Adjuvant Gemcitabine Versus Neoadjuvant/Adjuvant FOLFIRINOX in Resectable Pancreatic Cancer: The Randomized Multicenter Phase II NEPAFOX Trial.

BACKGROUND: Although addition of adjuvant chemotherapy is the current standard, the prognosis of pancreatic cancers still remains poor. The NEPAFOX trial evaluated perioperative treatment with FOLFIRINOX in resectable pancreatic cancer. PATIENTS AND METHODS: This multicenter phase II trial randomized patients with resectable or borderline resectable pancreatic cancer without metastases into arm (A,) upfront surgery plus adjuvant gemcitabine, or arm (B,) perioperative FOLFIRINOX. The primary endpoint was overall survival (OS). RESULTS: Owing to poor accrual, recruitment was prematurely stopped after randomization of 40 of the planned 126 patients (A: 21, B: 19). Overall, approximately three-quarters were classified as primarily resectable (A: 16, B: 15), and the remaining patients were classified as borderline resectable (A: 5, B: 4). Of the 12 evaluable patients, 3 achieved partial response under neoadjuvant FOLFIRINOX. Of the 21 patients in arm A and 19 patients in arm B, 17 and 7 underwent curative surgery, and R0-resection was achieved in 77% and 71%, respectively. Perioperative morbidity occurred in 72% in arm A and 46% in arm B, whereas non-surgical toxicity was comparable in both arms. Median RFS/PFS was almost doubled in arm B (14.1 months) compared with arm A (8.4 months) in the population with surgical resection, whereas median OS was comparable between both arms. CONCLUSIONS: Although the analysis was only descriptive owing to small patient numbers, no safety issues regarding surgical complications were observed in the perioperative FOLFIRINOX arm. Thus, considering the small number of patients, perioperative treatment approach appears feasible and potentially effective in well-selected cohorts of patients. In pancreatic cancer, patient selection before initiation of neoadjuvant therapy appears to be critical.

Impact of lymphadenectomy on the oncologic outcome of patients with adrenocortical carcinoma.

OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare malignancy with an unfavorable prognosis. The impact of a locoregional lymph node dissection (LND) has never been defined in this disease. We report the disease-specific outcome of patients treated with or without LND during primary adrenalectomy. METHODS: The medical records of patients followed by the German ACC Registry were retrospectively reviewed. Patients with incomplete resection or distant metastases were excluded. Only if the histologic analysis retrieved 5 or more lymph nodes, an intended LND was assumed (LND group). The predefined primary end point of the study was disease-specific survival. RESULTS: Of 283 included patients, 47 patients (16.6%) were treated with LND, whereas 236 patients (83.4%) underwent surgery without LND. Patients who underwent LND had a larger median tumor size (12.0 cm, range: 2.3-30 cm vs 10.0 cm, range: 4.0-39 cm, P = 0.007) and were more often treated by multivisceral resection (LND: 47.8% vs no-LND: 18.1%; P < 0.001). The other baseline characteristics (age, sex, endocrine activity, Weiss score, Ki-67 index, and adjuvant treatment) did not differ significantly. Median follow-up of all patients still alive was 40 months (range: 6-326). Multivariate analysis adjusted for age, tumor stage, multivisceral resection, adjuvant treatment, and lymph nodes status on preoperative imaging demonstrated a significantly reduced risk for tumor recurrence (hazard ratio: 0.65; 95% confidence interval: 0.43-0.98; P = 0.042) and for disease-related death (hazard ratio: 0.54; 95% confidence interval: 0.29-0.99; P = 0.049) in LND patients when compared with no-LND patients. CONCLUSIONS: Our retrospective data indicate that locoregional LND improves tumor staging and leads to a favorable oncologic outcome in patients with localized ACC.

Laparoscopic removal of a perforating intrauterine device mimicking chronic appendicitis.

The intrauterine contraceptive device (IUD) is a common form of reversible birth control. One of the rare, but serious, complications is uterine perforation. In this paper, we report a case of a patient who underwent laparoscopy for presumed chronic appendicitis. Intraoperatively, uterine perforation by the IUD was found. The IUD was removed laparoscopically. The postoperative course was uneventful.

Pancreatic head resection for invasive colon cancer--apropos of a case.

BACKGROUND: Despite the possibilities for early detection of colon cancer, some patients present with locally advanced cancer with invasion of adjacent organs. A case of right colonic cancer with infiltration of the duodenum and pancreas that was treated with hemicolectomy and duodeno-pancreatectomy (DP) en bloc is reported. CASE REPORT: A 76-year-old man was admitted to the local hospital due to anaemia, loss of weight and worsening clinical condition. Clinical examination, including upper and lower intestinoscopy and computed tomography of the abdomen, revealed right-sided colonic cancer with infiltration of the duodenum and the pancreas causing a bleeding duodenal ulcer that was the origin of the anaemia. The patient was transferred to our hospital for surgical therapy. The primary colon cancer seemed to be resectable without suspicion of hepatic metastases or peritoneal seeding, and a right-sided hemicolectomy with en bloc duodeno-pancreatectomy was carried out. Histopathological examination classified the tumour as pT4 pN1 (3/24) M0 G3 R0 according to stage III of the UICC classification. The patient recovered uneventfully. CONCLUSION: This case demonstrates that even common diseases such as colonic cancer may require a careful preoperative diagnosis so that a patient with a locally advanced tumour may be transferred to a specialist centre. With colorectal carcinoma, monobloc resection is standard, but a monobloc hemicolectomy on the right side and pancreatic head resection can only be performed in hospitals having sufficient expertise in pancreatic surgery.

32-year survival with metastatic adrenal cortical carcinoma--update of a case report.

Adrenal cortical carcinoma (ACC) is a rare and highly malignant tumour with up to 70% of the patients diagnosed at an advanced clinical stage and up to 40% presenting with metastasis. In 2004, we reported a case of a 62-year-old woman with a non-functional ACC of the left adrenal gland (T2 N0 M0, classified as stage II) who survived the disease for 28 years with 3 operations for metastases of the contralateral adrenal gland and 4 operations for metastases of the lung. We can now give an update of a further four years of survival and one additional operation. The case again emphasises the need for thorough radiographic examination and follow-up for the possibility of a repeated re-operation whenever possible to provide long-term survival over decades.

Sarcomatoid Adrenal Carcinoma: Case Report with Contribution to Pathogenesis.

A tumor in the adrenal region with two metastases in the liver was classified as poorly differentiated sarcoma on the base of extensive immunostainings (expression of vimentin, desmin, myogenin, and CD31, no expression of inhibin, melan A). Four years later in a second examination with molecular methods for a study of adrenal sarcomas, this diagnosis must be revised due to the lack of MDM-2 gene amplification and FKHR translocation which exclude sarcoma. Further immunostainings of many other parts of the tumor showed in one area more mature tumor tissue expressing synaptophysin, SF-1, and melan A. From these findings we classified an adrenal cortical cancer with predominant dedifferentiation into a sarcomatoid adrenal carcinoma. The properties of this very rare cancer type are presented and discussed.

State of the art management of adrenal masses--"how to do it?".

By the frequent use of computed tomography or ultrasound the detection of incidentally found adrenal tumours has become a common problem. This is also reflected in the worldwide proliferation of literature over the past decades. Most incidentally-found adrenal tumours are benign non-functioning cortical adenomas. But benign functioning tumours producing aldosterone, cortisol or catecholamines, adrenocortical carcinoma or adrenal gland metastasis can also be found. Surgical therapy is always indicated in case of hormonal overproduction or in case of suspected adrenocortical carcinoma; in all other cases the correct and adequate therapeutic approach is still under debate and a controversial topic of discussion. This review deals with the different forms of adrenal tumours regarding the optimal diagnostic and therapeutic approach to give physicians an easy-to-follow guideline.

On the use of unsealed polypropylene mesh as tracheal replacement.

The necessity of a cervical tracheal replacement arises with thyroid carcinoma, which occasionally infiltrates the trachea extensively, the rare primary tracheal tumors and, sporadically, benign stenoses. In the present study, we used an uncoated porous polypropylene prosthesis as cervical tracheal replacement in sheep. Specifically, we implanted a tracheal prosthesis of polypropylene mesh as a cervical tracheal replacement in five sheep, protecting the airways with self-expanding stents. Healing-in of the prostheses was checked bronchoscopically. The animals were killed after increasing survival times (7, 28, 64, 68, and >90 days), and incorporation of the prosthesis was examined macroscopically, microangiographically and histologically. Although medium-term survival was possible with a sufficiently wide airway, all animals were ultimately euthanized because of complications (airway stenosis, prolapse of prosthesis). Nevertheless, the results show that replacement of the cervical trachea with a polypropylene mesh can be successful under different experimental conditions.

Enteric-coated mycophenolate sodium: tolerability profile compared with mycophenolate mofetil.

Mycophenolate mofetil is one of the most frequently used immunosuppressive drugs in solid organ transplantation. Although the adverse effect profile of mycophenolate mofetil is comparatively benign, gastrointestinal adverse effects are a major concern. The adverse effects may require a dose reduction or discontinuation, thus limiting its clinical efficacy. Enteric-coated (EC) mycophenolate sodium is a new formulation of mycophenolic acid (MPA) that delivers the active moiety MPA, the same active moiety delivered by mycophenolate mofetil. It has been developed to help protect the upper gastrointestinal tract. It is implied that a reduction of adverse drug effects as well as a reduction of dose may improve efficacy and compliance. Noncompliance is often underestimated in solid organ transplant recipients, and adverse drug effects increase medication nonadherence. Recent clinical trials comparing EC mycophenolate sodium and mycophenolate mofetil in kidney recipients reported similar rates of efficacy and adverse effects. It is noteworthy that systemic MPA exposure is higher with EC mycophenolate sodium than with mycophenolate mofetil, without increased gastrointestinal toxicity. This finding is quite surprising, because part of MPA-associated gastrointestinal toxicity is related to its antiproliferative effect on enterocytes. However, enteric coating of MPA did not markedly reduce the number of gastrointestinal adverse effects. Further studies focusing on dosage, therapeutic drug monitoring and immunosuppressive regimens may reveal benefits of EC mycophenolate sodium for optimal individualised immunosuppression and improved compliance. At present, EC mycophenolate sodium is an alternative immunosuppressant to mycophenolate mofetil in kidney transplant recipients with an almost identical efficacy and safety profile.

Partial resection of the sternum for osseous metastasis of differentiated thyroid cancer: case report.

BACKGROUND: Due to their resistance to radio-iodine therapy, skeletal metastases from differentiated thyroid cancer (DTC) are difficult to treat. Surgical resection of solitary skeletal metastasis may offer cure with prolonged survival. CASE REPORT: A patient with the simultaneous appearance of local recurrence of DTC and skeletal metastasis of the cranial sternum is reported. After radical excision of the tumour recurrence and the lymph nodes, a partial sternal resection was carried out, and the defect in the chest wall was reconstructed with polypropylene mesh. Radio-iodine ablation therapy was carried out 4 times after the operation for locally recurrent disease. At the follow-up, 4 1/2 years after the resection of the sternal metastasis, the patient is free of disease. CONCLUSION: Sternal resection for solitary osseous metastasis of DTC should be performed on selected, individual patients. Reconstruction of the sternum with polypropylene mesh, as a simple and effective method, produces satisfactory functional and cosmetic results and allows a more effective radio-iodine treatment.

Surgical treatment of primary hyperparathyroidism.

BACKGROUND: With the use of routine calcium evaluation, the incidence of primary hyperparathyroidism (pHPT) has considerably increased. The aim of our study was the assessment of the morbidity and the outcome of surgically treated patients with pHPT. METHODS: The charts of 279 patients (204 female, 75 male, median age: 58 years) who underwent surgery for pHPT between 1989 and 1999 were retrospectively reviewed. A follow-up was carried out on 235 patients after a mean period of 3.6 years (0.2-10 years). RESULTS: In 148 patients a unilateral, and in 130 patients a bilateral approach was taken. Transplanted parathyroid tissue was removed from the left forearm of one patient. At follow-up persistent hypocalcemia was seen in 30 patients (20 after bilateral, 10 after unilateral exploration). 6 patients (1 after bilateral, 5 after unilateral exploration) revealed a newly developed persistent paresis of the recurrent laryngeal nerve. In 5 patients persistent (1 after unilateral, 4 after bilateral exploration) and in 5 patients recurrent (2 after unilateral, 3 after bilateral exploration) pHPT could be observed. CONCLUSION: Both unilateral and bilateral cervical exploration for pHPT have a high rate of success with a low morbidity. Therefore, patients with assumed asymptomatic pHPT with unspecific neuropsychological abnormalities should also be evaluated for surgical intervention.

Failure of airway healing in an ovine autotransplantation model that includes basic fibroblast growth factor.

OBJECTIVE: Basic fibroblast growth factor is among the most potent promoters of angiogenesis. Its ability to enhance the blood supply to ischemic airways or nonvascularized tracheal autograft has been demonstrated. Its cumulative effect with muscular wrapping and its efficacy in a noncanine large animal model remain unknown. Treatment with basic fibroblast growth factor and muscular wrapping were compared with no special treatment and with muscular wrapping alone in an ovine tracheal autotransplantation model. METHODS: All sheep underwent orthotopic tracheal transplantation with 5 to 8 ring autografts in the cervical trachea. Fifteen sheep were classified randomly into the following three groups: no treatment (group A, n = 5), muscular wrapping with the right sternomastoid muscle (group B, n = 5), and topical administration of fibrin glue enriched with 2 microg/cm(2) basic fibroblast growth factor (group C, n = 5). RESULTS: Devascularized tracheal autografts were unable to maintain their structural integrity without other treatment (group A). However, the grafts were surrounded by well-vascularized connective tissue. In the muscular wrapping group (group B), infections occurred around the grafts, and the muscular wrapping was subject to necrosis. No neovascularization of the grafts occurred. Therapy with basic fibroblast growth factor (group C) led to improved muscular wrapping circulation and to adherence to the tracheal stumps. However, no success was achieved in validating the circulation in the grafts. CONCLUSIONS: In contrast to the results achieved by other authors with canine models, the neovascularization of tracheal autografts was not achieved in sheep with the topical administration of basic fibroblast growth factor. Cranially pediculated muscular wrapping led to poorer circulation in the tissue around the graft than did no therapy at all.

Long-term survival over 28 years of a patient with metastatic adrenal cortical carcinoma--case report.

Adrenal cortical carcinoma (ACC) is a rare and highly malignant tumour with up to 70% of the patients diagnosed at an advanced clinical stage, up to 40% presenting with metastases. Even after complete surgical excision, up to 80% of the patients show locoregional recurrence or metastases. We report a case of a 62-year-old woman with a non-functional ACC of the left adrenal gland (T2N0M0 classified as stage II). After the initial resection, 3 operations for metastasis of the contralateral adrenal gland and 4 operations for metastasis of the lungs were carried out, allowing survival for more than 28 years with a good quality of life. This case report emphasises the need for careful clinical and radiographic follow-up. A repeat surgical approach should be adopted whenever possible providing long-term survival over decades.

The mechanical stability under load of tracheal anastomoses after various phases in vivo.

OBJECTIVE: The objective of our study was to postoperatively examine the mechanical stability under load of tracheal anastomoses over different periods in time and to compare these with native tracheae. STUDY DESIGN: A randomized experimental study on animals. METHOD: We performed tracheal anastomoses on sheep with three different suturing techniques and different resection lengths (3, 6, and 9 cm): These anastomoses were subjected to a breaking test at different intervals in vivo (1, 2, 4, 8, and 24 wk) and compared with the tracheae of healthy sheep. RESULTS: After 1 week in vivo, the anastomosis itself tore off from the remaining trachea under tension, regardless of the suturing technique used and the length of resection. With all animals that survived for a longer period, the trachea broke a greater distance away from the anastomosis. The necessary breaking forces were only minimally lower than those required for breaking healthy tracheae and the difference is statistically insignificant. When all operated tracheae are combined and the forces compared with native tracheae, this reveals that the operated tracheae are significantly more stable (P =.015) and present a lower longitudinal elasticity (P =.004). CONCLUSION: During the first postoperative days, the stability under load of tracheal anastomoses is slightly lower than that of healthy trachea. This difference is, however, far from those values that can be measured intraoperatively on tracheal anastomoses. Thus, supplementary measures for the mechanical protection against suture line separation do not seem necessary.

A comparison of bronchial closure with the aid of staples or suture: an experimental study on pig tracheae.

The objective of this study was to determine the resistance to pressure of a bronchial stump depending upon the closure technique. For the experimental study, 30 pig tracheae were alternatively closed either by a double-layer running suture at 90 degrees to the cartilaginous rings or with an automatic stapling device. Sutures were placed under pressure until air leakage was observed. The air leakage pressure was digitally recorded. A statistically significant difference existed between the two groups. The mechanical suture proved more resistant to pressure (p =.011). Thus, under ideal conditions, the resistance to pressure of a mechanical suture is equal to, if not better than, that of the manual suture.

The mechanical influence of tissue engineering techniques on tracheal strength: an experimental study on sheep trachea.

Tissue engineering is an attractive concept for facilitating the transplantation of different tissue types with a low immunogeneity and a well-preserved tissue structure. We examined the influence of treatment with trypsin/ethylenediamine tetraacetic acid (EDTA) on the mechanical properties of tracheae. Fresh sheep tracheae were stored in a trypsin/EDTA solution for various periods of time (24, 46, and 72 h) and their breaking strength was subsequently examined. The results were compared with native trachea. The treatment with trypsin/EDTA results in a considerable reduction of the mechanical stability under load, in this case compared with the tensile strength, that does not correlate with the results obtained from light-optical microscopy. The results from this study reveal that tissue preparation with trypsin/EDTA does not seem to be a suitable method of preparatory treatment of tracheae intended for transplantation.

Bilateral endoscopic adrenalectomy for Cushing's syndrome in a patient with polycystic liver and kidney disease.

Microadenomectomy via a transsphenoidal approach is today's treatment of choice to achieve normal cortisol blood levels in patients with ACTH-secreting pituitary tumors. Should neurosurgery fail, bilateral adrenalectomy is recommended. Today the endoscopic, transabdominal or retroperitoneal adrenalectomy is regarded as the gold standard for the operation of endocrine-active adrenal tumors. Therefore, in principle, the question of the indication for the endoscopic operation no longer arises but only the question of the technical feasibility in individual cases. We report on a patient with a pituitary-dependent Cushing's syndrome after a twice-repeated unsuccessful transsphenoidal adenomectomy and with additional polycystic kidney and liver disease, who underwent bilateral retroperitoneoscopic adrenalectomy. Despite the massive enlargement of both kidneys, it was possible to safely perform a bilateral retroperitoneoscopic adrenalectomy. In the case of marked bilateral cystic kidneys, a bilateral retroperitoneoscopic adrenalectomy in Cushing's syndrome is technical possible and a safe and effective method of treatment.

Benign retroperitoneal schwannoma mimicking an adrenal mass.

Adrenal tumors are frequently incidental discoveries, and the therapy for them is the subject of controversial discussions. We report herein on such an incidentaloma, which proved to be a benign retroperitoneal schwannoma. A 48-year-old female with an unclear adrenal mass underwent retroperitoneoscopic tumor extirpation. A well-defined tumor that displaced the adrenal gland and adhered firmly to only one retroperitoneal nerve was discovered. The en bloc resection was performed without problem. The histopathologic examination revealed a benign schwannoma. Retroperitoneal schwannomas can mimic a multitude of different conditions. Because imaging methods frequently do not yield distinct results, quite often only the operative exploration can establish a definitive diagnosis. In a case of unclear retroperitoneal findings, an endoscopic extirpation should be considered.

Therapy-resistant metastasizing anaplastic spermatocytic seminoma: a cytogenetic hybrid: a case report.

BACKGROUND: Anaplastic spermatocytic seminoma is a rare variant of the conventional spermatocytic seminoma, with only 6 cases reported up to now. The anaplastic variant contains only the medium-sized cell type, hallmarked by large-sized nucleoli, whereas the small lymphocyte-like and giant cells typical of the conventional spermatocytic seminoma are lacking. CASE: We report herein an unusual case of a 40-year-old man with an anaplastic spermatocytic seminoma which metastasized first to the retroperitoneal lymph nodes and, something never before reported, subsequently to the lung and other organs. The immunophenotype with c-kit and SALL4 positive and PLAP, as well OCT 3/4 negative tumor cells were identical to those of conventional spermatocytic seminoma. Cytogenetically the tumor cells showed a gain of chromosome 9, typical for spermatocytic seminoma, but simultaneously also the short arm 12p were overexpressed--an overexpression crucial to the aggressive behavior of seminomas and other nonseminomatous tumors but never before encountered in spermatocytic seminoma. CONCLUSION: The current opinion is that seminoma and nonseminomatous germ cell tumors develop from a common primitive progenitor cell, whereas spermatocytic seminomas develop from differentiated spermatogonia. The herein presented cytogenetic hybrid tumor shows that a crossover between the two different histogenetic "tracks" is possible.