Dynamic and subtype-specific interactions between tumour burden and prognosis in breast cancer.

We investigated the relationship between the prognostic importance of anatomic tumour burden and subtypes of breast cancer using data from the Korean Breast Cancer Registry Database. In HR+/HER2+ and HR-/HER2-tumours, an increase in T stage profoundly increased the hazard of death, while the presence of lymph node metastasis was more important in HR+/HER2+ and HR-/HER2+ tumours among 131,178 patients with stage I-III breast cancer. The patterns of increasing mortality risk and tumour growth (per centimetre) and metastatic nodes (per node) were examined in 67,038 patients with a tumour diameter ≤ 7 cm and < 8 metastatic nodes. HR+/HER2- and HR-/HER2- tumours showed a persistent increase in mortality risk with an increase in tumour diameter, while the effect was modest in HER2+ tumours. Conversely, an increased number of metastatic nodes was accompanied by a persistently increased risk in HR-/HER2+ tumours, while the effect was minimal for HR-/HER2- tumours with > 3 or 4 nodes. The interactions between the prognostic significance of anatomic tumour burden and subtypes were significant. The prognostic relevance of the anatomic tumour burden was non-linear and highly dependent on the subtypes of breast cancer.

Retinal pigment epithelial cells undergoing mitotic catastrophe are vulnerable to autophagy inhibition.

The increased mitochondrial DNA damage leads to altered functional capacities of retinal pigment epithelial (RPE) cells. A previous study showed the increased autophagy in RPE cells caused by low concentrations of rotenone, a selective inhibitor of mitochondrial complex I. However, the mechanism by which autophagy regulates RPE cell death is still unclear. In the present study, we examined the mechanism underlying the regulation of RPE cell death through the inhibition of mitochondrial complex I. We report herein that rotenone induced mitotic catastrophe (MC) in RPE cells. We further observed an increased level of autophagy in the RPE cells undergoing MC (RPE-MC cells). Importantly, autophagy inhibition induced nonapoptotic cell death in RPE-MC cells. These findings indicate that autophagy has a pivotal role in the survival of RPE-MC cells. We next observed PINK1 accumulation in the mitochondrial membrane and parkin translocation into the mitochondria from the cytosol in the rotenone-treated RPE-MC cells, which indicates that increased mitophagy accompanies MC in ARPE-19 cells. Noticeably, the mitophagy also contributed to the cytoprotection of RPE-MC cells. Although there might be a significant gap in the roles of autophagy and mitophagy in the RPE cells in vivo, our in vitro study suggests that autophagy and mitophagy presumably prevent the RPE-MC cells from plunging into cell death, resulting in the prevention of RPE cell loss.

Complicated giant diverticulum of the transverse colon accompanied by right inguinal hernia of the greater omentum.

Giant colonic diverticulum is a very rare entity in colonic diverticular disease and is characterized by a high rate of complications such as perforation, abscess formation and even carcinoma. We report a case of a complicated giant diverticulum of the transverse colon accompanied by a right inguinal hernia of the greater omentum in a 52-year-old man, as demonstrated on CT.

Predicting baseline laparoscopic surgery skills.

BACKGROUND: Laparoscopic surgery requires specialized dexterity even beyond that required for open surgery. Decreased tactile feedback, different eye-hand coordination, and translation of a two-dimensional video image into a three-dimensional working area are just some of the obstacles in the performance of laparoscopic surgery. Possession of certain nonsurgical skills may help in overcoming some of these obstacles. Prediction of baseline laparoscopic surgery skills may help further to refine the education of basic laparoscopic surgery skills. This investigation explores whether nonsurgical skills and demographic data can predict baseline laparoscopic surgery tasks. METHODS: First- and second-year students were given a survey regarding nonsurgical dexterity skills. The survey inquired about typing skills, play with computer games, ability to sew, skill with music instruments, use of chopsticks, and experience operating tools. Demographic data were requested as well. All the students underwent four tasks: placing a piece of bowel in a retrieval bag, placing a stapler on the bowel, measuring a piece of bowel, and performing a liver biopsy in a porcine animal model. Both objective (time and error) and subjective evaluation were assessed for all the tasks. Statistical analysis using analysis of variances (ANOVA) Kruskal-Wallis test with post hoc tests, two-tailed unpaired t-tests/Mann-Whitney test, and Fischer's exact tests/chi-square tests was performed when appropriate. RESULTS: There were 68 students in this investigation. Gender, medical student year, ethnicity, desire to enter a surgical field, and age were not associated with increased performance in any of the tasks. Chopstick use was associated with statistically significantly better mean time in placing a piece of bowel in a retrieval bag and measuring a piece of bowel (p < 0.04). The other nonsurgical dexterity skills did not statistically increase performance, as indicated by time, errors, or subjective scores, for the four tasks. CONCLUSIONS: It is difficult to predict baseline laparoscopic surgery skills.

Fluorescence in situ hybridization analysis of nitrifiers in piggery wastewater treatment reactors.

Fluorescence in situ hybridization (FISH) was performed to analyze the nitrifying microbial communities in an activated sludge reactor (ASR) and a fixed biofilm reactor (FBR) for piggery wastewater treatment. Heterotrophic oxidation and nitrification were occurring simultaneously in the ASR and the COD and nitrification efficiencies depend on the loads. In the FBR nitrification efficiency also depends on ammonium load to the reactor and nitrite was accumulated when free ammonia concentration was higher than 0.2 mg NH3-N/L. FISH analysis showed that ammonia-oxidizing bacteria (NSO1225) and denitrifying bacteria (RRP1088) were less abundant than other bacteria (EUB338) in ASR. Further analysis on nitrifying bacteria in the FBR showed that Nitrosomonas species (NSM156) and Nitrospira species (NSR1156) were the dominant ammonia-oxidizing and nitrite-oxidizing bacteria, respectively, in the piggery wastewater nitrification system.

Synthetic bile acid derivatives induce nonapoptotic death of human retinal pigment epithelial cells.

PURPOSE: To study whether the synthetic ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) derivatives, which we have synthesized and have reported their apoptosis-inducing effect, have the effect on the proliferation of retinal pigment epithelial cells. METHODS: UDCA, CDCA, and their synthetic derivatives were administered in culture to the human retinal pigment cell line, ARPE-19. The effect on cell viability and growth was assessed by trypan blue dye exclusion. In order to evaluate the type of cell death, mitochondrial membrane potential assay, DNA electrophoresis, TUNEL assay, nuclear staining and Western blotting for caspase-3 and poly(ADP-ribose) polymerase (PARP) activities were conducted. RESULTS: Unlike UDCA and CDCA, which did not exhibit a significant effect on viability, their synthetic derivatives decreased the viability of ARPE-19 cells in a concentration-dependent manner. The cells treated with the synthetic derivatives did not demonstrate the characteristic findings of apoptosis, such as DNA ladder, DNA fragmentation, nuclear condensation or fragmentation, and caspase-3 and PARP activation. The reduction of mitochondrial membrane potential was shown. In electron microscopical study nuclear condensation was not shown. CONCLUSIONS: The synthetic UDCA and CDCA derivatives induced nonapoptotic death of ARPE-19 cells.

Amniotic membrane transplantation in infectious corneal ulcer.

PURPOSE: To evaluate the efficacy of amniotic membrane transplantation in the management of treated infectious corneal ulcer in which inflammatory reactions were responsible for corneal damage. METHOD: A prospective study of 21 consecutive eyes (21 patients) was performed. Sufficient antibacterial, antifungal, or antiviral agents were applied to eradicate causative organisms before permanent or temporary amniotic membrane transplantation, or a combination of the two in few patients. The amniotic membrane was soaked in antiinfective agents before transplantation in all cases. RESULTS: After amniotic membrane transplantation, follow-up times ranged from 4 to 28 months (mean, 18 months). Clinical indications included Staphylococcus species (four cases), Pseudomonas species (five cases), Acanthamoeba species (three cases), fungus (two cases), and herpesvirus (seven cases). The corneal surface was healed successfully and recurrences of microbial infection were not noted in any case. Visual acuity was improved in cases that were nonscarring or after additional penetrating keratoplasty. CONCLUSION: Amniotic membrane transplantation seems to be a useful adjunctive surgical procedure for the management of infectious corneal ulcer by promoting wound healing and reducing inflammation.

Reduction in corneal haze and apoptosis by amniotic membrane matrix in excimer laser photoablation in rabbits.

PURPOSE: To determine whether preserved human amniotic membrane can reduce corneal haze and keratocyte apoptosis induced by excimer laser photoablation in rabbit corneas. METHODS: Excimer photoablation was performed bilaterally in 30 rabbits with a 6.0 mm ablation zone and 120 microm depth using the VISX Star laser with the phototherapeutic keratectomy (PTK) mode. One eye was randomly covered by preserved human amniotic membrane secured with 4 interrupted 10-0 nylon sutures, and the other eye served as the control. The amniotic membranes were removed at 1 week, and corneal haze was graded with slitlamp biomicroscopy by 3 masked corneal specialists biweekly for the ensuing 12 weeks until the rabbits were killed. Another 18 rabbits were divided into 4 subgroups and received PTK alone, PTK with membrane, PTK with sham sutures, or PTK with tarsorrhaphy. All eyes were studied histologically, and 3 eyes in each group were studied by in situ terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling assay at 1, 3, and 7 days and 12 weeks, respectively. RESULTS: A consistent grading of differences in corneal haze scoring between the control corneas and the amniotic-membrane-covered corneas was noted among the 3 masked observers. Organized reticular post-PTK corneal haze peaked at 7 weeks in both groups, and the corneal haze score in the amniotic-membrane-covered group was significantly less than in the control group from 7 to 12 weeks (all P < .001). Compared to the control corneas, the amniotic-membrane-covered corneas had less inflammatory response at 1 and 3 days, less keratocyte apoptosis in the ablated anterior corneal stroma at 1, 3, and 7 days (P < .001), and less stromal fibroblast cellularity and epithelial hyperplasia at 12 weeks. CONCLUSIONS: Amniotic membrane matrix introduced at an early stage of the corneal wound healing process effectively reduced corneal haze induced by excimer laser photoablation in rabbits. Studies linking suppression of apoptosis in the acute wound-healing process with reduction of subsequent corneal scarring may have useful clinical applications.

Modulation of acute inflammation and keratocyte death by suturing, blood, and amniotic membrane in PRK.

PURPOSE: To investigate the role of acute inflammation in keratocyte death, which may influence corneal haze after photorefractive keratectomy (PRK). METHODS: Transepithelial PRK was performed on both eyes of 30 rabbits. Twenty-six rabbits were divided into 4 groups receiving autologous blood, suturing alone, suturing with amniotic membrane graft, or no treatment as the control. Twenty-four hours later, the ablated zone was analyzed for keratocyte death by TdT-dUTP terminal nick-end label (TUNEL) staining and transmission electron microscopy, for polymorphonuclear cell (PMN) infiltration by hematoxylin-eosin staining, and for oxygen radical-induced lipid peroxidation by malondialdehyde immunohistochemistry. The remaining four rabbits were subjected to PRK or mechanical scraping and analyzed immediately or after culturing for 24 hours. RESULTS: Compared with the control group where TUNEL-positive keratocytes were found only in the superficial ablated stroma, blood application or suturing caused more and deeper keratocyte death and PMN infiltration (P: < 0.05). The amniotic membrane graft group had less keratocyte death and PMN than the control or the suture group (P: < 0.05 and P: < 0.01, respectively). There was a strong correlation between keratocyte death and PMN infiltration (P: < 0.01, correlation factor = 0.786). Transmission electron microscopy revealed that the majority of keratocyte death was due to necrosis. Amniotic membrane stroma trapped and prevented PMN infiltration into the stroma. Malondialdehyde-modified antigen was found on the ablated surface and around infiltrated PMN. CONCLUSIONS: Transepithelial PRK causes oxygen radical-mediated lipid peroxidation on the superficial stroma and may contribute to superficial keratocyte death even in the absence of inflammation. Mechanical scraping leads to apoptosis without the participation of inflammation. Keratocyte death by necrosis spreads to the deeper part of the stroma and correlates with additional acute inflammation. Amniotic membrane precludes PMN infiltration and decreases lipid peroxidation and keratocyte death. Future studies are needed to discern whether prevention of inflammation-mediated keratocyte necrosis can reduce unwanted scarring caused by PRK.

Amniotic membrane transplantation for acute chemical or thermal burns.

PURPOSE: To determine whether preserved human amniotic membrane (AM) can be used to treat ocular burns in the acute stage. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: Thirteen eyes from 11 patients with acute burns, 10 eyes with chemical burns and 3 with thermal burns of grades II-III (7 eyes) and grade IV (6 eyes), treated at 7 different facilities. METHODS: Patients received amniotic membrane transplantation (AMT) within 2 weeks after the injury. MAIN OUTCOME MEASURES: Integrity of ocular surface epithelium and visual acuity during 9 months of follow-up. RESULTS: Ten patients were male and one patient was female; most were young (38.2 +/- 10.6 years). For a follow-up of 8.8 + 4.7 months, 11 of 13 eyes (84.63%) showed epithelialization within 2 to 5 weeks (23.7 +/- 9.8 days), and final visual acuity improved > or = 6 lines (6 eyes), 4 to 5 lines (2 eyes), and 1 to 3 lines (2 eyes); only one eye experienced a symblepharon. Eyes with burns of grade II to III showed more visual improvement (7.3 +/- 3 lines) than those with burns of grade IV (2.3 +/- 3.0 lines; P < 0.05, unpaired t test). In the group with grade II or III burns, none had limbal stem cell deficiency. All eyes in the group with grade IV burns did experience limbal stem cell deficiency. CONCLUSIONS: Amniotic membrane transplantation is effective in promoting re-epithelialization and reducing inflammation, thus preventing scarring sequelae in the late stage. In mild to moderate burns, AMT alone rapidly restores both corneal and conjunctival surfaces. In severe burns, however, it restores the conjunctival ocular surface without debilitating symblepharon and reduces limbal stromal inflammation, but does not prevent limbal stem cell deficiency, which requires further limbal stem cell transplantation. These results underscore the importance of immediate intervention in the acute stage of eyes with severely damaged ocular surface. Further prospective randomized studies including a control group are required to determine the effectiveness of AMT in acute chemical and thermal burns of the eye.

Racemization of lens crystalline constituents in UV-induced cataract evaluated by chiral GC/MS spectroscopy.

The racemization of amino acids is hypothesized to cause cataract by disrupting the crystalline's tertiary structure, which, in turn, alters the optical characteristics of the lens. To better understand the role of these modifications in cataractogenesis, the changes in stereoisomer ratio of amino acids from lens crystalline by UV-B-induced cataract in animal models were studied using chiral separation gas chromatography-single quadrupole mass spectroscopy. The anticataract action of a compound, ([1-(phenylmethyl)-1H-indazol-3-yl]oxy)acetic acid lysinate, was also evaluated by this method.

Long-term results and complications of preoperative radiation in the treatment of rectal cancer.

A retrospective study of 149 patients with rectal cancer diagnosed between 1972 and 1979 was undertaken to compare survival, disease-free survival, recurrence sites, and long-term complications of 40 patients who received 4000 to 4500 rads of preoperative adjuvant radiotherapy (radiation group) with those of 109 patients treated by resection alone (control group). After a mean follow-up of 84 months and 99 months, respectively, survival of the irradiated patients was significantly better than that of controls (68% versus 52%, p less than 0.05). Disease-free survival of those patients rendered free of disease by treatment was also superior for the irradiated group (84% versus 57%, p less than 0.005). Local recurrence without signs of distant metastases developed only one-third as often in irradiated patients (6% versus 18%). Distant metastases, alone or in combination with local recurrence, were also less common after radiation (12% versus 27%). Second primary tumors developed in 15% and 10% of the respective groups, a difference that was not statistically significant. When we consider the survival benefit of preoperative radiation therapy, long-term complications were relatively mild. Delayed healing of the perineum was noted in two irradiated patients. Persistent diarrhea was severe enough to warrant treatment in only one case, and one patient required a colostomy for intestinal obstruction from pelvic fibrosis.

Intestinal anastomosis after preoperative radiation therapy for carcinoma of the rectum.

A retrospective review was conducted on 133 patients who underwent anterior resection and primary intestinal anastomosis for adenocarcinoma of the rectum from 1973 to 1983 at the Baystate Medical Center. Forty patients received a moderate dose, 4,500 rads, of radiation therapy preoperatively. Twenty-six of these patients (65 per cent) underwent protective colostomy at operation. An additional 93 patients underwent an operation without radiation and 38 of these (42 per cent) had a colostomy. We found no significant difference between patients who did or did not undergo radiation therapy in the over-all rate of complications (25 per cent for those who underwent radiation and 29 per cent for those who did not). Furthermore, there was no significant difference in anastomotic leak rates between the two groups (10 and 7 per cent respectively), even after controlling for the presence of a protective colostomy. We did find that leak rates for both groups were markedly higher for patients with a colostomy (14 per cent) than for patients without (1 per cent) (p less than 0.005). We conclude that a moderate dose of radiation therapy preoperatively does not increase the risk of anastomotic leakage or other operative complications with anterior resection. Colorectal intestinal anastomosis may be safely performed without routine colostomy after planned preoperative adjuvant radiation therapy if the anastomosis is technically satisfactory.

Survival following moderate-dose preoperative radiation therapy for carcinoma of the rectum.

We performed a retrospective study of patients with carcinoma of the rectum or rectosigmoid undergoing surgical resection. Forty-two patients received adjuvant preoperative radiation therapy (4000-4500 rad). One hundred twenty patients underwent surgical resection alone. Survival of radiation patients was significantly improved over that of Surgery Only patients, even after adjusting for nontreatment factors using Cox regression. Crude 5-year survival was 63% for radiation patients (74% adjusted) compared to 46% for surgery-only patients (48% adjusted) (P less than 0.025). Radiation patients also had longer disease-free survival than surgery-only patients (P less than 0.05) and fewer recurrences (14% versus 37%; P less than 0.025). Fewer radiation patients had lymph nodes involved with tumor than surgery-only patients (20% versus 35%; P = 0.07). Although 71% of radiation patients experienced radiation reactions, these were primarily mild and transitory. We believe that preoperative radiation is an effective and safe adjunct to surgery in the treatment of rectal cancer and that its use can lead to improved survival rates.

A computer-assisted radiologic reporting system.

The patient registration and interpretation/reporting modules of a computer-assisted radiologic reporting system are described. Entries may be made at several levels of complexity, using bar codes or keyboard input. Several functions allow convenient access to the database. Output may be reformatted without programmer intervention via a maintenance file. The system allowed improved turnaround time, reduced costs, and better understanding of work patterns.

Adjuvant radiation therapy in colorectal carcinoma.

A series of sixty-five patients with adenocarcinoma of the rectum and rectosigmoid is reviewed. Thirty-two patients had surgery alone, fourteen patients underwent postoperative radiation therapy, and nineteen patients underwent preoperative radiation therapy. A moderate dose program of 4,000 to 4,500 r was used. The postoperative treatment group had a higher incidence of stage C lesions and a higher recurrence rate, but there were no statistically significant differences in survival. Postoperative radiation therapy in patients with stage C lesions did not prolong life and is of little benefit. The preoperative treatment group tolerated the radiation very well, and there were no major complications. Eight patients underwent anterior resections in irradiated fields. Two minor anastomotic leaks subsequently healed spontaneously. There were no pelvic recurrences in the preoperative treatment group, and the incidence of lymph node metastases was 26% as opposed to 41% in controls. We conclude that preoperative moderate dose radiation is not associated with increased risk of morbidity or mortality. It may be useful in reducing the incidence of lymph node metastases and pelvic recurrence. The effect on survival is not determined in this study.