The efficacy of sacituzumab govitecan and trastuzumab deruxtecan on stable and active brain metastases in metastatic breast cancer patients-a multicenter real-world analysis.

BACKGROUND: Fifteen to thirty percent of all patients with metastatic breast cancer (MBC) develop brain metastases (BCBMs). Recently, the antibody-drug conjugates (ADCs) sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) have shown to be highly effective in the treatment of MBC. However, there are only limited data whether these macromolecules are also effective in patients with BCBMs. We therefore aimed to examine the efficacy of SG and T-DXd in patients with stable and active BCBMs in a multicenter real-world analysis. PATIENTS AND METHODS: Female patients with stable or active BCBMs who were treated with either SG or T-DXd at three breast centers in Germany before 30 June 2023 were included. As per local clinical praxis, chemotherapy efficacy was evaluated by whole-body computed tomography and cranial magnetic resonance imaging at baseline and at least every 3 months according to local standards. Growth dynamics of BCBMs were assessed by board-certified neuroradiologists. RESULTS: Of 26 patients, with a median of 2.5 prior therapy lines in the metastatic setting (range 2-15), 12 (43%) and 16 (57%) patients received SG and T-DXd, respectively. Out of the 12 patients who received SG, 2 (17%) were subsequently treated with T-DXd. Five out of 12 (42%) and 5 out of 16 (31%) patients treated with SG and T-DXd, respectively, had active BCBMs at treatment initiation. The intracranial disease control rate was 42% [95% confidence interval (CI) 13% to 71%] for patients treated with SG and 88% (95% CI 72% to 100%) for patients treated with T-DXd. After a median follow-up of 12.7 months, median intracranial progression-free survival was 2.7 months (95% CI 1.6-10.5 months) for SG and 11.2 months (95% CI 7.5-23.7 months) for T-DXd. CONCLUSIONS: SG and T-DXd showed promising clinical activity in both stable and active BCBMs. Further prospective clinical studies designed to investigate the efficacy of modern ADCs on active and stable BCBMs are urgently needed.

The role of routine echocardiography in unselected patients with cerebrovascular ischaemic events.

BACKGROUND: Cardiac embolism is an important etiology of cerebrovascular ischaemic events (CIE). Echocardiography is routinely performed in patients with CIE despite guidelines recommending restriction of echocardiography to patients with clinically suspected cardioembolism. OBJECTIVE: The aim of this study was to examine the therapeutic impact and prognostic role of echocardiographic findings in an unselected population suffering from CIE. METHODS: Between November 2006 and November 2007, 319 patients with CIE underwent evaluation by transthoracic echocardiography (TTE) and in addition by transesophageal echocardiography (TEE) if deemed mandatory (n = 49). The combined clinical end-point included death or recurrent CIE, occurring during a follow-up period of 3 and 12 months, respectively. RESULTS: After 3 months of follow-up, the combined end-point was noted in 30 (9%) and after 12 months in 43 (13%) patients. In multivariate analysis, atrial fibrillation (AF) (HR 2.12, 95% CI 1.38-3.25; P < 0.001) and coronary artery disease (CAD: HR 1.85, 95% CI 1.21-2.81; P = 0.004) were predictors of events occurring during short-term follow-up. After 1 year of follow-up, AF (HR 1.67, 95% CI 1.19-2.32; P = 0.003) and CAD (HR 1.5, 95% CI 1.09-2.06; P = 0.01) were associated with the combined end-point. Echocardiographic parameters assessed at study entry were not independently related to an adverse outcome. CONCLUSION: Whereas AF and CAD appear to increase the risk of events after suffering from CIE, echocardiographic findings were not independently associated with the combined end-point of recurrent CIE or death.

Early prediction in acute pancreatitis: the contribution of amylase and lipase levels in peritoneal fluid.

CONTEXT: Predicting the severity of acute pancreatitis early in the course of the disease is still difficult. OBJECTIVE: The value of amylase and lipase levels in serum and peritoneal fluid might be of value in predicting the course of acute pancreatitis. DESIGN: Prospective study. PATIENTS: One-hundred and sixty-seven patients with acute pancreatitis as confirmed by computed tomography scan within 24 hours of admission were studied. MAIN OUTCOME MEASURES: Each patient was given an enzymatic score which reflected the predominance of serum or peritoneal levels of amylase and/or lipase. Enzymatic score was 0 if neither enzyme was predominant in the peritoneal fluid, 1 if amylase or lipase alone were predominant and 2 if both enzymes were predominant. The predictive value of the enzymatic score or computed tomography scan for a severe attack was determined. RESULTS: One-hundred and thirty-three attacks were graded as mild (79.6%) and 34 were considered as severe (20.4%). The frequency of severe acute pancreatitis significantly increased as the enzymatic score increased (5.4%, 12.5%, and 31.7% in 0, 1, and 2 enzymatic score patients, respectively; P<0.001). An enzymatic score greater than 0 predicted a severe outcome in 32 of 34 patients (sensitivity 94.1%, specificity 26.3%), whereas an enzymatic score of 2 predicted a severe attack in 26 of 34 patients (sensitivity 76.5%, specificity 57.9%). Edema on computed tomography scan was found in 97 of 129 mild attacks (specificity 75.2%) and necrosis in 25 of 33 severe attacks (sensitivity 75.8%), whereas all patients with severe attacks exhibited extrapancreatic acute fluid collection (sensitivity 100%, specificity 34.9%). CONCLUSIONS: Peritoneal dialysis is less predictive and more cumbersome than a computed tomography scan in the early prediction of acute pancreatitis.

Colon cancers and peritoneal mesothelioma occurring 29 years after abdominal radiation for testicular seminoma. A case report and review of the literature.

Secondary malignancies represent an increasing problem for long survivors of primary malignancies treated by chemo- and/or radiotherapy. The occurrence of secondary myelodysplasia and leukaemias after treatment for Hodgkin's disease is well established. Secondary solid tumors are mostly observed following radiation therapy. We report the case of a patient who presented 3 abdominal solid malignancies within 3 years, 29 years after abdominal radiotherapy for a testicular seminoma, namely 2 colon cancers and a peritoneal mesothelioma. Both types of cancer are independently reported in the literature to be more frequent in patients with a history of abdominal radiation than in the general population. To our knowledge there is no other reported case with 3, nearly simultaneously occurring separate solid tumors, which could all be related to former abdominal irradiation. Such a radiotherapy-related long-term side effect should be taken into account when considering adjuvant radiotherapy in patients with low-risk stage I testicular seminoma.

[Risk in major hepatectomy. A consecutive series of 113 extensive hepatectomies]. / Le risque des hépatectomies majeures. Une série consécutive de 113 hépatectomies larges.

Up to now, liver resections have been the initial treatment of almost all cancers and benign tumors limited to a liver lobe. This retrospective review assesses the results of a consecutive series of 113 major elective hepatic resections during a ten-year period. Major hepatectomy was defined by the resection of at least 3 Couinaud segments. Mean age was 52 years (20 to 79 years). There were 62 women and 51 men. 35 resections were performed for colorectal metastases, 22 for a benign tumor, 20 for non-colorectal metastases, 11 for hydatid disease, 10 for hepatocarcinoma, 7 for cholangiocarcinoma and 8 for other indications. The resections performed were 86 right hepatectomies with 18 extended right hepatectomies, 24 left hepatectomies with 4 extended left hepatectomies and 3 trisegmentectomies. Total vascular exclusion was used in 22 patients (19%). Mortality rate was zero. Significant morbidity was encountered in 24 patients (21%). These results suggest that the mortality rate may be independent of the extent of liver resection, provided that hepatic function is normal and preoperative selection adequate. With improving surgical management and techniques, and the use of intra-operative sonography, extensive liver surgery can now be performed with a very low mortality rate.

[Cephalic duodenopancreatectomy for pancreatic adenocarcinoma]. / Duodénopancréatectomie céphalique pour adénocarcinome pancréatique.

Cephalic duodenopancreatectomy is certainly the operation of choice in cases of adenocarcinoma of the pancreatic head. We evaluated the results of this operation in order to justify its indication and to pinpoint the factors that have an influence on the patients' prognosis after the operation. From 1982 to 1992, 386 patients were hospitalized in our department with the diagnosis of pancreatic cancer, all histological types included. Of these, 21 men and 18 women, mean age 65 years, underwent cephalic duodenopancreatectomy for adenocarcinoma. Associated with these operations were 3 liver metastasis excisions, 2 vascular resections, 1 colectomy and 1 splenectomy. All the tumors were operated on whenever technically possible, except those associated with distant metastasis. Postoperatively, only one patient died (on the 29th day, of viral meningitis). Postoperative morbidity was 51% with 23% local complications. There was one leakage of the anastomosis. Age, weight loss, history of pancreatitis or cirrhosis, anesthetic risk (ASA) and tumor staging were not found to be factors increasing the risk of postoperative complications. Survival after 1 year was 34% and after 5 years 6%. The degree of histological differentiation was the only factor that had any significant influence on the postoperative survival rate in our study. We conclude that cephalic duodenopancreatectomy is the treatment of choice which is capable of improving the quality, and to a lesser extent the length, of survival of patients suffering from pancreatic cancer, with acceptable postoperative mortality and morbidity rates.

Surgery for adult polycystic liver disease.

BACKGROUND: Occasionally patients with adult polycystic liver disease (APLD) have symptoms. For these patients surgery may represent a valuable therapeutic option to relieve symptoms. METHODS: From September 1977 to August 1993 at our institution, 10 women with APLD were examined and surgically treated. They underwent a partial hepatic resection together with cyst fenestration. The surgical outcome and long-term follow-up were retrospectively analyzed. RESULTS: Postoperative morbidity consisted of one case of pneumonia, and one case of acute pancreatitis with deep vein leg thrombosis. One patient died after acute Budd-Chiari syndrome developed as a result of liver collapse after fenestration of a posterior cyst. In the long term six of nine patients were symptom free. Late surgical complications included acute cholecystitis (one patient), small bowel obstruction (one), and incisional hernia (two). CONCLUSIONS: A combined surgical approach of hepatic resection and cyst fenestration has proved feasible for patients with highly symptomatic APLD. Extensive fenestration of posterior cysts should be avoided; transverse hepatic resection (frontal hepatectomy) up to the costal margin is proposed. This therapy provides good results at long-term follow-up.

[Islets of Langerhans allografts in the pig: initial results]. / Allogreffes d'îlots de Langerhans chez le porc: premiers résultats.

Islet of Langerhans transplantation represents a promising treatment of diabetes. Use of porcine islets for xenotransplantation could offer a solution to shortage of organ donors. However, isolation of pig islets remains a real challenge because of their marked fragility. Using a modified automated method for islet isolation, we performed 10 intraportal islet allografts in pigs. Surgically pancreatectomized pigs were transplanted with purified islet preparations pooled from pancreases of 3 donors (slaughter-house pigs, age 5-8 months). Six recipients were not immunosuppressed and four received an immunosuppressive treatment of Cyclosporine and Azathioprine. In the first group (non-immunosuppressed recipients), insulin secretion was observed for a mean of 4.8 days after transplantation. In the second group (with immunosuppressive treatment) the recipients sustained an insulin secretion for 6-9 days. However, in both groups liver biopsies showed signs of acute rejection and destruction of the transplanted islets. Pig islet allotransplantation, using as recipients surgically pancreatectomized pigs, can be considered as a suitable model to assess the functional results of mass islet isolation. We were able to reverse diabetes transitory in a large animal, by transplantation of purified pig islet preparations. However, even when an immunosuppressive treatment was administered to the recipients, rejection seemed to represent an important factor in the functional outcome of the islet grafts.

Surgical pitfalls in a patient with type IV Ehlers-Danlos syndrome and spontaneous colonic rupture. Report of a case.

PURPOSE: This paper intends to stress the importance of early diagnosis and discuss surgical treatment of Type IV Ehlers-Danlos syndrome (EDS-4), an autosomal dominant connective tissue disease characterized by typical features of the face and extremities, inappropriate and easy bruising, and extreme tissue fragility, which may lead to dramatic and often fatal complications, mostly spontaneous arterial or intestinal rupture. METHODS: We report the case of a 41-year-old female who presented with spontaneous perforation of the sigmoid colon. RESULTS: The patient was seen over a nine-year period, during which time she required six operations and presented with a great number of surgical complications including stenosis of an end-colostomy, repeated subocclusive episodes caused by intraperitoneal adhesions, and enterocutaneous fistulas, finally ending with an ileostomy and short bowel syndrome. It is only after a difficult laparotomy for ovarian cyst excision, marked by numerous adhesions and friable bowel, that the diagnosis of EDS-4 was considered and established. CONCLUSIONS: In case of "idiopathic" spontaneous perforation of the colon in a young adult, features of EDS-4 should be thoroughly looked into and, if found, skin fibroblast culture with collagen Type III analysis performed. The surgical treatment of choice consists of subtotal colectomy and permanent end-ileostomy. In case of patient refusal, a second-stage ileorectal anastomosis can be performed but carries the high risk of anastomotic leakage.

Acute left colonic diverticulitis in young patients.

BACKGROUND: This prospective study was done to compare acute left-sided colonic diverticulitis in young patients (50 years of age or less) and older patients (more than 50 years of age) for severity of disease and immediate and late outcome. STUDY DESIGN: Of the 265 patients studied, 61 were 50 years of age or less; of these, 49 were men. In all instances, diagnosis was confirmed radiologically or histologically. RESULTS: Operations were performed less often upon younger patients than older patients (15 versus 33 percent, p = 0.001). Severe diverticulitis was found more often in younger men than older men (39 versus 23 percent). After successful conservative treatment during the first hospitalization period, younger men had a statistically greater risk of poor outcome than older men (29 versus 5 percent, p = 0.003). CONCLUSIONS: Although younger men have severe acute diverticulitis more often than older men, operative treatment during the first episode is less often needed. On the other hand, after conservative treatment, younger men have a statistically greater chance of poor secondary outcome than older men.

[Insulinoma: experience in our hospital]. / Insulinomes: expérience dans notre clinique.

Insulinoma is the most frequent endocrinal tumor of the pancreas despite its very low incidence. This lesion induces hyperinsulinism, which has an atypical clinical symptomatology consisting of neurological symptoms and of signs by stimulation of the adrenergic system. Biological analyzes serve to confirm the presence of uncontrolled hyperinsulinism. Preoperative abdominal echography, abdominal CT-SCAN, angiography and portal catheterization serve to detect the pancreatic site of the insulinoma only in about 3/4 of the cases. However, the perioperative combination of manual palpation and abdominal echography reveal the exact site in almost all cases. For all these reasons we do not recommend attempting preoperative localization of the insulinoma and propose surgery as the treatment of choice when the diagnosis is established by biological features. Medical treatment is only applied to inoperable cases or in the presence of metastatic lesions. Surgical treatment should be economical on the pancreas and should be based solely on resection of the lesion, simple enucleation being the treatment of choice when the neighboring vascularly, biliary and digestive structures do not represent any technical risk. Whenever this is impracticable, right or left pancreatectomy seems to be the best option. We report our experience with 25 patients and analyze the benefits of pre- and perioperative examinations in the localization of insulinomas.

Acute left colonic diverticulitis: a prospective analysis of 226 consecutive cases.

BACKGROUND: The purpose of this prospective study was to evaluate the immediate and late outcome of acute left colonic diverticulitis and to correlate it with age (younger and older than 50 years of age), gender, and initial computed tomography (CT) findings. METHODS: Analysis was made of data collected prospectively from all patients admitted because of acute colonic diverticulitis between October 1986 and January 1992. Diagnosis relied on results of operation, CT, and Gastrografin enema. Two hundred twenty-six patients were urgently hospitalized for acute left colonic diverticulitis; 47 were younger than 50 years of age (21%). RESULTS: Sixty-six patients (29%) were operated on during their first hospitalization. The remaining 160 patients treated conservatively underwent CT and an enema within 72 hours of admission. Fifty-nine of 179 patients (33%) older than 50 years of age required operation during their first attack, compared with 7 in 47 patients (15%) younger than 50 years of age (p = 0.02), although on CT severe diverticulitis was found in 36 of 141 patients (26%) older than 50 years of age and in 16 of 43 patients (37%) younger than 50 years of age (p = 0.13). Of the 160 patients treated conservatively, 11 of 40 patients (28%) younger than 50 years of age experienced recurrences or complications after their first discharge, compared with 16 in 120 patients (13%) older than 50 years of age (p = 0.04). CONCLUSIONS: Patients younger than 50 years of age were significantly more prone to recurrences and complications after conservative treatment of their diverticulitis, whereas older patients required operation significantly more often during their first hospitalization.

[Cytomegalovirus in liver transplantation: incidence and groups at risk]. / Le cytomégalovirus chez les transplantés du foie: incidence et groupes à risques.

Cytomegalovirus (CMV) belongs to the family of Herpes viridae and has become the single most important viral pathogen in clinical transplantation. This is an endemic and ubiquitous virus. After transplantation it is necessary to distinguish CMV infection (positive seroconversion and/or isolation of the virus in the blood, urine, sputum or tissues in the absence of clinical symptoms) from CMV disease, which is a clinical expression of viremia in association with a documented CMV infection. The overall incidence of CMV infection in transplant recipients is about 50% and the incidence of CMV disease ranges from 15 to 25% whatever the transplanted organ. In this study (52 liver transplantations in 48 patients), 12 patients had CMV infection and 10 patients developed CMV disease (24%). The onset of CMV disease was 33 +/- 7 days after transplantation. Cytomegalovirus hepatitis was observed 7 times, CMV pneumonia once and 2 CMV infections characterized by oscillating fever in association with a hematological syndrome. 8 patients were treated with intravenous gancyclovir (DHPG, 9-[1,3-dihydroxy-2-propoxymethyl]-guanine) for 15 days and 2 patients by reduction of their immunosuppressive therapy only. There were significantly more (p < 0.05) opportunistic infections and/or bacteremia in patients with CMV disease. The association of CMV IgG negative recipients and CMV IgG positive donors appeared to be a significant factor (p < 0.05) for CMV disease. The number of transfusions, the level of immunosuppression and the absence of prophylaxis did not influence the incidence of CMV disease. Despite prolonged hospitalization and increased morbidity, there were no deaths in patients who developed CMV disease, which is good evidence of the efficacy of gancyclovir.(ABSTRACT TRUNCATED AT 250 WORDS)