A Case of Mandibular Cancer Involving Almost Entire Attached Gingiva.

Here we describe a rare case of mandibular cancer involving almost the entire attached gingiva in a 71-year-old man. First, marginal resection of the entire mandible was performed, followed by one-stage reconstruction comprising application of a split-thickness skin graft onto the wound. This resulted in good alveolar ridge morphology, allowing for a mandibular prosthesis to be installed soon postoperatively. Histopathological analysis revealed a well-differentiated squamous cell carcinoma extending throughout most of the resected attached gingiva, but no malignant features in the stumps. Furthermore, no infiltration into the jawbone was observed, and no vascular or lymphatic invasion or perineural infiltration. At 3 years postoperatively, the patient's clinical course has remained uneventful, with no recurrence or problems arising in the remaining mandible. The patient is also able to eat regularly using the mandibular prosthesis provided.

Dysregulation of Intestinal Microbiota Elicited by Food Allergy Induces IgA-Mediated Oral Dysbiosis.

Food allergy is a life-threatening response to specific foods, and microbiota imbalance (dysbiosis) in gut is considered a cause of this disease. Meanwhile, the host immune response also plays an important role in the disease. Notably, interleukin 33 (IL-33) released from damaged or necrotic intestinal epithelial cells facilitates IL-2-producing CD4 helper T (Th2) responses. However, causal relationships between the gut and oral dysbiosis and food allergy remain unknown. In this study, we analyzed effects of gut and oral dysbiosis on development of food allergy. A murine model of food allergy was established via ovalbumin (OVA) injection in BALB/c mice. Viable fecal bacteria were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). il33 expression in colon-26 mouse colon cells stimulated by isolated fecal bacteria was quantified by real-time PCR. Intestinal T cells from the mice were analyzed by flow cytometry. Salivary IgA levels were quantified by enzyme-linked immunosorbent assay (ELISA), and IgA-bound oral bacteria were detected by flow cytometry. Among fecal bacteria, the abundance of Citrobacter sp. increased in the feces of allergic mice and induced il33 expression in colon-26 cells. Orally administered Citrobacter koseri JCM1658 exacerbated systemic allergic symptoms and reduced intestinal Th17 cells. Salivary IgA and IgA-bound oral bacteria increased in the allergic mice. Based on the results described above, food allergy induced both gut and oral dysbiosis. Citrobacter sp. aggravated allergy symptoms by inducing IL-33 release from intestinal epithelial cells.

Calcineurin B1 Deficiency in Glial Cells Induces Mucosal Degeneration and Inflammation in Mouse Small Intestine.

Although calcineurin is abundantly expressed in the nervous system and involved in neurite extension and synaptic plasticity in neurons, little is known about its roles in glial cells. To investigate the roles of calcineurin in glial cells, we generated glial calcineurin B1-conditional knockout (CKO) mice and analyzed the abnormalities in the small intestine. The CKO mice were generated by crossing floxed calcineurin B1 mice with glial fibrillary acidic protein (GFAP)-Cre mice. The CKO mice exhibited growth retardation approximately from the third postnatal week and died mostly within the fourth postnatal week. The small intestine of the CKO mice was thin and hemorrhagic. The mucosal layer was degenerated and GFAP expression was reduced in the CKO small intestine. These pathological changes were associated with inflammation and increased intestinal permeability. In contrast, no apparent abnormalities were observed in the large intestine of the CKO mice. Nuclear factor of activated T cells failed to translocate into the nucleus after stimulation in enteric glial cells of the CKO small intestine. In conclusion, the calcineurin B1 deficiency in glial cells impairs the small intestine and leads to malnutrition and eventual death in mice, suggesting that calcineurin plays a novel and important role in enteric glial cells.

A case of rectal neuroendocrine carcinoma in a patient with long-standing ulcerative colitis involving alterations of the p16-Rb pathway.

The patient was a 54-year-old male who had been suffering from extensive ulcerative colitis (UC) for 17 years. Colonoscopy revealed an elevated lesion in the affected rectum, and its biopsy demonstrated neuroendocrine carcinoma (NEC). The surgical specimen obtained on laparoscopic high anterior resection showed extensive active inflammatory and dysplastic lesions and three grossly visible multifocal malignant lesions: a polypoid fungating tumor of NEC (type 1, 20 mm in diameter, pT3) that had been preoperatively noticed, a polypoid fungating tumor of adenocarcinoma (type 1, 22 mm, pT2) and a protruded sessile polypoid tumor (0-Is, 5 mm, pTis) of adenocarcinoma. The NEC was adjacently accompanied by dysplasia-carcinoma sequential lesions and showed a diffuse immunohistochemical overexpression of p53 and p16 proteins and the loss of Rb with no abnormal immunohistochemical staining of microsatellite instability markers and no KRAS mutations. Fifteen months later, the patient showed liver metastasis from the NEC component, followed by bone and spinal metastasis; he died 22 months after the initial diagnosis. A rare case of lethal NEC arising from long-standing extensive UC was reported. The NEC appeared to be UC-related, not incidental, and complicated by progression from dysplasia to carcinoma involving alterations of the p16-Rb pathway.

Positive detection of exfoliated colon cancer cells on linear stapler cartridges was associated with depth of tumor invasion and preoperative bowel preparation in colon cancer.

BACKGROUND: The aim of this study was to investigate exfoliated cancer cells (ECCs) on linear stapler cartridges used for anastomotic sites in colon cancer. METHODS: We prospectively analyzed ECCs on linear stapler cartridges used for anastomosis in 100 colon cancer patients who underwent colectomy. Having completed the functional end-to-end anastomosis, the linear stapler cartridges were irrigated with saline, which was collected for cytological examination and cytological diagnoses were made by board-certified pathologists based on Papanicolaou staining. RESULTS: The detection rate of ECCs on the linear stapler cartridges was 20 %. Positive detection of ECCs was significantly associated with depth of tumor invasion (p = 0.012) and preoperative bowel preparation (p = 0.003). There were no marked differences between ECC-positive and ECC-negative groups in terms of the operation methods, tumor location, histopathological classification, and surgical margins. CONCLUSIONS: Since ECCs were identified on the cartridge of the linear stapler used for anastomosis, preoperative mechanical bowel preparation using polyethylene glycol solution and cleansing at anastomotic sites using tumoricidal agents before anastomosis may be necessary to decrease ECCs in advanced colon cancer.

Efficacy of transanal tube for prevention of anastomotic leakage following laparoscopic low anterior resection for rectal cancers: a retrospective cohort study in a single institution.

BACKGROUND: Anastomotic leakage is one of the most serious complications following laparoscopic low anterior resection (LAR) for rectal cancers. The purpose of this study was to investigate whether transanal tube placement can reduce anastomotic leakage following laparoscopic LAR. METHODS: Retrospective assessment was performed on 205 patients with rectal cancers who underwent laparoscopic LAR. A transanal tube was placed after anastomosis in 96 patients (group A). Another 109 patients were operated on without a transanal tube (group B). Clinicopathological and operative variables, the frequencies of anastomotic leakage and re-operation after leakage were investigated. RESULTS: Patient age, gender, body mass index, tumor size, Dukes' stage, intra-operative blood loss, and the rate of left colic artery preservation were comparable between the two groups. Tumor location was lower and operative time was significantly longer in group A than group B (p < 0.001). Overall rate of leakage was 9.3 % (19/205). The frequency of leakage was 4.2 % (4/96) in group A and was 13.8 % (15/109) in group B. The rate of leakage was significantly lower in group A (p < 0.05). Furthermore, the re-operation rate for symptomatic anastomotic leakage was 0 % (0/4) in group A, while in contrast it was 73.3 % (10/15) in group B. The rate of re-operation was lower in group A than group B (p < 0.05) and all cases with symptomatic leakage in group A were cured by conservative treatment. CONCLUSIONS: Transanal tube placement was effective for prevention of anastomotic leakage following laparoscopic LAR and avoiding re-operation after symptomatic leakage.

[A Case of Colorectal Cancer with Anaphylactic Shock to Oxaliplatin].

We present the case of a 61-year-old woman with cecum cancer, ileal and multiple hepatic metastases, and peritoneal dissemination. Surgery (right hemicolectomy) was performed on December 2013. After surgery, 7 courses of mFOLFOX6 plus bevacizumab were administered. In May 2014, 4 minutes after starting the 8th course of oxaliplatin, dyspnea, nausea, vomiting, and general malaise were observed. Oxaliplatin administration was immediately discontinued and an injection of an antiemetic drug was administered, but the patient's blood pressure dropped to 87/53 mmHg and the SpO2 decreased to 87% (room air). The patient showed facial pallor; oxygen administration was initiated. Although blood pressure recovered to 124/69 mmHg 3 minutes after oxygen administration, reddening of the palms, pruritus, and headache were observed. The dyspnea eased 8 minutes after oxygen administration, the SpO2 recovered 18 minutes after oxygen administration, and the headache ceased. The patient subsequently was admitted to the hospital for observation, but no significant change was observed, and she was discharged the following day. Anaphylaxis due to oxaliplatin occurring after the 6th course is commonly reported, and the symptoms in this case were comparable to those described in the literature.

Malignant peritoneal mesothelioma with lymph node metastasis that originated in the transverse colon.

BACKGROUND: We report an extremely rare case of resection of localized biphasic malignant peritoneal mesothelioma of the transverse colon. CASE REPORT: Computed tomography and magnetic resonance imaging in a 72-year-old man showed a tumor with enhanced borders consistent with the transverse colon. Colonoscopy showed ulcerative lesions in the transverse colon, but histological examination showed no malignancy. A gastrointestinal stromal tumor was strongly suspected, so an extended right hemicolectomy was performed. Histopathological examination showed that the tumor was a localized malignant peritoneal mesothelioma of the transverse colon. The patient did not receive postoperative chemotherapy and died 18 months after surgery. CONCLUSIONS: The number of patients with malignant mesotheliomas is predicted to increase in the future both in Japan and in western countries. We report this case due to its probable usefulness in future studies pertaining to the diagnosis and treatment of malignant mesotheliomas.

[A case of severe enteritis induced by adjuvant chemotherapy for colon cancer].

A 77-year-old man underwent surgery for sigmoid colon cancer. He was diagnosed with Stage IIIa colon cancer; there- fore, we initiated oral administration of adjuvant chemotherapy comprising uracil/tegafur(UFT)plus Leucovorin(LV). However, chemotherapy was stopped after 21 days because of fatigue and diarrhea. He recovered after 3 weeks, and we administered the same regimen with a dose reduction. However, he again experienced fatigue and diarrhea after 20 days; therefore, chemotherapy was discontinued. Subsequently, he was hospitalized 8 times for conditions such as diarrhea, hypoalbuminemia, and fever. Computed tomography revealed thickening of the transverse colonic wall and colonoscopy revealed colitis, which we believe was induced by UFT plus LV. Twelve months after the last chemotherapy session, he was diagnosed with Clostridium difficile colitis. Therefore, we initiated the oral administration of vancomycin, which resulted in rapid recovery from colitis. However, he developed liver metastasis and died 29 months after the initiation of chemotherapy. We believe that this severe case of intractable colitis was caused by UFT plus LV. Therefore, we report this case with a review of the literature on enteritis induced by fluorouracil-based anticancer agents in Japan.

Two cases of prostheses for flap protection after buccal mucosal incision.

Here we describe two patients in whom prostheses were applied for flap protection after buccal mucosal incision. In the first case, the patient was a 65-year-old man with a diagnosis of buccal mucosa squamous cell carcinoma (T2N0M0). Left buccal mucosa squamous cell tumor resection and dermoplasty were performed, followed by alveolar ridge augmentation and buccal mucosal graft in the scar area. The carcinoma recurred, however, and left buccal mucosa carcinoma resection was performed, followed by reconstruction surgery using a free forearm flap. After a 12-week healing period, a molar support was constructed on the unaffected side and a protective prosthesis placed on the affected side. Training in ingestion and swallowing were given postoperatively. The patient in the second case was a 62-year-old woman with a diagnosis of buccal mucosa squamous cell carcinoma (T2N1M0). Right buccal mucosa carcinoma resection and supraomohyoid neck dissection were performed, followed by reconstruction surgery using a free forearm flap. A molar support was constructed on the unaffected side and a protective prosthesis placed on the affected side at 5 months postoperatively. Training was given in ingestion and swallowing postoperatively. The prostheses prevented bite wounds to the flaps in the affected areas due to jaw movement during swallowing or speaking. The postoperative courses were uneventful, and the average masticatory score was 92.5 (85, 100), not affecting daily life. The prostheses were placed after reconstruction surgery using free flaps after buccal mucosa squamous cell carcinoma resection. Dysphasia recovered to the preoperative level by dysphasia and pronunciation training in both cases. The postoperative prognosis was favorable, with the prosthesis preventing damage to the flap.

Therapeutic Outcome of Multidisciplinary Treatment in Unresectable Biliary Tract Cancer: A Multicenter Retrospective Analysis.

Background: There is little established evidence regarding treatment strategies for unresectable biliary tract cancer (BTC). This study aimed to clarify the situation of multidisciplinary treatment for unresectable BTC in the 2000s when there was no international standard first-line therapy. Methods: We retrospectively reviewed 315 consecutive patients with unresectable BTC who had been treated at seven tertiary institutions in Kanagawa Prefecture, Japan between 1999 and 2008. Results: The unresectable factors were as follows: locally advanced, 101 cases (32.1%); hematogenous metastases, 80 cases (25.4%); and peritoneal dissemination, 30 cases (9.5%). Chemotherapy or radiation therapy was administered to 218 patients (69.2%). The best supportive care was provided in 97 cases (30.8%). The most common regimen was gemcitabine monotherapy, followed by gemcitabine combination therapy and S-1 monotherapy. The 1- and 2-year survival rates of all patients were 34.6% and 12.2%, respectively. The median survival time (MST) was 8 months in all patients. The 1-year survival rate was 65%, and the MST was 12 months among the locally advanced patients, whereas patients with peritoneal dissemination had the worst outcome; the 1-year survival rate was 7%, and the MST was 5 months. Among treated 90 cases of perihilar cholangiocarcinoma, patients who received chemoradiotherapy (n = 24) had a significantly better outcome than those who received chemotherapy alone (MST: 20 vs. 11 months, P < 0.001). Conclusions: Unresectable BTC has heterogeneous treatment outcomes depending on the mode of tumor extension and location. Multidisciplinary treatment seems useful for patients with locally advanced BTC, whereas patients with metastatic disease still have a poor prognosis.

The rs6983267 SNP is associated with MYC transcription efficiency, which promotes progression and worsens prognosis of colorectal cancer.

BACKGROUND: The oncogenic single nucleotide polymorphism rs6983267, located on 8q24.21, may affect copy number aberrations and/or expression profiles in colorectal cancer (CRC). We investigated the role of this single nucleotide polymorphism in the clinical outcome of CRC. METHODS: Array comparative genomic hybridization (aCGH) and oligomicroarrays were performed on cancer cells from 157 primary CRC tissues. Expression profiles were analyzed by means of extraction expression module (EEM) analyses. Mutations in TP53, KRAS, and BRAF and microsatellite instability were also examined in 107 of the 157 cases. RESULTS: aCGH analysis revealed two clusters; more frequent genomic copy number alteration (CNA) was observed in the 89 cases in cluster B than in the 18 cases in cluster A. The average CNA was higher in samples containing the major allele (GT/TT) of rs6983267 than in those containing the minor allele (GG). Additionally, MYC expression was the highest in samples containing the GG allele (n = 18), followed by the GT and TT alleles (n = 41 and 48, respectively). EEM analysis revealed dominant up-regulation of MYC in samples containing the minor allele. Moreover, the presence of the minor allele in a MYC-positive, CNA-negative context predicted a poorer prognosis than the presence of the major allele in a MYC-negative, CNA-positive context in CRC. CONCLUSIONS: The presence of the minor allele of rs6983267 at 8q24.21 worsened the prognosis of CRC through up-regulation of MYC transcription. Furthermore, progression of CRC may require global CNA in the presence of the major allele and with lack of MYC transcription.

Increased risk for CRC in diabetic patients with the nonrisk allele of SNPs at 8q24.

BACKGROUND: Colorectal cancer (CRC) oncogenesis was considered to be determined by interactions between genetic and environmental factors. Specific interacting factors that influence CRC morbidity have yet to be fully investigated. METHODS: A multi-institutional collaborative study with 1511 CRC patients and 2098 control subjects was used to compare the odds ratios for the occurrence of polymorphisms at 11 known single nucleotide polymorphisms (SNPs). TaqMan PCR and questionnaires were used to evaluate the effects of environmental exposures. RESULTS: Variants of rs6983267 on 8q24 were the most significant markers of risk for CRC (odds ratio 1.16, 95% confidence interval 1.06-1.27, P = 0.0015). Non-insulin-dependent diabetes mellitus (DM), a higher body mass index at age 20, and meat consumption were environmental risk factors, whereas a tuna-rich diet and vitamin intake were protective factors. The cohort of rs6983267 SNP major (T) allele at 8q24 and DM had a 1.66-fold higher risk ratio than the cohort of major allele patients without DM. CONCLUSIONS: We confirmed that interactions between the genetic background and environmental factors are associated with increased risk for CRC. There is a robust risk of the minor G allele at the 8q24 rs6983267 SNP; however, a major T allele SNP could more clearly reveal a correlation with CRC specifically when DM is present.

Genomic copy number of a carcinogenic single nucleotide polymorphism at 8q24 in non-risk allele colorectal cancer associated with insulin growth factor 2 receptor expression.

BACKGROUND AND AIM: The incidence of both diabetes mellitus and hyperlipidemia is increasing and they are risk factors for colorectal cancer (CRC). On the other hand, the carcinogenic significance of the single nucleotide polymorphism (SNP), rs6983267 at 8q24, in CRC has been reported. The association between the SNP genotype and genes associated with diabetes or hyperlipidemia was investigated in cases of CRC. METHODS: In 107 cases of CRC diagnosed in eight institutes from 2003 to 2008, array-CGH and cDNA microarray was performed and the data analyzed from two groups subdivided according to SNP genotype. RESULTS: In the array-CGH data, we selected 38 genes related to diabetes or fat metabolism, and of these 10 had a correlation coefficient between the genome copy number at 8q24 locus and that of each gene. Of the 10 genes, insulin growth factor 2 receptor (IGF2R) was the only one with an expression level significantly associated with the 8q24 genotype. IGF2R expression was significantly lower in non-risk allele than in risk allele cases (P = 0.012). There was neither a diabetes- nor a fat metabolism-related gene that was significantly associated with CRC cases with the risk allele at 8q24. CONCLUSIONS: SNP at 8q24 makes diabetes a risk factor of CRC via IGF2R, especially in genetically non-risk allele cases. We speculate that the risk allele of 8q24 might be risky enough that diabetes is not necessary to worsen the risk for CRC.

Expression of myelin and lymphocyte protein (MAL) in oral carcinogenesis.

In the pathological diagnosis of oral squamous cell carcinoma, we often confront the difficulty of determining whether it is invasive carcinoma or epithelial dysplasia. Recently, myelin and lymphocyte protein (MAL; T-cell differentiation-related gene) has been reported to be a candidate gene suppressed in esophageal carcinoma. When we performed cDNA microarray analysis, we found that gene expression of MAL was significantly downregulated in oral squamous cell carcinoma (OSCC). We evaluated the expression of the MAL gene by laser microdissection and real-time PCR methods and protein localization by immunohistochemistry. The gene expression of MAL was significantly decreased in OSCC compared with normal epithelium (P < 0.05). Furthermore, protein expression of MAL disappeared gradually in proportion to malignancy. The results suggest that MAL plays an important role during oral carcinogenesis and that the gene may have potential as a biomarker target for OSCC.

[A case of cecal cancer with abdominal wall abscess].

A 63-year-old woman was admitted to our hospital for a palpable mass and abdominal pain. Abdominal CT showed an abscess in the abdominal wall and a contiguous mass in the intraperitoneal cavity. After drainage of the abscess was performed, we conducted a colonoscopy to investigate the cause of the mass. It revealed a type 2 tumor and a whole-circumferential stenosis in the cecum. It required preoperative chemotherapy with CPT-11 and S-1 to achieve radical cure characteristics with the operation. Because there was tumor reduction, right hemicolectomy and resection of the abdominal wall were performed. The patient was discharged 15 days after the operation with an eventful clinical course. Although 5 years have passed since the operation, she is alive and has had no recurrence. This patient accepted tumor reduction by chemotherapy , and the abdominal wall deficit that resulted from excision did not have it was it with a small range, and to rebuild the abdominal wall. The utility of preoperative chemotherapy is recommended in colon cancer which invades other organs.

Surgical procedure and results of cisternal washing therapy for the prevention of cerebral vasospasm following SAH.

In 1994, we started cisternal washing therapy (CWT) using urokinase combined with head-shaking method in order to prevent cerebral vasospasm. In this paper, we showed the surgical procedure for CWT and reported the effect of this therapy in preventing vasospasm following SAH. A total of 332 consecutive cases with Fisher group 3 SAH since 1988 were analyzed. Of these patients, 118 cases (56 cases before 1994 and 62 cases after 1994) had not CWT, and, 214 cases after 1994 had this therapy. All of these patients had clipping surgery within 3 days following SAH, and had postoperative management both with normovolemia and normal to mild hypertension. In these two groups, the incidence of symptomatic vasospasm (transiently symptomatic vasospasm without infarction), cerebral infarction due to vasospasm on CT, and mortality and morbidity (M&M) due to vasospasm were analyzed. In the group without CWT, the incidences of symptomatic vasospasm, cerebral infarction on CT, and M&M due to vasospasm were 4.2%, 28.8%, and 17.8%, respectively. On the other hand, in the group with CWT, they were 3.7%, 6.5%, and 2.8%, respectively. In the patients with CWT, the incidence of cerebral infarction on CT due to vasospasm and M&M due to vasospasm were significantly (p < 0.05) decreased. CWT was effective in preventing cerebral vasospasm.

Importance of the initial grade of subarachnoid hemorrhage in the patients with the age of 80 years and older from a single center analysis.

In the developed countries, especially Japan, elderly population is rapidly increasing, but outcomes of elderly patients with the age of 80 years and older suffering from subarachnoid hemorrhage (SAH) remain still unclear. We retrospectively reviewed the medical records of nontraumatic SAH patients aged 80 years and older, who were hospitalized in a single center between 1998 and 2009. There were 28 patients (80-90 years old and 75% female), representing 5.9% of all non-traumatic SAHs (n = 474). Of those, 16 patients received an intervention (ten clipping and six endovascular coiling) and the remaining 12 patients were managed conservatively. The median survival time of intervention group was 110 days and that of conservative group 49 days (p = 0.12, log rank analysis). Cox's proportional hazards model yielded two variables, the Japan Coma Scale (JCS) grade on admission ( hazard ratio: 2.93 [p = 0.009]) and conservative treatment (hazard ratio: 2.14 [p = 0.054]). In the outcome of the modified Rankin Scale between these two groups, logistic regression analysis had significant variable; the JCS grade on admission (odds ratio: 280, [p = 0.020]). In the elderly patients with good initial clinical condition, an acute intervention may have good outcome.

[Effects of anticoagulant therapy for rapidly progressive interstitial pneumonias].

To clarify the effects of anticoagulant therapy, we investigated patients with rapidly progressive interstitial pneumonias, retrospectively. We defined rapidly progressive pneumonia as idiopathic or secondary interstitial pneumonia with acute exacerbation of respiratory symptoms within 2 months, without infection or heart failure. A total of 20 cases admitted to our hospital between April 1999 and January 2010 met our criteria. Of those 20 cases, 6 were non-idiopathic pulmonary fibrosis (non-IPF), 3 were IPF, 6 were amyopathic dermatomyositis (ADM), 2 were DM, 2 were rheumatoid arthritis, and 1 was mixed connective-tissue disease. We divided the 20 cases into two groups according to whether they were treated with anticoagulant therapy (dalteparin and/or warfarin) (group A, n = 11) or not (group B, n = 9), and compared their outcomes. They were all given standard therapy. There was significantly better survival time in group A than in group B by the Kaplan-Meier survival curve (p = 0.0389). Anticoagulant therapy may improve the survival of patients with rapidly progressive interstitial pneumonias.

[A case or resection of synchronous multiple liver metastases from rectal cancer after FOLFOX4 therapy].

A 7 0-year-old man with multiple liver metastases from rectal cancer was admitted to our hospital. From imaging inspection, a resection was determined to be difficult, so he was treated with FOLFOX4 therapy. After ten courses of FOLFOX4, the liver metastases showed 52% reduction in size and were judged to be PR. Therefore low anterior resection of the rectum, left lobectomy of the liver and partial resection of the liver(S7, S8)were performed. He was able to undergo curative surgery after FOLFOX4 therapy.