Preoperative Watchful-Waiting Time and Surgical Outcome of Patients with Non-small Cell Lung Cancer Found by Chest Low-Dose CT Screening.

BACKGROUNDS: Chest low-dose CT screening (LDCTS) has been finding unprecedented numbers of peripheral non-small cell lung cancers (NSCLC) at an early stage and increased the number of patients with surgical indication. It is important to explore the influence of preoperative watchful-waiting time (WWT) on surgical outcomes. Objective is to clarify relationship between WWT and surgical outcomes of LDCTS-finding NSCLC from the view point of treatment delay. METHODS: Total 283 cases of NSCLC, found by LDCTS and consecutively resected, were surveyed for preoperative WWT and surgical outcomes. Validity of the present guideline for management of pulmonary nodules detected by LDCTS was verified whether WWT before surgery was suitable for eradication of NSCLC. RESULTS: The median value of WWT was 4.0 months in total, and the distribution of WWT exhibited long-tail-type pattern. That was 5.0 months in the group of pure ground-glass nodule (pGGN), 4.0 months in the group of part-solid nodule (PSN), and 1.7 months in the group of solid nodule (SON). During long-term postoperative observation time (median 79 months), 10-year progression-free survival rates were 100% in pGGN, 96% in PSN, and 72% in SON (P < .0001). They decreased significantly depending on enlargement of size: 91% or higher in size of 2 cm or smaller, and 71% or lower in size of larger than 2 cm (P < .0001). CONCLUSIONS: Limited to LDCTS-finding nodules, surgical outcome will depend mainly on some malignant potential of NSCLC per se, rather than on duration of WWT or treatment delay.

Cloning of Helicobacter suis cholesterol α-glucosyltransferase and production of an antibody capable of detecting it in formalin-fixed, paraffin-embedded gastric tissue sections.

Helicobacter suis (H. suis), formerly called Helicobacter heilmannii type 1 (H. heilmannii), is a gram-negative bacterium of the Helicobacter species. This pathogen infects the stomach of humans and animals such as dogs, cats, pigs, and rodents, the latter giving rise to zoonotic infection. Here, we generated a H. suis-specific antibody useful for immunohistochemistry with formalin-fixed, paraffin-embedded tissue sections. To do so, we began by cloning the gene encoding H. suis cholesterol α-glucosyltransferase (αCgT). αCgT is the key enzyme responsible for biosynthesis of cholesteryl α-D-glucopyranoside (CGL), a major cell wall component of Helicobacter species including H. suis. The deduced amino acid sequence of H. suis αCgT had 56% identity with the corresponding Helicobacter pylori (H. pylori). We then developed a polyclonal antibody (anti-Hh-I205R) by immunizing rabbits with a 205 amino acid H. suis αCgT fragment. Immunohistochemistry with the anti-Hh-I205R antibody could differentiate H. suis from H. pylori in gastric mucosa sections derived from mice infected with either pathogen. We then probed formalin-fixed, paraffin-embedded sections of human gastric mucosa positive for H. suis infection with the anti-Hh-I205R antibody and detected positive staining. These results indicate that anti-Hh-I205R antibody is specific for H. suis αCgT and useful to detect H. suis in gastric specimens routinely analyzed in pathological examinations.

Curative resection by splenectomy for solitary splenic metastasis from early gastric cancer: a case report and literature review.

BACKGROUND: Solitary metastasis of a malignancy to the spleen is rare, particularly for gastric cancer. Only a few case reports have documented isolated splenic metastasis from early gastric cancer. We describe a case of splenic metastasis from early gastric cancer. CASE PRESENTATION: A 60-year-old man underwent a distal gastrectomy for early gastric cancer. It infiltrated the submucosa with pathological nodal involvement (pT1bN2M0, stage IIB). One year after the gastrectomy, an abdominal computed tomography scan showed a low-density lesion, 17 mm in diameter, at the upper pole of the spleen. Positron emission tomography/computed tomography showed focal accumulation of fluorine-18 fluorodeoxyglucose in the spleen without extrasplenic tumor dissemination or metastasis. We diagnosed splenic metastasis of gastric cancer, and performed a splenectomy. Histological examination confirmed moderately differentiated tubular adenocarcinoma and poorly differentiated adenocarcinoma (solid type) that was consistent with the features of the primary gastric cancer. The splenic tumor was pathologically and immunohistochemically diagnosed as a metastasis from the gastric carcinoma. More than 18 months after the splenectomy, the patient has had no evidence of recurrent gastric cancer. CONCLUSION: When solitary metastasis to the spleen is suspected during the postoperative follow-up of a patient with gastric cancer, a splenectomy is a potentially effective treatment.

Gastric hepatoid adenocarcinoma resulting in a spontaneous gastric perforation: a case report and review of the literature.

BACKGROUND: Gastric hepatoid adenocarcinoma (GHAC) is an atypical form of gastric cancer (GC) that has similar tissue morphology to hepatocellular carcinoma and frequently produces alpha-fetoprotein. We present an exceedingly rare case of GHAC resulting in a spontaneous gastric perforation. CASE PRESENTATION: A 61-year-old man presented at our institution complaining of abdominal and back pain. A computed tomography scan revealed a spontaneous gastric perforation with a solitary liver tumor and lymph node swelling. Following a diagnosis of advanced-stage GC with a gastric perforation, perforative peritonitis, multiple lymph node metastases, and a solitary metastasis of the lateral segment of the liver, the patient underwent distal gastrectomy. Histopathology of the resected specimen revealed that the tumor cells were arranged in a hepatoid pattern. On immunohistochemical staining, the tumor cells were positive for alpha-fetoprotein and Sal-like protein 4. Thus, the patient was diagnosed with GHAC. Hepatic resection of the solitary liver metastasis was performed. However, recurrence occurred and the patient achieved complete response following tegafur/gimeracil/oteracil-based chemotherapy. CONCLUSIONS: GHAC is a highly malignant histological subtype of GC. We reported on an extremely rare case of GHAC resulting in a spontaneous gastric perforation and reviewed the literature, including epidemiological data, treatment regimens, and the association between GHAC and alpha-fetoprotein-producing GC.

[A Case of Retroperitoneal Abscess Due to Acute Appendicitis during Neo-Adjuvant Chemotherapy for Breast Cancer].

When acute appendicitis occurs in patients treated with chemotherapy, neutropenia and abdominal complaints caused by chemotherapy can contribute to the diagnostic difficulty, masking the increase in white blood cell(WBC)counts and physical findings of acute appendicitis. A 43-year-old premenopausal woman who was diagnosed with stage IIIA left breast cancer was scheduled for neoadjuvant chemotherapy includingfluorouracil plus epirubicin plus cyclophosphamide(FEC), followed by docetaxel and trastuzumab(DOC plus HER). The patient developed fever and lower abdominal pain on day 17 of DOC plus HER cycle 1, and was diagnosed with acute gastroenteritis in the emergency room. These symptoms were almost improved 4 days later, and then cycle 2 was performed as scheduled. WBC counts decreased to 1,530 cells/mL due to DOCinduced myelosuppression on day 8 of cycle 2 when the patient developed lower abdominal pain again. However, WBC counts increased to 21,680 cells/mL on day 13 of cycle 2. Computed tomography scans revealed an intraperitoneal abscess due to acute appendicitis, and consequently urgent operation was performed. It is necessary to understand that patients with acute appendicitis duringchemotherapy can present less clinical findings.

Postoperative complications in elderly patients with gastric cancer.

BACKGROUND: Elderly patients undergoing gastrectomy are expected to be at high risk of postoperative complications. This retrospective multicenter cohort study assessed complications and long-term outcomes after gastrectomy for gastric cancer (GC). METHODS: A total of 993 patients with GC who had undergone gastrectomy were included, comprising 186 elderly patients (age ≥ 80 y, E group) and 807 nonelderly patients (age ≤ 79 y, NE group). Preoperative comorbidities, operative results, postoperative complications, and clinical outcomes were compared between the groups. RESULTS: Clavien-Dindo grade ≥1 postoperative complications, pneumonia (P = 0.02), delirium (P < 0.001), and urinary tract infection (P < 0.001) were more common in the E group. Postoperative pneumonia was associated with mortality in this group (P < 0.001). Three patients (1.6%) died after surgery, each of whom had pneumonia. Severe postoperative complication was independently prognostic of overall (hazard ratio, 4.69; 95% confidence interval, 2.40-9.14; P < 0.001) and disease-specific (hazard ratio, 6.41; 95% confidence interval 2.92-14.1; P < 0.001) survival in the E group. CONCLUSIONS: In elderly patients with GC, clinical outcomes are strongly associated with severe postoperative complications. Preventing such complications may improve survival.

Prevalence of synchronous colorectal neoplasms in surgically treated gastric cancer patients and significance of screening colonoscopy.

BACKGROUND AND AIM: The existence of other primary tumors during the treatment and management of gastric cancer (GC) is an important issue. The present study investigated the prevalence and management of synchronous colorectal neoplasms (CRN) in surgically treated GC patients. METHODS: Of 381 surgically treated GC patients, 332 (87.1%) underwent colonoscopy to detect CRN before surgery or within a year after surgery. RESULTS: CRN were synchronously observed in 140 patients (42.2%). Adenoma was observed in 131 patients (39.4%). Endoscopic resection was done in 18 patients with adenoma. Colorectal cancer (CRC) was observed in 16 patients (4.8%), superficial CRC in 13 and advanced CRC in three patients. Endoscopic resection of superficial CRC was carried out in seven patients, whereas simultaneous surgical resection of CRC was done in nine patients. CRN were more frequently observed in men. CRC was more frequently observed in GC patients with distant metastasis, albeit without significance. The overall survival of GC patients with CRN or CRC was poorer than that of patients without CRN or CRC. CONCLUSION: Synchronous CRN were commonly associated with GC and screening colonoscopy should be offered to patients with GC.

[Juvenile gastric polyposis in a patient with antiphospholipid syndrome].

We report a case of juvenile gastric polyposis associated with antiphospholipid syndrome. A 42-year-old woman was admitted with a chief complain of fatigue. Six years earlier, antiphospholipid syndrome was diagnosed and treated with aspirin. Two years earlier, gastric polyps were endoscopically observed, the number and size of which subsequently increased. Juvenile gastric polyposis was diagnosed on the basis of the pathological features of the biopsy specimens. Bleeding was repeatedly identified from the polyposis. Total gastrectomy was performed because of worsening anemia and hypoalbuminemia.

Pulmonary adenocarcinoma possibly developed from the cut-end of small-sized adenocarcinoma in the lung periphery as recurrence 13 years after its wedge resection.

BACKGROUND: It is a big topic for general thoracic surgery whether still curability can be obtained by limited resection for peripheral small-sized nodules of non-small cell lung cancer (NSCLC) in the current era of frequent computed tomography (CT) use. Accumulation of information on problematic cases would be meaningful for surgeons to select better surgical procedures. CASE PRESENTATION: A 69-year-old man was pointed out an enlarged 2.1-cm solid nodule on the edge of staple line of the residual right upper lobe by chest CT. He had past history of the lung cancer surgery, wedge resection of the same right upper lobe 13 years ago. The pathological findings were 1.1-cm, p-TlbN0M0, p-stage IA2-adenocarcinoma. Thereafter, he received no adjuvant therapy. This time, the trans-bronchial lung biopsy revealed adenocarcinoma. After the completion lobectomy of the residual right upper lobe, the tumor was diagnosed as adenocarcinoma consistent with recurrence of small-sized adenocarcinoma in the lung periphery developed from the cut-end because of similarities between present and previous tumors on histopathology and p53-positivity. CONCLUSIONS: When limited resection has been performed for small-sized NSCLC presenting solid nodule on thin-slice CT images, long-term postoperative follow-up time will be necessary for monitoring, considering the possibility of cut-end recurrence.

In vivo bactericidal activities of Japanese rice-fluid against H. pylori in a Mongolian gerbil model.

PURPOSE: The antibiotic effect of rice-fluid on Helicobacter pylori infection was investigated using a Mongolian gerbil model. METHODS: Gerbils were divided into four groups: H. pylori -infected, rice-fluid-treated animals (group A); H. pylori -infected, untreated animals (group B); uninfected, rice-fluid-treated animals (group C); and uninfected, untreated animals (group D). Group A and B animals were killed 14 weeks after H. pylori infection and group C and D animals were killed at the same age. The stomachs were examined for histology, 5'-bromo-2'-deoxyuridine (BrdU) labeling, and the bacterial burden. Serum anti-H. pylori antibody titers were also tested. RESULTS: The positive incidence of H. pylori -culture was 25 and 84 % in groups A and B, respectively (p<0.01). Both the degree of inflammation and the BrdU labeling index in group A were significantly lower than those in group B. CONCLUSIONS: Rice-fluid showed an antibiotic effect on H. pylori and an anti-inflammatory effect on the H. pylori -associated gastritis.

A clinical study of docetaxel with or without 5'DFUR as a second-line chemotherapy for advanced gastric cancer.

We conducted a clinical pilot study to evaluate the efficacy and safety of the combination of docetaxel and 5'DFUR as a second-line chemotherapy for gastric cancer. Twenty-four patients were divided into two groups by simple randomization: group A (60 mg/m2 of docetaxel, every 3 wk) and group B (regimen A + 600 mg/body of 5'DFUR). The response rate was 17% and 42% in group A and B, respectively (p < 0.05). The MST from the start of the first-line was 17 mo in group B. The major adverse event was leukopenia in both groups.

Surgery for chronic mesh infection occurred 10 years after sacrectomy - Mesh resection and mesentric leaf repair: A case report.

INTRODUCTION: Sacrectomy to treat malignant tumors is often results in large pelvic defects to require reconstruction, using a prosthetic mesh. Importance is to avoid its direct contact of mesh with intestine to prevent adhesion between them. PRESENTATION OF CASE: An 83-year old woman who was diagnosed with a mesh infection caused by a small bowel penetration 10 years after sacrectomy combined with mesh reconstruction for chordoma. In the first operation, because of incomplete re-peritonealization due to a large defect in the retroperitoneum, a mesh unavoidably was compelled to contact with the small intestine. We subtotally removed the mesh and performed mesentric leaf repair of the pelvic defect. The postoperative course was complicated by infection of the pelvis. She was discharged 59days after surgery with a little purulent discharge from perineal wound, which was persisted for two years after operation. DISCUSSION/CONCLUSION: We used the mesenteric leaf to repair the pelvic defect at the operation. This procedure might be the best alternative, when the use of mesh has to be avoided like present case. To our knowledge, this is the first report of mesh infection after sacrectomy, so we report herein.

Nonocclusive Mesenteric Ischemia after Chemotherapy in an Adolescent Patient with a History of Three Allogeneic Hematopoietic Stem Cell Transplantations for Acute Lymphoblastic Leukemia.

Nonocclusive mesenteric ischemia (NOMI) is induced by intestinal vasospasm without thromboembolic occlusion and is associated with high morbidity and mortality. The estimated overall incidence of autopsy-verified fatal NOMI is 2.0 cases/100,000 person-years; however, no pediatric or adolescent cases have yet been reported. An 18-year-old female was diagnosed with B-cell precursor acute lymphoblastic leukemia at the age of 10 years. Our patient received three allogeneic hematopoietic stem cell transplantations but experienced hematological relapse after each. She received combination therapy of prednisolone, L-asparaginase, vincristine, and bortezomib after the third relapse. On Day 16 after the initiation of chemotherapy, she developed NOMI; therefore, we performed a right-sided hemicolectomy on Day 27. Nonocclusive mesenteric ischemia should be considered during the differential diagnosis of intestinal complications after chemotherapy, even in pediatric and adolescent patients.

Suppressive effect of rice extract on Helicobacter pylori infection in a Mongolian gerbil model.

BACKGROUND: Rice extract has been shown to protect gastric mucosa from stress-induced damage. In this study, the antibiotic effect and the anti-inflammatory effect of orally administered aqueous rice extract on Helicobacter pylori infection and H. pylori-induced gastritis, respectively, in Mongolian gerbils were investigated. METHODS: Fifty specific-pathogen-free male Mongolian gerbils, seven weeks old, were divided into four groups: uninfected, untreated animals (group A); uninfected, rice extract-treated animals (group B); H. pylori-infected, untreated animals (group C); and H. pylori-infected, rice extract-treated animals (group D). Group C and D animals were killed 12 weeks after H. pylori infection (i.e., at 19 weeks of age) and group A and B animals were also killed at age 19 weeks. The stomachs were removed for histopathological examination with hematoxylin-and-eosin staining and anti-5'-bromo-2'-deoxyuridine (BrdU) immunostaining, and to determine the bacterial burden. Serum anti-H. pylori antibody titers were also tested. RESULTS: In groups A and B, the gastric mucosa showed no inflammatory cell infiltration and a few BrdU-reactive cells. Group C animals developed marked chronic active gastritis in the gastric mucosa, and BrdU-labeled cells in the gastric mucosa markedly increased in number. In group D animals, a significant reduction occurred in the degree of neutrophilic polymorphonuclear cell infiltration into the gastric mucosa, in the BrdU-labeling indices of gastric epithelial cells, and in anti-H. pylori antibody titers in the serum (P < 0.01), compared with although H. pylori was not completely eradicated. CONCLUSIONS: The rice extract was effective in suppressing inflammation and epithelial cell proliferation in the gastric mucosa in H. pylori-infected Mongolian gerbils. The rice extract has potential to exhibit a protective effect on H. pylori-related gastric mucosal diseases.

Additional gastrectomy after endoscopic submucosal dissection for early gastric cancer patients with comorbidities.

Purpose. We investigated the clinicopathologic features of early gastric cancer (EGC) patients who have undergone additional gastrectomy after endoscopic submucosal dissection (ESD) because of their comorbidities. Methods. Eighteen (7.1%) of 252 GC patients were gastrectomized after prior ESD. Reasons for further surgery, preoperative and postoperative problems, and the clinical outcome were determined. Results. The 18 patients had submucosal EGC and several co-morbidities. Other primary cancers were observed in 8 (44.4%). Histories of major abdominal operations were observed in 6 (33.3%). Fourteen patients (77.8%) hoped for endoscopic treatment. Due to additional gastrectomy, residual cancer was suspected in 10, and node metastasis was suspected in 11. A cancer remnant was histologically observed in one. Node metastasis was detected in 3 (16.7%). Small EGC was newly detected in 4. Consequently, additional gastrectomy was necessary for the one third. No patient showed GC recurrence. However, 9 (50%) had new diseases, and 4 (22.2%) died of other diseases. The overall survival after surgery in these patients with additional gastrectomy was poorer than those with routine gastrectomy for submucosal EGC (P = 0.0087). Conclusions. Additional gastrectomy was safely performed in EGC patients with co-morbidities. However, some issues, including presence of node metastasis and other death after surgery, remain.

Fatal interstitial pneumonia associated with oxaliplatin-based therapy in a patient with metastatic rectal cancer.

Oxaliplatin in combination with 5-fluorouuacil and leucovorin (FOLFOX) is one of the most commonly used first-line chemotherapies for patients with advanced or metastatic colorectal cancer. Pulmonary toxicity, including interstitial pneumonia (IP)/peumonitis, is a very rare complication. We report a case of fatal IP associated with FOLFOX therapy in a patient with metastatic rectal cancer. A 74-year-old man with rectal adenocarcinoma and associated liver metastases underwent palliative surgery and 21 cycles of modified FOLFOX6 therapy. After starting the 22nd therapy cycle, the patient developed a high fever with non-productive cough. Chest X-ray demonstrated diffuse ground-glass opacities in both lungs, and computed tomography showed severe disorder of the bilateral lung architecture. On the basis of a lymphocyte stimulation test (DLST), oxaliplatin-induced IP was diagnosed. Intravenous administration of high-dose methylprednisolone was started, but the symptoms and radiological findings were not improved. The patient died of respiratory failure 16 days after the last administration of oxaliplatin. Although IP is a rare but potentially fatal complication of oxaliplatin-based treatment in colorectal cancer patients, clinicians should pay careful attention to the clinical respiratory symptoms and radiographic findings in colorectal cancer patients receiving FOLFOX therapy.

Surgical treatment for anorectal malignant melanoma: report of five cases and review of 79 Japanese cases.

INTRODUCTION: Anorectal malignant melanoma (AMM) is a relatively rare disease. Because of its poor prognosis, the optimal surgical treatment for AMM is still controversial and difficult to determine. In this paper, we report five cases of AMM that have been treated by surgery and/or other methods at Shinshu University Hospital within the last decade. We also review the present five cases along with 74 other Japanese cases reported between 1997 and 2006 and discuss the role of surgery in the treatment of AMM. RESULTS AND DISCUSSION: Among our AMM patients, two who underwent radical abdominoperineal resection had long survival, while the other three patients who underwent palliative surgery had a poor outcome. On the total of 79 AMM patients, those who underwent curative surgery had a better outcome than those who underwent palliative surgery (p < 0.0001). Furthermore, the outcome of AMM patients at stages 0 and I was better than that of AMM patients at stages II, III, and IV (p < 0.0001). There was no significant difference in survival between AMM patients with and without adjuvant chemotherapy. CONCLUSION: In conclusion, AMM patients treated by curative surgery can expect long-term survival, although the usefulness of adjuvant chemotherapy for AMM patients is controversial.

Modified Irinotecan/5FU/Leucovorin therapy in advanced colorectal cancer and predicting therapeutic efficacy by expression of tumor-related enzymes.

OBJECTIVE: To evaluate the efficacy and safety of a regimen using Irinotecan, 5FU and Leucovorin for patients with advanced or recurrent colorectal cancer. MATERIAL AND METHODS: Irinotecan (75 mg/m(2)) was administered biweekly, while 5FU (600 mg/m(2)) and Leucovorin (250 mg/m(2)) were administered weekly, for 6 weeks. RESULTS: The 21 consecutive patients subjected to this regimen showed a good response rate (43%) with minimal toxicity (incidence of grade 3/4: leukopenia and neutropenia, 5%, respectively, and vomiting, 10%). The mean survival time of all 21 patients was 15.7 months. This regimen could be a valid option for patients with advanced colorectal cancer, especially those seeking a good QoL (quality of life) for the remainder of their lives. We evaluated the expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) mRNAs, and sialyl Lewis X on formalin-fixed, paraffin-embedded colorectal tumor samples. Expression of TS mRNA or sialyl Lewis X was negatively correlated with the response from chemotherapy. Patients with low DPD mRNA expression in the tumor showed a significant longer survival than those with high expression. In patients with high TP mRNA expression, there was a tendency towards a high incidence of leukopenia. CONCLUSIONS: Some predictive factors elucidated in this study could contribute to the progress of the tumor-biology based, individualized chemotherapy for colorectal cancer patients.

Efficacy of S-1 for patients with peritoneal metastasis of gastric cancer.

BACKGROUND: This study was designed to examine the efficacy and compliance of S-1 for the patients with peritoneal metastasis of gastric cancer. METHODS: Sixteen consecutive patients with peritoneal metastasis of gastric cancer were treated with S-1. Their survival was compared with that of the historical control group (25 patients). Thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase and orotate phosphoribosyl transferase mRNA expression in the tumor were evaluated. RESULTS: The median survival time of S-1-treated patients was 550 days, which was significantly longer than that of the historical control group (215 days). We elucidated some factors to prolong the survival of the patients treated with S-1 for peritoneal metastasis: peritoneal metastasis without other distant metastases, the combination of S-1 treatment and gastrectomy, and low expression of thymidine phosphorylase mRNA in primary tumors. CONCLUSIONS: S-1 showed a surprisingly long-term survival with minimum toxicity in patients with peritoneal metastasis of gastric cancer.