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Background and Objectives: Anaplastic lymphoma kinase (ALK) rearrangement is a representative driver mutation in lung cancer. However, the biology of early-stage ALK-rearranged lung cancer remains unclear. We aimed to assess the clinicopathological features, prognostic implications, and influence of ALK rearrangement on the postoperative course in surgically resected lung cancer., Methods: We retrospectively analyzed data from the Japanese Joint Committee of Lung Cancer Registry database. Of the 12 730 patients with lung adenocarcinoma, 794 (6.2%) were tested for ALK rearrangement and were included., Results: ALK rearrangements were detected in 76 patients (10%). The 5-year overall survival (OS) rate was significantly higher in the ALK rearrangement-positive group than in the ALK rearrangement-negative group (p = 0.030). Multivariable analysis revealed that ALK rearrangement was an independent prognostic factor for improved OS (hazard ratio, 0.521; 95% confidence interval, 0.298-0.911; p = 0.022). Regarding the postrecurrence state, there was no difference in the initial recurrence sites between both groups. Administration of ALK-tyrosine kinase inhibitors (TKIs) improved postrecurrence survival in any treatment lines., Conclusion: In one of the largest national surveys, ALK rearrangement was associated with improved long-term outcomes in surgically resected patients. ALK-TKIs may be an important treatment strategy for ALK rearrangement-positive lung adenocarcinoma in the postrecurrence state., (© 2023 Wiley Periodicals LLC.)

A 69-year-old man was referred for vomiting. CT and upper gastrointestinal endoscopy revealed a circumferential stenotic lesion in the third portion of the duodenum, and partial duodenectomy and lymph node dissection were performed for the diagnosis of duodenal adenocarcinoma. The histopathological diagnosis was pT3, pN0, pStage ⅡA(UICC 8th)well differentiated tubular adenocarcinoma. The patient was treated with FOLFOX as adjuvant chemotherapy and is alive 2 years and 4 months postoperatively without recurrence. Primary duodenal adenocarcinoma in the third portion is rare, and further case experience is required for selection of the operation and adjuvant therapy.

Objective: We studied the prognosis and clinicopathological background of lung adenocarcinoma predominance among patients who underwent lobectomy using data from the Japanese Joint Committee of Lung Cancer Registry., Methods: Two thousand eight hundred sixty-three cases were extracted. Recurrence free survival (RFS) rates, overall survival (OS) rates and clinicopathological factors and epidermal growth factor receptor (EGFR) mutation status were examined., Results: Median follow-up period was 65.5 months. Adenocarcinoma predominance was sub-grouped according to OS and RFS rate. In pathological stage I, 5-year RFS and OS rates were respectively 92.2% and 95.8% in group A (adenocarcinoma-in-situ + minimally invasive adenocarcinoma), 89.3% and 92.1% in group B (lepidic), 79.2% and 89.7% in group C (papillary + acinar + variants) and 69.0% and 79.0% in group D (solid + micropapillary). In pathological stage II + IIIA, they were, 43.6% and 72.4% in B, 39.5% and 66.9% in C and 31.0% and 53.7% in D. Group D showed significant worst outcome both in stage I and II + IIIA. Up stage rate from clinical stage I to pathological stage II + IIIA was 0.0%, 3.7%, 15.9% and 33.3%. The frequency of lymph-vessel, vascular, pleura invasion and positive EGFR mutation were 0.0%, 0.0%, 0.0% and 57.1% in group A, 15.6%, 10.0%, 12.1% and 55.1% in B, 36.6%, 31.8%, 29.7% and 44.9% in C, 50.2%, 57.8%, 38.9% and 21.3% in D. In group D, lymph-vessel, vascular and pleura invasion were most, EGFR mutation was least frequent not only in pathological stage I but also stage II + IIIA. In multivariate analysis, age, pathological stage, vascular invasion, and group D were independent factors affected RFS and OS., Conclusion: Limited to lobectomy cases, solid + micropapillary was independent prognostic factor both in early and locally advanced stage. Its malignant degree was related to the frequency of pathological invasive factors and EGFR mutation status., (© 2022. The Author(s).)

Anal canal cancer (ACC) has been reported to be an uncommon cancer in Japan, as in the USA, Europe, and Australia. This retrospective multi-institutional study was conducted to clarify the characteristics of ACC in Japan. First, the histological ACC type cases treated between 1991 and 2015 were collected. A detailed analysis of the characteristics of anal canal squamous cell carcinoma (SCC) cases was then conducted. The results of the histological types revealed that of the 1781 ACC cases, 435 cases (24.4%) including seven cases of adenosquamous cell carcinomas were SCC and 1260 cases (70.7%) were adenocarcinoma. However, the most common histological type reported in the USA, Europe, and Australia is SCC. Most ACC cases are adenocarcinomas and there is a low incidence of SCC in Japan which is different from the above-mentioned countries. Moreover, we reclassified T4 into the following two groups based on tumor size: T4a (tumor diameter of 5 cm or less) and T4b (tumor diameter of more than 5 cm). The results of the TNM classification of SCC revealed that the hazard ratio (HR) to T1 of T2, T3, T4a, and T4b was 2.45, 2.28, 2.89, and 4.97, respectively. As T4b cases had a worse prognosis than T4a cases, we propose that T4 for anal canal SCC in Japan be subclassified into T4a and T4b., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

A 66-year-old man with epigastric pain was admitted to our hospital for further evaluation of a pancreatic mass, as indicated on transabdominal ultrasonography performed by his family doctor. Using various imaging modalities, the 22-mm tumor was diagnosed as a cystic tumor with hemorrhagic necrosis. The tumor diameter reduced to 11mm over the course of 1 month. However, the tumor margin was irregular than that at the initial diagnosis, and circumferential rim enhancement was observed in equilibrium phase computed tomography images. Therefore, we diagnosed the patient with pancreatic ductal adenocarcinoma with a necrotic component. Distal pancreatectomy with splenectomy was performed, and the subsequent histological diagnosis was poorly differentiated adenocarcinoma. This case had an interesting course as described by the diagnostic images.

Background: Alternate-day administration of S-1 is thought to reduce toxicities. This phase II study evaluated S-1 on alternate days combined with bevacizumab as first-line treatment for elderly patients with metastatic colorectal cancer., Patients and Methods: Eligible patients had histologically proven colorectal adenocarcinoma, measurable metastatic lesions, age ≥ 75 years, Eastern Cooperative Oncology Group performance status ≤ 1, no previous chemotherapy, and refused oxaliplatin- or irinotecan-containing regimens. Patients received 40 mg, 50 mg, or 60 mg (body surface area ≤ 1.25 m 2 , > 1.25 to ≤ 1.50 m 2 , or > 1.50 m 2 , respectively) of S-1 twice orally on Sunday, Monday, Wednesday, and Friday every week. Bevacizumab (7.5 mg/kg) was administered every 3 weeks. The primary endpoint was progression-free survival., Results: Of 54 enrolled patients, 50 patients were evaluated for efficacy and 53 for safety. The median age was 79 years (range 75-88 years). The median progression-free survival was 8.1 months (95% confidence interval (CI) 6.7-9.5 months). The median overall survival was 23.1 months (95% CI 17.4-28.8 months). The response rate was 44% (95% CI 30.2-57.8%), and the disease control rate was 88% (95% CI 79.0-97.0%). Grade 3 or higher hematologic, non-hematologic, and bevacizumab-related adverse events occurred in 9%, 11%, and 25% of patients, respectively. The most common grade 3 and 4 treatment-related adverse events were hypertension (11%), nausea (6%), fatigue (6%), anemia (6%), and proteinuria (6%). Only 6 patients discontinued treatment due to adverse events., Conclusion: S-1 on alternate days combined with bevacizumab showed better tolerability and comparable survival compared with the results of similar studies.

A 73-year-old man was admitted to our hospital with anal pain. The 10 cm tumor was observed externally at the 3 o' clock side of his anus. He was unable to maintain the sitting position because of pain and had fecal incontinence and erosive skin inflammation. We identified this anal stenosis as anal canal adenocarcinoma(moderately differentiated). Thereby, no distant metastasis was found; we decided to treat the patient with conventional therapy. We made a double-hole colostomy in the sigmoid colon, and then the patient received preoperative chemoradiotherapy(CRT). Radiation therapy(RT)was adminis- tered at 40 Gy/20 Fr and oral capecitabine of 825mg/m / 2/time was administered twice a day on the RT days. The tumor shrinkage was good, and then we performed a laparoscopy-assisted abdominoperineal resection of the rectum. Pathologically therapeutic effect was Grade 1b. His activity of daily living was dramatically improved, and he can now main tan the sitting position. Twelve months postoperatively, he has no sign of recurrence. In this case, we experienced an anal canal adenocarcinoma that was possibly locally controlled by preoperative CRT and rectal amputation.

Many tumors evolve sophisticated strategies to evade the immune system, and these represent major obstacles for efficient antitumor immune responses. Here we explored a molecular mechanism of metabolic communication deployed by highly glycolytic tumors for immunoevasion. In contrast to colon adenocarcinomas, melanomas showed comparatively high glycolytic activity, which resulted in high acidification of the tumor microenvironment. This tumor acidosis induced Gprotein-coupled receptor-dependent expression of the transcriptional repressor ICER in tumor-associated macrophages that led to their functional polarization toward a non-inflammatory phenotype and promoted tumor growth. Collectively, our findings identify a molecular mechanism of metabolic communication between non-lymphoid tissue and the immune system that was exploited by high-glycolytic-rate tumors for evasion of the immune system.

A 94-year-old woman, who had been treated for multiple colon cancers 4 years ago, complained of umbilicus induration and had been followed up in a previous hospital with a diagnosis of periumbilical inflammation. Four years and 3 months postoperatively, the umbilical induration was enlarged, and umbilical metastasis of adenocarcinoma was diagnosed on biopsy. Umbilical resection was performed, and multiple peritoneal metastases were revealed. Umbilical metastases may worsen the patient's quality of life; thus, local resection was recommended positively.

Background: The benefit of pancreatectomy for elderly patients with pancreatic ductal adenocarcinoma (PDAC) remains controversial. Moreover, adjuvant chemotherapy (AC) for elderly patients has not been fully evaluated. We investigated the long-term outcomes after pancreatectomy for PDAC in elderly patients with special reference to AC., Methods: The medical records of 123 patients who underwent pancreatectomy for PDAC from 2007 to 2016 were retrospectively reviewed. The patients were divided into two groups: young (<75 years) and elderly patients (≥75 years)., Results: The study population comprised 91 young and 32 elderly patients. The postoperative clinical courses were not different between the two groups. AC was more frequently administered to young (85%) than elderly patients (66%; P = 0.04). The weekly dose of tegafur/gimeracil/oteracil potassium (S1) for AC was significantly lower in elderly (median 423 mg/m 2 ) than young patients (median 491 mg/m 2 ; P = 0.02). The prevalence of adverse events and the completion rate of AC were not significantly different between the two groups. There were no significant differences in recurrence-free survival (P = 0.73) or overall survival (P = 0.68) between the two groups in univariate analysis. Receipt of AC was not a significant independent factor for survival, and completion of planned AC was a significant independent factor for recurrence-free survival and overall survival in multivariate analysis., Conclusions: The benefit of pancreatectomy for PDAC was the same between young and elderly patients. Completion of planned AC was important, and lowered-dose AC using S1 for elderly patients might be safe and therapeutically useful.

Chemotherapy resistance is a major problem in the treatment of cancer, but the underlying mechanisms are not fully understood. We found that the expression levels of claudin-1 (CLDN1) and 3, tight junctional proteins, are upregulated in cisplatin (CDDP)-resistant human lung adenocarcinoma A549 (A549R) cells. A549R cells showed cross-resistance to doxorubicin (DXR). Here, the expression mechanism and function of CLDN1 and 3 were examined. CLDN1 and 3 were mainly localized at tight junctions concomitant with zonula occludens (ZO)-1, a scaffolding protein, in A549 and A549R cells. The phosphorylation levels of Src, MEK, ERK, c-Fos, and Akt in A549R cells were higher than those in A549 cells. The expression levels of CLDN1 and 3 were decreased by LY-294002, a phosphoinositide 3-kinase (PI3K) inhibitor, and BAY 11-7082, an NF-κB inhibitor. The overexpression of CLDN1 and 3 decreased the paracellular permeability of DXR in A549 cells. Hypoxia levels in A549R and CLDN1-overexpressing cells (CLDN1/A549) were greater than those in A549, mock/A549, and CLDN3/A549 cells in a spheroid culture model. In contrast, accumulation in the region inside the spheroids and the toxicity of DXR in A549R and CLDN1/A549 cells were lower than those in other cells. Furthermore, the accumulation and toxicity of DXR were rescued by CLDN1 siRNA in A549R cells. We suggest that CLDN1 is upregulated by CDDP resistance through activation of a PI3K/Akt/NF-κB pathway, resulting in the inhibition of penetration of anticancer drugs into the inner area of spheroids., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Claudins, tight junctional proteins, regulate the paracellular permeability of ions and small molecules. Claudin-2 is highly expressed in human lung adenocarcinoma cells and is involved in the up-regulation of cell proliferation. However, the effect of claudin-2 on cellular sensitivity to anticancer agents has not been clarified. The cytotoxicity of anticancer agents such as cisplatin, gefitinib and doxorubicin (DXR) was increased by claudin-2 knockdown in A549 cells. Claudin-2 knockdown also significantly decreased the expression level of multidrug resistance-associated protein/ABCC2. The expression levels of other drug efflux transporters were unchanged. The intracellular accumulation of 5-chloromethylfluorescein diacetate (CMFDA) and DXR, substrates of ABCC2, was increased by claudin-2 knockdown, whereas the efflux was decreased. MK-571, an inhibitor of ABCC2, enhanced the cytotoxicity of anticancer agents. Claudin-2 knockdown decreased the levels of p-c-Jun and nuclear Sp1. SP600125, an inhibitor of c-Jun, and mithramycin, an inhibitor of Sp1, decreased the level of ABCC2. The promoter activity of ABCC2 was decreased by claudin-2 knockdown, SP600125 and mithramycin treatments, suggesting that claudin-2 is involved in the up-regulation of ABCC2 expression at the transcriptional level. Claudin-2 knockdown increased the paracellular permeability of DXR in a 2D monolayer culture model. In addition, the accumulation of DXR into spheroids was enhanced by claudin-2 knockdown, resulting in a reduction in cell viability. We suggest that claudin-2 may be a novel therapeutic target in lung adenocarcinoma, because claudin-2 knockdown increased the accumulation of anticancer agents in cancer cells and spheroids., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The major driver mutations of lung cancer, EGFR mutations and EML4-ALK fusion, are mainly detected in terminal respiratory unit (TRU)-type lung adenocarcinomas, which typically show lepidic and/or papillary patterns, but are rarely associated with a solid or invasive mucinous morphology. In order to elucidate the key genetic events in non-TRU-type lung cancer, we carried out whole-exome sequencing on 43 non-TRU-type lung adenocarcinomas based on morphology (17 acinar, nine solid, and two enteric adenocarcinomas, and 15 adenocarcinomas with a mucinous morphology). Our analysis identified mutations in TP53 (16/43, 37.2%), KRAS (13/43, 30.2%), and NKX2-1/TTF-1 (7/43; 16.3%) as the top three significantly mutated genes, while the EGFR mutation was rare (1/43, 2.3%) in this cohort. Eight NKX2-1/TTF-1 mutations (five frameshift, two nonsense, and one missense) were identified, with one case harboring two distinct NKX2-1/TTF-1 mutations (one missense and one frameshift). Functional assays with the NK2 homeobox 1 (NKX2-1)/thyroid transcription factor 1 (TTF-1) mutants revealed that none of them retain the activity as a transcriptional factor. Histologically, invasive mucinous adenocarcinomas accounted for most of the NKX2-1/TTF-1 mutations (five cases), as well as one enteric and one acinar adenocarcinoma. Immunohistochemistry showed that the cohort was largely divided into TTF-1-postive/hepatocyte nuclear factor 4-α (HNF4-α)-negative and TTF-1-negative/HNF4-α-positive groups. NKX2-1/TTF-1 mutations were exclusively found in the latter, in which the gastrointestinal markers, mucin 5AC and cytokeratin 20, were frequently expressed. Bisulfite sequencing revealed that the NKX2-1/TTF-1 gene body was highly methylated in NKX2-1/TTF-1-negative cases, including those without the NKX2-1/TTF-1 mutations. The genetic or epigenetic inactivation of NKX2-1/TTF-1 may play an essential role in the development and aberrant differentiation of non-TRU-type lung adenocarcinomas., (© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Decreased cell-substratum adhesion is crucially involved in metastasis. Previous studies demonstrated that lung cancer with floating cell clusters in histology is more likely to develop metastasis. In the present study, we investigated whether cancer cells in long-term, three-dimensional low attachment cultures acquire high metastatic potential; these cells were then used to examine the mechanisms underlying metastasis. Two KRAS-mutated adenocarcinoma cell lines (A549 and H441) were cultured and selected on ultra-low attachment culture dishes, and the resulting cells were defined as FL (for floating) sublines. Cancer cells were inoculated into NOD/SCID mice via an intracardiac injection, and metastasis was evaluated using luciferase-based imaging and histopathology. In vitro cell growth (in attachment or suspension cultures), migration, and invasion were assayed. A whole genomic analysis was performed to identify key molecular alterations in FL sublines. Upon detachment on low-binding dishes, parental cells initially formed rounded spheroids with limited growth activity. However, over time in cultures, cells gradually formed smaller spheroids that grew slowly, and, after 3-4 months, we obtained FL sublines that regained prominent growth potential in suspension cultures. On ordinary dishes, FL cells reattached and exhibited a more spindle-shaped morphology than parental cells. No marked differences were observed in cell growth with attachment, migration, or invasion between FL sublines and parental cell lines; however, FL cells exhibited markedly increased growth potential under suspended conditions in vitro and stronger metastatic abilities in vivo. A genomic analysis identified epithelial-mesenchymal transition (EMT) and c-Myc amplification in A549-FL and H441-FL cells, respectively, as candidate mechanisms for metastasis. The growth potential of FL cells was markedly inhibited by lentiviral ZEB1 knockdown in A549-FL cells and by the inhibition of c-Myc through lentiviral knockdown or the pharmacological inhibitor JQ1 in H441-FL cells. Long-term three-dimensional low attachment cultures may become a useful method for investigating the mechanisms underlying metastasis mediated by decreased cell-substratum adhesion.

Claudin-2 is highly expressed in human lung adenocarcinoma tissues and may be a novel target for cancer chemotherapy because knockdown of claudin-2 decreases cell proliferation. We found that flavonoids including kaempferol, chrysin, and luteolin concentration-dependently decrease claudin-2 expression in lung adenocarcinoma A549 cells. Claudin-2 expression is up-regulated by mitogen-activated protein kinase kinase (MEK)/ extracellular signal-regulated kinase (ERK)/c-Fos and phosphoinositide 3-kinase (PI3K)/Akt/nuclear factor-κB (NF-κB) pathways, but these activities were not inhibited by kaempferol, chrysin, and luteolin. Promoter deletion assay using luciferase reporter vector showed that kaempferol and luteolin inhibit the function of transcriptional factor that binds to the region between -395 and -144 of claudin-2 promoter. The decrease in promoter activity was suppressed by mutation in signal transducers and activators of transcription (STAT)-binding site, which is located between -395 and -144. The phosphorylation level of STAT3 was not decreased, but the binding of STAT3 on the promoter region is suppressed by kaempferol and luteolin in chromatin immunoprecipitation assay. The inhibition of cell proliferation caused by kaempferol and luteolin was partially recovered by ectopic claudin-2 expression. Taken together, kaempferol and luteolin decreased claudin-2 expression and proliferation in A549 cells mediated by the inhibition of binding of STAT3 on the promoter region of claudin-2. The intake of foods and nutrients rich in these flavonoids may prevent lung adenocarcinoma development., Competing Interests: The authors declare no conflict of interest.

Background: The clinical importance of intraoperative peritoneal cytology in patients with pancreatic cancer remains incompletely understood., Methods: Peritoneal washing samples were collected from 411 consecutive patients with pancreatic ductal adenocarcinoma from 1996 to 2014. Of the 411 patients, 335 underwent macroscopically curative resection and 76 with noncurative factors did not undergo resection. We compared long-term outcomes between patients with positive cytology (cytology+) and those with negative cytology (cytology-) and investigated the importance of clinicopathologic factors., Results: Of 335 patients with curative resection, 300 (89.6%) were cytology- and 35 (10.4%) were cytology+. The median overall survival of cytology+ patients was less than that of cytology- patients (16 vs 31 months, respectively; P < .0001). The median overall survival of cytology+ patients with noncurative factors was significantly worse than that of cytology+ patients with curative resection (6.9 vs 16.0 months, respectively; P = .0023). The median disease-free survival of cytology+ patients was less than that of cytology- patients (6.5 vs 16 months, respectively; P < .0001). In the multivariate analysis, cytology+ was an independent prognostic factor for overall survival and disease-free survival., Conclusion: Cytology+ without noncurative factors was a predictive factor for a poor prognosis. Therefore, it is important to regard patients with pancreatic cancer characterized by cytology+ as a special group that may warrant more aggressive adjuvant therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Claudin-2 is highly expressed in lung adenocarcinoma tissues and increases proliferation in adenocarcinoma cells. The chemicals that reduce claudin-2 expression may have anti-cancer effects, but such therapeutic medicines have not been developed. We found that azacitidine (AZA), a DNA methylation inhibitor, and trichostatin A (TSA) and sodium butyrate (NaB), histone deacetylase (HDAC) inhibitors, decrease claudin-2 levels. The effect of AZA was mediated by the inhibition of phosphorylated Akt and NF-κB. LY-294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K), and BAY 11-7082, an NF-κB inhibitor, decreased claudin-2 levels. The reporter activity of claudin-2 was decreased by AZA and LY-294002, which was blocked by the mutation in a putative NF-κB-binding site. NF-κB bound to the promoter region of claudin-2, which was inhibited by AZA and LY-294002. AZA is suggested to decrease the claudin-2 mRNA level mediated by the inhibition of a PI3K/Akt/NF-κB pathway. TSA and NaB did not change phosphorylated Akt and NF-κB levels. Furthermore, these inhibitors did not change the reporter activity of claudin-2 but decreased the stability of claudin-2 mRNA mediated by the elevation of miR-497 microRNA. The binding of histone H3 to the promoter region of miR-497 was inhibited by TSA and NaB, whereas that of claudin-2 was not. These results suggest that HDAC inhibitors decrease claudin-2 levels mediated by the elevation of miR-497 expression. Cell proliferation was additively decreased by AZA, TSA, and NaB, which was partially rescued by ectopic expression of claudin-2. We suggest that epigenetic inhibitors suppress the abnormal proliferation of lung adenocarcinoma cells highly expressing claudin-2., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

We report a case of rectal metastasis of gastric cancer associated with dermatomyositis showing paraneoplastic syndrome. The patient was a 70-year-old man who had undergone curative total gastrectomy for Stage III Agastric cancer in March 2005. He was diagnosed with dermatomyositis and treated with prednisolone after gastrectomy. In April 2006, erythema of his face relapsed, and his serum CPK level was abnormally elevated. He experienced muscle weakness and dysphagia, and was treated with increased doses of prednisolone and gamma-globulin. At this time, endoscopic examination and computed tomography(CT)revealed a rectal tumor with hepatic metastasis. We performed Hartmann's operation in July 2006. The rectal tumor was predominantly submucosal, was 7 cm in diameter, involved #251 lymph node, and had positive peritoneal lavage cytology. The histopathological findings of the rectal tumor were comparable with those of gastric cancer, and we therefore diagnosed metastatic adenocarcinoma of gastric cancer. After surgery, we could control the patient's dermatomyositis with prednisolone at a reduced dose. However, chemotherapy with S-1 was ineffective and the patient died 8 months postoperatively.

Background: It remains controversial whether open or laparoscopic surgery should be indicated for elderly patients with colorectal cancer and a poor performance status., Methods: In those patients aged 80 years or older with Eastern Cooperative Oncology Group performance status score of 2 or greater who received elective surgery for stage 0 to stage III colorectal adenocarcinoma and had no concomitant malignancies and who were enrolled in a multicenter case-control study entitled "Retrospective study of laparoscopic colorectal surgery for elderly patients" that was conducted in Japan between 2003 and 2007, background characteristics and short-term and long-term outcomes for open surgery and laparoscopic surgery were compared., Results: Of the 398 patients included, 295 underwent open surgery and 103 underwent laparoscopic surgery. There were no significant differences in the baseline characteristics between open surgery and laparoscopic surgery patients, except for previous abdominal surgery and TNM stage. The median operation duration was shorter with open surgery (open surgery, 153 min; laparoscopic surgery, 202 min; P < 0.001), and less blood loss occurred with laparoscopic surgery (median open surgery, 109 g; median laparoscopic surgery, 30 g; P < 0.001). An operation duration of 180 min or more (odds ratio, 1.97; 95 % confidence interval, 1.17-3.37; P = 0.011) and selection of laparoscopic surgery (odds ratio, 0.41; 95 % confidence interval, 0.22-0.75; P = 0.003) were statistically significant in the multivariate analysis for postoperative morbidity. Moreover, laparoscopic surgery did not result in an inferior overall survival rate compared with open surgery (log-rank test P = 0.289, 0.278, 0.346, 0.199, for all-stage, stage 0-I, stage II, and stage III disease, respectively)., Conclusions: Laparoscopic surgery in elderly colorectal cancer patients with a poor performance status is safe and not inferior to open surgery in terms of overall survival.

We report a long surviving case of gastric cancer with a synchronous adrenal metastasis in a patient who underwent curative resection. The patient was a 74-year-old man. Endoscopic examination revealed a type 3 gastric cancer in the proximal stomach. Abdominal computed tomography (CT) revealed a soft tissue density mass in the right adrenal gland and a high-density mass suspected as hemangioma in the left adrenal gland. The CT scan indicated no other distant metastasis. The patient had no endocrine abnormalities according to blood test results. Total gastrectomy with D2 lymphadenectomy and right adrenalectomy were performed in August 2003. On histopathological examination, the gastric tumor was diagnosed as a poorly differentiated adenocarcinoma. The histopathological findings of the right adrenal tumor were compatible with those of gastric cancer. The final diagnosis was por1, 105×65 mm, pT2 (SS), pN1 (#1: 2/8, #3: 1/11), P0, H0, CY0, pM1 (ADR), pStage Ⅳ. Two months after the surgery, the patient was treated with adjuvant TS-1 monotherapy (80 mg/m2 day 1-28/q6w) for 1 year 9 months. The patient had been in good health without a recurrence for more than 9 years 3 months after the operation.

We report a case of human epidermal growth factor receptor 2 (HER2) -positive advanced gastric cancer effectively treated via capecitabine, cisplatin, and trastuzumab (XPT) chemotherapy followed by curative gastrectomy. The patient was a 66- year-old man with type 2 gastric cancer in the greater curvature of the gastric angle. Biopsy revealed that the tumor was a well or moderately differentiated adenocarcinoma, and immunohistochemistry showed positive expression of HER2(3+). Chest and abdominal computed tomography(CT)showed a liver tumor 21×9 mm in size in the caudate lobe and swollen lymph nodes in the paragastric, para-aortic, and left supraclavicular regions. After 4 courses of XPT, a clinical complete response was obtained. The patient received additional 13 courses of trastuzumab and capecitabine and underwent Billroth I distal gastrectomy with D2 lymph node dissection and resection of the para-aortic and left supraclavicular lymph nodes. Liver metastasis was not detected. No residual cancer cells were found in the stomach or lymph nodes except for the left supraclavicular lymph nodes. Pathological classification according to the Japanese Classification of Gastric Carcinoma, 14 th edition, was ypT0, ypN0, ypM1(LYM), Grade 2, ypStage IV. The patient developed a post-operative anastomotic leakage that required drainage via laparotomy, but was discharged 76 days after surgery in good condition.

A strategy of multidisciplinary therapy is considered necessary for the longer survival of a patient diagnosed with advanced colorectal cancer. We report a successful multi-disciplinary therapy case of a 70's-year-old male who received pulmonary resection for metastatic lung cancer twice after primary resection for rectal cancer. Solitary metastatic liver cancer with portal vein tumor thrombus (PVTT) was diagnosed 5 years and 4 months after primary surgery. Although systemic chemotherapy was started immediately, disease control was poor and local pulmonary recurrence appeared. Although intrahepatic metastasis was considered the most important prognostic factor, radiation therapy against PVTT (50 Gy) was initially performed to control disease. After verifying that no new recurrent lesions had arisen during radiation therapy, a third pulmonary resection (in the left upper remnant lobectomy)was performed. Hepatectomy(in the right lobectomy)was then performed for curative purposes. Pathological efficacy of radiation therapy to PVTT was revealed as GradeIb according to Evans' classification. In accordance with the patient's request, no adjuvant treatment was planned. Seven years after primary resection no sign of recurrence is evident. Radiation therapy is suggested to be most useful for disease control and patient selection.

Background: Submucosal and lymphovascular (SM/LV) invasions of early gastric cancer (EGC) are difficult to diagnose accurately prior to endoscopic submucosal dissection (ESD), and are occasionally found in resected specimens, requiring additional gastrectomy and lymph node dissection. We performed a retrospective study to determine the risk factors for SM/LV invasions., Methods: We analyzed clinicopathological data (age, sex, cancer location, gross morphology, multifocality, tumor size, histological differentiation, depth of invasion, and the presence or absence of lymphovascular invasion) in patients receiving ESD between 2007 and 2012 and presenting with EGC of 2.0 cm or smaller in size, a differentiated-type adenocarcinoma, and without ulceration., Results: Of 208 lesions consecutively resected by ESD, 143 lesions in 132 patients were included in this study. Submucosal and lymphovascular invasions were detected in 16 lesions. Multivariate analysis revealed three independent risk factors for SM/LV invasions: dominant histology of moderately-differentiated or papillary adenocarcinoma, gross type of 0-IIa + IIc or IIc + IIa, and tumor size of ≥1.5 cm. Lesions exhibiting more than two of these three risk factors were associated with having a 47 % increased incidence of SM/LV invasion (odds ratio 15; 95 % confidence interval 4.6-49.0; P < 0.0001)., Conclusions: Moderately-differentiated or papillary adenocarcinoma, 0-IIa + IIc or IIc + IIa, and a tumor size of ≥1.5 cm were identified as independent risk factors for SM/LV invasion among EGCs which appeared to be an endoscopically good indication for ESD. Careful surveillances including endoscopic ultrasonography or enhanced computed tomography might be needed for high risk patients before ESD.

Claudin-2 is expressed in human lung adenocarcinoma tissue and cell lines, although it is absent in normal lung tissue. However, the role of claudin-2 in cell proliferation and the regulatory mechanism of intracellular distribution remain undefined. Proliferation of human adenocarcinoma A549 cells was decreased by claudin-2 knockdown together with a decrease in the percentage of S phase cells. This knockdown decreased the expression levels of ZONAB and cell cycle regulators. Claudin-2 was distributed in the nucleus in human adenocarcinoma tissues and proliferating A549 cells. The nuclear distribution of ZONAB and percentage of S phase cells were higher in cells exogenously expressing claudin-2 with a nuclear localization signal than in cells expressing claudin-2 with a nuclear export signal. Nuclear claudin-2 formed a complex with ZO-1, ZONAB, and cyclin D1. Nuclear distribution of S208A mutant, a dephosphorylated form of claudin-2, was higher than that of wild type. We suggest that nuclear distribution of claudin-2 is up-regulated by dephosphorylation and claudin-2 serves to retain ZONAB and cyclin D1 in the nucleus, resulting in the enhancement of cell proliferation in lung adenocarcinoma cells., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Adenocarcinomas arising from the ectopic pancreas in the gastrointestinal wall are rarely described in the literature. In addition, obtaining an accurate preoperative diagnosis is difficult in most cases because these adenocarcinomas occur primarily in the submucosal layer and form submucosal tumors. Endoscopic ultrasonography-guided fine-needle aspiration and endoscopic mucosal resection with a transparent plastic cap-fitted panendoscope followed by a biopsy are useful for histological typing and making the differential diagnosis of adenocarcinoma, gastrointestinal stromal tumor, malignant lymphoma or other. These procedures represent the first step toward diagnosing ectopic pancreatic adenocarcinoma. We herein report two such cases with a review of the pertinent literature.

BRG1 and BRM, two core catalytic subunits in SWI/SNF chromatin remodeling complexes, have been suggested as tumor suppressors, yet their roles in carcinogenesis are unclear. Here, we present evidence that loss of BRG1 and BRM is involved in the progression of lung adenocarcinomas. Analysis of 15 lung cancer cell lines indicated that BRG1 mutations correlated with loss of BRG1 expression and that loss of BRG1 and BRM expression was frequent in E-cadherin-low and vimentin-high cell lines. Immunohistochemical analysis of 93 primary lung adenocarcinomas showed loss of BRG1 and BRM in 11 (12%) and 16 (17%) cases, respectively. Loss of expression of BRG1 and BRM was frequent in solid predominant adenocarcinomas and tumors with low thyroid transcription factor-1 (TTF-1, master regulator of lung) and low cytokeratin7 and E-cadherin (two markers for bronchial epithelial differentiation). Loss of BRG1 was correlated with the absence of lepidic growth patterns and was mutually exclusive of epidermal growth factor receptor (EGFR) mutations. In contrast, loss of BRM was found concomitant with lepidic growth patterns and EGFR mutations. Finally, we analyzed the publicly available dataset of 442 cases and found that loss of BRG1 and BRM was frequent in E-cadherin-low, TTF-1-low, and vimentin-high cases and correlated with poor prognosis. We conclude that loss of either or both BRG1 and BRM is involved in the progression of lung adenocarcinoma into solid predominant tumors with features of epithelial mesenchymal transition and loss of the bronchial epithelial phenotype. BRG1 loss was specifically involved in the progression of EGFR wild-type, but not EGFR-mutant tumors., (© 2012 Japanese Cancer Association.)

Rearranged during transfection (RET) fusions have been newly identified in approximately 1% of patients with primary lung tumors. However, patient-derived lung cancer cell lines harboring RET fusions have not yet been established or identified, and therefore, the effectiveness of an RET inhibitor on lung tumors with endogenous RET fusion has not yet been studied. In this study, we report identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line LC-2/ad. LC-2/ad showed distinctive sensitivity to the RET inhibitor, vandetanib, among 39 non-small lung cancer cell lines. The xenograft tumor of LC-2/ad showed cribriform acinar structures, a morphologic feature of primary RET fusion-positive lung adenocarcinomas. LC-2/ad cells could provide useful resources to analyze molecular functions of RET-fusion protein and its response to RET inhibitors.

We report on a 68-year-old male with a multistation mediastinal lymph node adenocarcinoma, who had no primary lesions occurring within 48 months. After diagnosis by lymph node biopsy via right-sided thoracoscopy, the bilateral mediastinal lymphadenopathy responded to platinum-based chemotherapy. At 30 months after completion of chemotherapy, left mediastinal lymphadenopathy recurred. Left anterior mediastinal dissection via left-sided thoracoscopy was successful. After surgery, the patient did well with no primary lesions for more than a year. The etiology of mediastinal lymph node carcinoma of unknown origin is discussed.

Bronchial stump necrosis is a lethal complication after pulmonary resection. We report a patient who had extensive necrosis of the intermediate bronchus after right lower lobectomy. The large bronchial defect was successfully fixed with latissimus dorsi muscle and replaced by bronchial epithelialization.

Anatomical variations in the pulmonary vessels present a potential risk for intraoperative bleeding and damage to the pulmonary circulation during pulmonary resection. Here, we present a patient who underwent left upper lobectomy for lung cancer. The patient had a dangerous mediastinal basal pulmonary artery variation that could be mistaken for the mediastinal lingular pulmonary artery and be divided during left upper lobectomy.

Background: The strategy for treating extremely aged patients with gastric carcinoma is controversial. This study reviews the prognoses of patients aged 85 years and older who were diagnosed with gastric carcinoma., Methods: One hundred seventeen patients aged 85 years and older were diagnosed as having gastric carcinoma after 1969 in our institution. After excluding those at stage IV, 36 cases underwent curative resection and 30 cases received best supportive care (BSC), which we reviewed retrospectively., Results: Surgical methods included distal gastrectomy for 28 cases, total gastrectomy for five cases, and other procedures for three cases. Postoperatively, pneumonia developed in four cases, anastomotic leakage in two cases, and pancreatic fistula in one case. Two patients died of pneumonia within 1 month of surgery. Univariate analysis demonstrated that age, surgery, performance status, and sodium level were statistically significant prognostic factors. Multivariate analysis demonstrated that surgery was the only independent prognostic factor. When patients with a performance status of 4 were excluded, the clinical characteristics of the surgery group (n = 36) and BSC group (n = 20) were statistically identical, and the overall survival was significantly better in the surgery group (p = 0.0078)., Conclusions: Postoperative outcomes were relatively acceptable. Surgery may be feasible and beneficial even for extremely aged patients 85 years and older, except for those with a performance status of 4.

Anatomical variations of the pulmonary vessels present a potential risk of intraoperative bleeding and damage to pulmonary circulation during pulmonary resection. We present details of a dangerous variation of the superior pulmonary vein associated with thoracoscopic right lower lobectomy that could potentially be divided if there was no preoperative foreknowledge of individual vessel configurations.

Background: Endoscopic submucosal dissection (ESD) with a knife is a technically demanding procedure associated with a high complication rate. The shortcoming of this method is the difficulty of fixing the knife to the target lesion. It can lead to an unexpected incision and result in major complications, such as perforation and bleeding. To reduce the risk of complications related to ESD, we developed a new grasping-type scissors forceps (GSF), which can grasp and incise the targeted tissue by using electrosurgical current., Objective: To evaluate the efficacy and safety of ESD by using GSF for the removal of gastric neoplasms in human beings., Design: Prospective, uncontrolled, single center., Setting: Department of Gastroenterology, Aso Iizuka Hospital, Iizuka, Japan., Patients: Four patients with early gastric neoplastic lesions., Interventions: After marking and injection of a solution into the submucosa, the lesion was separated from the surrounding normal mucosa by complete incision around the lesion by using the GSF. A piece of submucosal tissue was grasped and cut with the GSF by using electrosurgical current to achieve submucosal excision., Main Outcome Measurement: Technical success and complications., Results: All lesions were treated easily and safely, without any unexpected incisions. No delayed hemorrhage and perforation occurred. An en bloc resection and a negative resection margin was obtained in all cases., Limitations: The small number of patients and an uncontrolled study., Conclusions: ESD with GSF appeared to be an easy, safe, and technically efficient method for resecting GI neoplasms.

Background: Dissection of anterior segmental artery anatomically crossing over apico-posterior segmental bronchus during left upper lobectomy may sometime cause life-threatening vascular injury., Patients and Technique: Between August 2006 and July 2007, 12 patients with clinical stage IA-lung cancer underwent the video-assisted thoracoscopic left upper lobectomy with bronchial dissection prior to anterior and apico-posterior pulmonary artery dissections following dissection of lingular segmental artery., Results: Operation time ranged from 75 minutes to 190 minutes (average 132 +/- 39 minutes). Operative blood loss ranged from 10 ml to 400 ml (124 +/- 112 ml). Postoperative course was uneventful except 1 patient who had left recurrent nerve palsy., Conclusions: Bronchial dissection prior to the upper segmental pulmonary artery dissections can produce better surgical field around left main pulmonary artery, leading to safe pulmonary arterial dissection during video-assisted thoracoscopic left upper lobectomy.

We report a 58-year-old male with localized pleural adenocarcinoma, the origin of which was not identified. The disk-shaped pleural tumor was 8 x 6 x 2 cm in size and involved the left upper chest wall including the ribs. A fine needle biopsy showed adenocarcinoma, but whole body survey revealed no neoplasm other than the chest wall tumor. The left chest wall resection was followed by the left pleuropneumonectomy, because a few disseminations were identified in the visceral pleura. Pathological examinations showed no primary tumor in the lung. Immunohistochemical examinations suggested that micro-adenocarcinoma originating the subpleural lung invaded chest wall. It may be possibly a subtype of pseudomesotheliomatous adenocarcinoma. The patient has no recurrent tumor 1 year after the operation.

A 71-year-old man who had undergone surgery for stage II adenocarcinoma of the lung followed by adjuvant tegafur-uracil (UFT; 300 mg/day) therapy was admitted. Multiple nodules were found in both lungs on chest radiographs obtained 1.5 years after the surgery. Imaging characteristics of the nodules resembled those of pulmonary metastases. Histologic assessment of a biopsy specimen obtained during thoracoscopic resection revealed pulmonary cryptococcosis. The patient was administered 200 mg/day fluconazole for 6 months. Physicians need to be aware of the possibility of pulmonary cryptococcosis mimicking pulmonary metastases in patients treated with UFT after surgery for lung cancer.

We achieved a complete response of recurrent pancreatic cancer using a multimodal treatment with intravenous, oral and intraarterial chemotherapies and radiotherapy. A 55-year-old female patient had a recurrent pancreatic cancer, which had invaded the portal vein, 2 years after pancreatoduodenectomy. Angiography demonstrated prominent stenosis of the portal vein, which was enlarged by the insertion of a metalic stent to maintain blood flow to the liver. Chemotherapy included intravenous mitomycin C, 5-FU and 4'-epirubicin (EPI), oral UFT and cyclophosphamide, and intraarterial cisplatin, 5-FU and EPI through a catheter inserted into the celiac artery. Furthermore, the patient received a total of 50 Gy radiotherapy. Four months after the initiation of therapy, a computed tomography image demonstrated a complete disappearance of the recurrent tumor and a prominent decrease in the serum CA19-9 level. At present, 11 months have passed after the initiation of therapy, and she has been followed at our outpatient department without any symptoms of recurrence.

Background: Helicobacter pylori (H pylori) infection has been suggested to be a risk factor for gastric carcinogenesis. However, those previous studies have been concerned with advanced cancer cases. To the authors' knowledge, no detailed investigation on the prevalence of H pylori in early stage gastric cancer tissue has been performed. The relationship between early stage gastric cancer and the prevalence of H pylori was studied by a immunohistochemical staining analysis., Methods: Sixty-eight patients who were endoscopically and surgically diagnosed as having early stage gastric cancer were enrolled in this study. All tissue specimens were obtained from patients by endoscopic biopsy, and were classified histopathologically as the intestinal-type of early stage gastric cancer in 34 patients (male-to-female ratio, 28:6; age, 64 +/- 11 years) and the diffuse-type of early stage gastric cancer (male-to-female ratio, 23:11; age, 57 +/- 14 years) in the other 34 patients. The amount of H pylori in tissue samples was graded from 0 (no characteristic bacteria) to 3 (numerous bacteria) using the fluorescent microscopic and an immunohistochemical technique., Results: Twenty-nine of the 34 cases of the intestinal-type of gastric cancer had H pylori infection, as compared with 11 of the 34 cases of diffuse-type early stage gastric cancer. A significantly higher incidence (85%; P < 0.001) of H pylori infection and, thus, higher grading scores of the number of H pylori were found in the intestinal-type early stage gastric cancer., Conclusions: These findings suggest that the infection of H pylori may have a crucial relationship to the early stages of carcinogenesis of intestinal-type gastric cancer.

Treatment of female CD-1 mice with the synthetic estrogen diethylstilbestrol (DES) on days 1 through 5 after birth results in a 90% incidence of endometrial adenocarcinomas by 18 months of age Three cell lines were established from DES-induced uterine carcinomas and studied for specific chromosomal changes. Each cell line exhibited numerical decreases in chromosomes 9, 11, 13, and X as common abnormalities. Structural alterations involving chromosomes 3, 6, 11, and 19 occurred nonrandomly among the three cell lines. Every cell line showed a rearrangement in the long arm of chromosome 3 (3q+), a translocation between chromosomes 3 and 19 [t(3;19)], isochromosome of chromosome 11 [i(11)], and a marker chromosome (M2) either as common abnormalities or recurrent abnormalities. t(3;19), i(11), and M2 were observed also in the primary colonies from which the cell lines arose. The changes were not observed in a cell line derived from the uterus of one untreated control mouse, suggesting that these chromosomal alterations may have occurred during DES-induced neoplastic transformation. The chromosomal alterations found in the present study may prove useful in investigating the genetic changes involved in DES carcinogenesis.

Neonatal treatment with estrogens is associated with development of uterine adenocarcinomas in CD-1 mice. Treatment with the synthetic estrogen diethylstilbestrol (DES) on Days 1 to 5 after birth results in 90% incidence of these hormone-dependent lesions in 18-mo.-old mice. Three cell lines were established from these DES-associated tumors. Each of these cell lines exhibited morphologic and ultrastructural characteristics of transformed epithelial cells, including an increased nuclear:cytoplasmic ratio, enlarged and irregular nuclei with multiple nucleoli and areas of chromatin condensation, positive staining for cytokeratin, desmosomes, and microvilli. After subcutaneous injection into nude mice, all three cell lines formed solid tumors within 4 wk. Although the primary uterine tumors and tumor transplants in nude mice had been shown to be estrogen-dependent and estrogen-receptor positive, neither the monolayer growth nor the tumorigenicity of any of the three cell lines in this study was enhanced by or dependent on estrogen. Estrogen receptor levels were low in early and intermediate passage cells. Allele-specific oligonucleotide hybridization analysis of PCR-amplified cell line DNA revealed no point mutations in the 12th, 13th, or 61st codons of the K-ras or H-ras protooncogenes. Southern analysis revealed no changes in genomic organization of the putative tumor suppressor gene DCC, but demonstrated a three- to four-fold amplification of the c-myc gene in one cell line. Expression of c-myc RNA was concomitantly increased in the same cell line. These three transformed cell lines represent the end point in the process of hormone-associated tumorigenesis and as such should prove useful in investigating the molecular changes and the mechanisms involved in hormonal carcinogenesis.

This 74-year-old female suddenly complained of severe headache, nausea, vomiting and dizziness on June 19, 1981. She was brought to nearby hospital. During the following six days, the state of consciousness gradually worsened and left-sided hemiparesis and convulsion attack arose and she was admitted to our clinic on June 25, 1981. Cerebral angiograms revealed an aneurysm of the right middle cerebral artery. Diagnosis of subarachnoid hemorrhage due to the rupture of an aneurysm was tentatively made and conservative therapy was done. On the second hospital day, she had nasal bleeding and began to excrete tar-like stool. Laboratory examination revealed thrombocytopenia, increase of FDP and prolongation of prothrombin time. Her liver and renal functions gradually worsened after this episode. On the 13th hospital day, she expired. General autopsy showed wide spread adenocarcinoma with metastases to the lung, lymph nodes and bones. Examination of the head revealed an unruptured aneurysm and bilateral diffuse subdural clotted hemorrhage. The dura was tightly adherent to the skull and partially thickened. No abnormal findings were found in the brain. On microscopical examination of the dura, there were fresh hemorrhage and many of the innumerable dilated small vessels contained tumor in the inner dural layer. Even by extensive examination, the origin of the malignancy could not be identified. We concluded that the initial symptoms just like of subarachnoid hemorrhage were due to the dural metastasis and subdural hematoma. Sixteen cases of subdural hematoma secondary to metastatic neoplasm were reported previously. We made some discussion about the pathogenesis and symptomatology of this type of subdural hematoma.

Three rectal cancer patients with partial response (PR) were obtained by oral administration of 800-1200 mg/day of SF-SP. One of them showed I-A grade and other I-B in Karnofsky evaluation.

Twelve patients with advanced or relapsed head and neck adenocarcinoma received a combination chemotherapy regimen of either cyclophosphamide (C), tetrahydropyranyl-adriamycin (T), and cis-platinum (P) (CTP) or cyclophosphamide, adriamycin (A), and cis-platinum (CAP). Cyclophosphamide (300 mg/sq m), either etrahydropyranyl-adriamycin (30 mg/sq m) or adriamycin (30 mg/sq m), and cis-platinum (50 mg/sq m) were administered intravenously in a single day. Nine patients received the CTP regimen, and three patients, the CAP regimen. Prior to chemotherapy, five patients had received surgery or radiation therapy, and the other seven patients received no special treatment. A response rate 75% was achieved (9/12); there were 7 complete responses, whose duration was a mean 6.8 months, ranging from 2 to 18 months, and 2 partial responses, whose duration was 2 months. Virtually all patients experienced nausea and vomiting. Alopecia developed in 7 patients; however, the patients with the CTP regimen experienced less alopecia, if any. Leucopenia and anemia of either a slight or moderate degree were observed, but there was no patient for whom it was necessary to discontinue the treatment. Both CTP and CAP regimens appear to be of significant value in controlling head and neck adenocarcinoma.

A case of sebaceous carcinoma of the forehead of a 77-year-old male is reported and discussed and included in a review of all such cases reported in Japan. The patient had a round erosion on the right forehead that had caused itching for 15 months. An excisional biopsy of that lesion disclosed a malignancy and a subsequent wide excision was performed. The tumor recurred several times after excision and partially effective radiation therapy. The patient finally died of aspiration pneumonia 3 years after the first operation. An autopsy revealed that he had a recurrent sebaceous carcinoma extending to the periosteum of the right temporal bone and a solitary pulmonary metastasis.