Two cases of gastric cancer with elevated serum levels of KL-6.

BACKGROUND: The serum level of Krebs von den Lungen-6 (sKL-6) is a biomarker of interstitial pneumonia and has been reported to be elevated in patients with cancers. However, there have been few cases of gastric cancer (GC) with elevated sKL-6 that were treated by chemotherapy. We herein report two cases of GC with elevated sKL-6 that were treated with oxaliplatin plus S-1 (SOX) chemotherapy and discussed the resulting changes in sKL-6. CASE PRESENTATION: The first patient was a 79-year-old woman complaining of loss of appetite. Esophagogastroduodenoscopy (EGD) showed a type-3 tumor in the gastric antrum and biopsy specimens showed adenocarcinoma. Computed tomography (CT) showed multiple liver metastases. sKL-6 was elevated to 1,292 U/ml, but a CT revealed no obvious lesions of the lungs, including interstitial pneumonia. The tumor was diagnosed as GC with liver metastases and elevated sKL-6. Respiratory function data were normal. SOX therapy using oxaliplatin and S-1 was performed. After 3 courses of SOX therapy, CT showed reductions of the liver metastases as well as the primary tumor, and sKL-6 was decreased to 201 U/ml. After the 44 courses, sKL-6 was slightly elevated. Chest CT showed interstitial pneumonia and chemotherapy was stopped. The patient is still alive without any metastasis 72 months later. The second patient was a 69-year-old woman complaining of upper abdominal pain. EGD revealed a type-3 tumor in the gastric antrum showing adenocarcinoma with HER2-positive pathology. CT showed multiple node metastases around the abdominal aorta. sKL-6 was elevated to 2,239 U/ml, but a respiratory function test showed no abnormalities, and CT of the lungs showed no obvious lesions. The tumor was diagnosed as GC with distant node metastases and elevated sKL-6. The patient received SOX therapy combined with trastuzumab. After 6 courses, the size of the primary tumor and multiple node metastases were reduced, and sKL-6 was decreased to 284 U/ml. CONCLUSIONS: These two cases suggest that sKL-6 may be important not only as an indicator of interstitial pneumonia in chemotherapeutic courses, but also as a tumor marker in GC patients with multiple metastases.

A case report of adenosquamous carcinoma of the esophagogastric junction.

BACKGROUND: Many types of tumors can arise in the esophagogastric junction (EGJ). Squamous cell carcinoma (SCC) arising from the esophageal epithelia, adenocarcinoma arising from the gastric mucosa, or Barrett's esophageal mucosa are frequently observed in the EGJ. However, adenosquamous carcinoma (ASC) has been rarely observed in this area. We herein report a rare case of ASC of the EGJ. CASE PRESENTATION: An 81-year-old man visited our hospital complaining of dysphagia. Esophagogastroduodenoscopy detected an elevated tumor in the gastric cardia. Biopsy specimens taken from the tumor showed SCC. Computed tomography revealed a tumor located in the EGJ and node metastases surrounding the EGJ. The tumor was diagnosed as SCC, overhanging in the stomach, of the EGJ. The patient underwent a proximal gastrectomy with a lower esophagectomy and node dissection for the metastases surrounding the EGJ, and esophagogastrostomy in the lower mediastinum. Histopathologic examination showed the tumor consisted of SCC and adenocarcinoma. The adenocarcinoma consisted of nests scattered in the SCC. We observed adenocarcinoma component in 35% of the tumor and epithelial spread of SCC in the lower esophagus. Thus, we diagnosed the tumor as ASC of the EGJ. Eight metastatic nodes were dissected; both SCC and adenocarcinoma were observed in seven. CONCLUSIONS: In the present case, SCC may be originated from the squamous epithelia of the lower esophagus and grew into the stomach, and the adenocarcinoma may have differentiated from SCC through the infiltration.

A case of gastric cancer that developed thrombocytopenia during treatment with nivolumab.

A 72-year-old man was treated by two-regimen chemotherapies for unresectable advanced gastric cancer with metastatic lymph nodes near the pancreatic head, followed by the third-line chemotherapy using nivolumab (Nivo). Ten days after the two-course Nivo chemotherapy, grade 4 thrombocytopenia (TCP) occurred according to the Common Terminology Criteria for Adverse Events. He was treated by steroid and Helicobacter pylori (HP) eradication therapies. Consequently, the platelet count improved rapidly without any complications. Before resuming the Nivo therapy, the platelet count was already improved. Fourth-line chemotherapy was then started using irinotecan. After three courses, his general condition worsened. Unfortunately, the patient died 18 months after gastric cancer diagnosis. Although rare, severe TCP is potentially a fatal complication of chemotherapy using immune checkpoint inhibitors. In addition to standard treatment with steroids, HP eradication therapy may be effective for Nivo-associated TCP.

Lung adenocarcinoma initially presenting as Trousseau's syndrome treated successfully with pembrolizumab: A case report.

A 60-year-old woman was urgently admitted to our hospital because of vertigo and left hemiplegia. Laboratory examination showed thrombocytopenia, high levels of D-dimer and carcinoembryonic antigen. Brain magnetic resonance imaging (MRI) revealed multiple bilateral cerebral infarctions. Chest computed tomography (CT) showed an irregularly shaped tumor in the upper lobe of the left lung and mediastinal node swelling. The histopathological findings revealed adenocarcinoma negative for anaplastic lymphoma kinase fusion gene, sensitive epidermal growth factor receptor mutations. A diagnosis of lung adenocarcinoma initially presenting as arterial thromboembolism was made, and she was treated with direct oral anticoagulant (DOAC). Subsequently, pembrolizumab therapy was initiated because tumor cells were positive for programmed cell death protein 1 (PD-L1;60%), and resulted in reduction of the tumor with normalization of the platelet count and d-dimer. The treatment has been continued for over one year without any recurrence of the disease or thromboembolism.

High incidence of other primary malignancies in patients with synchronous multiple gastric cancers "a multi-center retrospective cohort study".

This study evaluated the relationship between synchronous multiple gastric cancer and other primary malignancies. During 2002-2013, 1094 consecutive surgically treated gastric cancer patients were enrolled. Preoperatively, we performed total colonoscopy and whole-body computed tomography. When malignancies in other organs were suspected, detailed organ-specific examinations were performed. Synchronous multiple gastric cancer occurred in 102 patients (9.3%)which was frequently observed in patients with preoperative other primary malignancies (p < 0.001). Preoperative other primary malignancy was an independent risk factor for synchronous multiple gastric cancer (p = 0.001; hazard ratio: 2.145, 95% confidence interval: 1.354-3.399) and an independent prognostic factor of overall survival in patients undergoing gastrectomy with curative intent (p = 0.021; hazard ratio: 1.481, 95% confidence interval: 1.060-2.070). Thus, patients with preoperative other primary malignancies have a high risk of synchronous multiple gastric cancer. Careful preoperative examination is recommended to improve survival.

Postoperative complications in elderly patients with gastric cancer.

BACKGROUND: Elderly patients undergoing gastrectomy are expected to be at high risk of postoperative complications. This retrospective multicenter cohort study assessed complications and long-term outcomes after gastrectomy for gastric cancer (GC). METHODS: A total of 993 patients with GC who had undergone gastrectomy were included, comprising 186 elderly patients (age ≥ 80 y, E group) and 807 nonelderly patients (age ≤ 79 y, NE group). Preoperative comorbidities, operative results, postoperative complications, and clinical outcomes were compared between the groups. RESULTS: Clavien-Dindo grade ≥1 postoperative complications, pneumonia (P = 0.02), delirium (P < 0.001), and urinary tract infection (P < 0.001) were more common in the E group. Postoperative pneumonia was associated with mortality in this group (P < 0.001). Three patients (1.6%) died after surgery, each of whom had pneumonia. Severe postoperative complication was independently prognostic of overall (hazard ratio, 4.69; 95% confidence interval, 2.40-9.14; P < 0.001) and disease-specific (hazard ratio, 6.41; 95% confidence interval 2.92-14.1; P < 0.001) survival in the E group. CONCLUSIONS: In elderly patients with GC, clinical outcomes are strongly associated with severe postoperative complications. Preventing such complications may improve survival.

Prevalence and management of colorectal neoplasia in surgically treated esophageal cancer patients.

AIMS: The existence of other primary tumors during the treatment of esophageal cancer patients has been an important issue. Our aim is to investigate the prevalence and management of colorectal neoplasia (CRN) in surgically treated esophageal cancer patients. METHODS: Between 2002 and 2008, 93 patients with esophageal cancer were surgically treated. Seventy-three patients underwent subtotal esophagectomy and 20 underwent lower esophagectomy for esophageal cancer. Colonoscopy was available for detecting CRN before and after surgery. RESULTS: Eighty-nine (95.7%) of the 93 patients were screened by colonoscopy preoperatively or within a year from the operation. Thirty-nine patients (43.8%) with CRN were synchronously identified: adenoma in 34 (38.2%) and adenocarcinoma in 5 patients (5.6%). Eleven adenomas with high grade-dysplasia and 8 adenomas with low grade-dysplasia were removed endoscopically. Three superficial adenocarcinomas were endoscopically removed before surgery, and 2 adenocarcinomas were surgically removed. Seventy-four patients (83.1%) were followed using colonoscopy, and 11 subsequent CRN, including 2 superficial adenocarcinomas, were endoscopically detected in 8 patients (10.8%). The size of esophageal cancer was larger in the patients with than without CRN (p = 0.036). The body mass index in esophageal cancer patients with CRN tended to be higher than in those without CRN (p = 0.065). CONCLUSIONS: We noted that esophageal cancer is frequently associated with synchronous and/or metachronous colorectal cancer and adenomas. Colonoscopy is useful to detect and manage CRN before and after esophagectomy, although a few limitations exist.

Synchronous ipsilateral carcinoma of the accessory mammary gland and primary lymphoma of the breast with subsequent rectal carcinoma: report of a case.

A case of synchronous carcinoma of the accessory mammary gland and primary breast lymphoma with subsequent rectal carcinoma has not been reported previously. We present a very rare case of primary non-Hodgkin lymphoma of the left breast diagnosed simultaneously with invasive lobular carcinoma of the left axillary accessory mammary gland and rectal adenocarcinoma. An 82-year-old Japanese woman presented with two palpable masses on the left chest wall. She was given a diagnosis of suspected breast malignant tumor and axillary accessory mammary gland. She underwent excision of the axillary accessory mammary gland and left mastectomy with axillary lymph node dissection. Histopathological examination revealed diffuse large B-cell lymphoma of the breast and invasive lobular carcinoma of the axillary accessory mammary gland with lymph nodes metastasis. Three months after the surgery, primary rectal adenocarcinoma was also detected by F-18 fluorodeoxyglucose positron emission tomography. Hartmann's operation was performed, since which time the patient has been doing well.

Relationships of obesity and diabetes mellitus to other primary cancers in surgically treated gastric cancer patients.

BACKGROUND: Other primary cancers (OPC) have been reported in gastric cancer (GC) patients. Recent studies have shown relationships of obesity and diabetes mellitus to cancer development in several organs. The purpose of this study was to investigate the relationships of obesity and diabetes mellitus (DM) to the prevalence of OPC in GC patients. METHODS: We reviewed 435 GC patients who were treated surgically and followed their outcomes after surgery. Patients with body mass index (BMI) ≥ 25 kg/m(2) were defined as obese. Fasting plasma glucose (FPG) and HbA1c levels were examined before surgery. RESULTS: OPC was observed in 109 GC patients (25.1%): 40 (9.2%) with synchronous OPC and 76 (18.2%) with metachronous OPC. The most common OPC was colorectal cancer (22.8%). OPC was frequently observed in patients with DM (p = 0.0022), and DM was an independent risk factor for the occurrence of OPC (odds ratio, 2.215; 95% confidence interval, 1.2007-4.0850; p = 0.011). Synchronous OPC was frequently observed in patients with obesity (p = 0.025), and obesity was an independent risk factor for the occurrence of synchronous OPC (odds ratio, 2.354; 95% confidence interval, 1.1246-4.9279; p = 0.023). Metachronous OPC was frequently observed in patients with DM (p = 0.0071), and DM was an independent risk factor for the occurrence of OPC (odds ratio, 2.680; 95% confidence interval, 1.0291-6.9780; p = 0.044). CONCLUSION: There is a need to be aware of the possibility of OPC in GC patients with DM/obesity. They should undergo intensive screening for OPC before and after gastrectomy.

Helicobacter heilmannii sensu stricto-related gastric ulcers: a case report.

A spiral bacterium (SH9), morphologically different from Helicobacter pylori (H. pylori), was found in a 62-year-old woman's gastric mucosa. Gastroscopic examination revealed multiple gastric ulcers near the pyloric ring; mapping gastric biopsy showed mild mononuclear infiltration with large lymphoid follicles in the antrum, without corpus atrophy. Urea breath test and H. pylori culture were negative, but Giemsa staining of biopsies revealed tightly coiled bacteria that immunostained with anti-H. pylori antibody. Sequencing of SH9 16S rRNA and the partial urease A and B subunit genes showed that the former sequence had highest similarity (99%; 1302/1315 bp) to Helicobacter heilmannii (H. heilmannii) sensu stricto (H. heilmannii s.s.) BC1 obtained from a bobcat, while the latter sequence confirmed highest similarity (98.3%; 1467/1493 bp) to H. heilmannii s.s. HU2 obtained from a human. The patient was diagnosed with multiple gastric ulcers associated with H. heilmannii s.s. infection. After triple therapy (amoxicillin, clarithromycin, and lansoprazole) with regimen for eradicating H. pylori, gastroscopy showed ulcer improvement and no H. heilmannii s.s. upon biopsy.

Prevalence of synchronous colorectal neoplasms in surgically treated gastric cancer patients and significance of screening colonoscopy.

BACKGROUND AND AIM: The existence of other primary tumors during the treatment and management of gastric cancer (GC) is an important issue. The present study investigated the prevalence and management of synchronous colorectal neoplasms (CRN) in surgically treated GC patients. METHODS: Of 381 surgically treated GC patients, 332 (87.1%) underwent colonoscopy to detect CRN before surgery or within a year after surgery. RESULTS: CRN were synchronously observed in 140 patients (42.2%). Adenoma was observed in 131 patients (39.4%). Endoscopic resection was done in 18 patients with adenoma. Colorectal cancer (CRC) was observed in 16 patients (4.8%), superficial CRC in 13 and advanced CRC in three patients. Endoscopic resection of superficial CRC was carried out in seven patients, whereas simultaneous surgical resection of CRC was done in nine patients. CRN were more frequently observed in men. CRC was more frequently observed in GC patients with distant metastasis, albeit without significance. The overall survival of GC patients with CRN or CRC was poorer than that of patients without CRN or CRC. CONCLUSION: Synchronous CRN were commonly associated with GC and screening colonoscopy should be offered to patients with GC.

Reduced expression of αGlcNAc in Barrett's oesophagus adjacent to Barrett's adenocarcinoma--a possible biomarker to predict the malignant potential of Barrett's oesophagus.

AIMS: Gastric gland mucin contains O-glycans exhibiting terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc). Recently we demonstrated that mice deficient in αGlcNAc in gastric gland mucin develop gastric adenocarcinoma spontaneously, indicating that αGlcNAc is a tumour suppressor for gastric cancer. However, the role of αGlcNAc in Barrett's oesophagus (BO) remains unknown. In this study, we investigated whether reduced αGlcNAc expression in BO is associated with development of Barrett's adenocarcinoma (BAC). METHODS AND RESULTS: Thirty-five BO lesions adjacent to BAC were examined by immunohistochemistry for αGlcNAc, MUC6 and CDX2. As controls, 35 BO lesions without BAC obtained from patients with oesophageal squamous cell carcinoma were also analysed. Expression of αGlcNAc relative to its scaffold MUC6 in BO adjacent to BAC was reduced significantly compared to control BO. Decreased αGlcNAc expression in BO adjacent to BAC was particularly significant in patients with smaller tumour size (<20 mm) and minimal invasion of tumour cells to the superficial muscularis mucosae. There was also a significant inverse correlation between αGlcNAc and CDX2 expression in BO adjacent to BAC. CONCLUSIONS: Decreased expression of αGlcNAc compared with MUC6 in BO is a possible hallmark in predicting BAC development.

[Juvenile gastric polyposis in a patient with antiphospholipid syndrome].

We report a case of juvenile gastric polyposis associated with antiphospholipid syndrome. A 42-year-old woman was admitted with a chief complain of fatigue. Six years earlier, antiphospholipid syndrome was diagnosed and treated with aspirin. Two years earlier, gastric polyps were endoscopically observed, the number and size of which subsequently increased. Juvenile gastric polyposis was diagnosed on the basis of the pathological features of the biopsy specimens. Bleeding was repeatedly identified from the polyposis. Total gastrectomy was performed because of worsening anemia and hypoalbuminemia.

[A case of squamous cell carcinoma of the esophagogastric junction with bulky no.7-metastatic node successfully treatedby chemoradiation followed by surgery].

The patient was a 59-year-old man showing an ulcerative tumor. He had squamous cell carcinoma diagnosed by biopsy specimens, found in the esophagogastric junction by esophagogastroduodenoscopy. Abdominal CT showed a No.7 nodeswelling( 40mm in diameter), and the metastatic tumor directly invaded the pancreas(cStage IVa). We scheduled surgery followed by chemoradiotherapy, because it was difficult to remove the metastatic node completely. Two courses of chemotherapy consisting of 5-FU and CDDP were performed, and 2 Gy/day-irradiation(total amount of 40 Gy)was performed over 20 days. After chemoradiation, the tumor changed to a superficially depressed lesion, and the metastatic huge node was shrunk. Thirty-five days after chemoradiation, transhiatal a lower esophagectomy with proximal gastrectomy was performed. Histopathologic findings after surgery showed no cancer remnant in the primary site and the node(pCR). Three years later, the patient is well without recurrence. Although there was no evidence of preoperative chemoradiation limited in squamous cell carcinoma of the esophagogastric junction, surgery followed by chemoradiotherapy may be an effective treatment in advanced cases, such as the present one.

Treatment of a GIST patient with modified dose of sunitinib by measurement of plasma drug concentrations.

In this study we report the pharmacokinetics and severe adverse effects of sunitinib in a woman with a gastrointestinal stromal tumor (GIST). A 60-year-old woman with small intestinal GIST developed severe thrombocytopenia (1.7×10(4)/µl) following 1 week of treatment with sunitinib at 50 mg/day. Although the dose of sunitinib was reduced to 25 mg/day, platelet levels remained low. On day 7, the trough concentration of sunitinib plus SU12662 was 46.1 ng/ml and the area under the curve (AUC) was 1,393.0 ng·h/l. The dose was again reduced to 12.5 mg/day. However, the day after resumption of treatment, the patient developed symptoms of left heart failure due to myocardosis caused by sunitinib. Sunitinib has been reported to inhibit platelet-derived growth factor receptor (PDGFR) phosphorylation at concentrations over the range of 50-100 ng/ml (sunitinib plus SU12662) in vivo. In this case, the plasma concentration was sufficient to inhibit PDGFR at 25 or 50 mg/day. However, thrombocytopenia appeared at both dosages. Although the results in this case did not suggest a correlation between thrombocytopenia and plasma concentration, the degree of thrombocytopenia was decreased by reduction of the dose. In conclusion, the findings reported here indicate that the plasma concentration of sunitinib plus SU12662 is an important indicator to reduce adverse effects.

Additional gastrectomy after endoscopic submucosal dissection for early gastric cancer patients with comorbidities.

Purpose. We investigated the clinicopathologic features of early gastric cancer (EGC) patients who have undergone additional gastrectomy after endoscopic submucosal dissection (ESD) because of their comorbidities. Methods. Eighteen (7.1%) of 252 GC patients were gastrectomized after prior ESD. Reasons for further surgery, preoperative and postoperative problems, and the clinical outcome were determined. Results. The 18 patients had submucosal EGC and several co-morbidities. Other primary cancers were observed in 8 (44.4%). Histories of major abdominal operations were observed in 6 (33.3%). Fourteen patients (77.8%) hoped for endoscopic treatment. Due to additional gastrectomy, residual cancer was suspected in 10, and node metastasis was suspected in 11. A cancer remnant was histologically observed in one. Node metastasis was detected in 3 (16.7%). Small EGC was newly detected in 4. Consequently, additional gastrectomy was necessary for the one third. No patient showed GC recurrence. However, 9 (50%) had new diseases, and 4 (22.2%) died of other diseases. The overall survival after surgery in these patients with additional gastrectomy was poorer than those with routine gastrectomy for submucosal EGC (P = 0.0087). Conclusions. Additional gastrectomy was safely performed in EGC patients with co-morbidities. However, some issues, including presence of node metastasis and other death after surgery, remain.

Gastric composite tumor of alpha fetoprotein-producing carcinoma/hepatoid adenocarcinoma and endocrine carcinoma with reference to cellular phenotypes.

Alpha-fetoprotein-producing carcinoma (AFPC)/hepatoid adenocarcinoma (HAC) and neuroendocrine carcinoma (NEC) are uncommon in the stomach. Composite tumors consisting of these carcinomas and their histologic phenotypes are not well known. Between 2002 and 2007, to estimate the prevalence of composite tumors consisting of tubular adenocarcinoma, AFPC/HAC and NEC, we reviewed specimens obtained from 294 consecutive patients treated surgically for gastric cancer. We examined histological phenotype of tumors of AFPC or NEC containing the composite tumor by evaluating immunohistochemical expressions of MUC2, MUC5AC, MUC6, CDX2, and SOX2. Immunohistochemically, AFPC/HAC dominantly showed the intestinal or mixed phenotype, and NEC frequently showed the gastric phenotype. In the composite tumor, the tubular and hepatoid components showed the gastric phenotype, and the neuroendocrine component showed the mixed type. The unique composite tumor predominantly showed the gastric phenotype, and the hepatoid and neuroendocrine components were considered to be differentiated from the tubular component.

Mediastinoscopy-assisted esophagectomy for esophageal cancer in patients with serious comorbidities.

PURPOSE: We evaluated the results of mediastinoscopy-assisted esophagectomy (MAE), performed for esophageal cancer patients with comorbidities, versus those of thoracoscopic esophagectomy (TSE), performed for esophageal patients with or without comorbidities. METHODS: Among 153 patients who underwent esophageal cancer surgery at our hospital, 17 (11.1%) underwent MAE and 37 (24.2%) underwent TSE. RESULTS: Many of the MAE group patients had pulmonary (P < 0.001), cardiovascular (P = 0.031), or hepatic (P = 0.0029) diseases preoperatively, and these comorbidities frequently overlapped (P < 0.0001). The %VC and FEV(1)/FVC were lower (P = 0.0099 and P = 0.0057, respectively), and the ICG-R15 and serum level of HbA1c were higher (P = 0.0014 and P = 0.043, respectively) in the MAE group. There were no differences in postoperative complications or in the modified Clavien classification between the groups. There was no mortality in either group. After MAE, 5 (29.4%) patients died of other diseases. The 5-year overall survival rate after MAE was poorer than that after TSE (56.1 vs. 71.8%), but the 5-year cause-specific survival rates were similar in the two groups. CONCLUSIONS: MAE is feasible for esophageal cancer patients with serious comorbidities and may decrease morbidity and mortality.

Pseudo-Meigs syndrome caused by sigmoid colon cancer metastasis to the ovary.

We present a patient with pseudo-Meigs syndrome (PMS) secondary to sigmoid colon cancer metastasis to the ovary with elevated serum levels of carcinoembryonic antigen, CA19-9, and CA-125 who showed a marked change in pleural effusion before and after surgery. We have to consider PMS associated with colon cancer in patients with pleural effusion/ascites and ovarian tumors.