Combined regression score predicts outcome after neoadjuvant treatment of oesophageal cancer.

BACKGROUND: Histopathologic regression following neoadjuvant treatment (NT) of oesophageal cancer is a prognostic factor of survival, but the nodal status is not considered. Here, a score combining both to improve prediction of survival after neoadjuvant therapy is developed. METHODS: Seven hundred and fifteen patients with oesophageal squamous cell (SCC) or adenocarcinoma (AC) undergoing NT and esophagectomy were analysed. Histopathologic response was classified according to percentage of vital residual tumour cells (VRTC): complete response (CR) without VRTC, major response with <10% VRTC, minor response with >10% VRTC. Nodal stage was classified as ypN0 and ypN+. Kaplan-Meier and Cox regression were used for survival analysis. RESULTS: Survival analysis identified three groups with significantly different mortality risks: (1) low-risk group for CR (ypT0N0) with 72% 5-year overall survival (5y-OS), (2) intermediate-risk group for minor/major responders and ypN0 with 59% 5y-OS, and (3) high-risk group for minor/major responders and ypN+ with 20% 5y-OS (p < 0.001). Median survival in AC and SCC cohorts were comparable (3.8 (CI 95%: 3.1, 5.3) vs. 4.6 years (CI 95%: 3.3, not reached), p = 0.3). CONCLUSIONS: Histopathologic regression and nodal status should be combined for estimating AC and SCC prognosis. Poor survival in the high-risk group highlights need for adjuvant therapy.

[Molecular predictors for the course of disease and individualized therapy in pancreatic cancer]. / Molekulare Prädiktoren für den Krankheitsverlauf und die individualisierte Therapie beim Pankreaskarzinom.

The understanding of the development of pancreatic cancer has undergone considerable development over the last two decades. This is mainly due to the progress and use of methods for molecular biological analysis of pancreatic carcinomas. There is now a fundamental understanding with respect to the genetic drivers for the development of pancreatic cancer and the correlation with clinical data as well as the classification of different genetic characteristics of individual tumors even enables an estimation of the prognosis in some cases. The most common mutation in ductal adenocarcinoma, which if found in >90% of tumors, is the mutation of the KRAS oncogene. The other three, CDKN2A, p53 and SMAD4, are all tumor suppressor genes and are mutated in approximately 90%, 70% and 50% of carcinomas, respectively. In addition, genetic mutations predisposing to pancreatic cancer have been identified. Among the most important are BRCA2, p16/CDKN2A, STK11, PRSS1, PALP2, FANCC, FANCG and ATM. The classification of different subtypes and the knowledge of individual mutations (especially BRCA) can also be used to assess the response to treatment in individual cases. This applies to "conventional" combination chemotherapies (especially FOLFIRINOX) and also to targeted treatment approaches with tyrosine kinase inhibitors, PARP inhibitors and PD­1 inhibitors. If knowledge about the course of the disease and decisions on individual therapies become established in everyday clinical practice in the future, this may also have a decisive impact on surgery as the most important pillar of curative treatment. This ranges from the increased achievement of secondary operability to the expansion of indications with respect to resection even in patients with metastases.

[Oligometastasis in pancreatic cancer : Current state of knowledge and spectrum of local therapy]. / Oligometastasierung beim Pankreaskarzinom : Aktueller Kenntnisstand und Spektrum der Lokaltherapie.

BACKGROUND: Several case series reported results of surgical resection in patients with pancreatic ductal adenocarcinoma in a metastasized stage. AIM: A summarized overview of the current state of knowledge and a summary of the results of currently available studies. MATERIAL AND METHODS: A systematic search was carried out in MEDLINE and PubMed with respect to metastasized pancreatic cancer and surgical resection. RESULTS: The evidence level for surgical resection in the metastasized stage is weak and so far no prospective trials are available. The largest single-arm trial included 85 patients with hepatic metastasis. In cases of hepatic oligometastasis an overall survival of 11-14 months was observed. In the presence of pulmonary metastasis, overall survival seems to be prolonged compared to intra-abdominal metastasis, although the evidence level is relatively weak. CONCLUSION: According to the available results, a general recommendation for surgical resection in a metastasized stage cannot be given; however, the results show a possible benefit for some well-selected patient subgroups. Prospective trials must validate these data and investigate the use of combined surgical and systemic treatments in the case of resectable metastatic pancreatic cancer.

Individualized multimodal treatment strategy for anaplastic thyroid carcinoma-Case report of long-term remission and review of literature.

INTRODUCTION: The prognosis of anaplastic thyroid cancer (ATC) is poor with a mean survival time of six months following diagnosis. Despite various attempts to modify common treatment modalities including surgery, external beam radiation and chemotherapy, an effective treatment is not available yet. We report, here, a patient who achieved long-term survival based on multimodal treatment, including in vitro evaluation of drug response of his tumor cells. PRESENTATION OF CASE: A 42 years old male patient underwent total thyroidectomy with central and lateral neck dissection for ATC (pT4b, pN0 (0/36), L0, V0, Pn1, R0 cM0 - UICC-Stage: IV b). From the tumor tissue a primary cell culture was established. While the patient received a combined radio-chemotherapy cell viability assays were performed using Sorafenib, Vandetanib und MLN8054 (Aurora kinase inhibitor) as inhibitors. Cell viability was determined by MTT-assay after 72 and 144h of treatment. DISCUSSION: All the three compounds affected cell viability in a time- and dose dependent manner. These effects were most pronounced by Sorafenib. Based on in vitro findings, the patient was treated daily with 400mg Sorafenib for 75days. 43 months after initial diagnosis, the patient had no evidence of disease as shown by MRI, CT and FDG-PET-CT imaging. CONCLUSION: In the setting of multimodal treatment, in vitro drug evaluation of individual tumor cells of patients might be a promising tool to ameliorate the fatal prognosis of selected ATC patients.

["Practical clinical competence" - a joint programme to improve training in surgery]. / "Praktische klinische Kompetenz" - ein Verbundprojekt zur Verbesserung der chirurgischen Lehre.

INTRODUCTION: Practical clinical competence is, as a result of the complexity of the required skills and the immediate consequences of their insufficient mastery, fundamentally important for undergraduate medical education. However, in the daily clinical routine, undergraduate training competes with patient care and experimental research, mostly to the disadvantage of the training of clinical skills and competencies. All students have to spend long periods in compulsory surgical training courses during their undergraduate studies. Thus, surgical undergraduate training is predestined to exemplarily develop, analyse and implement a training concept comprising defined learning objectives, elaborated teaching materials, analysed teaching methods, as well as objective and reliable assessment methods. THE PROJECT: The aim of this project is to improve and strengthen undergraduate training in practical clinical skills and competencies. The project is funded by the German Federal Ministry of Education and Research with almost two million Euro as a joint research project of the medical faculties of the universities of Frankfurt/Main, Gießen and Marburg, in collaboration with the German Society of Surgery, the German Society of Medical Education and the German Medical Students' Association. Nine packages in three pillars are combined in order to improve undergraduate medical training on a methodical, didactic and curricular level in a nation-wide network. Each partner of this network provides a systematic contribution to the project based on individual experience and competence. Based on the learning objectives, which were defined by the working group "Education" of the German Society of Surgery, teaching contents will be analysed with respect to their quality and will be available for both teachers and students as mobile learning tool (first pillar). The existing surgical curricula at the cooperating medical faculties will be analysed and teaching methods as well as assessment methods for clinical skills will be evaluated regarding their methodological quality and evidence. The existing surgical curricula will be revised and adapted on the basis of these results (second pillar). Qualification programmes for physicians will be implemented in order to improve both undergraduate education and the attractiveness of educational research, the required teaching quality will be imparted in a nationwide "train-the-teacher" program for surgical clinical skills (third pillar).

Prevalence of diplopia related to cataract surgery among cases of diplopia.

PURPOSE: To evaluate the prevalence of diplopia in Greece after cataract surgery among diplopia cases. METHODS: The authors retrospectively reviewed the medical records of 571 patients with diplopia over an 8-year period in order to evaluate the prevalence of diplopia related to cataract surgery. The surgical and anesthetic records were also reviewed. All patients had full orthoptic assessment including prisms with cover test in all gaze positions. The chi-square and cross-tabulation statistical tests were used for statistical analysis. RESULTS: Thirty-nine cases (6.8%) were having persistent diplopia related to cataract surgery. Type of anesthesia was peribulbar. Hyaluronidase was not used. Thirteen patients were men and 26 were women. Left eyes were involved in 22 cases (56.4%), right in 17 cases (43.6%). Mean age was 72.5 years. Patients were divided into four groups. Group 1 consisted of 29 patients related to surgical trauma due to anesthesia. Group 2 consisted of 7 patients related to pre-existing disorders. Group 3 consisted of 2 patients related to aniseikonia or anisometropia. Group 4 with 1 patient related to macular pathology. Vertical diplopia was mostly noted (28 cases). Twenty-nine patients were corrected with prisms, 9 needed strabismus surgery, and 1 needed both surgery and prisms. CONCLUSIONS: Cataract surgery is not a common cause of persistent diplopia. However, this report highlights that prevalence of diplopia related to cataract is high among cases of diplopia in general, with diplopia being mostly vertical (p=0.001), affecting females (p=0.006), and being more common in left eyes, although results did not reach statistical significance (p=0.133).

Presumed congenital ocular toxoplasmosis in two successive siblings.

We present the cases of 2 consecutive siblings with bilateral macular lesions, for which there is strong clinical and laboratory evidence supporting the diagnosis of congenital ocular toxoplasmosis. These cases raise the possibility of maternal parasitemia during Toxoplasma gondii reinfection, leading to transmission to the fetus and congenital ocular toxoplasmosis despite prior immunity and lack of an immune disturbance in the mother.

Bilateral medial rectus recession in convergence excess esotropia, with and without distance orthophoria.

PURPOSE: To evaluate the effectivity and safety of bilateral medial rectus recession for the correction of acquired convergence excess esotropia, with and without distance orthophoria. METHODS: Thirty-five pediatric patients with acquired convergence excess esotropia were operated with bilateral medial rectus recessions based on the near angle measured through the distance correction. Preoperatively, in 26 patients, full hypermetropic correction did not fully correct the distance angle; these patients were operated for the residual angle for distance and near. In nine patients full hypermetropic correction produced distance orthophoria and these cases also had near orthophoria through a near add; these patients could have used bifocals, but surgery was chosen instead. RESULTS: Postoperatively, 19 of the 26 patients with distance esotropia (73%) and 6 of the 9 with distance orthophoria (66.6%) were successfully aligned. Consecutive exotropia developed in two patients (7.6%) in the distance esotropia group and one (11.1%) in the distance orthophoria group. CONCLUSIONS: These results suggest that bilateral recession of the medial recti based on the near deviation is effective in eliminating the near angle in convergence excess esotropia. In patients with distance orthophoria this operation can be used as an initial treatment instead of bifocals. Although the risk of consecutive exotropia was low in this series, a larger number of patients would determine its actual rate more accurately.

Ophthalmic dirofilariasis.

PURPOSE: To report a rare case of ophthalmic dirofilariasis in a 68-year-old man with sudden, intense pain and itching in the left eye. The nematode was located in the eye and recognized as Dirofilaria repens. METHODS: Slit-lamp examination disclosed a moving nematelminth under the bulbar conjunctiva of the left eye. The nematode was surgically removed. RESULTS: The nematelminth surgically removed from the subconjunctival space was identified as D repens on the basis of transverse sections and its macroscopic characteristics. CONCLUSION: It is important to identify the nematode as D repens, based on both its microscopic and macroscopic characteristics, to avoid treatment with anthelminthic agents. The surgical removal of the worm is the sole recommended treatment.

Coloboma of the optic disk associated with retinal vascular abnormalities.

PURPOSE: We studied a case of congenital optic disk pit and coloboma with associated malformations of the retinal vessels. METHODS: Slit-lamp biomicroscopy and fluorescein angiography were performed. RESULTS: Multiple retinal venous anastomoses associated with a congenital coloboma and pit of the optic disk were observed. The retinal vascular anomalies extended from the optic disk to the temporal periphery. CONCLUSIONS: We consider the coexistence of retinal venous anastomoses with optic disk coloboma and pit to be an extremely rare congenital retinal anomaly.

8 mm bimedial rectus recession in infantile esotropia of 80-90 prism dioptres.

Sixteen patients with large angle infantile esotropia with deviations of 80-90 prism dioptres were operated at the age of about 2 years. All patients underwent 8 mm bilateral medial rectus recessions. At the last follow up examination, 6 to 48 months postoperatively (average 16.3 months), successful horizontal alignment was achieved in 12 patients (75%). Four patients (25%) were undercorrected. Clinically significant limitation of adduction or convergence was not observed postoperatively in any of the patients. Consecutive exotropia was not encountered in this series but a longer follow up is probably needed in order to assess its delayed appearance. These results suggest that 8 mm recession of the medial recti is an effective procedure for the correction of large angle infantile esotropia of 80-90 prism dioptres and can be considered as an acceptable alternative to operations on three or four muscles.

Effect of posterior fixation sutures on the accommodative element of partially accommodative strabismus.

In a prospective study, we investigated the effect of posterior fixation sutures on the accommodative element of partially accommodative strabismus. Twenty patients were included in the study. Recession of one or both medial rectus muscles combined with bilateral posterior fixation sutures was performed on each patient. The results showed that this combined operation had a greater effect on the angle without glasses at both distance and near fixation, but not enough to eliminate the angle without glasses in all the cases. The results in patients with convergence excess are not satisfactory, as far as the reduction of the angle without glasses is concerned. In patients without convergence excess, this operation is effective in satisfactorily reducing the squint without glasses when the difference of the angle with and without glasses does not exceed 15 delta.

Use of argon laser photocoagulation in the treatment of recurrent trichiasis: long-term results.

We describe our technique and analyze the long-term results of the use of argon laser photocoagulation in the treatment of 92 eyes with recurrent trichiasis. In spite of an incidence of recurrences of 64.1% which had to undergo a new laser photocoagulation session, the final success rate of the method was impressive (91.3%). The number of misdirected cilia per lid seems to constitute an important factor which affects both the rate of recurrences and the success rate of the procedure.

[Diminution of myopia following operation of macular hole-induced retinal detachment]. / Abnahme der Myopie nach Operation makulalochbedingter Netzhautablösungen.

This paper presents an assessment of the diminution of myopia in 25 eyes after surgery according to the technique of G. P. Theodossiadis for retinal detachment due to a macular hole. The procedure consists in the stretching and fixation of a silicone sponge at the posterior pole and dispenses entirely with either cryocoagulation or light coagulation. The sponge is stretched and fixed to the sclera at both ends (12 and 6 o'clock), far from the posterior pole. The scleral protrusion thus obtained in the macular area leads to a considerable diminution of the high myopia usually present in such cases. The reduction of myopia is proportionate to the degree of protrusion of the scleral buckle, which in turn depends on the stretching of the sponge and on the amount of subretinal fluid released.