Heterotopic ossification in primary rectal cancer with squamous cell carcinoma-like differentiation.

Objectives: Heterotopic ossification (HO), which occurs when bone tissue forms outside the skeleton, is extremely rare in rectal cancer. Adenocarcinoma is the histological type of all reported primary colorectal cancers with HO. However, in the present case, we observed areas of adenocarcinoma with squamous cell carcinoma-like differentiation. Here we conducted histopathological and immunohistochemical analyses to identify the mechanisms of HO development, to differentiate between adenocarcinoma and squamous cell carcinoma-like phenotypes, and to understand the associated prognostic implications. Case report: A 62-year-old woman was admitted to our hospital with symptoms of intermittent hematochezia without abdominal pain. Colonoscopy revealed stenosis with a protuberant mass in the rectum. Abdominopelvic contrast-enhanced computed tomography showed irregular wall thickness of the rectum, multiple lymph node metastases, and liver metastases. The rectal tumor exhibited calcified deposits with marked hyperintensity. We then performed Hartmann's operation and D3 lymph node resection. The biopsy specimen revealed tubular and solid adenocarcinoma nests and squamous carcinoma-like components over a necrotic extent without secreted mucin. She received chemotherapy (mFOLFOX6 with bevacizumab) as the first option and is alive 5 months after surgery. Conclusion: To the best of our knowledge, this is the first case of heterotopic ossification in a primary rectal cancer with squamous cell carcinoma-like differentiation that was surgically resected. This case suggests that BMP-2 transformed fibroblasts and pluripotent stem cells into osteocytes. We conclude that the squamous cell carcinoma-like lesion was squamous metaplasia of adenocarcinoma.

Lower accuracy of cytological screening for high-grade squamous intraepithelial neoplasia in women over 50 years of age in Japan.

BACKGROUND: As the population ages in developed countries, the number of Pap smears for cervical cancer screening of older women is increasing. There is concern that cervical atrophy may cause misinterpretation of results for this segment of the population. The present study evaluated the accuracy of screening for high-grade intraepithelial lesions (HSILs) in women younger or older than 50 years, to determine whether aging affects cytological interpretation. METHODS: Patients with HSIL cytology (N = 1565) were dichotomized into those aged 20-49 years or aged ≥ 50 years. Association between histology results and age was examined. Pearson's chi-squared test and Cochran-Armitage trend test were used for statistical analysis. RESULTS: The positive predictive value (PPV) for cervical intraepithelial neoplasia (CIN)2 and worse was 65.2% (62/95) in older women but 87.3% (482/552) in younger women (p < 0.001). Older patients had a significantly lower PPV (p = 1.69 × 10-8). Separately analyzing chronic cervicitis, CIN1 and overt cancer grouped together, compared with another group composed of CIN2 and CIN3, we found that the PPV for CIN2 and CIN3 was lower in older than in younger women [44.2% (42/95)-vs-82.4% (455/552), p < 0.001], respectively. CONCLUSIONS: HSILs are associated with a wide range of disease categories as age increases, and the accuracy of HSIL interpretation is lower in older women.

Resection of pancreatic and splenic metastases from alveolar soft part sarcoma: a case report.

BACKGROUND: We present a case of pancreatic and splenic metastases following alveolar soft part sarcoma (ASPS), which was successfully treated by surgery. CASE PRESENTATION: A 41-year-old male was referred to our hospital in 2012. Computed tomography (CT) showed the presence of a pancreatic tumor. In 2002, the patient had undergone surgical resection of an ASPS of the anal region. In 2009, during follow-up, CT revealed lung metastases, which prompted surgical resection of the lung, followed by resection of the head skin in 2011. Abdominal ultrasonography (US) revealed the presence of isodense masses sized 34 mm in the pancreatic head and 60 mm within the spleen. The contrast-enhanced US revealed a solitary lesion with enhancement. Contrast-enhanced CT revealed solitary lesions with enhancement within the pancreatic head, spleen, and liver. The patient underwent metastasectomies from the pancreas, spleen, and liver. The patient was discharged on postoperative day 22 without recurrence for 18 months after metastasectomy. Twelve years after primary resection and 2 years after metastasectomy, the patient died as a consequence of multiple metastases. CONCLUSIONS: We have presented a rare case of pancreatic and spleen metastases from ASPS. Resection by radical metastasectomy was successful without morbidity. Thus, for improved survival of patients with multiple metastases from ASPS, metastasectomy may be indicated. If multiple metastases are resectable, surgical approaches may be the preferred treatment.

[Safety and Efficacy of TAS-102 with Bevacizumab for the Treatment of Unresectable Metastatic Colorectal Cancer - A Case Report].

Chemotherapywith TAS-102 with bevacizumab(Bmab)is a new treatment for metastatic colorectal cancer. A 67-year-old male patient with synchronous multiple liver metastases was treated with TAS-102 with Bmab as a fifth-line chemotherapy. It was demonstrated that liver metastases decreased in size by1 3%bycomputed tomography(CT)after 3 months of TAS-102 with Bmab therapy. The Grade 3 or worst adverse event that was experienced was neutropenia. The patient was able to continue treatment with TAS-102 with Bmab for 6 months. TAS-102 with Bmab treatment was safetyand efficacious as a late-line chemotherapytreatment for metastatic colorectal cancer.

Laparoscopic sigmoidectomy combined with uterus excision for colouterine fistula caused by sigmoid colon diverticulitis: A case report.

A case of colouterine fistula caused by colonic diverticulitis that was successfully treated laparoscopically is presented. A 74-year-old woman visited us with lower abdominal discomfort and vaginal excretion with minor fecal contamination. Mild tenderness was observed in her lower abdomen. Blood examinations revealed elevated white blood cell count and C-reactive protein. Sigmoid colon diverticulitis was revealed on CT, and her condition was diagnosed as colouterine fistula. Hinchey classification was stage I. After 2 weeks of conservative therapy, her symptoms were reduced, and the white blood cell count and C-reactive protein level decreased. However, fecal contaminated vaginal excretion continued. The patient underwent laparoscopic sigmoidectomy combined with uterus excision, and she has been in good health for the 3 years since the operation. Although colouterine fistula is usually treated with open surgery, patients with controlled and well-localized inflammation may be good candidates for a laparoscopic approach.

[A case and literature review of ovarian carcinosarcoma with long-term survival after repeated recurrences].

Ovarian carcinosarcoma is a rare and aggressive tumor with a poor prognosis. We report a case of ovarian carcinosarcoma and also review the literature. In 2000, a 63-year-old woman underwent optimal cytoreductive surgery for ovarian carcinosarcoma( International Federation of Gynaecology and Obstetrics[FIGO]stage III c[pT3cN0M0]). She received adjuvant chemotherapy with paclitaxel and carboplatin(TC). In 2005, a recurrent tumor was noted anterior to the sacrum. The patient had a complete response after 6 cycles of TC chemotherapy; however, a year later, the tumor recurred and was resected. In 2013, the tumor recurred adjacent to the right kidney and was surgically removed after a partial response to 3 cycles of TC chemotherapy. The pathologic findings included epithelial and non-epithelial components with histologic variation and differentiation; specifically, a leiomyosarcoma, cartilaginous tissues with cellular atypia, and a rhabdomyosarcoma were identified in specimens obtained during the first, second, and third surgical procedures, respectively. In keeping with the combination theory of histogenesis, the ovarian carcinosarcoma described herein may have originated from a monoclonal stem cell. The long survival of this patient is attributed to optimal cytoreduction during the primary operation, solitary recurrent tumors that were completely resected, and sensitivity to chemotherapy.

Increase in E-selectin expression in umbilical vein endothelial cells by anticancer drugs and inhibition by cimetidine.

E-selectin is expressed on the surfaces of stimulated vascular endothelial cells and is sometimes involved in cancer cell metastasis. The H2-receptor antagonist cimetidine inhibits the increase in E-selectin expression on vascular endothelial cells that is induced by interleukin-1beta (IL-1beta) and cimetidine. It also inhibits the adhesion of sialyl-Lewis-antigen-positive cancer cells to vascular endothelial cells, ultimately inhibiting hematogenous metastasis. Anticancer drugs are essential to cancer therapy, but whether they can alter the expression of E-selectin in vascular endothelial cells remains unclear. Whether cimetidine inhibits the expression of E-selectin in the same manner in the presence or absence of anticancer drugs also remains unknown. Human umbilical vein endothelial cells were cultured with 5-fluorouracil (5-FU), doxorubicin (DXR), cisplatin (CDDP), or IL-1beta and with or without cimetidine. The expression of E-selectin at the mRNA and protein levels was then determined using quantitative reverse transcription-polymerase chain reaction and immunohistochemical staining, respectively. The E-selectin mRNA level increased in cells exposed to 5-FU, DXR, or CDDP, but the addition of cimetidine had no effect on the E-selectin mRNA level. The expression of E-selectin protein was also significantly higher after the addition of 5-FU, DXR, or CDDP, compared with that of a negative control. However, when cimetidine was added prior to the addition of 5-FU, DXR, or CDDP, the expression of E-selectin was significantly suppressed. Thus, cimetidine significantly inhibited the expression of E-selectin at the protein level without affecting its expression at the mRNA level in cells treated with anticancer drugs. In conclusion, anticancer drugs increased the expression of E-selectin and this increase was inhibited by cimetidine. These findings suggest that the administration of cimetidine during treatment with anticancer drugs might be useful for preventing metastasis.

Ki-67, p53 and epidermal growth factor receptor expression in early glottic cancer involving the anterior commissure treated with radiotherapy.

OBJECTIVE: TNM staging system is not a sufficiently accurate method for predicting the response of an individual patient to a course of radiotherapy. After irradiation, it can become very difficult to assess data obtained by imaging and endoscopy for the diagnosis of both minimal persistent disease and early recurrence. The search for biological parameters that could be used to identify patients who will respond to radiotherapy is crucial. At this study we aimed at evaluating the prognostic significance of immunohistochemical expression of Ki-67, p53 and epidermal growth factor receptor (EGFR) in laryngeal glottic cancer involving the anterior commissure and treated with radiotherapy. METHODS: From January 1995 to August 2005, 24 patients with glottic cancer involving the anterior commissure were primary treated with radiotherapy. Six patients presented with T1a, 12 patients with T1b and 6 patients with T2. Biopsies were taken before the radiotherapy treatment started. Radiotherapy was done with the same technique for all patients using a linear accelerator device with beam energy of 4-MV photons. Immunohistochemical staining was performed using avidine-biotin-peroxidase technique with antibodies to Ki-67, p53 and EGFR. RESULTS: p53 and EGFR positive expression values and labeling indices were greater in radioresistant than in radiosensitive tumors but without significant differences. On the other hand, Ki-67 was expressed in all radiosensitive tumors and Ki-67 labeling indices were significantly higher in radiosensitive tumors than radioresistant tumors (p=0.01). CONCLUSION: We identified overexpression of Ki-67 as predictive marker of radiosensitivity in glottic cancer involving the anterior commissure, with the results showing significant difference between radiosensitive and radioresistant tumors.

[Usefulness of contrast-enhanced ultrasonography in the differential diagnosis of polypoid gallbladder lesions].

We investigated the usefulness of contrast-enhanced ultrasonography for differential diagnosis of polypoid gallbladder lesions in 60 patients, consisting of gallbladder carcinoma in 20, adenoma in 2, benign polyp in 29, and adenomyomatosis in 9, comparing contrast enhancement patterns with pathologic findings. We monitored vascular flow for 120 sec, constructing a time intensity curve (TIC) by flash-echo imaging. We compared the number of vessels and vessel diameter determined by contrast enhancement patterns and by pathologic examination. Contrast enhancement patterns were classified as linear, scattered, diffuse, or branched. When diffuse type and branched type were considered as indicative of cancer, accuracy was 84.5%, sensitivity 100%, and specificity 76.9%. In gallbladder carcinoma, the TIC rose from no contrast to early-phase contrast sooner than in other diseases. In adenocarcinoma, high-intensity values persisted at 120 sec. With an intensity of 90 or greater at 120 sec taken as indicating cancer, accuracy was 89.7%, sensitivity 89.5%, and specificity 89.7%; Vessels were significantly more numerous in diffuse type cases than in those with other patterns. Vessel diameter was greatest in the diffuse type and the branched type patterns, both differing significantly from the linear type. Ultrasonographic contrast enhancement patterns show characteristic associations with pathologic findings and serve as valuable adjuncts in the diagnosis of gallbladder diseases.

[Effect of cimetidine on E-selectin expression on the vascular endothelium stimulated by anti-cancer drug].

Various anticancer drug treatments have contributed to elongating survival of cancer patients. However, cancer often metastasizes and recurs in spite of anti-cancer drug treatment. It is important to control metastasis in order to achieve a favorable outcome. In this study, we confirmed that an expression of E-selectin in human umbilical vein endothelial cells (HUVEC) was stimulated by 5-FU, and that the expression of E-selectin was inhibited by cimetidine which was a H2 receptor antagonist.

[An interesting change of E-selectin in cimetidine administration during anticancer drug use].

E-selectin is an adhesion molecule developed as an important material for hematogenous metastasis of cancer cells on vascular endothelial cells. It is expected that if we can restrain a manifestation of E-selectin then hematogenous metastasis can be restrained. We divided gastric cancer and the colorectal cancer patients, who performed chemotherapy, into two groups of cimetidine administrated group and a non-administration group, and reviewed whether cimetidine inhibited an expression of E-selectin on vascular endothelial cells by measuring E-selectin in plasma. We experienced one example that showed an interesting change of E-selectin and the quantity of E-selectin in plasma fell during the cimetidine dosage. However, we report that E-selectin has risen after the cimetidine dosage was cancelled in the cimetidine administrated group.

[Cimetidine inhibits the adhesion of cancer cells with sialyl Lewis epitope onto the vascular endothelium].

The attachment of circulating cancer cells to vascular endothelium is considered an important initial step in hematogenous metastasis. We believe that hematogenous metastasis can be inhibited by blocking the adhesion of cancer cells to vascular endothelium. We demonstrated that cimetidine suppressed the expression of E-selectin on the surface of HUVECs, which was a ligand to the sialyl Lewis (sLe) epitope. Thereby, adhesion of HT-29 cells to HUVECs was inhibited by cimetidine pretreatment. In this study, adhesion between cancer cells and HUVECs was observed by a high-speed video recording system. We examined whether or not cimetidine inhibited the adhesion of cancer cells with the sLe epitope, such as gastric, esophageal and breast cancers, to HUVECs. Cimetidine was able to block the adhesion of gastric, esophageal and breast cancer cells with the sLe epitope. We conclude that cimetidine would be effective for inhibiting hematogenous metastasis on gastric, esophageal and breast cancer cells with the expression of sLe epitope.