Intramural cancer recurrence in the rectum after curative surgery for proximal sigmoid colon cancer: a case report.

BACKGROUND: Intramural metastasis distant from the primary tumor is rare in colorectal cancer. Here, we present a notably rare and probably the first case of asynchronous intramural recurrence in the rectum after curative surgery for proximal sigmoid colon cancer. CASE PRESENTATION: A 44-year-old man underwent curative sigmoidectomy for proximal sigmoid colon cancer with T3N0M0, Stage IIA tubular adenocarcinomas. After 15 months, the tumor marker level had increased, and positron emission tomography-computed tomography (PET-CT) revealed abnormal fluorodeoxyglucose uptake in the rectum; colonoscopy revealed a submucosal tumor (SMT)-like lesion in the upper rectum, and biopsy revealed a tubular adenocarcinoma. We performed curative low anterior resection with tumor-specific mesorectal excision (TSME). The SMT-like tumor was located approximately 20 cm from the initial sigmoid colon anastomosis (i.e., at least 20 cm distal to the initial sigmoid colon cancer). The pathological findings revealed cancer cells with the same features as the initial sigmoid colon cancer, only in the intestinal wall but not in the mucosa and extramural tissue. Therefore, the lesion was determined to be an intramural recurrence. After 24 months, lung recurrence, and local recurrence, which might have involved the lymph nodes in the preserved mesorectum after TSME at the bottom of the pelvis was detected on PET-CT. Hence, we started systemic chemotherapy. CONCLUSIONS: This case report suggests that PET-CT and short-interval repeat colonoscopy may help detect a rare intramural recurrence. A long distal margin may be necessary to achieve local control in the rectal resection for intramural recurrence.

Pathological complete response after neoadjuvant chemotherapy with FOLFOX for locally advanced sigmoid colon cancer with diverticulitis: A case report.

INTRODUCTION AND IMPORTANCE: The standard treatment for locally advanced colon cancer (LACC) without distant metastasis is curative surgery followed by adjuvant chemotherapy, but the long-term outcomes of this strategy are not satisfactory. Neoadjuvant chemotherapy (NAC) is a promising novel option to overcome this issue. Tumor regression is an expected effect of NAC for LACC, but pathological complete response (pCR) is rare. In this report, we present a rare case of pCR after NAC with FOLFOX for LACC in the sigmoid colon. PRESENTATION OF CASE: A 66-year-old woman presented to our hospital with fever and abdominal pain. The diagnosis was LACC in the sigmoid colon with possible invasion of the uterus and pelvic wall, stage IIIC (T4bN1bM0). Furthermore, the tumor was complicated by diverticulitis. A colostomy was performed, followed by NAC with FOLFOX. Six cycles were completed without significant adverse events, and the lesion shrunk remarkably. We performed a curative sigmoidectomy without any postoperative complications. Pathological examination revealed no viable cancer cells, indicating pCR. DISCUSSION: To the best of our knowledge, this is the first report of pCR after NAC for LACC complicated by diverticulitis. Colostomy before NAC, regimen, and cycle of NAC may be the key to this favorable course. CONCLUSION: We present a rare case of pathological complete after neoadjuvant chemotherapy with FOLFOX for locally advanced colon cancer in the sigmoid colon complicated by diverticulitis. Our experience may be valuable in determining the optimal treatment strategy for LACC complicated by diverticulitis.

Sudden death caused by Clostridium perfringens sepsis presenting as massive intravascular hemolysis.

An 80-year-old Japanese woman with diabetes mellitus was admitted with gastrointestinal symptoms and pyrexia. At presentation, liver abscesses and severe hemolytic anemia were noted. Before detailed diagnostic evaluation and adequate treatment, she suddenly died 2.5 hours after admission. The autopsy and bacteriological examinations revealed liver abscesses and massive intravascular hemolysis caused by Clostridium perfringens as well as other miscellaneous critical pathological findings, including acute renal tubular necrosis, lung edema, and pulmonary fat embolism. In this article, the detailed autopsy results are described and clinicopathologic characteristics on Clostridium perfringens-related sudden death are discussed with a review of the literature.

Sudden death caused by Clostridium perfringens sepsis presenting as massive intravascular hemolysis

An 80-year-old Japanese woman with diabetes mellitus was admitted with gastrointestinal symptoms and pyrexia. At presentation, liver abscesses and severe hemolytic anemia were noted. Before detailed diagnostic evaluation and adequate treatment, she suddenly died 2.5 hours after admission. The autopsy and bacteriological examinations revealed liver abscesses and massive intravascular hemolysis caused by Clostridium perfringens as well as other miscellaneous critical pathological findings, including acute renal tubular necrosis, lung edema, and pulmonary fat embolism. In this article, the detailed autopsy results are described and clinicopathologic characteristics on Clostridium perfringens-related sudden death are discussed with a review of the literature.

Sudden death caused by pulmonary fat embolism in a patient with miliary tuberculosis.

An 84-year-old Japanese woman with myelodysplastic syndrome was admitted with pyrexia and dyspnea, but died suddenly during diagnostic evaluation. The autopsy revealed miliary tuberculosis in addition to myelodysplastic syndrome in the bone marrow. The immediate cause of the patient's sudden death was pulmonary fat embolism derived from bone marrow necrosis. This case shows that the infiltration of the myelodysplastic bone marrow by tuberculosis and consequent bone marrow necrosis and fat embolism can be the cause of sudden death. In this article, we report the autopsy results of this unusual cause of sudden death, and discuss tuberculosis-related sudden death with a review of the literature.

Sudden death caused by pulmonary fat embolism in a patient with miliary tuberculosis

An 84-year-old Japanese woman with myelodysplastic syndrome was admitted with pyrexia and dyspnea, but died suddenly during diagnostic evaluation. The autopsy revealed miliary tuberculosis in addition to myelodysplastic syndrome in the bone marrow. The immediate cause of the patient's sudden death was pulmonary fat embolism derived from bone marrow necrosis. This case shows that the infiltration of the myelodysplastic bone marrow by tuberculosis and consequent bone marrow necrosis and fat embolism can be the cause of sudden death. In this article, we report the autopsy results of this unusual cause of sudden death, and discuss tuberculosis-related sudden death with a review of the literature.

Intestinal spirochetosis: An unusual cause of postantibiotic diarrhea.

(A) A blue fringe along the surface epithelium of the colonic mucosa on hematoxylin-eosin staining, a characteristic histology of intestinal spirochetosis. (B) Numerous spirochetes highlighted on Warthin-Starry silver staining.

Klebsiella pneumoniae liver abscess.

Klebsiella pneumoniae liver abscess is no longer fatal but causes catastrophic disabilities. To prevent severe complications, early diagnosis is essential. Gram stain and string test are important for early diagnosis.

Comparison of endoscopic stenting for malignant biliary obstruction: A single-center study.

AIM: To evaluate the efficacy and safety of single-step endoscopic placement of self-expandable metallic stents (SEMS) for treatment of obstructive jaundice. METHODS: A retrospective study was performed among 90 patients who underwent transpapillary biliary metallic stent placement for malignant biliary obstruction (MBO) between April 2005 and October 2012. The diagnosis of primary disease and MBO was based on abdominal ultrasound, computed tomography, magnetic resonance imaging, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography with brush cytology, biopsy, and/or a combination of these modalities. The type of SEMS (covered or non-covered, 8 mm or 10 mm in diameter) was determined by the endoscopist. Ninety patients were divided into two groups: group 1 (49 patients) who underwent a single-step SEMS placement and group 2 (41 patients) who underwent a two-step SEMS placement. The technical success rate, complication rate, stent patency, and patient survival rate were compared between the groups. In addition, to identify the clinical prognostic factors associated with patient survival, the following variables were evaluated in Cox-regression analysis: gender, age, etiology of MBO (pancreatic cancer or non-pancreatic cancer), clinical stage (IVb; with distant metastases or IVa >; without distant metastases), chemotherapy (with or without), patency of the stent, and the use of single-step or two-step SEMS. RESULTS: Immediate technical success was achieved in 93.9% (46/49) in group 1 and in 95.1% (39/41) in group 2, with no significant difference (P = 1.0). Similarly, there was no difference in the complication rates between the groups (group 1, 4.1% and group 2, 4.9%; P = 0.62). Stent failure was observed in 10 cases in group 1 (20.4%) and in 16 cases in group 2 (39.0%). The patency of stent and patient survival revealed no difference between the two groups with Kaplan-Meier analysis, with a mean patency of 111 ± 17 d in group 1 and 137 ± 19 d in group 2 (P = 0.91), and a mean survival of 178 ± 35 d in group 1 and 222 ± 23 d in group 2 (P = 0.57). On the contrary, the number of days of hospitalization associated with first-time SEMS placement in group 1 was shorter when compared with that number in group 2 (28 vs 39 d; P < 0.05). Multivariate analysis revealed that a clinical stage of IVa > (P = 0.0055), chemotherapy (P = 0.0048), and no patency of the stent (P = 0.011) were independent prognostic factors associated with patient survival. CONCLUSION: Our results showed that single-step endoscopic metal stent placement was safe and effective for treating obstructive jaundice secondary to various inoperable malignancies.

Evidence for an association between increased oxidative stress and derangement of FOXO1 signaling in tumorigenesis of a cellular angiofibroma with monoallelic 13q14: a case report.

Cellular angiofibroma (CAF) is a rare soft tissue tumor characterized by random arrangement of spindle tumor cells in the stroma with short collagen bundles and thick- and hyalinized small vessels. CAFs share histological characteristics with spindle cell lipomas and mammary type myofibroblastomas. Because these tumors harbor monoallelic 13q14, common genetic and molecular mechanism for tumorigenesis is presumed. In this study, we reported a case of CAF in a 69-year-old man with monoallelic 13q14. Immunohistochemical analysis revealed that FOXO1, which is located in chromosome 13q14, was not expressed in the tumor. We also detected oxidative stress markers and found p38 MAPK activation, which is often induced by cellular stressors such as reactive oxygen species (ROS). Because FOXO1 induces the expression of genes encoding enzymes that generate antioxidants, oxidative stress induced by loss of FOXO1 expression may be common among CAFs, spindle cell lipomas, and mammary type myofibroblastomas.

Severe Pulmonary Hypertension Caused by Smoldering Plasma Cell Myeloma: An Autopsy Case of POEMS Syndrome.

The POEMS syndrome (coined to refer to polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) is a rare variant of plasma cell disorders with multiple systemic manifestations. Recently, pulmonary hypertension (PH) has become established as a complication, but pathological studies of this condition are scarce and the detailed pathogenesis remains to be elucidated. We present herein a case of a 49-year-old woman who was diagnosed as having idiopathic PH and was treated in accordance. However, she eventually died of respiratory failure and an autopsy revealed the presence of smoldering plasma cell myeloma and multiple organomegaly in addition to severe PH. The latter was attributed to stenosis and occlusion of the arterioles of the lungs due to marked plasma cell proliferation, quite different from the histology of idiopathic PH. From these findings, together with the clinical details, we concluded that the patient's PH was a complication of the POEMS syndrome. This case showed a unique pulmonary vascular pathology featuring plasma cell proliferation and it provides clues towards understanding the pathogenesis with this background.

Reduced ghrelin secretion in the hypothalamus of rats due to cisplatin-induced anorexia.

Although chemotherapy with cisplatin is a widely used and effective cancer treatment, the undesirable gastrointestinal side effects associated with it, such as nausea, vomiting, and anorexia, markedly decrease patients' quality of life. To elucidate the mechanism underlying chemotherapy-induced anorexia, focusing on the hypothalamic ghrelin secretion-anorexia association, we measured hypothalamic ghrelin secretion in fasted and cisplatin-treated rats. Hypothalamic ghrelin secretion changes after vagotomy or administration of cisplatin. Cisplatin + rikkunshito, a serotonin 2C receptor antagonist or serotonin 3 receptor antagonist, was investigated. The effects of intracerebroventricular (icv) administration of ghrelin or the serotonin 2C receptor antagonist SB242084 on food intake were also evaluated in cisplatin-treated rats. Hypothalamic ghrelin secretion significantly increased in 24-h-fasted rats compared to freely fed rats and was markedly reduced 24 and 48 h after cisplatin treatment in cisplatin-treated rats compared to saline-treated rats, although their plasma ghrelin levels were comparable. In cisplatin-treated rats, icv ghrelin administration reversed the decrease in food intake, vagotomy partially restored hypothalamic ghrelin secretion, and hypothalamic serotonin 2C receptor mRNA expression increased significantly. Administration of rikkunshito (an endogenous ghrelin enhancer) or a serotonin 2C receptor antagonist reversed the decrease in hypothalamic ghrelin secretion and food intake 24 h after cisplatin treatment. Cisplatin-induced anorexia is mediated through reduced hypothalamic ghrelin secretion. Cerebral serotonin 2C receptor activation partially induces decrease in hypothalamic ghrelin secretion, and rikkunshito suppresses cisplatin-induced anorexia by enhancing this secretion.

Comparison of the actions of acylated and desacylated ghrelin on acid secretion in the rat stomach.

BACKGROUND: Ghrelin, a growth-hormone-releasing peptide, has two major molecular forms: acylated (acyl) and desacylated (desacyl). Recent studies suggest different roles for these two forms. In the present study, we compared desacyl and acyl ghrelin with regard to acid secretion and histamine production in the rat stomach. METHODS: We performed in vivo experiments using gastric lumen-perfused rats. The effects of the two forms of ghrelin on gastrin (gastrin-17)-stimulated acid secretion were also examined. Furthermore, to examine the effects of ghrelin on histamine production, histidine decarboxylase messenger ribonucleic acid in the gastric corpus mucosa was measured by reverse transcription-polymerase chain reaction. RESULTS: Intravenous administration of acyl ghrelin at 20 µg/kg increased gastric acid secretion to 4.8 times greater than control levels. However, desacyl ghrelin had no effect on acid secretion, even at 200 µg/kg. Acyl ghrelin enhanced gastrin-stimulated acid secretion while desacyl ghrelin did not. Vagotomy markedly inhibited the enhancement of gastrin-stimulated acid secretion by acyl ghrelin. Acyl ghrelin increased histidine decarboxylase messenger ribonucleic acid concentration by 2.3 times compared with basal levels at 1 h after administration and by 2.7 times at 2 h after administration; desacyl ghrelin had no such effect. Synergism between acyl ghrelin and gastrin was seen regarding histidine decarboxylase messenger ribonucleic acid concentration. CONCLUSIONS: The results indicate that acyl ghrelin stimulates gastric acid secretion via a mechanism involving activation of the vagus nerve and histamine release and synthesis and that desacyl ghrelin has no action on gastric acid secretion. Furthermore, the results demonstrate synergism between gastrin and acyl ghrelin in terms of gastric acid secretion via a mechanism involving histamine release and synthesis.

Pulmonary tumor thrombotic microangiopathy in patients with gastric carcinoma: an analysis of 6 autopsy cases and review of the literature.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare clinicopathological entity causing severe pulmonary hypertension (PH). Its histological features include widespread tumor emboli of the small arteries and arterioles of the lung, associated with thrombus formation and fibrocellular and fibromuscular intimal proliferation. Although PTTM has drawn increased attention as a fatal complication of gastric carcinoma (GC), comprehensive studies are still lacking. In order to clarify clinical and pathological features of GC-induced PTTM, recent autopsy cases were analyzed with a review of the literature. Of 36 autopsy cases with GC, 6 (16.7%) were affected by PTTM. Four were male and 2 female, with a mean age of 72.7 years. Three patients presented with PTTM-related clinical manifestations and died of PTTM. They showed clear morphological evidence of PH. The other 3 patients had PTTM as an incidental finding irrespective of clinical manifestations or PH. No patient was diagnosed antemortem as PTTM. All PTTM cases were associated with advanced GC, with a histology of adenocarcinoma of poorly differentiated type (n=4) or signet-ring cell type (n=2). Expression of tissue factor and vascular endothelial growth factor was confirmed immunohistochemically in tumor cells in all cases. The results were all in line with previous studies. In addition, the current study revealed vascular lesions characteristic of PTTM morphology to be present exclusively in the lung. In conclusion, our study shows a 16.7% incidence of PTTM in GC patients, with half of them developing PH and dying of PTTM, confirming a clinical significance as a non-negligible lethal complication of GC. In addition to many known clinicopathological characteristics of PTTM, the current study pointed to some PTTM issues requiring clarification, including the pathogenesis of the exclusive pulmonary distribution of vascular lesions of PTTM. Since details remain to be elucidated, interdisciplinary research is a high priority with a close collaboration between pathologists and clinicians in order to overcome this lethal condition.

Intervals between symptom onset and clinical presentation in cancer patients.

OBJECTIVE: We aimed to investigate relative values of the intervals between symptom onset and clinical presentation in cancer patients and to correlate them with diagnosis of distant metastasis. METHODS: Cancer registry and medical records of all cancer patients for over a 10-year period in a medical center of Japan were reviewed. We examined the intervals of symptom onset to clinical presentation and the presence of metastasis at diagnosis. RESULTS: In 3,893 cancer patients, the mean interval of symptom onset to clinical presentation was 89 days (median, 30 days). The cancer group with a short interval of only days to weeks included hepatobiliary, ovary, brain, and acute leukemia. The group with a long interval of months to years included head and neck, thyroid, and skin cancers. Other types of cancer were included in the middle group with an interval of weeks to months. Among patients with head & neck, skin, and ovarian cancers, the longer interval was significantly associated with a lower likelihood of distant metastasis. A longer interval with an increment of each month was associated with a lower likelihood for distant metastasis with an odds ratio of 0.97 (95% CI, 0.96-0.99). CONCLUSION: Hepatobiliary, ovary, brain, and acute leukemia are among the cancer types with an interval of days to weeks, while head and neck, thyroid, and skin cancers are among the types with an interval of months to years. Among patients with solid tumors, those with metastasis are likely to present to a physician more promptly.

Pulmonary tumor thrombotic microangiopathy caused by an ovarian cancer expressing tissue factor and vascular endothelial growth factor.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare clinicopathologic entity causing severe pulmonary hypertension, right-side heart failure, and sudden death. Its histologic features include widespread tumor emboli of the small arteries and arterioles of the lung, associated with thrombus formation and fibrocellular and fibromuscular intimal proliferation. The most frequent causative neoplasm for PTTM is gastric cancer, but lesions in other organs, including the ovary, have been occasionally identified as primary causes. Detailed molecular mechanisms underlying PTTM remain unclear, but some studies have suggested that tissue factor (TF) and vascular endothelial growth factor (VEGF) expressed by tumor cells may be involved in the pathogenesis for cases of gastric cancer. However, little is known about these molecules in PTTM caused by neoplasms of non-gastric origin. Here, we report the autopsy findings of a 42-year-old woman with ovarian cancer showing positive immunoreactivity for both TF and VEGF who died suddenly of PTTM. The present case provides support for the conclusion that these factors may be involved in the pathogenesis of PTTM, independent of the causal neoplasm.