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.

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.

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.

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.

Incarcerated femoral Littre's hernia-transperitoneal preperitoneal hernia repair (TAPP) and laparoscopic resection of the necrotic diverticulum.

Littre's hernias in the region of a femoral hernial orifice have been described in numerous cases in the literature. Open inguinal or femoral access was selected for all surgical procedures. We are describing the first case of an incarcerated Littre's hernia in the region of a femoral hernial orifice treated by means of transperitoneal preperitoneal hernia repair with simultaneous laparoscopic resection of the diverticulum. On the basis of the example, it is shown that the laparoscopic procedure is safe and efficient when performed by an experienced laparoscopic surgeon, even for treating incarcerated hernias, including the resection of necrotic tissue.

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.

The fate of homograft tracheal transplants in sheep.

OBJECTIVE: An established method of tracheal substitution is not yet available, but homograft tracheal transplantation might provide a realistic tracheal replacement. With the objective of sequentially examining the healing of tracheal homografts, we have established a suitable large-animal model. METHODS: Five sheep received orthotopic tracheal transplantation of a 4-cm cervical tracheal homograft. The trachea was supported for 6 weeks with a self-expanding polyester stent. The plan was to euthanize the animals after 2, 4, 8, 12 and 16 weeks, or whenever complications occurred. RESULTS: The implantation itself was performed without complications. After 2 weeks the homograft was firmly encapsulated by connective tissue, without signs of necrosis or abscess. The original mucous membrane no longer existed; the cartilage rings were exposed. In all animals that were euthanized at the later dates, the homografts were completely absorbed and replaced by inflammatory scar tissue. This, in turn, was covered with a shiny cellular surface layer. CONCLUSIONS: The results from this animal experiment reveal-contrary to data published to date-that tracheal homografts are not incorporated but absorbed. They are replaced by scar/granulation tissue that cannot secure the stability of the trachea. Therefore, further experiments with respect to the biocompatability of homografts appear to be necessary.

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.

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.

Basic immunosuppressive drugs outside solid organ transplantation.

Immunosuppressive drugs are the backbone of solid organ transplantation. The introduction of new immunosuppressive drugs led to improved patient and organ survival rates. Nowadays, acute rejection can be reduced to a minimum. Individualization and avoidance of drug-related adverse effects became a new goal to achieve. The potency of immunosuppressive drugs makes them attractive for use in various autoimmune diseases; therefore, the experience on immunosuppressive drugs outside the field of organ transplantation is analysed in this review.

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.

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.

Presentation and therapy of myelolipoma.

BACKGROUND: Adrenal myelolipoma is a rare and benign, hormonally inactive tumor frequently discovered incidentally. Because of the increasing rate of detection of adrenal myelolipoma, use of the correct diagnostic examination and treatment, with respect to surgical excision or regular controls, is continually gaining importance. We report herein on the largest series of surgically treated patients with adrenal myelolipoma from a single institute. METHODS: The clinical charts of 12 patients who underwent adrenal surgery for myelolipoma were reviewed. Follow up was carried out by means of re-examination or by personal contact with the primary physician. It was possible to perform a re-examination on eight of the 12 patients 6.9 years after the operation: one patient had died 5.2 years after surgery. RESULTS: Diagnosis of adrenal myelolipoma was made incidentally in seven patients, and during examination for reasons of unspecific abdominal or flank pain in five patients. A transabdominal approach was taken in five patients, a subcostal approach was taken in three patients and a translumbal approach was taken in four patients. At the follow up, all formerly symptomatic patients were free of symptoms. No recurrence could be seen; however, in one patient a contralateral adrenal myelolipoma had developed. CONCLUSIONS: Symptomatic tumors, growing tumors or tumors larger than 10 cm should be excised surgically by means of an endoscopic or conventional approach, depending on the size. Surgical indication should not be liberalized by the introduction of more gentle operative techniques such as the translumbal or the endoscopic approach. A close follow up should be maintained in the case of patients free of symptoms, and for those with a definite diagnosis from imaging procedures.

Long-term follow-up after adrenalectomy for primary aldosteronism.

The objective of this study was to assess the long-term effects of adrenalectomy on the blood pressure and antihypertensive medication in patients with primary aldosteronism (PA). Twenty-four patients (15 female and 9 male) with a mean age of 48.3 +/- 10.8 years underwent surgery for PA in our institution between 1988 and 2001. All subjects were re-examined with a complete clinical work-up after a mean follow-up period of 86 +/- 48 months, including blood pressure readings (<140/90 mmHg defined as normal), endocrine adrenal function, and specific medication. All patients suffered from hypertension (onset 8.5 +/- 5.5 years prior to surgery). In 92% of the patients, hypokalemia was present (onset 2.0 +/- 2.6 years prior to surgery). The histopathologic examinations revealed unilateral adenomas in 23 patients and a bilateral hyperplasia in one patient. At follow-up, 33% (8) of the patients were completely cured (normal blood pressure and no antihypertensive treatment), with seven of these eight patients being under 50 years of age at the time of surgery. One patient revealed a contralateral aldosterone-secreting adrenal adenoma during the subsequent endocrine and imaging examination 44 months after the first operation. Despite normalized plasma-aldosterone concentration (PAC), plasma-renin-activity (PRA) and serum potassium levels, a long-lasting insufficiently treated hypertension due to the delayed diagnosis in patients with PA may explain the persistent blood pressure elevation, indicating the necessity of a life-long, regular control of the blood pressure and antihypertensive medication.

Cushing's syndrome: adrenalectomy and long-term results.

BACKGROUND: The objective of this study was to assess the preoperative symptoms, intra- and postoperative complications and follow-up in patients after uni- or bilateral adrenalectomy due to Cushing's syndrome (CS), independent of etiology. METHODS: Clinical charts of 42 patients (5 with ACTH-dependent, 37 with ACTH-independent CS) were reviewed, and follow-up data were obtained from re-examination of the patients. RESULTS: The symptoms most frequently seen were hypertension, changes of the skin and obesity. Eight bilateral and 36 unilateral adrenalectomies were carried out without any intraoperative complications. Postoperative complications occurred in 5 patients, 1 patient died on the fourth postoperative day. After a mean duration of 4.6 years 28 of 41 patients could be re-examined, 5 patients had died. One patient showed recurrence 4.3 years after unilateral adrenalectomy due to nodular hyperplasia, contralateral adrenalectomy again revealed nodular hyperplasia. CONCLUSION: Early diagnosis is essential in order to decrease the rate of pre-, intra- and postoperative complications. Endoscopic approach should be taken in a specialized center due to poor patient's condition. Recurrent disease on the contralateral side may represent bilateral adrenal hyperplasia with sequential tumor formation, demonstrating the importance of extensive preoperative biochemical and imaging testing and close follow-up.

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.