Conversion surgery for metastatic gastric cancer at 2 years after initial diagnosis of cancer of unknown primary with metastasis of cervical lymph nodes and ovary: a case report.

BACKGROUND: Patients with stage IV gastric cancer have a poor prognosis despite improvements in intensive treatment regimens, including chemotherapy. Recently, conversion surgery has received much attention as it can provide long-term survival in stage IV gastric cancer patients who are responsive to chemotherapy. Herein, we describe the case of a patient who underwent conversion surgery for metastatic gastric cancer that was performed over 2 years after an initial diagnosis of cancer of unknown primary (CUP) with metastasis of the cervical lymph nodes and the ovary. CASE PRESENTATION: A 67-year-old woman with cervical lymphadenopathy was referred to our hospital. Computed tomography showed left cervical lymphadenopathy and bilateral ovarian enlargement. Endoscopic survey revealed no signs of malignancy in the upper or the lower gastrointestinal tract. Pathological findings after cervical lymphadenectomy revealed a signet-ring cell carcinoma and were suggestive of gastric cancer metastases. However, multiple evaluations yielded no evidence of gastric cancer and the patient was diagnosed with CUP. She was prescribed chemotherapy for gastric cancer and underwent bilateral oophorectomy after undergoing chemotherapy for 18 months. Pathologic analysis of oophorectomy tissue revealed findings identical to those seen in the cervical lymph nodes. At about 2 years after the initial diagnosis, an esophagogastroduodenoscopy revealed evidence of gastric cancer. We performed a distal gastrectomy with D2 lymphadenectomy. Her postoperative course was uneventful and she remains alive with no signs of disease recurrence at 3 months post-surgery. CONCLUSIONS: To the best of our knowledge, this is the first report describing successful conversion surgery for stage IV gastric cancer in a patient whose cancer was definitively diagnosed 2 years after an initial diagnosis of CUP.

Ramucirumab-related Oral Pyogenic Granuloma: A Report of Two Cases.

Pyogenic granuloma (PG) is a granulomatous elevated lesion that occurs on the skin and mucous membranes. We herein report two cases of intra-oral PG that developed during the administration of ramucirumab for gastric cancer. Case 1 involved a 55-year-old man with a 6-mm tumor on the right tongue, and case 2 involved a 67-year-old man with a 5-mm tumor on the upper lip. The imbalance in angiogenesis caused by ramucirumab and the deterioration in the local oral environment were suggested to have caused the PG. Medical and dental collaboration is essential during the administration of ramucirumab.

Four stay-sutures method: a simplified hand-sewn purse-string suture in laparoscopic circular-stapled esophagojejunostomy.

Laparoscopic esophagojejunostomy is a challenging procedure because of its technical difficulty. We herein report a new method involving circular-stapled anastomosis using a hand-sewn suture with four stay-sutures and evaluate its outcomes. Esophagojejunostomy using this method was performed in 36 consecutive patients with clinical stage I gastric cancer at the authors' institutions. The key feature of our procedure was the placement of four full-thickness stay-sutures to anchor the esophageal stump prior to the hand-sewn purse-string suture. The median operation time and mean anvil fixation time were 315.5 and 21.9 min, respectively. The mortality rate was 0%, although anastomotic leakage following esophagojejunostomy was observed in 1 patient (2.8%), and anastomotic stenosis was observed in another patient (2.8%). Intracorporeal esophagojejunostomy using the four stay-sutures method appears to be safe and feasible. We believe that this method enables hand-sewn purse-string suturing to be performed more easily.

Relationship between functional end-to-end anastomosis for colon cancer and surgical site infections.

PURPOSE: Surgical site infections (SSI) are a common complication of gastrointestinal tract surgery. In this study, we explored the correlation between the anastomosis method and the incidence of SSI. METHODS: A total of 110 patients underwent ileocecal resection or right hemicolectomy for the excision of colon cancer. Two methods (open and closed, 28 and 82 patients, respectively) of functional end-to-end anastomosis were adopted. RESULTS: Increased perioperative blood loss (p = 0.029214), a longer hospital stay (p = 0.026668) and the development of SSI (p = 0.000181) were significantly correlated with the open method. There was no correlation between SSI and the body mass index, or between SSI and the length of the surgery or diabetes mellitus. However, patients that developed SSI tended to be obese. CONCLUSION: The open method was associated with a higher incidence of SSI. Therefore, it is necessary to consider potential contamination of the surgical field at the time of anastomosis to reduce the incidence of SSI.

Primary esophageal adenocarcinoma with distant metastasis to the skeletal muscle.

Hematogenous metastasis of esophageal adenocarcinoma to the skeletal muscle is uncommon. We report a rare case of esophageal adenocarcinoma with metastasis to the skeletal muscle. During pretherapeutic examination, a painful mass was detected in the left thigh of a 49-year-old man. Endoscopic biopsy identified poorly differentiated, advanced esophageal adenocarcinoma. Computed tomography (CT) revealed wall thickening in the distal esophagus. Two enlarged lymph nodes were detected--the middle thoracic paraesophageal lymph node in the mediastinum and the right cardiac lymph node. (18)F-fluorodeoxyglucose (FDG) positron emission tomography demonstrated left thigh metastasis, which had not been detected by CT 3 weeks previously, with increased accumulation of FDG. Therefore, ultrasound-guided core-needle biopsy was performed. Histologic and immunohistochemical findings supported a diagnosis of poorly differentiated adenocarcinoma. The final diagnosis was primary esophageal adenocarcinoma with distant metastasis to the skeletal (left thigh) muscle. The rate of disease progression in this case emphasizes the malignant potential of esophageal adenocarcinoma. A few cases of skeletal metastasis from advanced esophageal adenocarcinoma have been previously reported. However, rapid metastasis to a distant skeletal muscle with no other hematogenous metastasis is quite rare. Early detection and rapid treatment are especially important in cases of esophageal adenocarcinoma.

Video-assisted thoracic surgery for esophagus for treating locally recurrent gastric cancer at the anastomotic site.

OBJECTIVE: To report a case of video-assisted thoracic surgery for esophagus (VATS-E) for the treatment of locally recurrent gastric cancer at the anastomotic site. CLINICAL PRESENTATION AND INTERVENTION: A 59-year-old man underwent total gastrectomy for gastric cancer. Histopathologically, it was mucinous adenocarcinoma [pT1(sm), pN1, sM0, PM(-), DM(-), stage IB]. Local recurrence was detected and he received chemotherapy and radiotherapy; histopathologically, it was identified as mucinous adenocarcinoma [pT1(sm), pN0, sM0, stage IA]. As the local recurrence was uncontrollable, he underwent VATS-E. At the 1-year follow-up, he was recurrence-free. CONCLUSION: The VATS-E minimally invasive surgery was a very useful technique for anastomotic recurrence after total gastrectomy in our patient.

[A case of advanced gastric cancer with regional lymph node metastasis showing pathological complete response after preoperative chemotherapy with docetaxel, cisplatin, and S-1].

A 64-year-old man was diagnosed with advanced gastric cancer type 3 and regional celiac trunk lymph node metastases. We performed preoperative chemotherapy with docetaxel, cisplatin, and S-1(DCS therapy). Total gastrectomy with lymph node dissection was performed after 2 courses of DCS. Pathologically, no viable cells were found in the primary lesion or in the dissected lymph nodes. The pathological response to preoperative DCS therapy was classified as grade 3. The postoperative course was uneventful; the patient is currently healthy and receives periodic medical examinations.

Expression of receptor tyrosine kinases in esophageal carcinosarcoma.

Esophageal carcinosarcoma (ECS) is a rare malignant neoplasm associated with a poor patient prognosis. It is characterized by the presence of both malignant epithelial and mesenchymal components. Molecular-targeted therapy of several receptor tyrosine kinases (RTKs) has been reported to be effective in the treatment of various malignant tumors, including carcinosarcoma of several organs. This study aimed to assess the therapeutic potential of targeting RTKs in ECS. Overexpression of RTKs was assessed in 21 ECS cases by immunohistochemistry (IHC). Positively stained cases were further examined for RTK gene mutations and amplifications by direct sequencing analysis and fluorescence in situ hybridization. In epithelial components, KIT, platelet-derived growth factor receptor (PDGFR)A, PDGFRB, MET, epidermal growth factor receptor (EGFR) and HER-2 were overexpressed in 1 (4.8%), 1 (4.8%), 0 (0%), 11 (52.4%), 13 (61.9%) and 2 (9.5%) cases, respectively. In the mesenchymal components the corresponding numbers of cases were 2 (9.5%), 2 (9.5%), 0 (0%), 12 (57.1%), 11 (52.4%) and 0 (0%). No mutations in the c-kit, PDGFRA and c-met genes were found. Among 19 EGFR-positive tumors, 2 had EGFR missense mutations (T790A, exon 20) only in the mesenchymal component. Gene amplification or high polysomy of c-kit, PDGFRA, c-met and EGFR was observed in 1 (33.3%), 0 (0%), 3 (18.8%) and 10 (52.6%) cases, respectively. In conclusion, various RTKs, particularly MET and EGFR were overexpressed in ECSs suggesting that molecular-targeted therapies directed to MET, EGFR or other RTKs may be effective in inhibiting the growth or progression of the epithelial and/or mesenchymal component of ECS.

Asymptomatic spontaneous cervical and mediastinal emphysema.

We report our experience with four patients presenting with spontaneous pneumomediastinum (SPM) within a 3-month period. The patients (three male and one female, aged 15-17 years) were hospitalised with SPM. All patients were kept under observation, successfully treated and followed up for several years, with no recurrences reported. Two patients had histories of asthma, while the other two developed SPM during sporting activities. SPM carries the possibility of being latent. For symptoms such as chest pain without evidence of pneumothorax in young people, it is necessary to always consider SPM and make the diagnosis accordingly.

Primary malignant melanoma of the rectum: report of two cases.

We report two cases of rectal malignant melanomas. The patients were an 84-year-old male and a 66-year-old female who had blood in their stools. They were preoperatively diagnosed with poorly differentiated adenocarcinoma of the rectum. The clinical diagnosis for each was rectal carcinoma at stage IIIc according to the tumor-node-metastasis classification (6th edition), and the patients underwent abdominoperineal resection with dissection of lymph nodes. Pathological examination of the resected specimens revealed a malignant melanoma. Immunohistochemical analysis results were positive for HMB-45 and negative for cytokeratin AE1/AE3, CD45, and synaptophysin. Primary anorectal melanoma is an uncommon and aggressive disease that carries a poor prognosis. Therefore, it is necessary to provide systemic treatment. To improve prognosis, it is important to detect anorectal melanoma at an early stage.

Prognostic significance of heat shock protein 110 expression and T lymphocyte infiltration in esophageal cancer.

BACKGROUND/AIMS: Heat shock proteins (HSPs) are well known as tumor rejection antigens, most notable of which is HSP70. HSP110 is classified as a member of the HSP70/DnaK superfamily. The objective of this study was to clarify the clinicopathological and prognostic significance of Heat Shock Protein 110 expression and T lymphocyte infiltration in esophageal cancer. METHODOLOGY: Immunohistochemical staining of HSP110, CD4 and CD8 were performed on surgical specimens obtained from 124 patients with esophageal cancer. RESULTS: The expression of HSP110 correlated inversely with depth of invasion (p<0.0001), lymph node metastasis (p=0.0163), pathological stage (p<0.0001), lymphatic invasion (p=0.0104), blood vessel invasion (p=0.0027), infiltrative growth pattern (p=0.0368) and correlated positively with CD4+ T lymphocyte infiltration (p=0.0018). Reduction of HSP110 expression was significantly correlated with poor prognosis (p=0.0010). CONCLUSIONS: The present findings suggest that HSP110 expression and T lymphocyte infiltration is a significant prognostic factor for esophageal cancer.

Overexpression of Cap43 is associated with malignant status of esophageal cancer.

Cap43 protein has been proven to be upregulated by nickel compounds or hypoxic stress, often during cell differentiation or cell growth arrest. However, the function of this gene remains unknown. Although, several studies have been performed, none of these have evaluated the expression of Cap43 in esophageal cancer. To clarify its function and role in esophageal cancer, a clinical archive of cancer specimens was examined for the expression of Cap43 by immunohistochemistry. The expression level of Cap43 protein was also investigated by Western blotting and mRNA by realtime RT-PCR using esophageal cancer cell lines. Immunohistochemistry results showed that overexpression of Cap43 was correlated with malignant status of esophageal cancer and that was considered as an independent prognostic marker. Interestingly, adenocarcinoma of the esophagus did not express Cap43. In esophageal cancer cell lines, Western blotting and real-time RT-PCR, showed a variation in the expression level of Cap43 and there was no obvious correlation between protein and mRNA levels. The present report shows for the first time that the expression of the Cap43 gene has a function in tumor progression and that its expression correlates independently with patient survival. Cap43 gene could be considered as a new and important cancer marker.

Tumor immune systems in esophageal cancer with special reference to heat-shock protein 70 and humoral immunity.

UNLABELLED: The objective of this study was to clarify the participation of heat-shock protein 70 (HSP70) and the humoral immune system in antitumor immunity in esophageal cancer. PATIENTS AND METHODS: Immunohistochemical staining for HSP 70, and CD4(+) T-, CD8(+) T-, B- and plasma cells was performed on surgical specimens obtained from 125 patients with esophageal cancer. An enzyme-linked immunosorbent assay (ELISA) was then performed to measure serum anti-HSP70 antibodies in the azygos vein. RESULTS: The expression of HSP 70 correlated inversely with depth of invasion (p<0.0001), pathological stage (p<0.0001) and blood vessel invasion (p<0.001), and there was a positive correlation between HSP70 and CD4(+) T-, CD8(+) T-, B- and plasma cells. Of these, the B- and plasma cells had the strongest correlation to HSP70 expression. Serum anti-HSP70 antibody levels in the azygos vein correlated with HSP70 expression, and B and plasma cell infiltration. Patients positive for HSP70, and B- and plasma cell infiltration had good prognosis compared to other cases. According to multivariate analyses, simultaneous occurrence of HSP70 expression, and B- and plasma cell infiltration is a stronger prognostic factor than simultaneous occurrence of HSP70 expression, and CD4(+) T- and CD8(+) T-cell infiltration. CONCLUSION: It is suggested that the HSP70-humoral immune cell system might play an important role in antitumor effects in patients with esophageal cancer.

Expression of the prolyl isomerase Pin1 is a useful indicator of sensitivity to chemoradiotherapy in advanced esophageal squamous cell carcinoma.

Cell cycle regulators, such as cyclinD1 and p53, play major roles in the tumor response to radiation and chemotherapy in esophageal squamous cell carcinoma (SCC). Pin1-mediated prolyl-isomerization potentiates cell cycle progression and cell proliferation, including the regulation of cyclinD1 and p53. Herein, we investigated the effect of Pin1 in association with cyclinD1 and p53 on the sensitivity of esophageal SCC to chemoradiotherapy (CRT). The expression levels of Pin1, cyclinD1 and p53 were examined immunohistochemically in endoscopic biopsy specimens from 68 advanced esophageal SCC patients before CRT to determine whether their expression levels predicted the clinical effectiveness of CRT in individual cancers. Forty-six of the 68 patients (67.6%) had an effective response to CRT, whereas 22 patients (32.4%) had an ineffective response. There was no significant correlation between clinical responses and expression levels of cyclinD1 or p53. However, the clinical response of the high Pin1 expression group was significantly higher than that of the low expression group (P=0.0200). Moreover, our data indicate that the combined immunohistochemical evaluation of Pin1, cyclinD1 and p53 expression in pretreatment biopsy samples is a useful indicator of sensitivity to CRT in advanced esophageal SCC. Thus, Pin1 may influence cyclinD1 and p53 functions and predict CRT sensitivity.

Correlation between connexin 26 expression and poor prognosis of esophageal squamous cell carcinoma.

BACKGROUND: Failure of gap junction formation affects the development of various types of cancer. We aimed to clarify the clinicopathologic outcome and prognostic significance of connexin (Cx) 26 in human esophageal squamous cell carcinoma (ESCC). METHODS: Immunohistochemical staining for Cx26 was performed on surgical specimens obtained from 123 patients with ESCC. RESULTS: There was no positive staining for Cx26-specific expression in normal esophageal squamous cells. Primary ESCC with Cx26-positive expression was detected in the cytoplasm of cancer cell nests in 60 cases. Cx26 expression was correlated with N (lymph node metastasis, P = 0.014) and the number of metastatic lymph nodes (P = 0.047). The 5-year survival rates of ESCC patients with Cx26-positive expression were significantly lower than those with Cx26-negative expression (positive, 39.7%; negative, 65.7%; P = 0.007). By multivariate analysis, tumor-node-metastasis (TNM) clinical classification (T, P < 0.001; N, P = 0.002; M, P = 0.046) and Cx26 (P = 0.024) were independent prognosis predictors of ESCC. CONCLUSIONS: These results suggest that abnormal expression of Cx26 participates in the progress of ESCC.

The additional value of integrated PET/CT over PET in initial lymph node staging of esophageal cancer.

The purpose of the present study was to assess the contribution of simultaneous functional/anatomical imaging using integrated 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT), compared with PET alone for the evaluation of initial lymph node staging in esophageal cancer. We studied 167 consecutive patients with thoracic esophageal squamous cell carcinoma (SCC) who had radical esophagectomy performed between January 1999 and April 2007. For individual nodal group evaluation, PET/CT showed 46.0% sensitivity (p<0.05 vs. PET), 99.4% specificity, 95.1% accuracy (p<0.05 vs. PET), 87.0% positive and 95.5% negative predictive values. PET showed 32.9% sensitivity, 98.9% specificity, 93.1% accuracy, 74.7% positive predictive value and 93.9% negative predictive value. Thus, the sensitivity and accuracy of PET/CT were significantly higher than those of PET. Comparisons between CT, PET and PET/CT in detecting lymph node metastasis by each region showed that PET/CT had a higher sensitivity in lower thoracic regions than PET and CT (p<0.05 vs. CT and PET). Lymph node staging (N0 vs. N1) was not significantly different, but staging per lymph nodal group was significantly better with PET/CT. Integrated PET/CT imaging with co-registration of anatomic and functional imaging data is useful in the initial lymph node staging of patients with operable esophageal cancer compared with PET alone.

Esophageal granular cell tumor covered by intramucosal squamous cell carcinoma: report of a case.

We report a case of a granular cell tumor (GCT) covered by squamous cell carcinoma (SCC) in the esophagus. A 69-year-old Japanese man was admitted to our hospital for treatment of superficial esophageal cancer detected by upper gastrointestinal endoscopy. Endoscopic examination revealed a shallow ulcer in the esophagus, 28-32 cm from the incisor teeth. The pathological findings of a biopsy of the lesion were moderately differentiated SCC. Thus, we performed partial esophagectomy with two-field (thoraco-abdominal) lymph node dissection. Microscopic examination of the surgical specimen revealed intraepithelial SCC with minimal invasion, and a GCT, 3 x 1 mm in size, in the submucosa just beneath the SCC. Cytoplasmic granules in the GCT were positive for periodic acid-Schiff. Immunohistochemically, the GCT was strongly positive for S-100 protein. To our knowledge, this is the first published report of a GCT covered by SCC in the esophagus.

Preoperative serum vascular endothelial growth factor-C (VEGF-C) levels predict recurrence in patients with esophageal cancer.

BACKGROUND: Circulating vascular endothelial growth factor-C (VEGF-C) levels were measured in patients with esophageal cancer to assess the value of VEGF-C as a biomarker for predicting tumor recurrence. PATIENTS AND METHODS: Preoperative serum samples were acquired from 80 patients and healthy volunteers who served as normal controls. VEGF-C levels were assessed using enzyme-linked immunosorbent assay (ELISA). RESULTS: The preoperative serum VEGF-C level in patients with esophageal cancer was significantly higher than in healthy volunteers. Furthermore, patients with recurrence had significantly higher preoperative serum VEGF-C levels than patients without recurrence, and a high preoperative serum VEGF-C level was found to be an independent risk factor for recurrence, in addition to lymph node metastasis. CONCLUSION: Preoperative VEGF-C levels may reflect malignancy, such as lymph node metastasis, and predict recurrence in patients with esophageal cancer. Therefore, the preoperative VEGF-C level may be a useful biomarker for choice of multimodality therapy.

Prediction of response to definitive chemoradiotherapy in esophageal cancer using positron emission tomography.

BACKGROUND: Positron emission tomography (PET) with 18-F-fluorodeoxyglucose (FDG) has already proven useful in assessing the extension of esophageal carcinomas, detecting tumor recurrence and monitoring responses to therapy. The current study aims to assess the potential role of FDG-PET in predicting the response of esophageal squamous cell carcinoma (SCC) to definitive chemoradiotherapy (CRT). PATIENTS AND METHODS: Twenty-seven patients with thoracic esophageal SCC who received definitive CRT between January 2001 and December 2005 underwent PET before and after CRT. The clinical evaluation of the primary tumor response to treatment was classified as either complete response (CR) or non-CR. RESULTS: All patients had intensive FDG uptake in the primary tumor prior to CRT. The standardized uptake value (SUV) averaged 8.2+/-4.7 before CRT and decreased significantly to 2.8+/-1.8 after CRT (p<0.0001). The SUV before CRT averaged 10.2 in the non-CR group (n=17) and 4.9 in the CR group (n= 10). The SUV after CRT averaged 3.7 in the non-CR group and 1.4 in the CR group. The change in SUV for the CR group was higher than that in the non-CR group (p<0.05). The relationship between clinical features and clinical CR was analyzed using logistic regression analysis which revealed significant correlations between clinical CR and the longitudinal dimension of the tumor (p <0.05), SUV before CRT (p<0.05), SUV after CRT (p<0.01) and tumor classification (p <0.05). If the clinical features before CRT were limited, multivariate analysis revealed that the SUV before CRT was an independent predictor for clinical CR (p<0.05). CONCLUSION: In predicting clinical evaluation of therapy prior to CRT, we suggest that SUV prior to definitive CRT is one of the most reliable predictors of response, along with tumor dimensions and classification.

Endoscopic clips prevent self-expandable metallic stent migration.

BACKGROUND/AIMS: Self-expandable metallic stents (SEMS) have been used for many years in the palliation of esophageal cancer symptoms. Stent migration is one of the most recognized complications of SEMS. To prevent SEMS migration, this study reported the use of endoscopic clips, and carefully analyzed the patients who underwent implantation. METHODOLOGY: From January 2000 to December 2002, nine patients consecutively underwent SEMS implantation. After successful placement of the SEMS and to maintain its position, endoscopic clips were used to fix the branch of the upper end of the stent to the esophageal mucosa. RESULTS: Stent implantation was technically successful in all patients, three of whom had strictures and six of whom had digestive-respiratory fistulas. No stent migration was observed in any of the patients, and dysphagia improved significantly after stent placement. Five patients did, however, experience delayed complications, two in the form of obstructions, two with recurrent fistulas, and one with a perforation. CONCLUSIONS: In conclusion, this new technique is recommended as endoscopic clipping can diminish the risks of stent migration, in particular those associated with esophago-respiratory fistulas without luminal obstruction.