Exploratory Analysis to Find Unfavorable Subset of Stage II Gastric Cancer for Which Surgery Alone Is the Standard Treatment; Another Target for Adjuvant Chemotherapy

The aim of the present study was to explore the unfavorable subset of patients with Stage II gastric cancer for whom surgery alone is the standard treatment (T1N2M0, T1N3M0, and T3N0M0). Recurrence-free survival rates were examined in 52 patients with stage T1N2-3M0 and stage T3N0M0 gastric cancer between January 2000 and March 2010. Univariate and multivariate analyses were performed to identify risk factors using a Cox proportional hazards model. The recurrence-free survival (RFS) rates of the patients with stages T1N2, T1N3, and T3N0 cancer were 80.0, 76.4, and 100% at 5 years, respectively. The only significant prognostic factor for the survival rates of the patients with stage pT1N2-3 cancer measured by univariate and multivariate analyses was pathological tumor diameter. The 5-year RFS rates of the patients with stage pT1N2-3 cancer were 60.0%, when the tumor diameters measured <30 mm, and 88.9% when the tumor diameters measured >30 mm (P = 0.0248). These data may suggest that pathological tumor diameter is associated with poor survival in patients with small T1N2-3 tumors. Because our study was a retrospective single-center study with a small sample size, a prospective multicenter study is necessary to confirm whether small tumors are risk factor for the RFS in T1N2-3 disease.Key words: Gastric cancer, Stage II, Adjuvant chemotherapyEvery year, more than 934,000 people develop gastric cancer worldwide. After lung cancer, gastric cancer is the second most frequent cancer-related cause of death.¹ Complete resection is essential to cure gastric cancer. Patients with stage II or stage III gastric cancer often develop tumor recurrence, even after complete curative resections.In 2007, the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) phase III trial demonstrated that S-1 is effective as adjuvant chemotherapy in Japanese patients who have undergone curative D2 gastrectomy for advanced gastric cancer.² In general, patients eligible for ACTS-GC were those diagnosed with pathological stages II and III. However, patients classified with pathological (p) stages T1N2M0, T1N3M0, and T3N0M0—which are classified as part of stage II—were excluded from the ACTS-GC trial. Because in the prior phase III studies comparing surgery alone and adjuvant chemotherapy, patients with stages T1N+ and T2-3/N0 cancer had excellent prognoses with 5-year overall survival (OS) rates of more than 80% from surgery alone,^3,4 these patients were excluded from receiving adjuvant chemotherapy. Japanese Gastric Cancer Association (JGCA) guidelines clearly state that the standard treatment for these patients is surgery alone.⁵Therefore, patients with stage II gastric cancer have been divided into two groups: one for whom the standard treatment is surgery alone, and the other for whom the standard treatment is surgery and adjuvant chemotherapy with S-1. Before the advent of ACTS-GC, survival rates were poorer in the latter group than in the former. However, treatment with adjuvant chemotherapy with S-1 has reversed this trend. Now, patients in the latter group receiving S-1 adjuvant chemotherapy have 5-year OS rates of 84.2%.⁶ Therefore, it may be old rationale that dictates that patients in the former group should be excluded from receiving adjuvant chemotherapy, because the 5-year OS rates are now more than 80% by S-1 adjuvant chemotherapy in the latter group. Five-year OS rates of 80% would not be obtained by surgery alone. Among those patients with stage II gastric cancer assigned to the surgery alone group, some may have a poor prognosis and be good candidates for adjuvant chemotherapy. The aim of the present study was to explore the unfavorable subset of patients among those with stage II gastric cancer for whom surgery alone is the standard treatment (T1N2M0, T1N3M0, and T3N0M0).     

Risk Factors of Cytomegalovirus Infection After Pediatric Liver Transplantation

PurposeCytomegalovirus (CMV) infection is known to be the most frequently viral infection among patients after liver transplantation. This is especially true in pediatric living-donor liver transplantation because the recipients have often not been infected with CMV and postoperative primary infection with CMV frequently occurs.Patients and MethodsOf 93 patients who underwent pediatric liver transplantation at our department, 33 patients (36.3%) were diagnosed with CMV infection using the antigenemia method (C7-HRP). Retrospective review and statistical analysis were conducted to confirm risk factors of post-transplantation CMV infection.ResultPositive lymphocytes were diagnosed between postoperative days 8 and 111 after transplantation. Ganciclovir or foscavir were administrated to 21 patients. The other 10 patients who had one positive lymphocyte were observed and the cell disappeared on follow-up examination. We did not observe any cases of positive lymphocytes with C7-HRP in patients who received a graft from a CMV antibody?negative donor. Independent predictors associated with CMV infection in the multivariable analysis were administration of OKT3 and grafts from CMV antibody?positive donors.ConclusionIn CMV infection after pediatric liver transplantation, cases with CMV antibody?positive donors and with OKT3 administration for acute rejection are considered high risk, and cases with CMV antibody?negative donors are considered low risk.     

Evaluation of QOL After Proximal Gastrectomy Using a Newly Developed Assessment Scale (PGSAS-45)

Background

Proximal gastrectomy with esophagogastrostomy (PGEG) has been widely applied as a comparatively simple method. In this study, we used a questionnaire survey to evaluate the influence of various surgical factors on post-operative quality of life (QOL) after PGEG.

Methods

In this post-gastrectomy syndrome assessment study, we analyzed QOL in 2,368 cases. Among these, 193 had undergone proximal gastrectomy and 115 had undergone PGEG. The Post-Gastrectomy Syndrome Assessment Scale (PGSAS)-45 is a questionnaire consisting of 45 items, including the SF-8, the Gastrointestinal Symptom Rating Scale (GSRS), and other symptom items seemed to be specific to post-gastrectomy. The 23 symptom items were composed of seven symptom subscales (SS), including esophageal reflux, abdominal pain, and meal-related distress. These seven SS, total symptom score, ingested amount of food per meal, necessity for additional meals, quality of ingestion SS, ability to work, dissatisfaction with symptoms, dissatisfaction with the meal, dissatisfaction with working, dissatisfaction with daily life SS and change in body weight were evaluated as main outcome measures. In PGEG cases, we evaluated the influence on QOL of various surgical factors, such as procedures to prevent gastroesophageal regurgitation and size of the remnant stomach.

Results

The scores for esophageal reflux and dissatisfaction with the meal were higher in patients who had not undergone an anti-reflux procedure. In most cases, the preserved remnant stomach was more than two-thirds the size of the pre-operative stomach. When comparing patients with a remnant stomach two-thirds the pre-operative size and those with more than three-quarters, the diarrhea SS and necessity for additional meals scores were lower in the group with more than three-quarters. The indigestion, constipation, and abdominal pain subscales, and the total symptom score, were higher in patients who had not undergone pyloric bougie than in those who had.

Conclusion

These results indicated that QOL was better in patients with a large remnant stomach. Procedures to prevent gastroesophageal reflux, and the use of pyloric bougie as a complementary drainage procedure, were considered effective ways to reduce the deterioration of QOL.     

Sialolithiasis in two areas of the upper lip

Objective

Minor salivary gland sialolithiasis occurs in ~1 % of all sialolithiasis cases. We report a case of sialolithiasis considered to have occurred in the minor salivary gland in two areas of the upper lip, with special emphasis on the findings from image examinations.

Case report

A 33-year-old male complained of a painless mass on the left upper lip. At the first examination, there was a nodular, hard swelling that involved the left cuspid area of the upper lip. Although a panoramic radiograph revealed no abnormality, an intraoral radiograph showed a small radiopaque body with a laminar pattern. Computed tomography images indicated that a calcified body was present in two areas of the upper lip. On magnetic resonance imaging, the lesion was observed as a lower-signal area than the surrounding soft tissue. The mass had a high signal in the central area in the T2 and short T1 inversion recovery images. The sonogram showed a hypoechoic mass with an echogenic structure in the central area. An excisional biopsy of the left upper lip was performed under local anesthesia. A well-demarcated mass with a calcified body was enucleated. The histopathologic diagnosis was sialoadenitis with sialolithiasis.

Conclusion

Most cases of minor salivary gland sialolithiasis are solitary, with multiple sialolithiasis being extremely rare. Sonograms are useful in the diagnosis of minor salivary gland sialolithiasis. Careful imaging examination is necessary to identify multiple lesions and select appropriate treatments.     

Multiple calcifying lesions in the maxilla and mandible of a 4-year-old girl: report of a rare case and literature review

Calcifying lesions in the jaws are usually solitary and can be diagnosed by intraoral, panoramic, and conventional extraoral radiographs. It is extremely rare for these calcifying lesions to be multiple, unless they are associated with certain systematic diseases. Herein, we report a rare case of multiple odontomas in a 4-year-old girl. The lesions were scattered throughout both jaws on the panoramic image. The reconstructed CT image showed lesions in the left maxilla that occupied the sinus and affected the floor of the left orbit. The lesions in the mandible were widespread and extended to the tooth-bearing area. Enucleations of the maxillary parts were performed, and the pathological diagnosis was a mixture of complex and compound odontomas. The 3-year postoperative follow-up by panoramic imaging was uneventful. Preoperative CT was useful for the differential diagnosis by depicting the internal calcifying lesions and revealing the extent and complex relationships among the lesions.     

Intraoperative prostaglandin E1 improves antimicrobial and inflammatory responses in alveolar immune cells

OBJECTIVE: Anesthesia and surgery decrease antimicrobial and increase proinflammatory functions of alveolar immune cells. Thus, anti-inflammatory agents that do not further suppress antimicrobial functions are required. We tested the hypothesis that intraoperative prostaglandin E1 (PGE1) suppresses proinflammatory responses and prevents the reduction in antimicrobial responses of alveolar immune cells. DESIGN: Prospective, randomized, controlled, double-blind study. SETTING: University hospital. PATIENTS: A total of 40 patients undergoing elective orthopedic surgery under propofol/fentanyl anesthesia. INTERVENTION: In double-blind fashion, the patients received PGE1 from the beginning to the end of surgery (PGE1 group, n = 20) or nothing (control group, n = 20). METHODS AND MAIN RESULTS: Alveolar immune cells were harvested by bronchoalveolar lavage immediately after induction of anesthesia; 2, 4, and 6 hrs after induction of anesthesia; and at the end of surgery. We measured opsonized and nonopsonized phagocytosis. Microbicidal activity was evaluated to directly kill Listeria monocytogenes in alveolar macrophages. Finally, we determined the expression of proinflammatory cytokines including interleukin (IL)-1beta, IL-8, interferon-gamma, and tumor necrosis factor-alpha, and that of anti-inflammatory cytokines (IL-4 and IL-10) by semiquantitative polymerase chain reaction. Nonopsonized and opsonized phagocytosis and microbicidal activity of alveolar macrophages decreased and the expression of genes for all pro- and anti-inflammatory cytokines increased significantly over time in both groups. Starting 2-4 hrs after induction of anesthesia, the increases in gene expression of proinflammatory cytokines were 1.5-3 times smaller in the PGE1 than in the control group. Starting 6 hrs after anesthesia, the increase in gene expression of IL-10 was 1.5-3 times greater in the PGE1 than in the control group. Intraoperative decreases in phagocytic and microbial activities were the same in the two groups. CONCLUSION: Intraoperative PGE1 not only suppressed proinflammatory responses, but also protected antimicrobial functions of alveolar macrophages, possibly because PGE1 is mostly inactivated in the pulmonary intravascular space. Our results suggest that intraoperative PGE1 protects the pulmonary immune defense in alveolar immune cells.     

Compared effects of calcium and sodium polystyrene sulfonate on mineral and bone metabolism and volume overload in pre-dialysis patients with hyperkalemia

Background

Hyperkalemia is prevalent in end-stage renal disease patients, being involved in life-threatening arrhythmias. Although polystyrene sulfonate (PS) is commonly used for the treatment of hyperkalemia, direct comparison of effects between calcium and sodium PS (CPS and SPS) on mineral and bone metabolism has not yet been studied.

Methods

In a randomized and crossover design, 20 pre-dialysis patients with hyperkalemia (>5 mmol/l) received either oral CPS or SPS therapy for 4 weeks.

Results

After 4-week treatments, there was no significant difference of changes in serum potassium (K) from the baseline (ΔK) between the two groups. However, SPS significantly decreased serum calcium (Ca) and magnesium (Mg) and increased intact parathyroid hormone (iPTH) values, whereas CPS reduced iPTH. ΔiPTH was inversely correlated with ΔCa and ΔMg (r = ?0.53 and r = ?0.50, respectively). Furthermore, sodium (Na) and atrial natriuretic peptide (ANP) levels were significantly elevated in patients with SPS, but not with CPS, whereas ΔNa and ΔANP were significantly correlated with each other in all the patients. We also found that ΔNa and Δ(Na to chloride ratio) were positively correlated with ΔHCO₃ ^?. In artificial colon fluid, CPS increased Ca and decreased Na. Furthermore, SPS greatly reduced K, Mg, and NH₃.

Conclusion

Compared with SPS, CPS may be safer for the treatment of hyperkalemia in pre-dialysis patients, because it did not induce hyperparathyroidism or volume overload.

     

Prediction of healing progress of pressure ulcers by distribution analysis of protein markers on necrotic tissue: A retrospective cohort study

Predicting the short‐term healing progress of pressure ulcers is important for providing timely and appropriate intervention. Although there are some prediction methods available, these are unsuitable for ulcers with abundant necrotic tissue. We aimed to elucidate the relationship between necrotic tissue alteration and protein distributions on ulcers to establish a new prediction method. Thirty‐eight pressure ulcers were retrospectively analyzed. Protein distributions on necrotic tissue were evaluated by the wound blotting at three levels: marker protein positivity, signal patterns (speckled, heterogeneous, or homogeneous), and the occupation of heterogeneous pattern. Peroxidase, alkaline phosphatase, tumor necrosis factor α, and matrix metalloproteinase‐2 were used as marker proteins. One‐week necrotic tissue alteration was classified as liquefaction or nonliquefaction, and associations with protein distributions were analyzed. The peroxidase positivity was significantly higher in the liquefaction than in the nonliquefaction (p = 0.031). In peroxidase‐positive samples, the proportion of nonliquefaction samples was significantly higher in the heterogeneous pattern (p = 0.029). In the heterogeneous‐patterned samples, the proportion of samples with an occupation values greater than the median value tended to be higher in the nonliquefaction (p = 0.087). There was no significant relationship between liquefaction and other markers. Peroxidase positivity predicts 1‐week liquefaction of necrotic tissue, while a heterogeneous pattern indicates nonliquefaction.