every 6 months after receiving DAA therapy. The risk factors for progressive GEVs were investigated. Results: DAA therapy resulted in improvements in liver function (indicated by aspartate transaminase, alanine transaminase, and serum albumin levels) and fibrosis (indicated by type IV collagen levels and the Fibrosis-4 index). After receiving DAA therapy, 27 patients had stable GEVs and 9 had progressive GEVs. With respect to GEV grades before DAA therapy, there was a significant difference between patients with stable and progressive GEVs (p = 0.027). Presence of grade-2 GEVs before starting DAA therapy was a risk factor for GEV progression (odds ratio: 5.83; p = 0.04). Patients with grade-2 GEVs had significantly shorter progression-free periods than those with grade < 2 GEVs (p = 0.025). Conclusions: DAA therapy does not ameliorate GEVs. Furthermore, grade-2 GEVs can worsen after DAA therapy. Therefore, patients with GEVs of grades ≥ 2 should undergo endoscopic surveillance after receiving DAAs.

Efficacy and safety of S-1 following gemcitabine with cisplatin for advanced biliary tract cancer.

Background Combination therapy of gemcitabine with cisplatin (GC) is a standard first-line therapy for unresectable or recurrent biliary tract cancer (BTC). S-1 is often used as a second-line therapy in clinical practice, based on the results of some clinical studies investigating its efficacy and safety following gemcitabine monotherapy. However, few studies have reported on the clinical outcomes of S-1 following GC. The purpose of this study was to elucidate the efficacy and safety of S-1 following GC for unresectable and recurrent BTC. Methods We retrospectively collected the data of 116 patients (pts) who were treated with S-1 as a second-line therapy following GC for unresectable or recurrent BTC at Shizuoka Cancer Center (November 2009 to July 2019). Results Of these 116 pts., 84 were assessable. Patient characteristics were as follows: intrahepatic bile duct/extrahepatic bile duct/gallbladder cancer, 30/23/31 pts.; metastatic/recurrent/locally advanced, 57/17/10 pts. The median time to treatment failure and overall survival were 2.5 and 6.0 months, respectively. Among 65 pts. with measurable lesions, the overall response rate was 3.1% (2/65 pts) and the disease control rate was 24.6% (19/65 pts). The common grade 3/4 toxicities included anemia (12%), neutropenia (4%), infections (16%), fatigue (6%), and diarrhea (4%). Dose reduction or treatment schedule modification of S-1 was required in 29 pts. (34.5%), and 17 pts. (20%) terminated S-1 due to adverse events. Conclusions The efficacy and safety of S-1 following GC were almost the same as those of S-1 following GEM monotherapy for unresectable or recurrent BTC.

Risk stratification and prognostic factors in patients with unresectable undifferentiated carcinoma of the pancreas.

BACKGROUND: Undifferentiated carcinoma (UC) of the pancreas has been considered a highly aggressive malignancy. However, only a few studies have systematically described the clinical course of UC patients. The aim of this study was to clarify the prognosis and construct a prognostic model for patients with unresectable UC. METHODS: This study was conducted at 17 institutions in Japan, and a total of 55 patients were analyzed. RESULTS: The median overall survival (OS) of patients with unresectable UC was 3.95 months. In the multivariate Cox proportional hazards (CPH) model, age ≥65 years, Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2, and C-reactive protein (CRP) >10 mg/L were independent prognostic factors for OS (age ≥65 years: hazard ratio [HR], 2.732; 95% confidence interval [CI], 1.353-5.515; ECOG PS ≥ 2: HR, 7.866; 95% CI, 1.981-31.241; CRP >10 mg/L: HR, 1.956; 95% CI, 1.013-3.775). Based on the ß coefficients from the CPH model, the prognostic scores were defined as follows: age ≥65 years (3 points), ECOG PS ≥ 2 (6 points), and CRP >10 ml/L (2 points). The final prognostic model was the sum of the points. The derived prognostic model stratified patients into high-risk (score ≥4) and low-risk (score 0-3) groups, with significant differences in OS (1.45 vs. 8.19 months, respectively; p < 0.001). CONCLUSIONS: The prognostic model stratified patients into high-risk and low-risk groups. These findings suggest that this model can serve as a tool for patient information and decision-making with regard to the therapeutic strategy for UC.

Clinical and radiation dose-volume factors related to pneumonitis after treatment with radiation and durvalumab in locally advanced non-small cell lung cancer.

Introduction Durvalumab has been shown to confer a survival benefit after definitive chemoradiotherapy in the patients with locally advanced non-small cell lung cancer, but no studies have attempted to identify risk factors for pneumonitis after durvalumab therapy. The purpose of this study was to investigate associations between clinical and radiation dose-volume factors, and the severity of pneumonitis. Methods We retrospectively assessed the cases of 30 patients who had been started on durvalumab therapy between July 2018 and February 2019. In this study we evaluated the percentage of lung volume receiving radiation dose in excess of 20 Gy (V20) as radiation dose-volume factor. We compared V20 and some baseline factors between a grade 0 or 1 (Gr 0/1) pneumonitis group and a grade 2 or more (≥Gr 2) pneumonitis group, and we performed a logistic regression analysis to establish the associations between variables and ≥ Gr 2 pneumonitis. Results Pneumonitis had developed in 22 patients (73.3%): Gr 1/2/3-5 in 8 (26.7%)/14 (46.7%) /0 (0%), respectively. The difference in V20 between the Gr 0/1 group and Gr 2 group (median: 20.5% vs. 23.5%, p = 0.505) was not statistically significant, and thus V20 was not a risk factor for Gr 2 pneumonitis (odds ratio: 1.047, p = 0.303). None of the clinical factors, including sex, age, smoking history, presence of baseline pneumonitis, type of radiation therapy, location of lesion and facility, were risk factors. Conclusions Our study suggest that the severity of pneumonitis after durvalumab is unrelated to V20 or any of the clinical factors assessed in this study.

Clinical outcomes of chemotherapy in patients with undifferentiated carcinoma of the pancreas: a retrospective multicenter cohort study.

BACKGROUND: Undifferentiated carcinoma (UC) of the pancreas is a rare subtype of pancreatic cancer. Although UC has been considered a highly aggressive malignancy, no clinical studies have addressed the efficacy of chemotherapy for unresectable UC. Therefore, we conducted multicenter retrospective study to investigate the efficacy of chemotherapy in patients with UC of the pancreas. METHODS: This multicenter retrospective cohort study was conducted at 17 institutions in Japan between January 2007 and December 2017. A total of 50 patients treated with chemotherapy were analyzed. RESULTS: The median overall survival (OS) in UC patients treated with chemotherapy was 4.08 months. The details of first-line chemotherapy were as follows: gemcitabine (n = 24), S-1 (n = 12), gemcitabine plus nab-paclitaxel (n = 6), and other treatment (n = 8). The median progression-free survival (PFS) was 1.61 months in the gemcitabine group, 2.96 months in the S-1 group, and 4.60 months in the gemcitabine plus nab-paclitaxel group. Gemcitabine plus nab-paclitaxel significantly improved PFS compared with gemcitabine (p = 0.014). The objective response rate (ORR) was 4.2% in the gemcitabine group, 0.0% in the S-1 group, and 33.3% in the gemcitabine plus nab-paclitaxel group. Gemcitabine plus nab-paclitaxel also showed a significantly higher ORR compared with both gemcitabine and S-1 (gemcitabine plus nab-paclitaxel vs. gemcitabine: p = 0.033; gemcitabine plus nab-paclitaxel vs. S-1: p = 0.034). A paclitaxel-containing first-line regimen significantly improved OS compared with a non-paclitaxel-containing regimen (6.94 months vs. 3.75 months, respectively; p = 0.041). After adjustment, use of a paclitaxel-containing regimen in any line was still an independent predictor of OS (hazard ratio for OS, 0.221; 95% confidence interval, 0.076-0.647; p = 0.006) in multiple imputation by chained equation. CONCLUSIONS: The results of the present study indicate that a paclitaxel-containing regimen would offer relatively longer survival, and it is considered a reasonable option for treating patients with unresectable UC.

Improvement in the medial meniscus posterior shift following anterior cruciate ligament reconstruction.

PURPOSE: Anterior cruciate ligament (ACL) reconstruction can reduce the risk of developing osteoarthritic knees. The goals of ACL reconstruction are to restore knee stability and reduce post-traumatic meniscal tears and cartilage degradation. A chronic ACL insufficiency frequently results in medial meniscus (MM) injury at the posterior segment. How ACL reconstruction can reduce the deformation of the MM posterior segment remains unclear. In this study, we evaluated the form of the MM posterior segment and anterior tibial translation before and after ACL reconstruction using open magnetic resonance imaging (MRI). METHODS: Seventeen patients who underwent ACL reconstructions without MM injuries were included in this study. MM deformation was evaluated using open MRI before surgery and 3 months after surgery. We measured medial meniscal length (MML), medial meniscal height (MMH), medial meniscal posterior body width (MPBW), MM-femoral condyle contact width (M-FCW) and posterior tibiofemoral distance (PTFD) at knee flexion angles of 10° and 90°. RESULTS: There were no significant pre- and postoperative differences during a flexion angle of 10°. At a flexion angle of 90°, MML decreased from 43.7 ± 4.5 to 41.4 ± 4.5 mm (P < 0.001), MMH from 7.5 ± 1.4 to 6.9 ± 1.4 mm (P = 0.006), MPBW from 13.1 ± 2.0 to 12.2 ± 1.9 mm (P < 0.001) and M-FCW from 10.0 ± 1.5 to 8.5 ± 1.5 mm (P < 0.001) after ACL reconstruction. The PTFD increased from 2.1 ± 2.8 to 2.7 ± 2.4 mm after ACL reconstruction (P = 0.015). CONCLUSIONS: ACL reconstruction affects the contact pattern between the MM posterior segment and medial femoral condyle and can reduce the deformation of the MM posterior segment in the knee-flexed position by reducing abnormal anterior tibial translation. It possibly prevents secondary injury to the MM posterior segment and cartilage that progresses to knee osteoarthritis. LEVEL OF EVIDENCE: IV.

[Dihydropyrimidine dehydrogenase deficiency causes severe adverse effects of capecitabine].

We report the case of a 61-year-old man who experienced severe adverse effects of capecitabine because of dihydropyrimidine dehydrogenase (DPD) deficiency. In 2016, he visited our hospital for adenocarcinoma of the gastroesophageal junction and was prescribed neoadjuvant chemotherapy with capecitabine, cisplatin, and trastuzumab. On day 14 of chemotherapy, he developed severe diarrhea, canker sores, enterocolitis, febrile neutropenia, and thrombocytopenia. He was then urgently hospitalized, and anticancer treatment was stopped. We administered antibiotics and G-CSF, and he gradually recovered. However, he complained of severe bloody stools due to hemorrhagic enteritis;hence, we performed a bowel resection. The level of DPD protein, which metabolizes 5-fluorouracil (FU), was very low (2.83U/mg). Therefore, he was diagnosed with DPD deficiency, based on DPD protein or urinary pyrimidine levels, which caused serious adverse effects of capecitabine. It is a rare condition, and 5-FU administration should be avoided in DPD deficiency cases.

Hyaluronan stimulates chondrogenic gene expression in human meniscus cells.

Purpose/Aim of the Study: Inner meniscus cells have a chondrocytic phenotype, whereas outer meniscus cells have a fibroblastic phenotype. In this study, we examined the effect of hyaluronan on chondrocytic gene expression in human meniscus cells. MATERIALS AND METHODS: Human meniscus cells were prepared from macroscopically intact lateral meniscus. Inner and outer meniscus cells were obtained from the inner and outer halves of the meniscus. The cells were stimulated with hyaluronan diluted in Dulbecco's modified Eagle's medium without serum to the desired concentration (0, 10, 100, and 1000 µg/mL) for 2-7 days. Cellular proliferation, migration, and polymerase chain reaction analyses were performed for the inner and outer cells separately. Meniscal samples perforated by a 2 mm diameter punch were maintained for 3 weeks in hyaluronan-supplemented medium and evaluated by histological analyses. RESULTS: Hyaluronan increased the proliferation and migration of both meniscus cell types. Moreover, cellular counts at the surface of both meniscal tissue perforations were increased by hyaluronan treatments. In addition, hyaluronan stimulated α1(II) collagen expression in inner meniscus cells. Accumulation of type II collagen at the perforated surface of both meniscal samples was induced by hyaluronan treatment. Hyaluronan did not induce type I collagen accumulation around the injured site of the meniscus. CONCLUSION: Hyaluronan stimulated the proliferation and migration of meniscus cells. Our results suggest that hyaluronan may promote the healing potential of meniscus cells in damaged meniscal tissues.

Histological and biological comparisons between complete and incomplete discoid lateral meniscus.

The discoid lateral meniscus (DLM) is an anatomically abnormal meniscus that covers a greater area of the tibial plateau than the normal meniscus. The DLM is classified into two types: complete (CDLM) and incomplete (ICDLM) types. In this study, we investigated the histological and cell biological characteristics of CDLM and ICDLM. The number of blood vessels, proteoglycan deposition, and collagen distribution were assessed using meniscal tissues. Collagen production was also investigated in CDLM and ICDLM cells. The intercondylar region of the CDLM had a higher number of blood vessels than the inner region of the ICDLM. Safranin O staining density and type II collagen deposition in ICDLM were higher than those in CDLM. Type II collagen-positive cells were higher in ICLDM than in CDLM. CDLM cells showed slender fibroblastic morphology, while ICDLM cells were triangular chondrocytic in shape. This study demonstrated that the intercondylar region of the CDLM showed similar properties to the outer region of the meniscus. The inner region of the ICDLM, on the other hand, differed from the intercondylar region of the CDLM. Our results suggest that the intercondylar region of the CDLM may have a high healing potential like the outer meniscus.

The anterior cruciate ligament-lateral meniscus complex: A histological study.

The anterior root of the lateral meniscus (LM) dives underneath the tibial attachment of the anterior cruciate ligament (ACL). Although the distinct role of meniscal attachments has been investigated, the relationship between the LM anterior insertion (LMAI) and ACL tibial insertion (ACLTI) remains unclear. This study histologically analyzed the LMAI and ACLTI. Samples were divided into four regions in an anterior-to-posterior direction. Histological measurements of these insertion sites were performed using safranin O-stained coronal sections. Distribution and signal densities of type I and II collagen were quantified. The ACLTI and LMAI formed the ACL-LM complex via fiber connections. The anterior part of the ACLTI had a widespread attachment composed of dense fibers. Attachment fibers of the LMAI became dense and wide gradually at the middle-to-posterior region. The ACL-LM transition zone (ALTZ) was observed between the LMAI and the lateral border of the ACLTI at the middle part of the ACL tibial footprint. Type II collagen density of the LMAI was higher than that of the ACLTI and ALTZ. Our results can help create an accurate tibial bone tunnel within the dense ACL attachment during ACL reconstruction surgery.

Features of human autologous hamstring graft elongation after pre-tensioning in anterior cruciate ligament reconstruction.

PURPOSE: Precise pre-tensioning protocol of the graft has not been determined in anterior cruciate ligament (ACL) reconstruction. The aims of this study are to measure the human autologous graft elongation, and to reveal what portion of the graft elongated greater after pre-tensioning in ACL reconstruction. METHODS: Twenty-four hamstring tendon grafts which were harvested from patients were included. A continuous load of 150 N was applied to the graft twice for 30 seconds each (150 N-1 minute), and the same loading was repeatedly applied (150 N-2 minute). The amount of elongation of the tendon portion (Length T) and the stitched portion (Length S) were measured after each pre-tensioning. RESULTS: Length S gradually increased by 1.57 ± 0.67 mm after the 150 N-1 minute pre-tensioning and by 2.12 ± 0.76 mm after the 150 N-2 minute pre-tensioning, respectively. Length T was not significantly elongated after 150 N-1 min (p = 0.66) and 150 N-2 min (p = 0.59). CONCLUSIONS: Graft elongation of the approximately 2 mm was observed, particularly in the stitched portion. It is necessary for a surgeon to focus on careful removal of slack from each stitch during suturing.

Postoperative change in the length and extrusion of the medial meniscus after anterior cruciate ligament reconstruction.

PURPOSE: The medial meniscus is a secondary stabilizer of anterior tibial translation in anterior cruciate ligament (ACL)-deficient knees. ACL reconstruction effectively restores an increased anterior tibial translation in the ACL-deficient knee. However, knee osteoarthritis sometimes develops in ACL-reconstructed patients during a long-term follow-up period. We hypothesized that the medial meniscal position would be different between the ACL-deficient and reconstructed knees. The aim of this study was to investigate pre-operative and postoperative location of the medial meniscus in patients who underwent ACL reconstruction. METHODS: ACL-reconstructed knees (28 knees) and normal knees (27 knees) were investigated. Medial tibial plateau length (MTPL) and medial tibial plateau width (MTPW) were determined using radiographic images. Magnetic resonance imaging (MRI)-based medial meniscal length (MML), medial meniscal width (MMW), and medial meniscal extrusion (MME) were measured. Postoperative change in the MML, MMW, and MME were evaluated and compared with those in normal knees. RESULTS: No significant differences between the ACL-deficient (pre-operative) and normal groups were noted. The ACL-reconstructed (postoperative) group showed an increase in the MML, in the percentage of the MML (%MML = 100 MML/MTPL), and in the MME. Significant differences between postoperative and normal groups were observed in the MML, %MML, and MME. MMW and MMW percentage (100 MMW/MTPW) were similar in all groups. CONCLUSIONS: The anteroposterior length and radial extrusion of the medial meniscus increased after ACL reconstruction. Transposition of the medial meniscus may be a possible cause of developing further degenerative knee joint disorders after ACL reconstruction.

CD34(+) cell therapy is safe and effective in slowing the decline of hepatic reserve function in patients with decompensated liver cirrhosis.

BACKGROUND AND AIM: Preclinical studies in rodent models of chronic liver fibrosis have shown that transplantation of peripheral blood (PB) CD34(+) cells leads to hepatic regeneration and a reduction of liver fibrosis by suppressing hepatic stellate cell activity and increasing matrix metalloproteinase activity. The aim of this study was to examine the safety and clinical efficacy of intrahepatic transplantation of autologous granulocyte colony-stimulating factor (G-CSF)-mobilized PB-CD34(+) cells in patients with decompensated liver cirrhosis. METHODS: PB-CD34(+) cells were isolated from G-CSF-mobilized apheresis products. Ten patients were treated with G-CSF-mobilized PB-CD34(+) cells (treatment group) and seven patients were treated with standard medical therapy. For mobilization, patients in the treatment group received subcutaneous injections of 10 µg G-CSF/kg/day for 5 days. The cells were then injected at three different doses (5 × 10(5) , 1 × 10(6) and 2 × 10(6) cells/kg) through the hepatic artery. Thereafter, all patients were followed up for 24 months. RESULTS: G-CSF treatment and leukapheresis were well tolerated, and no serious adverse events were observed. Patients in the treatment group had a significant but transient splenomegaly. After 24 weeks, serum albumin was significantly increased in patients who had received middle or high doses of CD34(+) cells compared with baseline. Doppler ultrasound showed a significant increase in hepatic blood flow velocity and blood flow volume after CD34(+) cell therapy. The hepatic vein pressure gradient decreased in two patients who received high-dose CD34(+) cells at week 16. CONCLUSIONS: CD34(+) cell therapy is feasible, safe and effective in slowing the decline of hepatic reserve function.

FOXA1/CK7-positive Esophageal Squamous Cell Carcinoma with Aggressive Liver Metastasis: A Case Report.

Cytokeratin (CK) is a specific marker of adenocarcinoma. However, cases of CK7-positive esophageal squamous cell carcinoma (ESCC) have only rarely been reported. We herein report a case of unresectable CK7-positive ESCC with aggressive liver metastasis following nivolumab treatment initiation. Nivolumab treatment was discontinued after one course because of complications. Notably, the liver metastases exhibited accelerated growth. Immunostaining of the necropsy specimens revealed diffuse positivity for forkhead box protein A1 (FOXA1)/CK7, thus indicating a potent poor immune response. The potential correlation between CK7 expression and the immune checkpoint inhibitor response may offer valuable insights into the development of effective therapeutic strategies.

Effect of Helicobacter pylori infection on esophagogastric variceal bleeding in patients with liver cirrhosis and portal hypertension.

BACKGROUND AND AIMS: Bleeding from esophageal and gastric varices is a fatal event in patients with liver cirrhosis and portal hypertension. However, the effects of Helicobacter pylori (H. pylori) infection on esophagogastric variceal bleeding are not known. The present study was aimed to elucidate the role of H. pylori infection in esophagogastric variceal bleeding. METHODS: The subjects were 196 cirrhotic patients who were admitted to the Kurume University Hospital to treat their esophagogastric varices consisted of 95 with acute bleeding and 101 with nonbleeding but high risk of bleeding. For the diagnosis of H. pylori infection, a (13) C-urea breath test was used, and serum pepsinogen (PG) I and II levels and the PG I/II ratio were also measured. RESULTS: Esophagogastric variceal bleeding was seen in 34.9% (n = 30) of the H. pylori-infected patients (n = 86) and in 59.1% (n = 65) of the noninfected patients (n = 110) (P < 0.0007). There was no significant difference in the infection rate between the bleeding sites of the esophagus and the stomach. The serum PG I and II levels and the PG I/II ratio were 65.6 ng/dL, 14.7 ng/dL, and 4.4, respectively, for the bleeding patients (n = 95), and 43.7 ng/dL, 17.7 ng/dL, and 3.1 for the nonbleeding patients (n = 101). Thus, the nonbleeding patients had significantly higher rate of H. pylori infection and lower acid secretion than bleeding patients (0.001). In addition, multivariate logistic regression analysis showed a significant negative association between H. pylori infection and esophagogastric variceal bleeding. CONCLUSIONS: These results suggest that H. pylori infection has a protective effect against esophagogastric variceal bleeding through the induction of gastric mucosal atrophy and concomitant hypoacidity.

Long-term results of balloon-occluded retrograde transvenous obliteration for gastric fundal varices: hepatic deterioration links to portosystemic shunt syndrome.

BACKGROUND AND AIMS: It is well known that a large portosystemic shunt develops during portal hypertension. In this study, we studied the long-term effects of a large splenorenal shunt (SRS) on liver function and survival. METHODS: The subjects were divided into three groups: an SRS (-) group consisting of cirrhotic patients without SRS; an SRS (+) group consisting of patients with gastric fundal varices and SRS; and a balloon-occluded retrograde transvenous obliteration (B-RTO) group with a completely obliterated SRS by B-RTO. We compared the following among these groups: the total bilirubin levels, serum albumin levels, prothrombin times, changes in Child-Pugh scores, and survival rates. RESULTS: After a 3-year follow-up period the Child-Pugh scores showed significant differences among the SRS (+), SRS (-), and B-RTO groups. The score worsened for the SRS (+) group. The cumulative survival rates were significantly different between the SRS (+) and SRS (-) groups and between the SRS (+) and B-RTO groups. The vital prognosis worsened for the SRS (+) group. CONCLUSIONS: The presence of a large splenorenal shunt (portosystemic shunt) was indicated to lower liver function and vital prognosis. B-RTO, which completely obliterates large splenorenal shunts, inhibited the lowering of hepatic functional reserve and the worsening of vital prognosis, indicating a protective role. Liver pathology and the presence of a large portosystemic shunt each separately result in progressive liver dysfunction and worsen the survival rate. We found that such a pathological condition had occurred due to a large portosystemic shunt, and it should be called 'portosystemic shunt syndrome.'

Pre-treatment tumor size impacts on response to nivolumab in head and neck squamous cell carcinoma.

OBJECTIVE: Baseline tumor size has been reported to be predictive of immune checkpoint inhibitor efficacy in melanoma and lung cancer. We investigated whether pre-treatment tumor size (PTS) is predictive of progression-free survival (PFS) and tumor shrinkage in head and neck squamous cell carcinoma (HNSCC) patients treated with nivolumab. METHODS: We retrospectively assessed 37 patients who had measurable tumor lesions. PTS and post-treatment tumor size were defined as the sum of the size in all measurable lesions. RESULTS: In univariate analysis, PTS below 42 mm, history of radiation therapy, and no use of cetuximab were significantly associated with longer PFS. Among them, small-PTS was an independent predictive factor for PFS in multivariate analysis (hazard ratio: 0.33, p = 0.022). In addition, significantly greater tumor shrinkage was observed for small-PTS than large-PTS (median: -10.0% vs. 23.1%, p = 0.033). CONCLUSION: PTS may impact the response to nivolumab in HNSCC patients.

Feasibility and efficacy of chemoradiotherapy with concurrent split-dose cisplatin after induction chemotherapy with docetaxel/cisplatin/5-fluorouracil for locally advanced head and neck cancer.

Chemoradiotherapy (CRT) with concurrent high-dose cisplatin (CDDP) is a standard treatment for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Docetaxel plus CDDP and 5-fluorouracil (TPF) induction chemotherapy (ICT) prior to CRT is considered for patients at high risk of distant metastases. The purpose of the current study was to evaluate the feasibility and efficacy of CRT with split-dose CDDP after TPF-ICT for LA-SCCHN. A total of 21 LA-SCCHN patients treated with TPF-ICT followed by concurrent CRT with split-dose CDDP between January 2011 and December 2017 were retrospectively analysed. The patients' characteristics were i) median age 66 years (48-75 years); ii) male/female, 21/0; iii) performance status 0-1/2, 20/1; iv) larynx/hypopharynx/oropharynx/oral cavity, 4/8/8/1 and v) clinical stage III/IV, 3/18. The numbers of TPF-ICT cycles 1/2/3 were 2/3/16. Median cumulative doses of CDDP in TPF-ICT and CRT were 180.0 and 206.7 mg/m2, respectively. All patients completed 70 Gy RT. The complete response rate was 76.2%. At a median follow-up of 51.5 months, median PFS and OS were not reached and 65.5 months, respectively. The most common grade 3 or worse toxicities during CRT-ICT were stomatitis (48%), dysphagia (21%), anorexia (17%) and leukopenia (14%). However, no grade 2 or worse nephrotoxicity, neurotoxicity or ototoxicity was observed. The results demonstrated that concurrent CRT with split-dose CDDP after TPF-ICT is feasible and effective for LA-SCCHN.