Long-Term Outcomes of S-1 Combined With Low-Dose Docetaxel as Neoadjuvant Chemotherapy (N-1 Study, Phase II Trial) in Patients With Operable Breast Cancer.

BACKGROUND: We previously reported that S-1 and low-dose docetaxel (DOC) (N-1 study, phase II trial) could be a well-tolerated and effective neoadjuvant chemotherapies (NACs) for patients with operable breast cancer. Herein, we analyzed the long-term outcomes and developed clinicopathological and molecular predictors of pathological complete response (pCR). PATIENTS AND METHODS: Eighty-three patients received S-1 (40 mg/m2 orally on days 1-14) and DOC (40 mg/m2 intravenously on day 1) every 3 weeks for 4 to 8 cycles. Disease-free survival (DFS) and overall survival (OS) were analyzed for each population with a pCR status. To assess the relationship between pCR and clinicopathological factors such as tumor-infiltrating lymphocytes (TILs, 1+ <10%, 2+ 10%-50%, and 3+ >50%) and nuclear grade (NG), microarray was used to compare the microRNA profiles of the pCR and non-pCR groups using core needle biopsy specimens. RESULTS: With a median follow-up duration of 99.0 (range, 9.0-129.0) months, the 5-year DFS and OS rates were 80.7% and 90.9%, respectively. The 5-year OS rate of the pCR group was significantly better than that of the non-pCR group (100% vs. 86.2%, p = .0176). Specifically, in triple-negative patients, the difference was significant (100% vs. 60.0%, p = .0224). Multivariate analysis revealed that high TILs (≥2-3+) and NG 2-3 independently predicted pCR. Microarray data revealed that 3 miRNAs (miR-215-5p, miR-196a-5p, and miR-196b-5p) were significantly upregulated in the pCR group. CONCLUSION: Our NAC regimen achieved favorable long-term outcomes and significantly improved OS in the pCR group. High TILs, NG 2-3, and some miRNAs may be predictors of pCR.

Absolute Lymphocyte Count Changes During Neoadjuvant Chemotherapy are Associated With Prognosis of Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Patients.

NTRODUCTION/BACKGROUND: Some reports have shown that absolute lymphocyte count (ALC) is associated with prognosis in breast cancer; however, the impact of ALC changes remains unclear. This study aimed to investigate the relationship between ALC changes during neoadjuvant chemotherapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients and disease prognosis. PATIENTS AND METHODS: This retrospective cohort study January 2010 to September 2020) included patients diagnosed with HER2-positive breast cancer and treated with trastuzumab-based neoadjuvant chemotherapy. The ALC ratio was defined as the ALC value after administration of the anti-HER2 drug divided by the ALC value before administration. The optimal ALC ratio cut-off value was identified using the receiver operating characteristic curve analysis and Youden's index. The relationship between the ALC ratio and disease-free survival was assessed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. RESULTS: Data from a total of 100 HER2-positive breast cancer patients were analyzed. The cut-off value of the ALC ratio was set as 1.142. The median follow-up period was 52.0 (range: 5.1-123.7) months. The 5-year disease-free survival rates were 88.4% and 60.9% in the high-and low-ALC ratio groups, respectively, and were significantly higher in the high-ALC ratio group (p = .0031). The ALC ratio was an independent prognostic factor in multivariate Cox proportional hazards analysis (p = .0032). CONCLUSION: HER2-positive breast cancer patients with a higher ALC ratio during trastuzumab-based neoadjuvant chemotherapy may have a better prognosis than their counterparts.

Sarcoidosis-lymphoma syndrome with portal hypertension: diagnostic clues and approach.

Sarcoidosis-lymphoma syndrome associated with portal hypertension is very rare. A 68-year-old female presented with a 5 kg weight loss in 6 months. Soluble interleukin-2 receptor activity was increased and total platelet count was decreased. Contrast-enhanced computed tomography showed the presence of hepatosplenomegaly and a 3 cm-sized tumor in segment 3 of the liver. The hepatic venous catheterization showed mild portal hypertension. On fluorodeoxyglucose-positron emission tomography/computed tomography, progressive malignant lymphoma was suspected. However, bone marrow biopsy showed multiple noncaseating granulomas. A laparoscopic liver biopsy revealed that the liver tumor had features of Hodgkin lymphoma. There were multiple noncaseating epithelioid granulomas in the portal tracts of the liver. Splenectomy for splenomegaly and partial hepatectomy for the liver tumor were performed. Pathological examination of the resected specimens revealed multiple noncaseating epithelioid granulomas in the liver and spleen. Histopathology of the liver tumor confirmed classic Hodgkin lymphoma with mixed cellularity. We conclude that hepatic venous catheterization, positron emission tomography/computed tomography, and pathological examinations of bone marrow, liver, and spleen are crucial for the diagnosis of sarcoidosis-lymphoma syndrome associated with portal hypertension.

Stepwise partial splenic embolization for portal hypertension based on a new concept: Splanchnic caput Medusae.

Management of splenomegaly with thrombocytopenia is important in the treatment of portal hypertension. We propose a new concept: "Splanchnic Caput Medusae" in which enlarged spleen is her face and portal collateral pathways are her snake hairs. We report 2 demonstrable cases who were treated based on this new concept. Case 1 with refractory esophageal varices and splenomegaly was treated by stepwise partial splenic embolization (PSE) and endoscopic injection sclerotherapy with ligation. Spleen/liver volume ratio changed from 0.33 to 0.10. Hepatic venous pressure gradient changed from 19 to 14 mmHg. Case 2 with mesenteric shunt and splenomegaly was treated by stepwise PSE and retrograde obliteration. Spleen/liver volume ratio changed from 0.70 to 0.05. Hepatic venous pressure gradient changed from 11 to 7 mmHg. In these 2 cases, 3D-CT reconstruction images after treatment revealed that spleen- portal system reversed almost to normal form. We conclude that splenomegaly and portal collateral pathways could be considered as "Splanchnic Caput Medusae" and have to be treated by stepwise PSE.

Flood syndrome managed by partial splenic embolization and percutaneous peritoneal drainage.

Flood syndrome is a rare complication of cirrhosis of liver accompanied by ascites and a sudden rupture of umbilical hernia causing drainage of ascitic fluid from abdominal cavity. We report management of a case of Flood syndrome which was caused by rupture of incisional hernia. The clinical picture was similar to well described and widely accepted Flood syndrome. A 70-year-old female with decompensated hepatitis C cirrhosis was transported to the emergency department with a sudden drainage of ascitic fluid after sudden dehiscence of pre-existing incisional hernia and diffuse abdominal tenderness. Initially, she was managed by applying ostomy bag and diuretics to reduce the ascites. On 8th day of admission, a 16 Fr. drain was percutaneously placed in the left lower abdominal quadrant to divert the fluid from the abdominal wall defect. On 13th day, 80% partial splenic embolization (PSE) was attempted to control portal hypertension to reduce the ascites volume. After PSE, the hepatic venous pressure gradient reduced from 28 to 21cm H2O. The peritoneal drain was removed on 16th day and she was discharged on 22nd day. We conclude that PSE and temporary percutaneous peritoneal drainage are useful option to manage Flood syndrome.

Hemoperitoneum and sepsis from transhepatic gallbladder perforation of acute cholecystitis: A case report.

We report a case of hemoperitoneum and sepsis from transhepatic gallbladder perforation in an 87-year-old male with acute cholecystitis who had past history of endoscopic sphincterotomy for common bile duct stone. Contrast-enhanced computed tomography (CT) showed intrahepatic and subcapsular low density areas. A wall defect of gallbladder was seen in coronal and sagittal - sections at the liver bed. Fluids obtained through the paracentesis were hemorrhagic. Percutaneous transhepatic gallbladder drainage (PTGBD) was attempted. First cholangiography revealed an orifice of fistula. Further injection of contrast medium drained into the intrahepatic secondary abscess and intraperitoneal cavity confirming the diagnosis of transhepatic gallbladder perforation. We conclude that contrast-enhanced CT with coronal and sagittal - sections and cholangiography via PTGBD tube are useful to confirm diagnosis of transhepatic gallbladder perforation.

Surfactant protein A suppresses lung cancer progression by regulating the polarization of tumor-associated macrophages.

Surfactant protein A (SP-A) is a large multimeric protein found in the lungs. In addition to its immunoregulatory function in infectious respiratory diseases, SP-A is also used as a marker of lung adenocarcinoma. Despite the finding that SP-A expression levels in cancer cells has a relationship with patient prognosis, the function of SP-A in lung cancer progression is unknown. We investigated the role of SP-A in lung cancer progression by introducing the SP-A gene into human lung adenocarcinoma cell lines. SP-A gene transduction suppressed the progression of tumor in subcutaneous xenograft or lung metastasis mouse models. Immunohistochemical analysis showed that the number of M1 antitumor tumor-associated macrophages (TAMs) was increased and the number of M2 tumor-promoting TAMs was not changed in the tumor tissue produced by SP-A-expressing cells. In addition, natural killer (NK) cells were also increased and activated in the SP-A-expressing tumor. Moreover, SP-A did not inhibit tumor progression in mice depleted of NK cells. Taking into account that SP-A did not directly activate NK cells, these results suggest that SP-A inhibited lung cancer progression by recruiting and activating NK cells via controlling the polarization of TAMs.

SU6668, a multiple tyrosine kinase inhibitor, inhibits progression of human malignant pleural mesothelioma in an orthotopic model.

BACKGROUND AND OBJECTIVE: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm of the mesothelium with high chemotherapeutic resistance. In this study, the preclinical therapeutic activity of the multiple tyrosine kinase inhibitor, SU6668, against MPM was examined. METHODS: Two human MPM cell lines with different pro-angiogenic cytokine expression, Y-MESO-14 cells that express high levels of vascular endothelial growth factor (VEGF) and MSTO-211H cells that express high levels of basic fibroblast growth factor (bFGF), were orthotopically inoculated into the thoracic cavities of mice with severe combined immunodeficiency. The mice with MPM were treated or not treated with SU6668 (200 mg/kg/day). RESULTS: SU6668 abrogated the proliferation of endothelial cells stimulated by VEGF or bFGF, but did not directly affect the growth of human MPM cells in vitro. In this orthotopic implantation model, treatment with SU6668 effectively reduced tumour weight and pleural effusion volumes, in association with inhibition of the growth of tumour vasculature. More importantly, treatment with SU6668 significantly prolonged survival time in mice with MPM. CONCLUSIONS: These findings suggest that SU6668 has a promising therapeutic effect on the progression of MPM in vivo through its anti-angiogenic effects.