Human epidermal growth factor 2 overexpressed alpha-fetoprotein-producing-gastric cancer.

PURPOSE: This study aimed to elucidate the clinicopathological characteristics of α-fetoprotein (AFP)-producing gastric carcinoma (AFP-GC) with human epidermal growth factor receptor (HER)2 overexpression to extend the treatment strategy for AFP-GC. METHODS: We analyzed 41 patients with AFP-GC who underwent surgical resection or chemotherapy from 1989 to 2019, and who had over 20ng/mL of serum AFP or positive immunohistochemical AFP expression. HER2 expression status was investigated by immunohistochemistry (IHC) for all patients and by fluorescence in situ hybridization (FISH) for cases with an IHC score of 2+. AFP-GC with an IHC score of 3 + or 2 + and FISH positivity was defined as HER2 overexpressed AFP-GC. The correlation between HER2 status and clinicopathological characteristics and prognosis in AFP-GC was analyzed. RESULTS: HER2 overexpression was detected in 17.1% of AFP-GC patients. The prognosis of the patients with HER2 overexpressed AFP-GC was not significantly different compared to HER2 non-overexpressed AFP-GC. HER2 overexpressed AFP-GC consisted of heterogeneous histology with a higher proportion of mixed-type tumors (p = 0.002). The clinical outcome of AFP-GC with mixed-type of histology tended to be better than other intestinal or diffuse types (p = 0.05). CONCLUSION: HER2 overexpressed AFP-GC consisted of a mixed type of histology, which showed a better prognosis. The results presented that HER2 status in AFP-GC is one of the molecular candidates to improve the prognosis.

Neoadjuvant Chemoradiotherapy for Stage II or III Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: The goal of this retrospective study was to investigate the efficacy and safety of neoadjuvant chemoradiotherapy (CRT) in patients with Stage II or Stage III esophageal squamous cell carcinoma (SCC). PATIENTS AND METHODS: Between January 2004 and December 2014, a total of 86 patients underwent surgical resection in conjunction with preoperative CRT for esophageal SCC in our Institute. RESULTS: A pathological complete response was achieved in 38.7% of patients with Stage II cancer and 20% of patients with Stage III. Postoperative complications were observed in 61.3% of Stage II and 76.4% of Stage III patients. The 5-year overall survival rate (OS) was 83.2% in Stage II and 22.8% in Stage III (p=0.0001). The 5-year disease-free survival (DFS) rate was 67.9% in Stage II and 29.9% in Stage III (p=0.0007). CONCLUSION: Neoadjuvant CRT may improve OS and DFS rates in patients with Stage II esophageal SCC.

Phase II Study of Neoadjuvant Chemotherapy With S-1 and CDDP in Patients With Lymph Node Metastatic Stage II or III Gastric Cancer.

OBJECTIVES: We conducted a phase II trial to investigate the efficacy and safety of neoadjuvant chemotherapy (NAC) comprising S-1 and cisplatin (CDDP) followed by extensive resection in the management of resectable locally advanced gastric cancer with lymph node (LN) metastases. METHODS: Patients with LN metastases from stage II or III gastric cancer received S-1 and CDDP, as NAC criteria for LN metastases were the involvement of ≥4 nodes <2 cm or ≥1 nodes ≥2 cm as confirmed by a total body computed tomography scan. All patients underwent extensive resection including D2 gastrectomy. The primary endpoint was complete resection rate and the secondary endpoints were 3-year relapse-free and overall survival. RESULTS: Fifty patients were assessable for the analysis. The complete resection rate was 87.8%. Three-year relapse-free survival was 44.9% and 3-year overall survival rate was 48.0%. CONCLUSIONS: NAC with S-1 and CDDP is safe and may improve the complete resection rate in patients with metastatic LN gastric cancer. This suggests that LN metastases would provide good target lesions in future clinical trials of NAC.

[Preoperative Chemoradiotherapy for Stage II or III Esophageal Squamous Cell Carcinoma].

BACKGROUND: The goal of this retrospective study was to investigate the efficacy and safety of preoperative chemoradiotherapy( NACR)in patients with Stage II or Stage III esophageal squamous cell carcinoma(SCC). METHODS: Between 2004 and 2014, a total of 86 patients underwent surgical resection in conjunction with NACR for esophageal SCC at our institute. Thirty-one patients(36.0%)had Stage II disease and 55 patients(64.0%)had Stage III disease. RESULTS: The median age was 64(43-81)years. A total of 78 patients received the full NACR regimen. The most common major Grade 3 hematologic toxic effects of NACR were leukopenia and neutropenia(48 cases), while the most common major Grade 3 non-hematologic toxic effect was anorexia(12 cases). One patient died in the hospital and no patients died within 30 days after surgery. A pathological complete response was achieved in 23 cases. Pathological staging(number of cases)was Stage 0(23), Stage I (8), Stage II (28), Stage III (25), and Stage IV (2). The 5-year overall survival rate(OS)was 51.0%, and was 83.2% in Stage II patients and 29.9% in Stage III patients. CONCLUSION: Preoperative NACR is safe and may improve OS and downstaging rates in patients with esophageal SCC.

Simultaneous ion and neutral evaporation in aqueous nanodrops: experiment, theory, and molecular dynamics simulations.

We use a combination of tandem ion mobility spectrometry (IMS-IMS, with differential mobility analyzers), molecular dynamics (MD) simulations, and analytical models to examine both neutral solvent (H2O) and ion (solvated Na(+)) evaporation from aqueous sodium chloride nanodrops. For experiments, nanodrops were produced via electrospray ionization (ESI) of an aqueous sodium chloride solution. Two nanodrops were examined in MD simulations: a 2500 water molecule nanodrop with 68 Na(+) and 60 Cl(-) ions (an initial net charge of z = +8), and (2) a 1000 water molecule nanodrop with 65 Na(+) and 60 Cl(-) ions (an initial net charge of z = +5). Specifically, we used MD simulations to examine the validity of a model for the neutral evaporation rate incorporating both the Kelvin (surface curvature) and Thomson (electrostatic) influences, while both MD simulations and experimental measurements were compared to predictions of the ion evaporation rate equation of Labowsky et al. [Anal. Chim. Acta, 2000, 406, 105-118]. Within a single fit parameter, we find excellent agreement between simulated and modeled neutral evaporation rates for nanodrops with solute volume fractions below 0.30. Similarly, MD simulation inferred ion evaporation rates are in excellent agreement with predictions based on the Labowsky et al. equation. Measurements of the sizes and charge states of ESI generated NaCl clusters suggest that the charge states of these clusters are governed by ion evaporation, however, ion evaporation appears to have occurred with lower activation energies in experiments than was anticipated based on analytical calculations as well as MD simulations. Several possible reasons for this discrepancy are discussed.

Effect of preoperative colonic drainage for obstructing colorectal cancer.

Obstructing colorectal cancer (OCRC) is believed to indicate poorer long-term survival. The purpose of this study was to compare retrospectively perioperative safety and long-term results in patients undergoing surgery for OCRC following preoperative colonic decompression with that in those undergoing elective surgery alone for nonobstructing colorectal cancer (CRC). A total of 656 consecutive CRC patients undergoing colectomy between 2001 and 2011 at our institute were eligible for inclusion in the study. The patients were divided into an OCRC group, which included 104 patients undergoing colectomy with preoperative colonic decompression, and a CRC group, which included 552 patients undergoing colectomy alone. Morbidity, mortality, and prognosis were assessed. In the OCRC group, decompression was performed by nasointestinal tube in 42 patients (40.4%), transanal tube in 15 (14.4%), and colostomy in 47 (45.2%). The mortality rate was 0% in the OCRC group and 0.4% in the CRC group (2 of 552 patients). The morbidity rate was 44.8% in the OCRC group (48 of 104 patients) and 36.6% in the CRC group (202 of 552 patients). The 5-year overall survival rate was 69.5% in the OCRC group and 72.9% in the CRC group [hazard ratio 0.76; 95% confidence interval, 0.35 to 1.16; P = 0.48)]. No statistically significant difference in survival was observed between the 2 groups in stage II, III, or IV, or overall. No difference was observed in safety or survival between advanced OCRC patients undergoing preoperative colonic decompression and advanced non-obstructing CRC patients undergoing surgery alone.

[A Study of Preoperative Chemotherapy with S-1 plus Cisplatin for Advanced Gastric Cancer].

We studied the effects of preoperative chemotherapy with S-1 plus cisplatin for advanced gastric cancer. There were 16 patients who underwent radical surgery with neoadjuvant chemotherapy between 2000 and 2015. The indications for this were advanced gastric cancer with bulky N2 or N3 lymph nodes, or stage above T4a. Seven patients (43%) showed adverse events, all of which were tumors above Grade 3. Response evaluation showed PR in 13 cases (81%). The histopathological evaluation was Grade 0 in 8 patients (50%) and Grade 1a or above in 8 (50%). Death from recurrence within a year occurred in 4 cases, and 7 patients survived with no recurrence for over 5 years. All cases of survivors with no recurrence had a histopathological evaluation of Grade 1 or above. Three cases (75%) with recurrence and death within a year all had with Grade 0 tumors. We concluded that neoadjuvant chemotherapy with S-1 plus cisplatin was effective for advanced gastric cancer and that histopathological evaluation was invaluable for accurate prognosis.

[A Case of Gemcitabine Refractory Lung Metastasis after Distal Pancreatectomy for Pancreatic Cancer, Effectively Treated with S -1 as Second Line Chemotherapy].

A 64-year-old man was diagnosed with pancreatic cancer by abdominal computed tomography (CT). The examination showed a pancreatic tail cancer and a distal pancreatectomy was performed in 2010. Histopathologically, this tumor was a moderately-differentiated tubular adenocarcinoma. He received gemcitabine adjuvant chemotherapy for a year. In 2012, a chest CT scan revealed 4 nodules in the lower left lobe. We diagnosed gemcitabine-refractory lung metastases after distal pancreatectomy for pancreatic cancer. S-1 chemotherapy was administered as a second line chemotherapy for metastatic pancreatic cancer. After 2 courses of this regimen, the lung metastases were reduced. After 6 courses, a clinical complete response was obtained. Four years and 6 months after the operation, the patient is well without any signs of recurrence, and S-1 chemotherapy is still ongoing.

[A Case of Advanced Gastric Cancer with Peritoneal Dissemination Effectively Treated with S-1 and Docetaxel Combination Chemotherapy].

A 72-year-old man underwent surgery for advanced gastric cancer. Systemic chemotherapy was started, using a regimen of S-1/CDDP for 4 courses, followed by 8 courses of S-1. Three years and 8 months after the surgery, abdominal CT demonstrated ascites, and the serum CA19-9 level was abnormally high (1,165.1 U/mL). Adenocarcinoma cells were found in the ascites. Treatment with S-1/docetaxel (DOC) was started. After 10 courses, the ascites disappeared and the serum CA19-9 value returned to normal. Four years and 7 months after the operation, the patient has been in good health, with no signs of recurrence.

[A Case of Advanced Gastric Cancer with Long-Term Survival after Chemotherapy with Combined S-1 and CPT-11].

Here, we report a 54-year-old man diagnosed with type 3 advanced gastric cancer who underwent a total gastrectomy and splenectomy plus D2 lymphadenectomy. The pathologic diagnosis was Stage Ⅳ (T3N0H0P0CY1M1). Sixteen courses of combined S-1/CPT-11 chemotherapy were completed, at which time the CPT-11 was discontinued because of malaise, and S-1 alone was continued for a year. The patient is well and has been recurrence-free for 7 years. Thus, he is considered a long- term survivor who was treated with combination S-1/CPT-11 chemotherapy.

[A Case of Colon Cancer with Multiple Liver Metastases Successfully Treated with Capecitabine/Oxaliplatin plus Bevacizumab].

A 69-year-old woman was diagnosed with descending colon cancer with multiple liver metastases, and a left hemicolectomy was performed. The patient was treated with capecitabine/oxaliplatin (CapeOX) plus bevacizumab (Bmab). After 5 courses of chemotherapy, the number and size of liver metastases remarkably reduced, and after the 12th course, because of peripheral neuropathy, a "stop-and-go"fashion of administering oxaliplatin (L-OHP) was initiated. After 14 courses, the liver metastases had disappeared. After the 33rd course of L-OHP treatment, the patient started receiving capecitabine therapy. The patient is recurrence-free 3 years after surgery, 14 months after achieving a complete response (CR). We report a case of long-term CR after surgery for descending colon cancer with multiple liver metastases, followed by a "stop-and-go" method of administering L-OHP or CapeOX plus Bmab therapy.

[Two Cases of Liver Metastasis from Pancreatic Cancer with a Complete Response Owing to Chemotherapy].

Case 1: The patient was a 42-year-old man who was diagnosed with intraductal papillary-mucinous carcinoma with liver metastasis. After S-1+gemcitabine and S-1 chemotherapy, the liver metastasis had disappeared and we performed a pancreaticoduodenectomy( PD). Case 2: The patient was a 70-year-old woman who was diagnosed with pancreatic cancer with liver metastasis. After gemcitabine chemotherapy, the liver metastasis had disappeared and we performed a PD. The prognosis of pancreatic cancer is dismal compared to other types of cancer, and for a Stage Ⅳb cancers, the 5-year survival rate is reported to be approximately 3%. We report 2 cases of liver metastases from pancreatic cancer that disappeared in response to chemotherapy. Both patients underwent primary tumor resection after chemotherapy and experienced long-term survival.

Radiochemotherapy for esophageal squamous cell carcinoma in elderly patients.

BACKGROUND/AIMS: The goal of this retrospective study was to investigate the efficacy and safety of curative radiochemotherapy (CRT) in elderly patients with esophageal squamous cell cancer (SCC). METHODOLOGY: Between 1986 and 2011, 38 consecutive patients aged over 75 years with esophageal SCC were initially treated with a CRT regimen comprising radiation therapy at a dose of 60 Gy and two cycles of chemotherapy with 5-fluorouracil/cisplatin. RESULTS: Fourteen patients were aged over 80 and 24 under 79 years. Complete treatment compliance was obtained in 30 (78.9%) of the patients. Chemotherapy was terminated and the dose of radiation reduced in 7 and 1 patients, respectively. The overall incidence of CRT-related complications was 86.8% (33 patients). Grade 3 leukocytopenia was observed in 6 (15.8%) patients, all of whom recovered promptly. A complete response was observed in 17 patients (44.7%). The overall 3-year survival rate was 32.0%. CONCLUSIONS: Curative CRT is safe and may improve overall and progression-free 3-year survival rates in elderly patients aged more than 75 years with esophageal SCC.

Complete response to uracil-tegafur alone in advanced rectal cancer.

We report a case of a complete response to treatment with uracil-tegafur (UFT) alone in advanced rectal cancer. The patient was an 84-year-old woman referred to our hospital complaining of anal bleeding. A colonoscopy revealed a Borrmann type II tumor in the rectum, which was diagnosed as an adenocarcinoma. Therefore, best supportive care was initiated in April 2011 with oral administration of UFT. The anal bleeding stopped 2 months later, and the patient's general condition remains good at one year. A further colonoscopy at one year after initiation of treatment in April 2012 resulted in reclassification of the tumor as an Isp lesion, and the biopsy was negative for cancer. The patient was still alive with no sign of recurrence at 21 months after commencing UFT alone with no surgical treatment. These results suggest that chemotherapy with UFT alone can yield complete remission from advanced rectal cancer.

Differing deregulation of HER2 in primary gastric cancer and synchronous related metastatic lymph nodes.

BACKGROUND: The aim of this study was to investigate how differences in expression of HER2 between primary gastric cancers (PGCs) and their corresponding metastatic lymph nodes (LMNs) might affect its potential as a prognostic indicator in treatments including anti-HER2 agents. METHODS: The analysis was conducted in 102 patients who underwent surgical resection for primary gastric cancers (PGCs; adenocarcinoma, intestinal type) with synchronous LNMs. HER2 gene status and protein expression were investigated by immunohistochemistry (IHC) in all patients; fluorescence in situ hybridization (FISH) was performed in 22 patients. The correlation between HER2 gene status in PGCs and their LNMs was evaluated. RESULTS: Positive HER2 expression as detected by IHC + FISH was observed in 27/102 PGC samples (26.5%) and 29/102 LNM samples (28.4%). HER2 amplification status in 102 paired PGC and LNM samples as evaluated by FISH + IHC was concordant in 92 patients (90.2%), 69 (67.6%) were unamplified and 23/102 (22.5%) were amplified at both sites, and discordant in 10 patients (9.8%), 4 (3.9%) were positive for PGC and negative for LNM, while 6 (5.9%) were positive for LNM and negative for PGC. The results of FISH + IHC showed very strong concordance in HER2 status between the PGC and LNM groups (k = 0.754). CONCLUSION: The high concordance between HER2 results for PGCs and their LNMs indicates that assessment of HER2 status in the primary cancer alone is a reliable basis for deciding treatment with anti-HER2 agents in patients with LNMs from gastric adenocarcinoma. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9365749431029643.

Alteration of ethanol tolerance caused by the deficiency in the genes associated with histone deacetylase complex in budding yeast.

Upon exposure to 8% ethanol, survival and growth of yeast strains deficient in histone deacetylase complex genes was examined. Of the 18 mutants tested, the Δsir3 and Δsir4 strains showed higher resistance to ethanol, while the Δrco1, Δhos3, Δhda2, and Δhst1 strains were more sensitive than the wild type. Furthermore, these ethanol-resistant patterns varied under aerobic and anaerobic culture conditions.